PHOTOPROTECTIVE SYSTEM CONSISTING OF 4 SUNSCREENS

Abstract

The present invention relates to a cosmetic or pharmaceutical composition comprising at least one cosmetically or pharmaceutically acceptable excipient and a photoprotective system consisting of: (a) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine, (b) 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine, (c) hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, and (d) a solar filter selected from the group comprised of ethylhexyl triazone, diethylhexyl butamido triazone and 2-ethylhexyl salicylate,
wherein the photoprotective system represents between 4% and 20% by weight of the composition relative to the total weight of the composition.

Claims

1. A cosmetic or pharmaceutical composition comprising at least one cosmetically or pharmaceutically acceptable excipient and a photoprotective system consisting of: (a) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine, (b) 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine, (c) hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, and (d) a solar filter selected from the group consisting of ethylhexyl triazone, diethylhexyl butamido triazone and 2-ethylhexyl salicylate, wherein the photoprotective system represents between 4% and 20% by weight of the composition relative to the total weight of the composition, said composition not comprising any solar filter other than those constituting said photoprotective system.

2. The composition according to claim 1, wherein 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine represents between 1% and 5% by weight relative to the total weight of the composition.

3. The composition according to claim 1, wherein 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine represents between 1% and 4% by weight of the composition relative to the total weight of the composition.

4. The composition according to claim 1, wherein hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate represents between 1% and 10% by weight of the composition relative to the total weight of the composition.

5. The composition according to claim 1, wherein the solar filter (d) represents between 1% and 5% by weight of the composition relative to the total weight of the composition.

6. The composition according to claim 1, wherein the solar filter (d) is ethylhexyl triazone.

7. The composition according to claim 1, wherein the size D.sub.50 of the 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine particles is comprised between 100 and 1000 nm.

8. The composition according to claim 1, further comprising C12-C15 alkyl benzoate, dicaprylyl carbonate and caprylic/capric triglycerides.

9. The composition according to claim 1, being free of ethanol and isopropanol.

10. The composition according to claim 1, being in the form of an emulsion.

11. The composition according to claim 1, wherein the composition has a SPF and the SPF is greater than or equal to 50.

12. The composition according to claim 11, wherein the composition has a SPF/UVA ratio and the SPF/UVA ratio is less than or equal to 3.

13. The composition according to claim 1, wherein the photoprotective system represents between 6% and 19% by weight of the composition relative to the total weight of the composition.

14. The composition according to claim 1, wherein the photoprotective system represents between 8% and 17% by weight of the composition relative to the total weight of the composition.

15. The composition according to claim 1, wherein 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine represents between 3% and 4% of the composition relative to the total weight of the composition.

16. The composition according to claim 1, wherein 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine represents between 2% and 3% by weight of the composition relative to the total weight of the composition.

17. The composition according to claim 1, wherein hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate represents between 4% and 9% by weight of the composition relative to the total weight of the composition.

18. The composition according to claim 1, wherein hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate represents between 5% and 6% by weight of the composition relative to the total weight of the composition.

19. The composition according to claim 1, wherein the solar filter (d) represents between 3% and 4% by weight of the composition relative to the total weight of the composition.

20. The composition according to claim 11, wherein the SPF is greater than or equal to 60.

Description

EXAMPLES

[0093] The following abbreviations are used:

TABLE-US-00001 TABLE 1 MED: minimum erythema dose SPF: Sun Protection Factor MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide PEG: polyethylene glycol PMMA: polymethylmethacrylate UV: ultraviolet radiation VP: N-vinylpyrrolidone

I. Compositions

[0094] In the following formulas, 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine is in the form of an aqueous dispersion comprising 45% (w/w) by weight of active material and is characterised by a D.sub.50 between 150 and 250 nm.

