Photochemical ultraviolet absorber precursors and compounds for increasing their photochemical conversion rates - Patents.com

Abstract

An effective amount of a compound of formula (I), a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof (wherein R', R 1、 R2, R4, R 5、 R 6、 R7, R9 and R 10 is selected from the list of possible radicals); and an effective amount of a phenylethyl ester selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate, and 1-phenylethyl benzoate, together with one or more pharmaceutically or cosmetically acceptable excipients or carriers. Use of the composition to provide protection for skin or hair against sunlight or other sources of UV radiation, and a method for increasing the photochemical conversion rate of a compound of formula (I) in a composition by adding an effective amount of the specific phenylethyl ester, are also provided. [Formula 1] TIFF2025525668000020.tif66159

Description

[Technical Field]

[0001] This application claims the benefit of European Patent Application No. 22382742.9, filed July 29, 2022.

[0002] The present invention relates to the field of cosmetics, and in particular to a cosmetic composition comprising a photochemical precursor of an ultraviolet (UV) absorber and a phenyl ethyl ester, and a method for photochemically converting the photochemical UV absorber precursor to a UV absorber with a high conversion rate. [Background technology]

[0003] Overexposure to the sun's invisible rays, ultraviolet A (UVA, 320-400 nm) and ultraviolet B (UVB, 290-320 nm), can cause skin damage, both immediate and long-term, with effects ranging from sunburn, rashes, cell and tissue damage to premature wrinkling and skin cancer.

[0004] Sunscreen helps prevent sunburn and reduces the harmful effects of the sun, including premature skin aging and skin cancer. Sunscreen should be applied 20 to 30 minutes before sun exposure.

[0005] Excessive exposure to both UVB (wavelengths 290-320 nm) and UVA (wavelengths 320-400 nm) is known to damage the skin. UVB is the most erythema-inducing form of solar radiation reaching the Earth's surface. SPF (Sun Protection Factor) indicates the degree of protection against UVB-induced erythema. SPF indicates the length of time it takes sunscreen-protected skin to develop minimal redness (erythema) after UV exposure compared to the length of time it takes unprotected skin. Thus, SPF primarily indicates the degree of protection against UVB. High SPF sunscreen products have led to the use of multiple individual sunscreen active agents, used in combination at the highest concentrations where they may interact.

[0006] Avobenzone (4-tert-butyl-4'-methoxydibenzoylmethane, Parsol 1789) is one of the most commonly used UVA filters because it provides excellent protection across most of the UVA range. However, as with other dibenzoylmethane derivatives, concerns have been raised regarding its photostability and its potential to degrade other sunscreen ingredients in the products in which it is used.

[0007] Several benzoic acid esters have been described as photochemical UV absorber precursors, and their photoprotective activity is due to the fact that they are susceptible to in situ photochemical conversion to sunscreen active agents with enhanced UV protection.

[0008] As an example, we first proposed methoxyphenylethenyl t-butylbenzoate (also known as 1-(4-methoxyphenyl)-vinyl 4-tert-butylbenzoate or 1-(4-methoxyphenyl)ethenyl 4-tert-butylbenzoate, CAS 910910-36-0), a vinyl ester precursor of avobenzone, as a solution to overcome the stability issues mentioned above.

[0009] Methoxyphenylethenyl t-butyl benzoate is converted to avobenzone according to the following reaction: [ka]

[0010] However, the conversion to avobenzone is relatively slow and incomplete, which has the drawback of delaying the action of avobenzone as a UVA filter.

[0011] Therefore, there remains a need to provide sunscreen compositions containing photochemical UV absorber precursors, such as methoxyphenyl ethenyl t-butyl benzoate, that overcome the problems of prior art formulations containing such precursors. Summary of the Invention

[0012] In an attempt to develop improved sunscreen formulations containing certain benzoic acid esters that are photochemical UV absorber precursors, such as methoxyphenylethenyl t-butyl benzoate (which is photochemically converted to avobenzone), the inventors have found that by combining the referenced benzoic acid esters with phenylethyl esters, the photochemical conversion of the benzoic acid esters to the corresponding UV absorbers occurs at a higher rate than in the absence of the referenced phenylethyl esters.

[0013] Surprisingly, it has been discovered that incorporating a phenylethyl ester, such as phenethyl benzoate (also known as 2-phenylethyl benzoate), into compositions containing certain benzoic acid esters, such as methoxyphenylethenyl t-butyl benzoate, and more specifically into sunscreen formulations containing certain UV sunscreen actives, can result in stable sunscreen compositions that provide rapid and high protection against both UVA and UVB radiation. Furthermore, the combination of the phenylethyl esters with the mentioned benzoic acid esters can increase the photostability of compositions, particularly sunscreen formulations containing UV sunscreen actives. As can be seen in Tables 2-8, absorbance values are maintained up to 10 MED for phenethyl benzoate (PEB), dibutyl adipate (DBA), and diisopropyl adipate (DIPA), while the absorbance values for the remaining emollients decrease as irradiation increases from about 2.5 MED.

[0014] Thus, one aspect of the present invention is A compound of formula (I), or a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof: [ka] (In the formula, R' is selected from the group consisting of H, (C1-C6)-alkyl, and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6, R7, R9, and R10 are radicals independently selected from the group consisting of H, hydroxy, amino, (C-C)-alkyl, (C-C)-alkoxy, (C-C)-alkylamino, and (C-C)-dialkylamino; and R and R are independently selected from the group consisting of (C-C)-alkyl, (C-C)-alkoxy, hydroxy, amino, (C-C)-alkylamino, and (C-C)-dialkylamino, such as 1-(4-methoxyphenyl)ethenyl 4-tert-butylbenzoate. an effective amount of, and an effective amount of a phenylethyl ester selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate, and 1-phenylethyl benzoate; together with one or more pharmaceutically or cosmetically acceptable excipients or carriers, Represents a composition.

[0015] Another aspect of the present invention refers to the use of a composition as defined hereinabove and below for providing protection to skin or hair against sunlight or other sources of UV radiation. This aspect may also be formulated as a composition as defined hereinabove and below for providing protection to skin or hair against sunlight or other sources of UV radiation. This use relates to a method for protecting a human or animal organism from UV radiation, comprising treating said human or animal organism with an effective amount of a composition as defined hereinabove and below. In particular, the human or animal organism is a human.

[0016] In another aspect, the present invention provides a method for increasing the rate of photochemical conversion of a compound of formula (I) as defined above or below to a compound of formula (II), a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof or a mixture thereof, in a composition, the method comprising the step of adding to the composition an effective amount of a phenylethyl ester selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate, and 1-phenylethyl benzoate: [ka] (In the formula, R' is selected from the group consisting of H, (C1-C6)-alkyl, and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6R7, R9, and R 10 are radicals independently selected from the group consisting of H, hydroxy, amino, (C-C)-alkyl, (C-C)-alkoxy, (C-C)-alkylamino, and (C-C)-dialkylamino; R and R are independently selected from the group consisting of (C-C)-alkyl, (C-C)-alkoxy, hydroxy, amino, (C-C)-alkylamino, and (C-C)-dialkylamino. This embodiment can also be described as the use of a phenyl ester selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate, and 1-phenylethyl benzoate to increase the rate of photochemical conversion of a compound of formula (I) as defined hereinabove and below to a compound of formula (II), a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof, in a cosmetic composition.

