ANTI-AGING COSMETIC COMPOSITIONS COMPRISING NMN

Abstract

The invention pertains to a cosmetic composition comprising NMN, a precursor thereof, a derivative thereof, against skin ageing.

Claims

1-12. (canceled)

13. A cosmetic composition comprising nicotinamide mononucleotide (NMN), a derivative thereof, a precursor thereof or a salt thereof, or combinations thereof, to prevent or treat at least one sign of ageing.

14. The cosmetic composition as claimed in claim 13, wherein the precursor can be nicotinamide riboside (NR) and/or dihydronicotinamide riboside (NR—H).

15. The cosmetic composition as claimed in claim 13, wherein the derivative of NMN can be selected from among alpha nicotinamide mononucleotide (α-NMN), dihydronicotinamide mononucleotide (denoted NMN-H), the compound of formula (I): ##STR00097## or one of the pharmaceutically acceptable stereoisomers, salts, hydrates, solvates or crystals thereof, in which: X is selected from among O, CH.sub.2, S, Se, CHF, CF.sub.2 et C═CH.sub.2; R.sub.1 is selected from among H, azido, cyano, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) thio-alkyl, (C.sub.1-C.sub.8) heteroalkyl, and OR; wherein R is selected from H and (C.sub.1-C.sub.8) alkyl; R.sub.2, R.sub.3, R.sub.4 et R.sub.5 are each independently selected from among H, halogen, azido, cyano, hydroxyl, (C.sub.1-C.sub.12) alkyl, (C.sub.1-C.sub.12) thio-alkyl, (C.sub.1-C.sub.12) heteroalkyl, (C.sub.1-C.sub.12) haloalkyl, and OR; wherein R is selected from among H, (C.sub.1-C.sub.12) alkyl, C(O)(C.sub.1-C.sub.12)alkyl, C(O)NH(C.sub.1-C.sub.12)alkyl, C(O)O(C.sub.1-C.sub.12)alkyl, C(O)aryl, C(O)(C.sub.1-C.sub.12)alkyl aryl, C(O)NH(C.sub.1-C.sub.12)alkyl aryl, C(O)O(C.sub.1-C.sub.12)alkyl aryl, and C(O)CHR.sub.AANH.sub.2; wherein R.sub.AA is a side chain selected from among a proteinogenic amino acid; R.sub.6 is selected from among H, azido, cyano, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 thio-alkyl, C.sub.1-C.sub.8 heteroalkyl and OR; wherein R is selected from H and (C.sub.1-C.sub.8) alkyl; R.sub.7 is selected from among H, P(O)R.sub.9R.sub.10, P(S)R.sub.9R.sub.10 and ##STR00098##  wherein n is an integer equal to 1 or 3; in which R.sub.9 and R.sub.10 are each independently selected from among OH, OR.sub.11, NHR.sub.13, NR.sub.13R.sub.14, a (C.sub.1-C.sub.8) alkyl, a (C.sub.2-C.sub.8) alkenyl, a (C.sub.2-C.sub.8) alkynyl, a (C.sub.3-C.sub.10) cycloalkyl, a (C.sub.5-C.sub.12) aryl, (C.sub.1-C.sub.8) alkyl aryl, (C.sub.1-C.sub.8) aryl alkyl, (C.sub.1-C.sub.8) heteroalkyl, (C.sub.1-C.sub.8) heterocycloalkyl, a heteroaryl, and NHCHR.sub.AR.sub.A′C(O)R.sub.12; in which: R.sub.11 is selected from among a group: (C.sub.1-C.sub.10) alkyl, (C.sub.3-C.sub.10) cycloalkyl, (C.sub.5-C.sub.18) aryl, (C.sub.1-C.sub.10) alkylaryl, substituted (C.sub.5-C.sub.12) aryl, (C.sub.1-C.sub.10) heteroalkyl, (C.sub.3-C.sub.10) heterocycloalkyl, (C.sub.1-C.sub.10) haloalkyl, a heteroaryl, —(CH.sub.2).sub.nC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nOC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nOC(O)O(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nSC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nC(O)O(C.sub.1-C.sub.15)alkyl, and —(CH.sub.2).sub.nC(O)O(C.sub.1-C.sub.15)alkyl aryl; wherein n is an integer selected from 1 to 8; and P(O)(OH)OP(O)(OH).sub.2, halogen, nitro, cyano, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, —N(R.sub.11a).sub.2, C.sub.1-C.sub.6 acylamino, —COR.sub.11b, —O COR.sub.11b; NHSO.sub.2(C.sub.1-C.sub.6 alkyl), —SO.sub.2N(R.sub.11a).sub.2 SO.sup.2 wherein each of R.sub.11a is independently selected from among H and (C.sub.1-C.sub.6) alkyl and R.sub.11b is independently selected from among OH, C.sub.1-C.sub.6 alkoxy, NH.sub.2, NH(C.sub.1-C.sub.6 alkyl) or N(C.sub.1-C.sub.6 alkyl).sub.2; R.sub.12 is selected from among H, C.sub.1-C.sub.10 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.10 haloalkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 heterocycloalkyl, C.sub.5-C.sub.18 aryl, C.sub.1-C.sub.4 alkylaryl, and C.sub.5-C.sub.12 heteroaryl; wherein the said aryl or heteroaryl groups are optionally substituted with one or two groups selected from among halogen, trifluoromethyl, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, and cyano; and R.sub.A and R.sub.A′ are independently selected from among H, a (C.sub.1-C.sub.10) alkyl, (C.sub.2-C.sub.10) alkenyl, (C.sub.2-C.sub.10) alkynyl, (C.sub.3-C.sub.10) cycloalkyl, (C.sub.1-C.sub.10) thio-alkyl, (C.sub.1-C.sub.10) hydroxylalkyl, (C.sub.1-C.sub.10) alkylaryl, and (C.sub.5-C.sub.12) aryl, (C.sub.3-C.sub.10) heterocycloalkyl, a heteroaryl, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, and