[0095] I.1. Formula 1

TABLE-US-00002 TABLE 2 Ingredients % (w/w) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine 3-4 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 2-3 Diethylamino hydroxybenzoyl hexyl benzoate 6-7 Ethyl hexyl Triazone 3-4 Glycerin 5.0 Demineralized water qs for 100 Xanthan gum 0.2 C12-C15 alkyl benzoate 12.0  Dicaprylyl carbonate 9.0 Caprylic/capric triglycerides 9.0 Preservatives Qs Stearyl alcohol 1.0 Glycerol monostearate 0.5 Glycerol behenate 0.4 PEG-100 stearate 0.5 VP/eicosene copolymer 1.0 Polyacrylate 0.2 Potassium cetyl phosphate 2.0

[0096] I.2. Formula 2

TABLE-US-00003 TABLE 3 Ingredients % (w/w) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine 3-4 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 2-3 Diethylamino hydroxybenzoyl hexyl benzoate 6-7 Ethyl hexyl Triazone 3-4 Glycerin 5.0 Demineralized water qs for 100 Xanthan gum 0.2 C12-C15 alkyl benzoate 12.0  Dibutyl adipate 9.0 Caprylic/capric triglycerides 9.0 Preservatives qs Stearyl alcohol 1.0 Glycerol monostearate 0.5 Glycerol behenate 0.4 PEG-100 stearate 0.5 VP/eicosene copolymer 1.0 Polyacrylate 0.2 Potassium cetyl phosphate 2.0

[0097] I.3. Formula 3

TABLE-US-00004 TABLE 4 Ingredients % (w/w) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine 3-4 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 2-3 Diethylamino hydroxybenzoyl hexyl benzoate 6-7 Diethylhexyl butamido triazone 3-4 Glycerin 5.0 Demineralized water qs for 100 Xanthan gum 0.2 C12-C15 alkyl benzoate 12.0  Dibutyl adipate 9.0 Caprylic/capric triglycerides 9.0 Preservatives qs Stearyl alcohol 1.0 Glycerol monostearate 0.5 Glycerol behenate 0.4 PEG-100 stearate 0.5 VP/eicosene copolymer 1.0 Polyacrylate 0.2 Potassium cetyl phosphate 2.0

[0098] I.4. Formula 4

TABLE-US-00005 TABLE 5 Ingredients % (w/w) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine 3-4 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 2-3 Diethylamino hydroxybenzoyl hexyl benzoate 6-7 Ethyl hexyl Triazone 3-4 Glycerin 6.0 Demineralized water qs for 100 Xanthan gum 0.2 C12-C15 alkyl benzoate 12.0  Dicaprylyl carbonate 9.0 Caprylic/capric triglycerides 9.0 Preservatives qs Glycerol stearate 0.5 Glycerol behenate 0.4 Lauryl glucoside 1.5 Polyacrylate 0.2 Polyglyceryl-2 dipolyhydroxystearate 1.5

[0099] I.4. Formula 5

TABLE-US-00006 TABLE 6 Ingredients % (w/w) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine 4-5 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 2-3 Diethylamino hydroxybenzoyl hexyl benzoate 6-7 Diethylhexyl butamido triazone 3-4 Glycerin 3.0 Demineralized water qs for 100 Xanthan gum 0.2 C12-C15 alkyl benzoate 18.0  Isopropyl adipate 6.0 Dicaprylyl carbonate 6.0 Preservatives qs Stearyl alcohol 1.0 Polyacrylate 0.2 Potassium cetyl phosphate 2.0

[0100] I.5. Formula 6

TABLE-US-00007 TABLE 7 Ingredients % (w/w) 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine 3-3.5 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 2.5-3 Diethylamino hydroxybenzoyl hexyl benzoate   5-6 Ethyl hexyl triazone 3.5-4 Glycerin 5.0 Demineralized water qs for 100 Xanthan gum 0.2 C12-C15 alkyl benzoate 12.0  Dicaprylyl carbonate 9.0 Caprylic/capric triglycerides 9.0 Preservatives qs Stearyl alcohol 1.0 Glycerol monostearate 0.5 Glycerol behenate 0.4 PEG-100 stearate 0.5 VP/eicosene copolymer 1.0 Polyacrylate 0.2 Potassium cetyl phosphate 2.0

II. Determination of the Size of 5,6,5′,6′-tetraphenyl-3,3′-(1,4-phenylene)-bis[1,2,4]triazine Particles

[0101] The D.sub.50 of phenylene bis-diphenyltriazine particles is determined using a Mastersizer 3000 laser diffraction granulometer by the wet method.