[0017] An example of a compound of formula (I) is methoxyphenylethenyl t-butyl benzoate, which is photochemically converted to avobenzone. [Brief explanation of the drawings]

[0018] [Figure 1] Figure 1 shows the results of UVA-PF values in photoactivation tests with 2 (w / w)% methoxyphenylethenyl t-butyl benzoate solutions in different emollients: phenethyl benzoate (PEB), dibutyl adipate (DBA), diisopropyl adipate (DIPA), C12-15 alkyl benzoate (C12-15 AB), dicaprylyl carbonate (DCC), cocoglyceride (CCG), and caprylic / capric triglyceride (CCT). [Figure 2] FIG. 2 shows the SPF results of a photoactivation test with a 2% (w / w) methoxyphenylethenyl t-butyl benzoate solution in different emollients. [Figure 3] FIG. 3 shows the absorbance at 360 nm (Abs 360 nm) results of a photoactivation study with 2% (w / w) methoxyphenylethenyl t-butyl benzoate solution in different emollients. [Figure 4] FIG. 4 shows the results of the absorption spectra of 2 wt % methoxyphenylethenyl t-butyl benzoate solutions in phenethyl benzoate at different irradiation doses. [Figure 5] FIG. 5 shows the absorbance results at 360 nm (Abs 360 nm) of 2 wt % methoxyphenylethenyl t-butyl benzoate solutions in phenethyl benzoate, C 12-15 alkyl benzoate, or dibutyl adipate at different irradiation doses. [Figure 6] Figures 6-a, 6-b, and 6-c show the activation rate of methoxyphenylethenyl t-butylbenzoate (PvB) with phenethyl benzoate (PEB), dibutyl adipate (DBA), and C12-15 alkyl benzoate (C12-15 AB), respectively. [Figure 7]FIG. 7 shows the UVA-PF results obtained with several oil phases including: A: a mixture of homosalate, bis-ethylhexyloxyphenol methoxyphenyl triazine, diethylaminohydroxybenzoyl hexyl benzoate, ethylhexyl triazone, and dibutyl adipate (Comparative Example 7); B: a mixture of A and methoxyphenylethenyl t-butyl benzoate (Comparative Example 8); C: a mixture of A and phenethyl benzoate (Comparative Example 9); and D: a mixture of A and methoxyphenylethenyl t-butyl benzoate and phenethyl benzoate (Example 2). [Figure 8] FIG. 8 shows the absorbance at 360 nm (Abs 360 nm) results obtained for oil phases A, B, C, and D described above. [Figure 9] Figure 9 shows the results of the SPF values obtained with the oil phases A, B, C and D described above. DETAILED DESCRIPTION OF THE INVENTION

[0019] Detailed Description All terms used herein in this application shall be understood to have the ordinary meaning known in the art unless otherwise stated.Other more specific definitions for specific terms used in this application are as follows, and are intended to be uniformly applied throughout the specification and claims unless other clearly defined definitions provide a broader definition.For the purpose of this disclosure, all ranges provided include both the lower and upper limits of this range.Provided ranges, such as temperature and amount, should be considered approximate unless specifically stated.

[0020] The term "sunscreen active," as used herein, refers to a single or combination of materials that are considered acceptable for use as an active sunscreen ingredient with respect to their ability to absorb, scatter, or reflect UV radiation. Such compounds are generally described as UVA sunscreen actives, UVB sunscreen actives, or UVA / UVB sunscreen actives, depending on the range of wavelengths of UV radiation.

[0021] The term "UV-A" refers to ultraviolet electromagnetic radiation having a wavelength of about 320 nm to about 400 nm.

[0022] The term "UV-B" refers to ultraviolet electromagnetic radiation having wavelengths between about 290 nm and about 320 nm.

[0023] The term "sunscreen composition" refers to a composition intended for topical application to provide protection to skin or hair against the sun's rays or other sources of UV radiation.

[0024] The terms "UVA absorber" or "UVB absorber" refer to an active agent that has the ability to absorb UVA radiation or UVB radiation, respectively.

[0025] SPF (Sun Protection Factor) refers to the ratio of the minimal erythema dose (MED) of skin protected by a sunscreen product to the minimal erythema dose (MED) of the same skin unprotected.

[0026] The minimal erythemal dose (MED) is the amount of UV radiation that produces minimal erythema (burn or redness caused by dilation of capillaries) on an individual's skin within a few hours after exposure.

[0027] UVA-PF (UVA protection factor) refers to the ratio of the minimum UVA radiation dose required to induce a consistent pigment darkening in skin protected by a sunscreen product to the minimum UVA radiation dose required to induce a minimal darkening effect on the same unprotected skin.

[0028] The term "effective amount," as used herein, refers to a sufficient amount of a designated active ingredient to provide a sought-after effect or desired performance attribute.

[0029] All percentages used herein are by weight of the total composition unless otherwise stated. In all compositions of this disclosure, the total of all components equals 100%.

[0030] As used herein, the indefinite articles "a" and "an" are synonymous with "at least one" or "one or more." Unless otherwise stated, definite articles such as "the" also include plural nouns.

[0031] Throughout this specification and claims, the terms (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, and (C1-C 6) -dialkylamino is understood to be linear or branched.

[0032] As mentioned above, an embodiment of the present invention is a compound of formula (I), or a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof, wherein R' is selected from the group consisting of H, (C1-C6)-alkyl, and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6, R7, R9, and R 10 are radicals independently selected from the group consisting of H, hydroxy, amino, (C-C)-alkyl, (C-C)-alkoxy, (C-C)-alkylamino, and (C-C)-dialkylamino; and R and R are independently selected from the group consisting of (C-C)-alkyl, (C-C)-alkoxy, hydroxy, amino, (C-C)-alkylamino, and (C-C)-dialkylamino), and a phenylethyl ester selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate, and 1-phenylethyl benzoate, together with one or more pharmaceutically or cosmetically acceptable excipients or carriers.

[0033] It is understood that the composition may be a pharmaceutical or cosmetic composition.

[0034] Compounds of formula (I) in which R' is different from H exhibit cis-trans isomerism. Thus, compounds of formula (I) may consist of a mixture of isomers. If desired, the isomers may be separated by conventional purification means.

[0035] In certain embodiments, R' is H in compounds of formula (I) and compounds of formula (II).

[0036] In another particular embodiment, in the compounds of formula (I) and compounds of formula (II), R, R, R, R, R, R, R and R 10 is a radical independently selected from the group consisting of H, hydroxy, amino, and methyl.

[0037] In another particular embodiment, in the compounds of formula (I) and compounds of formula (II), R2, R4, R7 and R9 are H.

[0038] In another particular embodiment, in the compounds of formula (I) and compounds of formula (II), R', R1, R2, R4, R5, R6, R7, R9 and R 10 is H; R3 is tert-butyl, and R8 is methoxyl. Preferred compounds of formula (I) are: 1-phenylvinyl 4-methoxybenzoate; methoxyphenylethenyl t-butylbenzoate; 1-(4-tert-butylphenyl)vinyl 4-methoxybenzoate; and 1-phenylvinyl 4-tert-butylbenzoate. More preferably, the compound of formula (I) is methoxyphenylethenyl t-butylbenzoate.

[0039] The term "cosmetically acceptable" refers to excipients or carriers that are suitable for use in contact with human skin, particularly without undue toxicity, incompatibility, instability, or allergic response.