a side chain selected from among a proteinogenic amino acid or a non-proteinogenic amino acid; wherein the said aryl groups are optionally substituted with a group selected from among a hydroxyl, (C.sub.1-C.sub.10) alkyl, (C.sub.1-C.sub.6) alkoxy, a halogen, a nitro, and a cyano; or R.sub.9 and R.sub.10, together with the phosphorus atoms to which they are attached, form a 6-membered ring in which —R.sub.9-R.sub.10— represents —CH.sub.2—CH.sub.2—CHR—; wherein R is selected from among H, a (C.sub.5-C.sub.6) aryl group, and (C.sub.5-C.sub.6) heteroaryl group, wherein the said aryl or heteroaryl groups are optionally substituted by a halogen, trifluoromethyl, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, and cyano; or R.sub.9 and R.sub.10, together with the phosphorus atoms to which they are attached, form a 6-membered ring in which —R.sub.9-R.sub.10— represents —O—CH.sub.2—CH.sub.2—CHR—O—; wherein R is selected from among H, a (C.sub.5-C.sub.6) aryl group, and (C.sub.5-C.sub.6) heteroaryl group, wherein the said aryl or heteroaryl groups are optionally substituted by a halogen, trifluoromethyl, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, and cyano; R.sub.8 is selected from among H, OR, NHR.sub.13, NR.sub.13R.sub.14, NH—NHR.sub.13, SH, CN, N.sub.3 and halogen; wherein R.sub.13 and R.sub.14 are each independently selected from among H, (C.sub.1-C.sub.8) alkyl and (C.sub.1-C.sub.8) alkyl aryl; and R.sub.13 and R.sub.14 are each independently selected from among H, C.sub.1-C.sub.8 alkyl and C.sub.1-C.sub.8 alkyl aryl; R.sub.15 and R.sub.16 are independently selected from among H, C.sub.1-C.sub.8alkyl and C.sub.1-C.sub.8alkyl aryl; and —CR.sub.BR.sub.C—C(O)—OR.sub.D in which R.sub.B and R.sub.C are independently selected from among H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, benzyl, indolyl or imidazolyl, wherein the groups C.sub.1-C.sub.6 alkyl and C.sub.1-C.sub.6 alkoxy can optionally and each independently be substituted by one or more from among a halogen, an amino, amido, guanidyl, hydroxyl, thiol or carboxyl group, and the benzyl group is optionally substituted by one or more from among a halogen or hydroxyl group, or R.sub.B and R.sub.C together with the carbon atom to which they are attached form a C.sub.3-C.sub.6 cycloalkyl group optionally substituted by one or more from among a halogen, an amino, amido, guanidyl, hydroxyl, thiol or carboxyl group, and R.sub.D is H, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl or C.sub.3-C.sub.6 cycloalkyl; Y is selected from among CH, CH.sub.2, C(CH.sub.3).sub.2 and CCH.sub.3; represents a single or double bond depending on Y; and represents an alpha or beta anomer depending on the position of R.sub.1 or one of the stereoisomers, salts, hydrates, solvates or crystals thereof or the compound of formula (Ia): ##STR00099## or one of the stereoisomers, salts, hydrates, solvates, or crystals thereof, in which X′.sub.1 and X′.sub.2 are independently selected from among O, CH.sub.2, S, Se, CHF, CF.sub.2, et C═CH.sub.2; R′.sub.1 and R′.sub.13 are independently selected from among H, azido, cyano, a C.sub.1-C.sub.8 alkyl, a C.sub.1-C.sub.8 thio-alkyl, a C.sub.1-C.sub.8 heteroalkyl, and OR, wherein R is selected from H and a C.sub.1-C.sub.8 alkyl; R′.sub.2, R′.sub.3, R′.sub.4, R′.sub.5, R′.sub.9, R′.sub.10, R′.sub.11, R′.sub.12 are independently selected from among H, a halogen, an azido, a cyano, a hydroxyl, a C.sub.1-C.sub.12 alkyl, a C.sub.1-C.sub.12 thioalkyl, a C.sub.1-C.sub.12 hetero-alkyl, a C.sub.1-C.sub.12 haloalkyl, and OR; wherein R may be selected from among H, a C.sub.1-C.sub.12 alkyl, a C(O)(C.sub.1-C.sub.12) alkyl, a C(O)NH(C.sub.1-C.sub.12) alkyl, a C(O)O(C.sub.1-C.sub.12) alkyl, a C(O) aryl, a C(O)(C.sub.1-C.sub.12) aryl, a C(O)NH(C.sub.1-C.sub.12) alkyl aryl, a C(O)O(C.sub.1-C.sub.12) alkyl aryl, or a C(O)CHR.sub.AANH2 group; wherein R.sub.AA is a side chain selected from a proteogenic amino acid; R′.sub.6 and R′.sub.8 are independently selected from among H, an azido, a cyano, a C.sub.1-C.sub.8 alkyl and OR, wherein R is selected from among H and a C.sub.1-C.sub.8 alkyl; R′.sub.7 and R′.sub.14 are independently selected from among H, OR, NHR, NRR′, NH—NHR, SH, CN, N.sub.3 and a halogen, wherein R and R′ are independently selected from among H and a (C.sub.1-C.sub.8) alkyl aryl; Y′.sub.1 and Y′.sub.2 are independently selected from among CH, CH.sub.2, C(CH.sub.3).sub.2 or CCH.sup.3; M′ is selected from among H or a suitable counter ion; represents a single or double bond depending on Y′.sub.1 and Y′.sub.2; and represents an alpha or beta anomer depending on the position of R′.sub.1 and R′.sub.13; and combinations thereof.