[0102] A sample of an aqueous dispersion of phenylene bis-diphenyltriazine is placed under magnetic stirring (2500 rpm) for 2 minutes.

[0103] 1 mL of the sample is taken and introduced into a flask which is completed to 100 mL with ultrapure water.

[0104] The solution thus obtained is placed under magnetic stirring (2500 rpm) for 30 seconds. The solution to be examined is taken and introduced into a measuring vessel up to the 15% obscuration limit.

[0105] Three independent tests are performed and three independent measurements (red laser: background measurement, 10 seconds, sample measurement, 10 seconds; blue laser: background measurement, 10 seconds, sample measurement, 10 seconds) are performed per test.

[0106] The results are obtained in volume, and then converted into numbers using the software.

III. Evaluation of Sun Protection

[0107] The evaluation of the parameters for quantifying the photoprotection provided by a composition according to the invention is carried out in accordance with the methods recommended by COLIPA (European Cosmetic and Perfumery Association) in its guidelines issued in March 2011.

[0108] III.1. Material

[0109] UV Spectrophotometer

[0110] The spectrophotometer measures the spectral transmittance through a plate with and without a layer of sunscreen composition on its surface.

[0111] The spectrophotometer should allow measurements comprised between 290 nm and 400 nm.

[0112] To reduce variability between measurement readings and to compensate for the lack of uniformity of the product layer, it is recommended that the reading zone of the sites be at least 0.5 cm.sup.2.

[0113] The spectrophotometer used for these measurements is the Labsphere® UV-1000S or 2000S.

[0114] Plate

[0115] The plate is the material onto which the sunscreen composition is applied. This material must be transparent to UV, non-fluorescent, photostable and inert with regard to the compounds of the compositions tested. For this protocol, the PMMA plates proved ideal.

[0116] UV Source

[0117] The UV source is a solar simulator with a xenon arc lamp diffusing a visible+UVA+UVB spectrum. The UV source used for this study is the Suntest CPS+(Atlas).

[0118] III.2. Methods for Determining SPF and Photostability

[0119] Measuring Transmission Through an Untreated Plate

[0120] Firstly, it is necessary to determine UV transmission through a control plate. This is prepared by spreading a few microlitres of glycerin so that the surface of the plate is completely covered.

[0121] Sample Application

[0122] The sample to be tested is applied to the PMMA plate in an amount of 1.3 mg/cm.sup.2 (actual quantity remaining on the plate). To guarantee the accuracy of the amount and the reproducibility of results, the application zone is larger than 10 cm.sup.2.

[0123] The sample to be tested is applied in the form of a large number of small drops of the same volume, distributed over the entire surface of the plate.

[0124] In order to ensure that the quantity of the product is correct, a method of validating the quantity of product applied must be adopted (for example: weighing the plate before and after application of the product).

[0125] After application of the defined quantity of sample, the sample should be spread over the entire plate as quickly as possible (less than 30 seconds).

[0126] The sample is then placed for 15 minutes in the dark at room temperature in order to encourage the formation of an even film.

[0127] Measuring Transmission Through a Plate Treated with a Sample

[0128] The plate treated with the sample is analysed with the spectrophotometer and the mean value of UV radiation transmission through the sample is determined for each wavelength from 290 nm to 400 nm (using the monochromatic absorbance data measured on the different areas of the plate).

[0129] Number of Measurements

[0130] At least three PMMA plates should be prepared for each sample. Each plate should be measured in at least nine different regions unless practically unless almost the entire surface is measured by spectrophotometry.