[0040] The expression "pharmaceutically acceptable excipient or carrier" refers to a pharmaceutically acceptable substance, composition, or vehicle. Each component must be pharmaceutically acceptable in the sense of being compatible with the other components of the pharmaceutical composition. It must also be suitable for use in contact with the tissues or organs of humans and animals without undue toxicity, irritation, allergic response, immunogenicity, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0041] The term "pharmaceutically or cosmetically acceptable salt" refers to a non-toxic salt. Since some compounds of formula (I) are basic compounds, salts may be prepared with pharmaceutically or cosmetically acceptable non-toxic acids. The compounds of formula (II) may also be in the form of pharmaceutically or cosmetically acceptable salts. As used herein, the term "pharmaceutically or cosmetically acceptable salt" in reference to compounds (I) and (II) includes any salt formed with organic and inorganic acids, such as hydrobromic acid, hydrochloric acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, adipic acid, aspartic acid, benzenesulfonic acid, benzoic acid, citric acid, ethanesulfonic acid, formic acid, fumaric acid, glutamic acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, 1,5-naphthalenesulfonic acid, oxalic acid, pivalic acid, propionic acid, p-toluenesulfonic acid, succinic acid, tartaric acid, etc.

[0042] Compounds of formula (I) can be obtained by a wide variety of methods disclosed in the art. Thus, WO 2006 / 100225 discloses benzoic acid ester compounds and a process for their preparation based on the reaction of an intermediate silyl enol ether with an acyl halide according to the following scheme (where R1 to R 21 and R' have the values defined therein). [ka]

[0043] The preparation of pharmaceutically or cosmetically acceptable salts of compounds of formula (I) can be carried out by methods known in the art.For example, they can be prepared from parent compounds containing a basic moiety by conventional chemical methods.Generally, such salts are prepared by, for example, reacting the free base form of these compounds with a stoichiometric amount of a suitable pharmaceutically or cosmetically acceptable acid in water or an organic solvent or a mixture thereof.

[0044] The compounds of formula (I) may be in crystalline form as free solvates or as solvates (e.g., hydrates), and it is intended that both forms are within the scope of the present invention. Methods of solvation are generally known in the art.

[0045] The term "solvate" refers to a molecular complex comprising a compound of formula (I) or a salt thereof and a stoichiometric or non-stoichiometric amount of one or more solvent molecules bound by non-covalent intermolecular forces. When one or more of the solvent molecules forming part of the molecular complex is water, the solvate is a hydrate.

[0046] The compound of formula (I) or a salt thereof can be further purified, for example, by crystallization in a suitable solvent. Examples of suitable solvents are (C2-C6)-alcohols such as ethanol or 2-propanol. The compound of formula (I) can be obtained with a purity of 99% or more by HPLC. In certain embodiments, the compound of formula (I) is obtained with a high purity of 99.5% or more. Other suitable solvents for the purification step are (C2-C6)-alcohols such as toluene or xylene. 6- The solvent may be a (C-C)-aromatic hydrocarbon, a (C-C)-chlorine-containing solvent such as dichloromethane, dichloroethane, or a mixture of a (C-C)-aromatic hydrocarbon and a (C-C)-alcohol. In a particular embodiment, the solvent mixture is 2-propanol / toluene.

[0047] As mentioned above, the compositions of the present invention also include a phenylethyl ester, which is typically used as an emollient, but which is used in the compositions of the present invention to increase the conversion rate of the photochemical UV absorber precursor compared to the conversion in the absence of the mentioned phenylethyl ester.

[0048] In one embodiment, optionally in combination with one or more features of the above-defined embodiments, the phenylethyl ester is phenethyl benzoate.

[0049] In another embodiment of the composition of the present disclosure, the compound of formula (I), optionally in combination with one or more features of the embodiments defined above, is present in an amount of 0.1 wt.% to 6 wt.%, preferably 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

[0050] In another embodiment of the composition of the present disclosure, the phenylethyl ester, optionally in combination with one or more features of the embodiments defined above, is present in an amount of 0.1 wt.% to 40 wt.%, preferably 0.5 wt.% to 25 wt.%, more preferably 2 wt.% to 15 wt.%, and even more preferably 2 wt.% to 6 wt.%, relative to the total weight of the composition.

[0051] In another embodiment of the composition of the present disclosure, the compound of formula (I), optionally in combination with one or more features of the embodiments defined above, is present in an amount of 0.1 wt.% to 6 wt.%, preferably 0.5 wt.wt.% to 5 wt.%, relative to the total weight of the composition; and the phenylethyl ester is present in an amount of 0.1 wt.% to 40 wt.%, preferably 0.5 wt.% to 25 wt.%, more preferably 2 wt.% to 15 wt.%, even more preferably 2 wt.% to 6 wt.%, relative to the total weight of the composition.

[0052] In another embodiment, optionally in combination with one or more features of the above-defined embodiments, the composition further comprises a UV sunscreen active. In particular, the composition of the present invention may be a sunscreen composition.

[0053] By way of example, the UV sunscreen active may be in an amount such that the composition has an SPF of at least 30, preferably at least 35 to at least 50, more preferably at least 50. The amount of UVB sunscreen active will depend on the particular UVB sunscreen active, or mixture of UVB sunscreen active, UVA sunscreen active, or UVA / UVB sunscreen active, used and can be readily determined by one of ordinary skill in the art.