16. The cosmetic composition as claimed in claim 13, wherein the at least one sign of ageing is selected from among wrinkles, increased skin roughness, reduced thickness of the epidermis and dermis, reduced firmness of the epidermis and dermis, reduced elasticity of the epidermis and dermis, diminished skin radiance, swelling of the lower eyelid, erythema of under-eye skin, dark circles and combinations thereof.

17. The cosmetic composition as claimed in claim 13, comprising between 0.01 weight % and 30 weight %, preferably between 0.1 weight % and 10 weight %, more preferably between 1 weight % and 5 weight %, and most preferably about 2 weight % of NMN, a derivative thereof, a precursor thereof or a salt thereof, relative to the total weight of the composition.

18. The cosmetic composition as claimed in claim 13, further comprising an extract of Edelweiss.

19. The cosmetic composition as claimed in claim 18, comprising between 0.001 weight % and 10 weight %, preferably between 0.005 weight % and 5 weight %, more preferably between 0.01 weight % and 1 weight %, and further preferably about 0.04 weight % of extract of Edelweiss, relative to the total weight of the composition.

20. The cosmetic composition as claimed in claim 13, further comprising hyaluronic acid, preferably sodium hyaluronate.

21. The cosmetic composition as claimed in claim 20, comprising between 0.01 weight % and 5 weight % of hyaluronic acid, preferably between 0.05 weight % and 2 weight % of hyaluronic acid, more preferably between 0.1 weight % and 1 weight % of hyaluronic acid, most preferably about 0.35% of hyaluronic acid by weight of the composition.

22. The cosmetic composition as claimed in claim 13, in the form of a gel, solution, water-in-oil emulsion, oil-in-water emulsion, oil, cream, ointment, liposomal dispersion or a liniment.

23. The cosmetic composition as claimed in claim 13, having a pH of between 4 and 9, preferably between 5 and 7.

24. The cosmetic composition as claimed in claim 13, selected from among a serum, universal cream, day cream, night cream, eye contour cream, makeup removing lotion, makeup removing milk, makeup removing oil, makeup removing balm, cosmetic mask, toning lotion, exfoliating product, cleansing gel, cleansing foam, cleansing milk, cleansing lotion, preferably a serum.

25. A non-therapeutic cosmetic method comprising the application to the skin surface of the cosmetic composition as claimed in claim 13.

Description

FIGURES

[0284] FIG. 1 is a graph showing the change in parameters Ra, Rz and Rt as a function of dry, normal or oily skin type and as a function of treatment with the composition comprising NMN of the invention or with the same cream without NMN as negative control.

[0285] FIG. 2 is a graph showing improvement in thickness of the skin as a function of dry, normal or oily skin type and as a function of treatment with the composition comprising NMN of the invention or with the same cream without NMN as negative control.

[0286] FIG. 3 is a graph showing the improvement in firmness and elasticity of the skin as a function of dry, normal or oily skin type and as a function of treatment with the composition comprising NMN of the invention or with the same cream without NMN as negative control.

[0287] FIG. 4 is a graph showing changes in wrinkles, fine lines, swelling of the eyelid, dark under-eye circles, and the tired appearance of the skin for all skin types as a function of treatment with the composition comprising NMN of the invention or with the same cream without NMN as negative control.

[0288] FIG. 5 is a schematic illustrating the principle of fringe projection.

[0289] FIG. 6 is a schematic illustrating the principle of calculating parameter Ra.

[0290] FIG. 7 is a schematic illustrating the principle of calculating parameters Rz and Rt.

[0291] FIG. 8 gives photographs of the Bazin grading scale for assessing crow's feet wrinkles and under-eye wrinkles and fine lines.

[0292] FIG. 9 shows a skin deformation curve obtained with the Cutometer®.

[0293] FIG. 10 gives photographs of the Bazin grading scale for assessing swelling of the lower eyelid.