[0131] Calculation of SPF In Vitro (Sun Protection Factor)

[0132] It is made from the absorbance data A(λ) before and after irradiation with doses of 5 and 10 MED, according to the following formula:

[00002]$\begin{array}{cc}\mathrm{in}\mathrm{vitro}SPF=\frac{{\int }_{\lambda =290\mathrm{nm}}^{\lambda =400\mathrm{nm}}E\left(\lambda \right).Math.S\left(\lambda \right).Math.d\lambda }{{\int }_{\lambda =290nm}^{\lambda =400nm}E\left(\lambda \right).Math.S\left(\lambda \right).Math.{10}^{-A\left(\lambda \right)}d\lambda }& \left[\mathrm{Math}.2\right]\end{array}$

[0133] In which:

[0134] E(λ) corresponds to the erythemal effective spectrum,

[0135] S(λ) corresponds to the solar spectral irradiance,

[0136] A(λ) corresponds to sample absorbance,

[0137] dλ is the wavelength variation (1 nm).

[0138] Calculation of Photostability

[00003]$\begin{array}{cc}\mathrm{Total}\mathrm{UV}\mathrm{photostability}=\frac{\mathrm{SPF}\mathrm{after}\mathrm{irradiation}}{\mathrm{SPF}\mathrm{before}\mathrm{irradiation}}\times 100& \left[\mathrm{Math}.3\right]\end{array}$

[0139] The compositions according to the invention can be classified according to the categories indicated below, based on their photostability.

TABLE-US-00008 TABLE 8 % of total SPF retained Category after 5 MED irradiation A ≥90% B 85%-<90% C 80%-<85% D ≤80%

[0140] III.3. Results

[0141] The following results were obtained for formulas 1 and 2:

TABLE-US-00009 TABLE 9 Formula Formula Formula Formula Formula 1 2 3 4 5 in vitro SPF >70 >80 >80 >60 >80 SPF/UVA <3 <3 <3 <3 <3 ratio Total Cate- Cate- Cate- Cate- Cate- photostability gory A gory A gory A gory A gory A after irradiation at 5 MED

IV. Evaluation of Ocular Tolerance

[0142] IV.1. In Vitro Model Using Reconstituted Human Corneal Epithelium

[0143] This test is an alternative method to animal experimentation for the evaluation of ocular irritant potential using reconstituted human corneal epithelium.

[0144] The principle is based on the determination of the mean cytotoxicity index over 24 hours by applying the products to reconstituted human corneal epithelium. Cell viability is studied by reduction of MTT incorporated in living cells to tetrazolium salt which forms violet crystals measurable by colorimetry.

[0145] The parameter calculated is MCI.sub.24h («mean cytotoxicity index» over 24 hours), i.e the average mortality generated per hour. It allows to determine if the product is irritating or not.

[0146] The method is described in the article by Doucet et al., Toxicology in vitro, 2006, 20, 499-512.

[0147] The compositions according to the invention can be classified according to the scoring system shown below, based on their MCI.sub.24h.

TABLE-US-00010 TABLE 10 Category MCI.sub.24 h 4: non irritating  <4 3: slightly irritating 4-<7  2: moderately irritating 7-<17 1: very irritant ≥17

[0148] IV.2. «Neutral Red Release» or (NRR) Method

[0149] This test is an alternative method to animal experimentation for the evaluation of ocular irritant potential.

[0150] The principle is based on the evaluation of cytotoxicity by determining the concentration causing 50% mortality (LC50) using the neutral red release method on rabbit corneal fibroblasts of the SIRC line after a contact time of 30 or 60 seconds.

[0151] The method is described in the Decree of 27 Dec. 1999 published in the French Official Bulletin of 30 Dec. 1999.

[0152] After incubation of the neutral red dye solution with cultured cells on a plate, each dilution of the product is contacted with the cells for 60 seconds or 30 seconds before being rinsed off. Cell viability is assessed by spectrophotometry after addition of a development solution.

[0153] The cytotoxicity of the product is given according to a scale described in the French Official Bulleting of 30 Dec. 1999, comprising 4 categories:

TABLE-US-00011 TABLE 11 Category Cytotoxicity 4 Negligible 3 Very slight 2 Moderate 1 Severe

[0154] IV.3. Results

[0155] The following results were obtained for formulas 1 and 2

TABLE-US-00012 TABLE 12 Formula 1 Formula 2 HCE model Score 3 Score 4 NRR method Score 4 Score 4

[0156] The results obtained for the in vitro ocular tolerance tests are good for the two formulas tested.