[0054] Examples of UV sunscreen actives include: octyl salicylate (2-ethylhexyl salicylate, Escarol 587); pentyl dimethyl PABA; octyl dimethyl PABA (padimate O, Escarol 507); benzophenone-1; benzophenone-6 (Uvinul D-49); 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (Uvinul 3028); ethyl-2-cyano-3,3-diphenylacrylate (Uvinul 3035); homomenthyl salicylate (homosalate); bis-ethylhexyloxyphenol methoxyphenyl triazine (bemotridinol, Escarol S); methyl-(1,2,2,6,6-pentamethyl-4-piperidyl)-sebacate (Uvinul 4092H); Benzenepropanoic acid, 3,5-bis(1,1-dimethyl-ethyl)-4-hydroxy-, C7-C9 branched alkyl ester (Irganox 1135); 2-(2H-benzotriazol-2-yl)-4-methylphenol (Uvinul 3033P); Diethylhexyl butamidotrizone (iscotrizinol, Uvasorb HEB); Amyl dimethyl PABA (risazimate, glyceryl PABA); 4,6-bis(octylthiomethyl)-o-cresol (Irganox 1520); CAS number 65447-77-0 (Uvinul 5062H, Uvinul 5062GR); Red petroleum; Ethylhexyl triazone (Uvinul T-150); Octocrylene (Escalol 597); Isoamyl-p-methoxycinnamate (amiloxate, Neo Heliopan E1000; drometrizole; titanium dioxide (including nanomaterials); 2,4-di-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-phenol (Uvinul 3027); 2-hydroxy-4-octyloxybenzophenone (Uvinul 3008); benzophenone-2 (Uvinul D-50); diisopropylmethylcinnamate; PEG-25 PABA;2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl-4-methylphenyl acrylate (Irganox 3052; Drometrizole trisiloxane (Mexoryl XL); Menthyl anthranilate (Melazimate); Bis-(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate; Butyl methoxydibenzoylmethane (Avobenzone, Escarol 517); 2-Ethoxyethyl p-methoxycinnamate (Cinoxate); Benzylidene camphorsulfonate (Mexoryl SL); Dimethoxyphenyl-[1-(3,4)]-4,4-dimethyl-1,3-pentanedione; Zinc oxide (including as a nanomaterial); N,N'-Hexane-1,6-diyl-bis[3-(3,5-di-tert-butyl-4-hydroxyphenylpropionamide)] (Irganox 1098); Pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] (Irganox 1010); 2,6-di-tert-butyl-4-[4,6-bis(octylthio)-1,3,5-triazinon-2-ylamino]phenol (Irganox 565); 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol (Uvinul 3034); salicylic acid trolamine (triethanolamine salicylate); diethanolamine (diethylanolamine) p-methoxycinnamate (DEA methoxycinnamate); polysilicone-15 (Parsol SLX); CAS number 152261-33-1 (Uvinul 5050H); 4-methylbenzylidene camphor (Eusolex 6300, Parsol 5000); bisoctrizole (Tinosorb 1010) containing nanomaterials M); Benzenamine, N-phenyl-, reaction products with 2,4,4-trimethylpentene (Irganox 50507); Sulisobenzone, Escalol 577); (2-Ethylhexyl)-2-cyano-3,3-diphenylacrylate (Uvinul 3039); Digalloyl trioleate; Polyacrylamidomethyl benzylidene camphor; Glyceryl ethylhexanoate dimethoxycinnamate;1,3-bis-[(2'-cyano-3',3'-diphenylacryloyl)oxy]-2,2-bis-{[(2'-cyano-.bis-(2,2,6,6-tetramethyl-4-piperidyl)-sebacate (Uvinul 4077H); Benzophenone-5 (sulisobenzone sodium); 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (Irganox 3114); 1,3,5-triazine, 2,4,6-tris(1,1'-biphenyl)-4-yl-, including as nanomaterials; Hexamethylenediamine (Uvinul 4050H); Benzophenone-8 (dioxybenzone); Ethyl-4-bis(hydroxypropyl)aminobenzoate (loxazimate); 6-tert-butyl-2-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol (Uvinul 3026); p-Aminobenzoic acid (PABA); 3,3',3'',5,5',5''-Hexa-tert-butyl-α-α'-α''-(mesitylene-2,4,6-triyl)tri-p-cresol (Irganox 1130); Dihydroxyacetone with Lawsone; Benzophenone-9 (Uvinul DS-49); Benzophenone-4 (sulisobenzone); Ethylhexyl Dimethoxybenzylidene dioxoimidazoline propionate; N,N'-bisformyl-N,N'-bis-(2,2,6,6-tetramethyl-4-piperidinyl)-; 3-benzylidene camphor (Mexoryl SD); terephthalylidene dicamphorsulfonic acid; camphor benzalkonium methosulfate (Mexoryl SO); bisdisulizole disodium (Neoheliopan AP); etocrylene; ferulic acid; 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol (Uvinul 3029); ecamsule (MexorylSX); 4,6-to(dodecylthiomethyl)-o-cresol (Irganox 1726); β-2-glucopyranoxypropyl hydroxybenzophenone; phenylbenzimidazole sulfonic acid (ensulizole, Eusolex 232, Parsol HS); Benzophenone-3 (oxybenzone, Escalol 567);Diethylamine hydroxybenzoyl hexyl benzoate (Uvinul A Plus); 3',3'-diphenylacryloyl)oxy]methyl}-propane (Uvinul 3030); 3,3#-(1,4-phenylene)bis(5,6-diphenyl-1,2,4-triazine); 2-ethoxyethyl (2Z)-2-cyano-2-[3-(3-methoxypropylamino)cyclohexyl-2-en-1-ylidene]acetate and p-methoxyethylhexyl cinnamate (Escalol 557).

[0055] The UV sunscreen active can be a UVB sunscreen active, a UVA sunscreen active, a UVA / UVB sunscreen active, or a mixture thereof. It is generally desirable to formulate sunscreen compositions with more than one UV sunscreen active, particularly to broaden the range of UV radiation absorption provided, more particularly to cover broad protection against both UVA and UVB radiation.

[0056] In another embodiment, the UV sunscreen active, optionally in combination with one or more features of the above-defined embodiments, is in an amount of 0.1 wt.% to 50 wt.%, preferably 0.5 wt.% to 45 wt.%, more preferably 1.0 wt.% to 35 wt.%, relative to the total weight of the composition.

[0057] The amount of UV sunscreen active will vary depending on the particular UV sunscreen active or mixture of UV sunscreen actives and can be easily determined by one skilled in the art. A list of UV sunscreen actives permitted in cosmetic products can be found in Annex VI of Regulation (EC) No. 1223 / 2009 relating to cosmetics in the EU Official Cosmetic Ingredients Database (CosIng), where the maximum concentrations in ready-to-use preparations are given.

[0058] In one embodiment, the UV sunscreen actives, optionally in combination with one or more features of the above-defined embodiments, include 3,3,5-trimethylcyclohexyl 2-hydroxybenzoate (homosalate), ethylhexyl triazone, diethylamino hydroxybenzoyl hexyl benzoate, and bis-ethylhexyloxyphenol methoxyphenyl triazine.

[0059] In another embodiment, 3,3,5-trimethylcyclohexyl 2-hydroxybenzoate (homosalate) is in an amount of 2 wt.% to 10 wt.%, ethylhexyl triazone is in an amount of 0.5 wt.% to 5 wt.%, diethylamino hydroxybenzoyl hexyl benzoate is in an amount of 0.5 wt.% to 10 wt.%, and bis-ethylhexyloxyphenol methoxyphenyl triazine is in an amount of 5 wt.% to 10 wt.%, based on the total weight of the composition.

[0060] In another embodiment, the composition, optionally in combination with one or more features of the above-defined embodiments, also comprises an emollient other than a phenylethyl ester.

[0061] Examples of suitable emollients include, but are not limited to, alkyl adipate, C12-15 alkyl benzoate, dicaprylyl carbonate, cocoglycerides, caprylic / capric triglyceride, propylene glycol dicaprylate / dicaprate, butylene glycol dicaprylate / dicaprate, coco-caprylate, coco-caprylate / caprate, butyloctyl salicylate, diisopropyl sebacate, isopropyl lauroyl sarcosinate, isononyl isononanoate, diethylhexyl 2,6-naphthalate, ricinus communis (castor) seed oil, almond (prunus amygdalus) seed oil, sorbitan stearate ... dulcis oil, Cocos nucifera (coconut) oil, Neopentyl glycol diheptanoate, Isoamyl laurate, Squalane, Isododecane, Propylene glycol dibenzoate, C13-14 alkane, Octyldodecyl neopentanoate, Argania spinosa kernel oil, Ethylhexyl palmitate, Ethylhexyl stearate, Dipropylheptyl carbonate Carbonate), hexyl laurate, dicaprylyl ether, caprylyl caprylate / caprylyl caprate, propylheptyl caprylate, cetearyl isononanoate, cetearyl ethylhexanoate, PEG-7 glyceryl cocoate, myristyl lactate, decyl oleate, undecane, tridecane, decyl oleate, cetyl palmitate, octyldodecanol, hexyldecanol, myristyl myristate, isopropyl myristate, isopropyl palmitate, hydrogenated polyisobutene, isohexadecane, isopropyl isostearate, isostearyl isostearate, isothidecyl isononanoate, diisopropyl dilinoleate dimer, diisostearyl dimer dilinoleate, pentaerythrityl tetraisostearate, triisononanoin, triethylhexanoin, and triisostearin. Preferably, the additional emollient is dialkyl adipate. Examples of dialkyl adipates include dimethyl adipate, diethyl adipate, dipropyl adipate, diisopropyl adipate, diisobutyl adipate, di-n-butyl adipate, di-2-ethylhexyl adipate, and dicyclohexyl adipate.Preferably, the dialkyl adipate is dibutyl adipate or diisopropyl adipate, more preferably dibutyl adipate.