[0294] FIG. 11 gives photographs of the Bazin grading scale for assessing under-eye dark circles.

[0295] FIG. 12 is a schematic illustrating the principle of analysis with the Glossymeter.

[0296] FIG. 13 is a graph giving the results on skin hydration.

[0297] FIG. 14 is a graph giving the results on skin elasticity.

[0298] FIG. 15 is a graph giving the results on skin roughness.

[0299] FIG. 16 is a graph giving the results on the volume of skin wrinkles.

[0300] FIG. 17 is a graph showing the change in hydration, with the face serum of the invention.

[0301] FIG. 18 is a graph showing the change in elasticity, with the face serum of the invention.

[0302] FIG. 19 is a graph showing the change in roughness, with the face serum of the invention.

[0303] FIG. 20 is a graph showing the change in wrinkle volume, with the face serum of the invention.

[0304] FIG. 21 is a graph showing the change in hydration, with the eye contour serum of the invention.

[0305] FIG. 22 is a graph showing the change in elasticity, with the eye contour serum of the invention.

[0306] FIG. 23 is a graph showing the change in roughness, with the eye contour serum of the invention.

[0307] FIG. 24 is a graph showing the change in wrinkle volume, with the eye contour serum of the invention.

[0308] FIG. 25 is a graph showing the change in the volume of under-eye bags, with the eye contour serum of the invention.

[0309] FIG. 26 is a graph showing the change in eye contour erythema, with the eye contour serum of the invention.

[0310] FIG. 27 is a graph showing the change in melanin content of the eye contour, with the eye contour serum of the invention.

EXAMPLES

[0311] In the remainder of the present description, the examples are provided to illustrate the invention and are not at all intended to limit the scope thereof.

[0312] In the examples below, the weight percentage of an ingredient is calculated as follows: weight percentage of ingredient (%)=(ingredient weight)×100/(total weight of composition)

Example 1

[0313] An example of the cosmetic composition of the invention was tested on two groups of healthy volunteers composed of women aged between 45 and 65 years, having dry skin (denoted S), normal skin (denoted N) or mixed type (denoted M). The phototype of the participants was between phototype II and IV. The first group, twice daily, applied to the face a cosmetic composition comprising 2% NMN. The second group, twice daily, applied to the face the same composition not comprising NMN as negative control. The study lasted 28 days. The composition of the invention was prepared using the control composition and mixing therewith the NMN in zwitterion form up to a final weight concentration of 2%. The study lasted 28 days.

TABLE-US-00007 TABLE 3 Function of Weight INCI EU CAS Ingredient % Aqua 7732-18- solvent 70 5 Caprylic/Capric 73398- moisturizing/ 2.00 Triglyceride 61-5 masking/fragrancing/ humectant/solvent Nicotinamide 1094-61- emollient 2.00 mononucleotide 7 Glycerin 56-81-5 denaturing/ 5.00 humectant/ fragrancing/solvent Butylene Glycol 107-88-0 humectant/masking/ 3.00 solvent/viscosity controlling Glyceryl Stearate SE 11099- emulsifying 1.00 07-3 Propylene Glycol 41395- moisturizing/viscosity 3.00 Dipelargonate 83-9 controlling Pentylene Glycol 5343-92- humectant/solvent 2.00 0 Dicaprylyl Carbonate 1680-31- moisturizing/ 2.00 5 humectant Butyrospermum 194043- humectant/viscosity 2.00 Parkii Butter (Shea 92-0 controlling/emollient Butter) Hydrogenated Palm 93334- moisturizing/ 2.00 Kernel Glycerides 20-4 humectant/viscosity controlling Glyceryl Stearate 31566- moisturizing/ 1.00 31-1 emulsifying Sodium Citrate 6132-04- buffering 0.30 3 Hydroxyethyl 111286- emulsion stabilising/ 0.40 Acrylate/Sodium 86-3 viscosity controlling Acryloyldimethyl Taurate Copolymer Polyacrylate / emulsion stabilising/ 0.50 Crosspolymer-6 viscosity controlling Steareth-21 9005-00- cleansing/ 0.50 9 emulsifying/ (Generic) surfactant Glyceryl Caprylate 26402- moisturizing/ 0.30 26-6 emulsifying Xanthan Gum 11138- binder/emulsifying/ 0.20 66-2 emulsion stabilising/ gelling/humectant/ surfactant/viscosity controlling Chlorphenesin 104-29-0 preserving <0.1 Tocopherol / antioxidant/masking/ 0.2 10191- humectant 41-0 59-02-9 Hydrogenated Palm 91744- moisturizing/ 2.00 Glycerides 66-0 emulsifying/ humectant/viscosity controlling Ethylhexylglycerin 70445- humectant 0.2 33-9 Citric Acid 77-92-9 buffering/masking <0.1 Glycine Soja Oil 8001-22- moisturizing/ <0.1 7 fragrancing/skin care Polysorbate 60 9005-67- emulsifying/ <0.1 8 surfactant Sorbitan Isostearate 71902- emulsifying <0.1 01-7

[0314] Different signs of ageing were assessed in the participants and in particular skin roughness via fringe projection, skin firmness and skin elasticity via Cutometry®, skin density via DermaScan® ultrasound, swelling of the lower eyelid, dark under-eye circles and tired appearance being clinically assessed by an expert. These parameters were measured in the patients at Day 0, at the time of inclusion in the study and before any treatment, and at Day 28 at the end of the study. The different parameters measured at Day 28 were compared with those measured at Day 0 for each group and the parameters measured at Day 28 were compared between the group treated with NMN and the control group. The results were evaluated with a Student's test on EXCEL software (Microsoft) and SAS 9.4.

[0315] In FIG. 1, the composition of the invention allowed a significant reduction in parameters Ra, Rz and Rt in particular for the dry skin type. The composition of the invention therefore allows skin roughness to be reduced and the skin to be smoothed, in particular for dry skin types.

[0316] In FIG. 2, the composition of the invention allowed an increase in skin thickness of about 5% for all skin types taken together. However, the composition gives a statistically significant increase in the dry skin types. One of the signs of ageing is a decrease in skin thickness. Therefore, the composition of the invention allows the prevention or treatment of a sign of ageing and in particular allows skin thickness to be increased.

[0317] In FIG. 3, the composition of the invention allowed a significant increase in the firmness of normal skin.

[0318] FIG. 4 shows the changes in different signs of ageing, irrespective of skin type. An improvement in wrinkles, fine lines, swelling of the lower eyelid, and dark circles was determined by the reduction of each of these parameter values. Reduction (as %) is denoted % D and is calculated as follows: % D=(value obtained on the area treated with the product at Day 28 −value obtained on the area treated with the product at D0)×100/(value obtained on the area treated with the product at D0). In FIG. 4, the composition of the invention allows a significant decrease in the size and depth of wrinkles and fine lines, and in swelling of the lower eyelid, in the size of under-eye dark circles and the tired appearance of the skin.

[0319] After use over 28 days, a significant improvement of 11% in the skin radiance of the participants was measured with the Glossymeter after use of the cosmetic composition of the invention comprising NMN (p=0.032). The composition of the invention comprising NMN therefore leaves a more radiant skin which therefore appears less tired and contributes towards the anti-age effect.

[0320] The participants were also invited to reply to a self-assessment questionnaire relating to the signs of ageing. As can be seen below, the majority of participants were satisfied with the composition of the invention:

TABLE-US-00008 TABLE 4 Percentage of participants in agreement with the assertion (%) The product is moisturizing 91 My skin is firmer 83 My skin appears denser 83 My skin appears plumper 69 My facial features are less tired- 82 looking My skin is softer 96 My skin is smoother 86 The skin feels comfortable and 78 restored The product leaves a glow on the skin 91 The product restores radiance to the 87 skin The wrinkles and fine lines of crow’s 52 feet have faded The sigs of ageing have decreased 65

[0321] The composition in Example 1 was also tested on 24 participants of Afro-American type aged 40-65 years, all having wrinkles, fine lines and crow's feet at the outer corner of the eyes. One half of these women had dry skin and the other half had normal skin. Measurements of wrinkles, dark circles, swelling of the lower eyelid, tired appearance of the skin (namely loss of skin radiance) and skin sagging (comprising loss of firmness and loss of elasticity) as indicated above were performed at days D0, D28 and D56. The results were obtained by comparing the measurements obtained at D28 with those at D0, and comparing D56 results with those at D0. The results were analysed using a Wilcoxon test and were considered significant for p<0.05.

[0322] As shown in Table 5 below, the cream of the invention allows an improvement in all the signs of ageing, whether for dry skin or normal skin in Afro-American skin types:

TABLE-US-00009 TABLE 5 Mean ± % subjects standard % showing deviation reduction p improvement Wrinkles D28-D0 −0.3 ± 0.1 −10% 0.0078 33% D56-D0 −0.5 ± 0.1 −14% 0.0039 38% Swelling D28-D0 −0.3 ± 0.1 −18% 0.0156 29% eyelid of lower D56-D0 −0.5 ± 0.1 −29% 0.0039 38% Dark D28-D0 −0.3 ± 0.1 −18% 0.0078 33% circles D56-D0 −0.5 ± 0.1 −26% 0.0020 42% Skin D28-D0 −0.7 ± 0.2 −17% 0.0002 54% sagging D56-D0 −0.9 ± 0.2 −22% <0.0001 67% Fatigue D28-D0 −0.4 ± 0.1 −15% <0.0001 71% D56-D0 −0.6 ± 0.1 −21% <0.0001 75%

[0323] The composition of Example 1 was also tested on 21 participants of Afro-American type aged 40-65 years, all having wrinkles, fine lines and crow's feet wrinkles at the outer corner of the eyes. One half of these women had dry skin and the other half had normal skin. Measurements on wrinkles, dark circles, swelling of the lower eyelid, tired appearance of the skin (namely loss of skin radiance) and skin sagging (comprising loss of firmness and loss of elasticity), as indicated above, were taken on days D0, D28 and D56. The results were obtained by comparing the measurements obtained at D28 with those at D0, and comparing D56 results with those at D0. The results were analysed using a Wilcoxon test and considered to be significant for p<0.05.