[0062] In one embodiment, the emollient other than a phenylethyl ester, optionally in combination with one or more features of the embodiments defined above, is present in an amount of 0.5 wt.% to 35 wt.%, preferably 5 wt.% to 25 wt.%, more preferably 5 wt.% to 20 wt.%, based on the total weight of the composition (the sum of all ingredients being 100%).

[0063] In another embodiment, the UV sunscreen actives, optionally in combination with one or more features of the above-defined embodiments, include UVB sunscreen actives, UVA sunscreen actives, and UVA / UVB sunscreen actives. In a particular embodiment, the compound of formula (I) is methoxyphenylethenyl t-butyl benzoate; methoxyphenylethenyl t-butyl benzoate in an amount of 0.1 wt% to 6 wt%; phenylethyl ester in an amount of 0.1 wt% to 40 wt%; the UVB sunscreen active agent is in an amount of 0.1 wt% to 25 wt%; the UVA sunscreen active agent is in an amount of 0.1 wt% to 15 wt%; the UVA / UVB sunscreen active agent is in an amount of 0.1 wt.% to 15 wt.%; The dialkyl adipate is present in an amount of 0.5 wt% to 35 wt%. Here, weight percent is a value based on the total weight of the composition, and the sum of all components is 100%.

[0064] In another particular embodiment, methoxyphenylethenyl t-butyl benzoate in an amount of 0.5 wt% to 5 wt%; phenylethyl ester in an amount of 2 wt% to 25 wt%; the UVB sunscreen active agent is in an amount of 1 wt.% to 20 wt.%; the UVA sunscreen active agent is in an amount of 1 wt.% to 10 wt.%; the UVA / UVB sunscreen active agent is in an amount of 1 wt% to 10 wt%; The dialkyl adipate is present in an amount of 5 wt% to 30 wt%. Here, weight percent is a value based on the total weight of the composition, and the sum of all components is 100%.

[0065] The composition defined above can contain other pharmaceutically or cosmetically acceptable excipients or carriers suitable for topical administration.These excipients or carriers include but are not limited to dispersants, preservatives, oils, waxes, propellants, emulsifiers, surfactants, thickeners, humectants, pH adjusters, film-forming agents, chelating agents, vehicles, and their mixtures.Suitable cosmetic excipients or carriers and their amount can vary according to the type of specific preparation, and can be easily determined by those skilled in the art.

[0066] The excipients or carriers mentioned above and discussed more particularly below are generally used in amounts of from about 0.1 wt% to about 10 wt% of the composition, unless otherwise specified.

[0067] Examples of suitable dispersing agents include those useful for dispersing organic or inorganic sunscreens in the water phase, oil phase, or part of an emulsion, including, for example, chitosan.

[0068] Examples of suitable preservatives or preservative-enhancing agents include phenoxyethanol, ethylhexylglycerol, alkanediols (e.g., 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, 2-methyl-1,3-propanediol), hydroxyacetophenone, sodium levulinate, glyceryl caprylate, glyceryl undecylenate, p-anisic acid, o-cymen-5-ol, phenylpropanol, methylparaben, ethylparaben, propylparaben, potassium sorbate, and sodium benzoate. The amount of preservative in the composition of the present invention can be 0.1 wt.% to 3 wt.% based on the total weight of the composition.

[0069] Examples of suitable antioxidants include, but are not limited to, tocopheryl acetate, tocopherol, butylated hydroxytoluene (BHT), pentaerythrityl tetra-di-t-butylhydroxyhydrocinnamate, diethylhexyl syringylidene malonate, ascorbyl palmitate, and vitamin C, p-hydroxybenzoic acid and its esters, salicylates, coumarin derivatives, flavones, hydroxy- or methoxy-substituted benzophenones, uric acid or tannic acid and its derivatives, hydroquinone, and benzophenone. The amount of antioxidant in the compositions of the present invention can be 0.001 wt.% to 1 wt.%, based on the total weight of the composition.

[0070] Examples of oils include, but are not limited to, animal oils, vegetable oils, mineral oils, and synthetic oils, particularly hydrogenated palm oil, hydrogenated castor oil, liquid paraffin, paraffin oil, Purcellin oil, and silicone oil.

[0071] Examples of waxes include, but are not limited to, animal waxes, fossil waxes, vegetable waxes, mineral waxes, and synthetic waxes, particularly beeswax, carnauba wax, candelilla wax, sugarcane wax, Japan wax, ozokerite, montan wax, microcrystalline wax, and paraffin wax.

[0072] Examples of suitable humectants include glycerin, ethoxylated glycerin, propoxylated glycerin, propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, butylene glycol, pentylene glycol, propanediol, sorbitol, polypropylene glycol, polyethylene glycol, L-arginine, sodium hyaluronate, hyaluronic acid, and mixtures thereof. The amount of humectant in the compositions of the present invention can range from 1 to 30 wt%, preferably from 2 to 20 wt%, optimally from about 5 to 10 wt%, based on the total weight of the composition.

[0073] Examples of suitable pH adjusters include acetic acid, lactic acid, citric acid, ethanolamine, formic acid, oxalic acid, potassium hydroxide, sodium hydroxide, triethanolamine, or mixtures thereof. The amount of pH adjuster in the composition of the present invention may be 0.01 wt.% to 1 wt.%, based on the total weight of the composition.

[0074] Examples of suitable film-forming agents include polyvinylpyrrolidone (PVP), copolymers of PVP such as PVP / hexadecene copolymer and PVP / eicosene copolymer, acrylate copolymers, acrylate / octylacrylamide copolymer, sodium polystyrene sulfonate, polyisobutene, polyacrylamide, polyvinyl alcohol, polyglycols, C10-30 polyates, trimethylpentanediol / adipic acid / glycerin crosspolymer, pullulan, chitosan, polyurethane-62, polyester-7, and polyurethane-99. The amount of film-forming agent in the compositions of the present invention can be from 0.01 wt% to 10 wt%.

[0075] Examples of suitable chelating agents include disodium EDTA, tetrasodium EDTA, trisodium EDTA, tetrasodium glutamic acid diacetate, disodium pyrophosphate, dipotassium pyrophosphate, phytic acid, and sodium phytate. The amount of chelating agent in the compositions of the present invention can be 0.01 wt% to 10 wt%.

[0076] Examples of emulsifiers include amphoteric emulsifiers, anionic emulsifiers, cationic emulsifiers, and nonionic emulsifiers. These emulsifiers are appropriately selected depending on the emulsion to be obtained (W / O, O / W, O / W / O, or W / O / W). Examples of suitable emulsifiers include glyceryl stearate citrate, glyceryl stearate (self-emulsifying), stearic acid, stearates, lauryl glucoside, myristyl glucoside, polyglyceryl-6 laurate, potassium cetyl phosphate, and polyglyceryl distearate. Examples of emulsifiers include 3-methylglucose, polyglyceryl-2 diisostearate, behenyl alcohol, stearyl alcohol, PEG-100 stearate, polyglyceryl-6 distearate, polyglyceryl-3 polyricinoleate, polyglycerin-3, cetyl alcohol, dimethicone copolyol phosphate, hexadecyl-D-glucoside, octadecyl-D-glucoside, sorbitan olivine, polyglyceryl-6 polyhydroxystearate, polyglyceryl-6 polyricinoleate, hydrogenated lecithin, lecithin, sodium cetearyl sulfate, sodium staloyl glutamate, polyglyceryl-10 stearate, cetearyl alcohol, cetearyl glucoside, glycol palmitate, and cetearyl sulfate phosphate. The amount of emulsifier in the composition of the present invention can be 0.5 wt% to 15 wt%.