[0324] As shown in Table 6 below, the cream of the invention allows an improvement in all the signs of ageing whether for dry skin or normal skin, for Afro-American skin types:

TABLE-US-00010 TABLE 6 Mean ± % subjects standard % showing deviation reduction p improvement Wrinkles D28-D0 −0.3 ± 0.1 −24% 0.0002  62% D56-D0 −0.4 ± 0.1 −33% 0.0002  68% Swelling D28-D0 −0.2 ± 0.1 −16% 0.0078  38% eyelid   of lower D56-D0 −0.4 ± 0.1 −44% 0.0003  74% Dark D28-D0 −0.3 ± 0.1 −17% 0.0000  57% circles D56-D0 −0.6 ± 0.1 −37% <0.0001  84% Skin D28-D0 −0.2 ± 0.1  −5% 0.1250  29% sagging D56-D0 −0.4 ± 0.1 −10% 0.0352  42% Fatigue D28-D0 −0.3 ± 0.1 −11% <0.0001  95% D56-D0 −0.9 ± 0.1 −41% <0.0001 100%

[0325] The composition of the invention therefore allows a significant reduction to be obtained in the signs of ageing.

[0326] The use of NMN and of compositions comprising the same according to the invention therefore allows the signs of ageing to be reduced, in particular in dry and normal skin types.

Example 2—Face Cream with Hyaluronic Acid

[0327] An example of a cosmetic composition of the invention was tested on a group of 20 healthy volunteers composed of women aged between 45 and 60 years. Each volunteer was self-assessed before and after: the comparison was made between D0 and D7, D28 or D56.

[0328] The volunteers, twice daily, applied to the face a cosmetic composition comprising 2% NMN and 0.35% hyaluronic acid in the form of sodium hyaluronate as shown in Table 7 below:

TABLE-US-00011 TABLE 7 Face cream Ingredients (INCI CAS Weight name) number Role percent Aqua 7732-18-5 Solvent q.s. to 100% Glycerine 56-81-5 Humectant, 4.5 solvent Squalane 111-01-3 Emollient 4.0 Glyceryl Stearate 11099-07-3 Emulsifying 3.0 SE Propanediol 504-63-2 Viscosity 3.0 controlling, solvent Propylene Glycol 41395-83-9 Emollient, 3.0 Dipelargonate viscosity controlling Caprylic/Capric 73398-61-5 Emollient, solvent, 2.0 Triglyceride fragrancing Nicotinamide 1094-61-7 Active cosmetic 2.0 Mononucleotide substance Pentylene Glycol 5343-92-0 Solvent, Emollient 2.0 Dicaprylyl 1680-31-5 Emollient 1.99 Carbonate C10-18 85665-33-4 Emollient, solvent 1.5 Triglycerides Butyrospermum 194043-92- Emollient, 1.5 Parkii Butter 0 viscosity controlling Glyceryl Stearate 31566-31-1 Emollient, 0.75 emulsifying Polyacrylate / Emulsion 0.5 Crosspolymer-6 stabilising, viscosity controlling Silica 7631-86-9 Absorbent, 0.5 viscosity controlling Steareth-21 9005-00-9 Surfactant, 0.5 (Generic) emulsifying Hydroxyethyl 111286-86- Emulsion 0.4 Acrylate/Sodium 3 stabilising, Acryloyldimethyl viscosity Taurate controlling Copolymer Isomalt 64519-82-0 Humectant 0.372 Sodium 9067-32-7 Humectant, 0.35 Hyaluronate emollient Glyceryl 26402-26-6 Emollient, 0.30 Caprylate emulsifying Sodium Citrate 6132-04-3 Buffering agent 0.30 chelating Xanthan Gum 6132-04-3 Binder, 0.20 emulsifying, surfactant, viscosity controlling, emollient Ethylhexylglycerin 70445-33-9 Lipid-replenishing 0.149850 Tocopherol 10191-41-0 Antioxidant, 0.140900 59-02-9 emollient Sodium 1310-73-2 Buffering agent 0.072 Hydroxide Glycine Soja Oil 8001-22-7 Emollient, 0.060 fragrance Citric Acid 77-92-9 Antioxidant 0.055515 Polysorbate 60 9005-67-8 Chelating/buffering 0.030 agent Sorbitan 71902-01-7 Emulsifying 0.030 Isostearate Sodium Benzoate 532-32-1 Preserving 0.0060 Lecithin 8002-43-5 Emulsifying 0.00320 Rhododendron 90106-21-1 Emollient 0.00320 Ferrugineum Leaf Cell Culture Extract

[0329] The study lasted 56 days. Follow-up visits were organised at D0, D7, D28 and D56. The improvement in the parameters of skin ageing signs were measured at the time of these four visits.

[0330] Different signs of ageing were assessed in the participants and in particular skin roughness via fringe projection (see FIG. 1), skin firmness and skin elasticity via Cutometry®. These parameters were measured in the patients at Day 0 at the time of study inclusion and before any treatment, at Day 7, at Day 28 in the middle of the study, and at Day 56 at the end of the study. The different parameters were also compared between the different measurement dates to evaluate the continuity of improvement. Wrinkle volume and assessment of skin roughness were evaluated using Antera 3D® software. The results were analysed with a Student's test on EXCEL software (Microsoft) and SAS 9.4.

[0331] With regard to moisturizing, the measured values were as follows (see FIG. 13):

TABLE-US-00012 TABLE 8 Day of measurement Mean Standard deviation T0 53.3 5.0 T7 58.3 5.5 T28 59.2 3.9 T56 59.8 4.0

[0332] Compared with the base value (TO), moisturization of the skin is improved by (see FIG. 13) [0333] 9%, after 7 days of use of the product (p<0.05); [0334] 11%, after 28 days of use of the product (p<0.05); and [0335] 12%, after 56 days of use of the product (p<0.05).

[0336] There was also recorded a statistically significant increase in skin moisturization of: [0337] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 day's treatment) (p<0.05); and [0338] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0339] The statistical significance of the values is given below:

TABLE-US-00013 TABLE 9 P value (statistically significant for p < 0.05) T0 T7 T28 T7 2.083E−07 / / T28 2.274E−09 0.1518291 / T56 7.913E−11 0.0321557 0.0010513

[0340] The composition of the invention therefore allows moisturization of the skin to be significantly improved on and after the first week.

[0341] Regarding elasticity, the measured values are the following (see FIG. 14):

TABLE-US-00014 TABLE 10 Day of measurement Mean Standard deviation T0 0.591 0.056 T7 0.611 0.055 T28 0.620 0.044 T56 0.636 0.046

[0342] Compared with the base value (T0), skin elasticity was improved by: [0343] 3%, after 7 days of use of the product (p<0.05); [0344] 5%, after 28 days of use of the product (p<0.05); and [0345] 8%, after 56 days of use of the product (p<0.05).

[0346] There was also recorded a statistically significant increase in skin elasticity of: [0347] 4% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0348] 3% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0349] The statistical significance of the values is given below:

TABLE-US-00015 TABLE 11 p value (statistically significant for p < 0.05) T0 T7 T28 T7  5.691E−05 / / T28 0.00044102 0.08746976 / T56 1.5745E−06 0.00011698 0.00013191

[0350] The composition of the invention therefore allows a significant improvement in elasticity of the epidermis to be obtained on and after the first week.

[0351] Regarding skin roughness, the measured values are the following (see FIG. 15):

TABLE-US-00016 TABLE 12 Day of measurement Mean Standard deviation T0 10.3 2.2 T7 10.0 2.1 T28 9.8 2.0 T56 9.7 2.0

[0352] Compared with the base value (TO), skin roughness was improved by: [0353] 2%, after 7 days of use of the product (p<0.05); [0354] 4%, after 28 days of use of the product (p<0.05); and [0355] 5%, after 56 days of use of the product (p<0.05).

[0356] There was also recorded a statistically significant decrease in skin roughness of: [0357] 2% between the values at T7 (after 7 days' treatment) and T28 (after 38 days' treatment) (p<0.05); [0358] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0359] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0360] The statistical significance of the values is given below:

TABLE-US-00017 TABLE 13 p value (statistically significant for p < 0.05) T0 T7 T28 T7 4.0915E−05 / / T28  7.452E−11 1.3951E−08 / T56 5.3622E−09 1.2843E−07 0.017617329

[0361] Regarding the smooth appearance of the skin, a statistically significant increase was measured in 40% of volunteers after 7 days of use, in 50% of volunteers after 28 days of use, and in 65% of volunteers after 56 days of use. The decrease in skin roughness was measured in 45% of volunteers after 56 days of use (p<0.05).

[0362] The composition of the invention therefore allows roughness of the epidermis to be decreased and the smooth appearance thereof to be improved in significant manner on and after the first week.

[0363] Regarding wrinkle volume, the measured volumes are the following (see FIG. 16):

TABLE-US-00018 TABLE 14 Day of measurement Mean Standard deviation T0 4.33 0.94 T7 4.22 0.85 T28 4.13 0.84 T56 4.09 0.84

[0364] Compared with the base value (TO), the volume of skin wrinkles was improved by: [0365] 2%, after 7 days of use of the product (p<0.05); [0366] 4%, after 28 days of use of the product (p<0.05); and [0367] 5%, after 56 days of use of the product (p<0.05).

[0368] There was also recorded a statistically significant reduction in the volume of skin wrinkles, of: [0369] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0370] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0371] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0372] The statistical significance of the values is given below:

TABLE-US-00019 TABLE 15 p value (statistically significant for p < 0.05) T0 T7 T28 T7 0.01311924 / / T28 0.00104163 0.03285423 / T56 0.00069357 0.01502898 0.026311258

[0373] The composition of the invention therefore allows the volume of wrinkles and fine lines to be significantly reduced on and after the first week.

[0374] An increase in skin radiance was measured to be statistically significant in 40% of volunteers after 7 days of use, in 50% of volunteers after 28 days of use and in 70% of volunteers after 56 days of use. A significant increase in even skin tone was measured in 35% of volunteers after 56 days of use.