[0077] Examples of suitable surfactants include, but are not limited to, nonionic, ionic (either anionic or cationic), or zwitterionic (or amphoteric, where the surfactant head contains two oppositely charged groups) surfactants. Examples of anionic surfactants include those based on sulfate, sulfonate, or carboxylate anions, such as perfluorooctanoate (PFOA or PFO), alkylbenzene sulfonate, soap, fatty acid salt, or alkyl sulfate, such as perfluorooctane sulfonate (PFOS), sodium dodecyl sulfate (SDS), ammonium lauryl sulfate, or sodium lauryl ether sulfate (SLES). Examples of cationic surfactants include those based on quaternary ammonium cations, such as alkyltrimethylammonium with cetyltrimethylammonium bromide (also known as CTAB) or hexadecyltrimethylammonium bromide, cetylpyridinium chloride (CPC), polyethoxylated tallow amine (POEA), benzalkonium chloride (BAC), or benzethonium chloride (BZT). Examples of zwitterionic surfactants include dodecylbetaine, cocamidopropyl betaine, or cocoamphoglycinate. Examples of nonionic surfactants include copolymers of alkyl poly(ethylene oxide), alkylphenol poly(ethylene oxide), poly(ethylene oxide), poly(propylene oxide) (trade names: poloxamer or poloxamine), alkyl polyglucosides including octyl glucoside and decyl maltoside, fatty alcohols including cetyl alcohol and oleyl alcohol, cocamide MEA, cocamide DEA, or polysorbates including Tween 20, Tween 80, or dodecyldimethylamine oxide. Preferably, the surfactant is foaming and gentle, including polysorbate 20 or 40, coco glucoside, lauryl glucoside, decyl glucoside, lauryl sulfate, e.g., ammonium, sodium, magnesium, MEA, triethylamine (TEA), or mipa lauryl sulfate, cocamidopropyl betaine, or sodium alkyl sulfosuccinate.The amount of surfactant in the composition of the present invention may be from 0.5 wt% to 20 wt%.

[0078] Examples of suitable thickeners include ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, microcrystalline cellulose, cetearyl alcohol, alginate, silicon dioxide, aluminum silicate, fumed silica, polysaccharides and their derivatives (e.g., xanthan gum and / or sclerotium gum), polyacrylates (e.g., carbomer), acrylate / C10-30 alkyl acrylate crosspolymer, acrylate copolymer, ammonium acryloyldimethyltaurate / VP copolymer, and sodium acryloyldimethyltaurate / VP crosspolymer. The amount of thickener in the composition of the present invention can be 0.001 wt% to 5 wt%, preferably 0.01 wt% to about 1 wt%.

[0079] Examples of propellants include volatile hydrocarbons such as n-butane, propane, or isobutane, chlorinated and / or fluorinated hydrocarbons, and mixtures thereof.Also usable as propellants are carbon dioxide gas, nitrous oxide, dimethyl ether, nitrogen, compressed air, and mixtures thereof.The amount of propellant in the composition of the present invention can be 1 wt% to 25 wt%.

[0080] In addition, the composition of the present invention can contain other ingredients, such as waterproofing agents, anti-foaming agents, fragrances, pigments, colorants, opacifiers, exfoliants, boosters, and other ingredients known in the art for use in topical formulations.The composition of the present disclosure can be prepared by conventional methods well known to those skilled in the art.The method for producing the composition can be carried out by conventional mixing techniques under normal processing conditions at atmospheric pressure.

[0081] The compositions of the present disclosure may be formulated in different ways, such as in the form of creams, ointments, emulsions, suspensions, powders, oils, lotions, gels, sticks, foams, emulsions (e.g., oil-in-water (O / W), water-in-oil (W / O), water-in-oil-in-water (W / O / W) or oil-in-water-in-oil (O / W / O)), dispersions, sprays, aerosols, etc. More specific forms include lipstick, foundation, makeup, loose or pressed powder, eye blush, eye shadow, mascara, nail varnish, nail lacquer, non-permanent hair dye compositions, etc.

[0082] The appropriate process for preparing each one of the formulations can be easily determined by one skilled in the art. As an example, the process for preparing an emulsion involves (i) first preparing an aqueous phase and an oily phase separately, and (ii) secondly, mixing both phases until an oil-in-water emulsion is obtained, as shown in the experimental section.

[0083] By way of example, an oil-in-water emulsion composition may be prepared by the general process defined herein below: (i) A process for preparing an aqueous phase A by mixing water-soluble ingredients, such as, inter alia, preservatives, film-forming agents, chelating agents, and humectants, with an aqueous solvent. (ii) A process for preparing Oil Phase B by mixing sunscreen actives, emollients, emulsifiers, and optionally surfactants, fragrances, and other water-insoluble ingredients. (iii) optionally preparing Phase C by mixing preservatives, antioxidants, and further active ingredients. (iv) mixing phase A and phase B; and (v) optionally, mixing the mixture resulting from step (iv) with Phase C.

[0084] For the purposes of the present invention, the term "aqueous solvent" refers to an aqueous solvent such as water, ie, a solvent in which water is the predominant component, such as water or a mixture of water and an alkanol such as ethanol.

[0085] In one example, the aqueous phase may be present in an amount greater than 50% by weight of the composition. The oil phase may be present in an amount less than 50% by weight of the composition. In a preferred embodiment, the aqueous phase comprises 55 to 97% by weight, more preferably 57 to 70% by weight, of the composition, and the oil phase comprises 3 to 35% by weight, more preferably 7 to 15% by weight of the composition.

[0086] Furthermore, the preparation according to the invention may contain one or more active ingredients selected from the group consisting of the compounds α-lipoic acid, folic acid, phytoene, D-biotin, coenzyme Q10, α-glucosylrutin, carnitine, carnosine, natural and / or synthetic isoflavonoids, flavonoids, creatine, creatinine, taurine, β-alanine, panthenol, magnolol, honokiol, dihydroxyacetone; 8-hexadecene-1,16-dicarboxylic acid, glycerylglycose, (2-hydroxyethyl)urea, vitamin E or a derivative thereof, and / or licochalcone A.

[0087] As mentioned above, another aspect of the present invention relates to a method for increasing the rate of photochemical conversion of a compound of formula (I) as defined above, such as methoxyphenylethenyl t-butyl benzoate, to a compound of formula (II) as defined above, such as avobenzone, in a cosmetic composition, comprising the step of adding to the composition an effective amount of a phenylethyl ester as defined above.

[0088] In one embodiment of the method of the present invention, the phenylethyl ester is phenethyl benzoate.When the present disclosure describes cosmetic compositions and methods for increasing the photochemical conversion rate of ultraviolet (UV) absorber photochemical precursors, compounds of formula (I), or phenylethyl esters as defined above, it should be noted that each one of the embodiments or features defined in any of the above-mentioned aspects can be considered applicable to other aspects, regardless of whether it is explicitly stated in the context of other aspects.Thus, for example, when defining an embodiment for the above-defined compound of formula (I) or compound of formula (II), their pharmaceutically or cosmetically acceptable salts, any stereoisomers thereof, or mixtures thereof in the present composition, such an embodiment also refers to the definition of the compound in the present method, and vice versa.

[0089] Throughout the specification and claims, the word "comprise" and variations thereof are not intended to exclude other technical features, additives, ingredients, or steps. Furthermore, the word "comprise" encompasses "consisting of." The following examples and figures are provided for illustrative purposes and are not intended to limit the present disclosure. Furthermore, the present disclosure is directed to all possible combinations of the specific and preferred embodiments described herein.

[0090] Example Equipment and Software Substrate: HD6 poly(methyl methacrylate) (PMMA) plate (Helioscreen); UV transmittance analyzer: UV 2000-S (Labsphere, Inc;) Sun simulator: Suntest CPS+ (Atlas Material Testing Technology); Water cooling unit for sample temperature control: ECO RE 630 S (Lauda); SuntestCPS+ Lamp: Xenon lamp NXE 1500B (Atlas Material Testing Technology); Diffuse transmittance measurement software: AS-02784-000 for UV 2000-S (Labpshere, Inc.).

[0091] Example 1 - Preparation of Methoxyphenylethenyl t-butylbenzoate Solutions in Different Emollients Samples were prepared by dissolving 2% (w / w) methoxyphenylethenyl t-butyl benzoate in the emollients shown in Table 1 below. [Table 1]

[0092] This solution was prepared at room temperature (i.e., about 20-25°C) with stirring until completely dissolved.

[0093] To evaluate the effect of different emollients on the photoactivation of methoxyphenylethenyl t-butylbenzoate, an in vitro study was conducted using the formulations in Table 1 above.

[0094] The formulations were applied to poly(methyl methacrylate) (PMMA) plates. For each one of the above samples (Example 1 and Comparative Examples 1-6), the plates were coated with 0.68 mg / cm 2 The samples were prepared by spreading the samples onto the substrate. The samples were applied evenly and in small amounts using a micropipette. They were then stretched along the substrate: first from left to right in a small circle for 30 seconds, then in a horizontal line for 20-30 seconds. The plates were protected from light for 30-45 minutes. Three replicates were prepared for each sample.

[0095] Before irradiation, the diffuse transmittance of each sample in the UV range of 250 to 450 nm was measured using a transmittance analyzer (Labsphere UV-2000S). Each sample was measured at five different points on the substrate.

[0096] The samples were then tested in a solar simulator (Atlas Suntest CPS+ lamp) over the full UV range (300-800 nm) and at 765 W / m 2 The samples were irradiated for 2 hours at a power of 100 W. To obtain absorbance, SPF, and UVA-PF data, measurements were taken using a transmittance analyzer at the following irradiation times: 1 MED, 2.5 MED, 5 MED, 7.5 MED, and 10 MED (120 minutes of irradiation), where 5 MED is 60 minutes of irradiation.

[0097] The SPF and UVA-PF values were obtained using software for diffuse transmittance measurement (AS-02784-000).

[0098] The behavior of methoxyphenylethenyl t-butylbenzoate was observed with increasing irradiation.

[0099] The results are shown in Tables 2 to 8 below. [Table 2]

[0100] [Table 3]

[0101] [Table 4]

[0102] [Table 5]

[0103] [Table 6]

[0104] [Table 7]

[0105] [Table 8]

[0106] As seen in Figure 1, the results indicate that the methoxyphenylethenyl t-butyl benzoate composition, containing both two alkyl adipates (dibutyl adipate and diisopropyl adipate) and phenethyl benzoate, provides a similar UVA-PF, higher than expected compared to the UVA-PF obtained with other emollients. Similarly, as shown in Figure 3, the absorbance at 360 nm (within the UVA range) is higher for the two alkyl adipates and phenethyl benzoate than for the remaining emollients. As observed in Figure 2, the SPF values are also higher. This effect may be due to a slight increase in the value around 300-320 nm (UVB range), which can be observed in Figure 4.

[0107] Example 2 - Activation Rate The absorbance data at 360 nm obtained in Example 1, Comparative Example 1, and Comparative Example 2 were used to calculate the activation rate.

[0108] The activation ratio is the time it takes for methoxyphenylethenyl t-butylbenzoate to convert to avobenzone. This ratio is the slope of the linear trend line obtained by using the first three values corresponding to 0 MED, 1 MED, and 2.5 MED. These results determine how fast the conversion occurs; the higher the slope, the faster the conversion.

[0109] As can be seen in Figure 5, Example 1 and Comparative Example 2 have similarly high activation rates compared to the slow activation when using Comparative Example 1. The activation rate values obtained are shown in Table 9. [Table 9]

[0110] As can be seen in Figures 5 and 6, the results show higher slope values in Example 1 and Comparative Example 2 compared to Comparative Example 1, indicating that the activation rate of methoxyphenylethenyl t-butyl benzoate is significantly increased with both dibutyl adipate and phenethyl benzoate relative to the C12-15 alkyl benzoate. The effect of phenethyl benzoate on the activation rate of methoxyphenylethenyl t-butyl benzoate was unpredictable in light of the effect of dibutyl adipate on the activation rate of methoxyphenylethenyl t-butyl benzoate. This is because the two softening agents are structurally and chemically very different.

[0111] Example 3 - Preparation of methoxyphenylethenyl t-butyl benzoate in oil phase Several oil phases were prepared containing the ingredients shown in Table 10 below. [Table 10]

[0112] As an example, emulsions can be prepared containing 30 wt.% to 40 wt.% of the oil phase described above.

[0113] As an example, the final amounts of the different components in the final composition, if present, may be as follows: Methoxyphenylethenyl t-butyl benzoate: 2 wt%; Homosalate: 5wt%; Bis-ethylhexyloxyphenol methoxyphenyl triazine: 4 wt%; Diethylaminohydroxybenzoylhexylbenzoate: 2 wt%; Ethylhexyltriazone: 4 wt%; Dibutyl adipate 15 wt%; Phenethyl benzoate: 5 wt%;

[0114] If a mixture of emollients (i.e., phenethyl benzoate and dibutyl adipate) had been used previously, their mixture with the rest of the ingredients was mixed in a 70-75°C bath.

[0115] The methoxyphenylethenyl t-butyl benzoate and sunscreen active were then added one at a time to the emollient or emollient mixture, with each sunscreen active being stirred for 10 minutes or until completely solubilized at the stated temperature.

[0116] Finally, the mixture was cooled to room temperature while stirring.

[0117] The results show that oil phase D (Example 2), which contains both methoxyphenylethenyl t-butyl benzoate and phenethyl benzoate, surprisingly provides increased UVF-PF protection (Figure 7), absorbance at 360 nm (Figure 8), and SPF protection (Figure 9) compared to the other oil phases A (Comparative Example 7), B (A + methoxyphenylethenyl t-butyl benzoate; Comparative Example 8), and C (A + phenethyl benzoate; Comparative Example 9).

[0118] As shown in Example 1, in the absence of a sunscreen active, dibutyl adipate has an enhancing effect on the conversion of methoxyphenylethenyl t-butyl benzoate to avobenzone in the presence of other sunscreen actives (particularly homosalate, bis-ethylhexyloxyphenol methoxyphenyl triazine, diethylamino hydroxybenzoyl hexyl benzoate, and ethylhexyl triazone), whereas the addition of phenethyl benzoate without methoxyphenylethenyl t-butyl benzoate does not result in a significant increase in the UVA-PF but merely helps maintain it (presumably due to the solubilizing effect of phenethyl benzoate on at least a portion of the sunscreen active).

[0119] Conversely, and unexpectedly, when phenethyl benzoate is added to a composition containing methoxyphenylethenyl t-butyl benzoate (oil phase D), a significantly higher increase in UVA-PF protection can be observed, even when the phenethyl benzoate is added in an amount one-third of the amount of dibutyl adipate.

[0120] As mentioned above, in the absence of sunscreen active agent, the UVA-PF protection and absorbance of the combination of methoxyphenylethenyl t-butylbenzoate and dibutyl adipate are similar to or slightly better than those provided by the combination of methoxyphenylethenyl t-butylbenzoate and phenethyl benzoate, so this is unexpected.Therefore, without wishing to be bound by theory, this result seems to indicate that the presence of other sunscreen active agent, in contrast to phenethyl benzoate, interferes with the action of dibutyl adipate on one or more components of composition.

[0121] It is worth noting that avobenzone is a UVA filter and therefore provides UVA-PF protection, which is consistent with the SPF results and shows that the presence of methoxyphenylethenyl t-butyl benzoate in the oil phase does not substantially improve it.

[0122] Example 4 - Sunscreen Formulation The formulation in Table 11 was prepared. Phase B, Phase C, and Phase D ingredients were prepared in separate suitable containers.

[0123] [Table 11]

[0124] Aqueous Phase A was prepared by combining the ingredients and heating to a temperature of 70-80°C until a homogeneous mixture was obtained. Oil Phase B was prepared as in Example 2. The two phases were then emulsified at the same temperature by adding Phase B to Phase A using a homogenizer. The mixture was then cooled to room temperature with stirring, Phase C was added, and the pH was adjusted.

[0125] Example 5 - Color Formulation The formulations in Table 12 were prepared. The ingredients for Phase B, Phase C, and Phase D were prepared in separate suitable containers. [Table 12]

[0126] Aqueous Phase A was prepared by combining the ingredients and heating to a temperature of 70-80°C until a homogeneous mixture was obtained. Oil Phase B was prepared by combining the ingredients under rapid mixing (rotor / stator 1500 rpm) and heating to a temperature of 70-80°C. The two phases were then emulsified at the same temperature by adding Phase B to Phase A using a homogenizer. The mixture was then cooled to room temperature with stirring, Phase C was added, and the pH was adjusted.

[0127] Citation List International Patent Publication No. 2006 / 100225 Annex VI to Regulation (EC) No 1223 / 2009 (amended 22 / 09 / 2021)

Claims

1. An effective amount of a compound of formula (I), a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof, 【Chemical 1】 During the ceremony, R' is H, (C １ -C ６ )-alkyl, and (C ３ -C ６ )-cycloalkyl; R １ , R ２ , R ４ , R ５ , R ６ , R ７ , R ９ , and R １０ is H, hydroxy, amino, (C １ -C ６ )-alkyl, (C １ -C ６ )-alkoxy, (C １ -C ６ )-alkylamino, and (C １ -C ６ )-dialkylamino; and R ３ and R ８ is (C １ -C ６ )-alkyl, (C １ -C ６ )-alkoxy, hydroxy, amino, (C １ -C ６ )-alkylamino, and (C １ -C ６ )-dialkylamino; an effective amount, and an effective amount of a phenylethyl ester selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate, and 1-phenylethyl benzoate; together with one or more pharmaceutically or cosmetically acceptable excipients or carriers, composition.

2. The composition of claim 1 wherein R' is H.

3. R １ , R ２ , R ４ , R ５ , R ６ , R ７ , R ９ , and R １０ 3. The composition of claim 1 or 2, wherein is a radical independently selected from the group consisting of H, hydroxy, amino, and methyl.

4. R ２ , R ４ , R ７ and R ９ The composition of any one of claims 1 to 3, wherein is H.

5. R', R １ , R ２ , R ４ , R ５ , R ６ , R ７ , R ９ , and R １０ is H; R ３ is tert-butyl, and R ８ The composition according to any one of claims 3 to 4, wherein is methoxyl.

6. The composition of any one of claims 1 to 5, wherein the phenylethyl ester is phenethyl benzoate.

7. The composition according to any one of claims 1 to 6, wherein the compound of formula (I) is present in an amount of 0.1 wt. % to 6 wt. % and the phenylethyl ester is present in an amount of 0.1 wt. % to 40 wt. % based on the total weight of the composition, where the sum of all components is 100%.

8. The composition of any one of claims 1 to 7, further comprising a UV sunscreen active.

9. 9. The composition of any one of claims 1 to 8, wherein the UV sunscreen active is present in an amount of 0.1 wt. % to 50 wt. %, with the sum of all ingredients being 100%.

10. The composition of any one of claims 1 to 9, further comprising an emollient other than a phenylethyl ester.

11. 11. The composition of claim 10, wherein the non-phenylethyl ester emollient is present in an amount of 0.5 wt. % to 35 wt. % based on the total weight of the composition, with the sum of all ingredients being 100%.

12. 12. The composition of claim 10 or 11, wherein the emollient other than a phenylethyl ester is a dialkyl adipate.

13. the UV sunscreens include a UVB sunscreen active, a UVA sunscreen active, and a UVA / UVB sunscreen active, and the compound of formula (I) is methoxyphenylethenyl t-butyl benzoate; methoxyphenylethenyl t-butyl benzoate in an amount of 0.1 wt. % to 6 wt. %; phenylethyl ester in an amount of 0.1 wt. % to 40 wt. %; the UVB absorber is in an amount of 0.1 wt. % to 25 wt. %; the UVA absorber is in an amount of 0.1 wt. % to 15 wt. %; the UVA / UVB absorber is in an amount of 0.1 wt. % to 15 wt. %; the dialkyl adipate is in an amount of 0.5 wt. % to 35 wt. %; 13. The composition of claim 12, wherein weight percentages are relative to the total weight of the composition, with the sum of components adding up to 100%.

14. A composition according to claims 1 to 13 for use in protecting skin or hair from sunlight or other sources of UV radiation.

15. 10. Use of a phenylethyl selected from the group consisting of phenethyl benzoate, 2-phenylethyl toluate, di-2-phenylethyl phthalate and 1-phenylethyl benzoate in a cosmetic composition to increase the rate of photochemical conversion of a compound of formula (I) as defined in claims 1 to 5 to a compound of formula (II), its pharmaceutically or cosmetically acceptable salt, or any stereoisomer thereof or a mixture thereof, comprising: 【Chemistry 2】 During the ceremony, R' is H, (C １ -C ６ )-alkyl, and (C ３ -C ６ )-cycloalkyl; R １ , R ２ , R ４ , R ５ , R ６ R ７ , R ９ , and R １０ is H, hydroxy, amino, (C １ -C ６ )-alkyl, (C １ -C ６ )-alkoxy, (C １ -C ６ )-alkylamino, and (C １ -C ６ )-dialkylamino; R ３ and R ８ is (C １ -C ６ )-alkyl, (C １ -C ６ )-alkoxy, hydroxy, amino, (C １ -C ６ )-alkylamino, and (C １ -C ６ )-dialkylamino; use.

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