[0375] The composition of the invention therefore allows the signs of ageing to be significantly reduced and in particular a statistically significant increase in moisturization of the skin, in skin elasticity, skin radiance, the smooth appearance of the skin, and a significant reduction in skin roughness and wrinkle volume.

Example 3—Face Contour Serum

[0376] An example of cosmetic composition of the invention formulated as a serum for the face contour was tested in 20 women aged between 45 and 60 years. The formulation of the composition of the invention is given in Table 16:

TABLE-US-00020 TABLE 16 Face serum Ingredients (INCI CAS Weight name) number Role percent Aqua 7732-18- Solvent q.s. to 5 100% Glycerin 56-81-5 Humectant, 6.588000 solvent Methylpropanediol 2163-42- solvent 3.0 0 Isopropyl Myristate 110-27-0 Binder, emollient, 2.0 fragrance, solvent Nicotinamide 1094-61- Active cosmetic 2.0 Mononucleotide 7 substance Pentylene Glycol 5343-92- Solvent, emollient 2.0 0 Squalane 111-01-3 Emollient 1.5 C14-C22 alcohols / Emulsion 1.975 stabilising Hydroxyethyl 111286- Emulsion 0.925 Acrylate/Sodium 86-3 stabilising, Acryloyldimethyl viscosity Taurate Copolymer controlling Maltodextrin 9050-36- Absorbent, binder, 0.78 6 emulsion stabilising, film- forming, emollient PANTHENOL 81-13-0 Emollient 0.5 C12-20 Alkyl / Emulsifying, 0.475 Glucoside surfactant Leontopodium / Antioxidant, 0.4 Alpinum Callus humectant, skin Culture Extract protecting Squalane 111-01-3 Emollient 0.357 Glyceryl Caprylate 26402- Emollient, 0.30 26-6 emulsifying Caprylic/Capric 73398- Emollient, solvent, 0.16 Triglyceride 61-5 fragrance Lecithin 8002-43- Emollient, 0.145 5 emulsifying Sodium Hydroxide 1310-73- buffering 0.111 2 Polysorbate 60 9005-67- Chelating/buffering 0.107 8 Sorbitan Isostearate 71902- Emulsifying 0.051 01-7 Biosaccharide Gum- 194237- Emollient 0.05 1 89-3 Ethylhexylglycerin 70445- Emollient 0.049950 33-9 Pistacia Lentiscus 61789- Film-forming 0.0400 Gum 92-2 Glucose 50-99-7 Humectant 0.025000 Citric Acid 77-92-9 Antioxidant 0.0115 Sodium Benzoate 532-32-1 Preserving 0.006 Xanthan Gum 6132-04- Binder, 0.006 3 emulsifying, surfactant, viscosity controlling, gelling, emollient Magnolia Officinalis / Emollient 0.002250 Bark Extract Tocopherol 10191- Antioxidant, 0.001550 41-059- emollient 02-9 Vitis Vinifera Seed 84929- Antioxidant, 0.000450 Extract 27-1 antimicrobial, UV absorbing, skin protecting

[0377] Different signs of ageing were assessed in the participants and in particular skin roughness via fringe projection, skin firmness and skin elasticity via Cutometry®, skin density via DermaScan® ultrasound, swelling of the lower eyelid, dark circles under the eye and tired appearance of the skin via clinical evaluation by an expert. These parameters were measured in patients at Day 0, at the time of inclusion in the study and before any treatment, at Day 7, at Day 28 in the middle of the study, and at Day 56 at the end of the study. The different parameters were also compared between the different measurement dates to assess the continuity of improvement. Wrinkle volume and assessment of skin roughness were evaluated with Antera 3D® software. The results were analysed with a Student's test on EXCEL software (Microsoft) and SAS 9.4.

[0378] Regarding moisturization, the measured values are the following (see FIG. 17):

TABLE-US-00021 TABLE 17 Day of measurement Mean Standard deviation T0 53.0 4.8 T7 55.8 4.3 T28 56.8 4.0 T56 58.0 3.7

[0379] Compare with the base value (T0), I moisturization of the skin was increased by: [0380] 5%, after 7 days of use of the product 7 (p<0.05); [0381] 7%, after 28 days of use of the product (p<0.05); and [0382] 9%, after 56 days of use of the product (p<0.05).

[0383] There was also recorded a statistically significant increase in skin moisturization of: [0384] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0385] 4% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0386] 2% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0387] The statistical significance of the values is given below:

TABLE-US-00022 TABLE 18 p value (statistically significant for p < 0.05) T0 T7 T28 T7 3.7498E−06 / / T28 9.0486E−11 0.01815949 / T56 1.8226E−09 0.00022906 0.002889285

[0388] The composition of the invention therefore allows an improvement in moisturization of the epidermis on and after the first week.

[0389] Regarding elasticity, the measured values are the following (see FIG. 18):

TABLE-US-00023 TABLE 19 Day of measurement Mean Standard deviation T0 0.620 0.034 T7 0.646 0.037 T28 0.660 0.031 T56 0.668 0.031

[0390] Compared with the base value (TO), skin elasticity was increased by: [0391] 4%, after 7 days of use of the product (p<0.05); [0392] 6%, after 28 days of use of the product (p<0.05); and [0393] 8%, after 56 days of use of the product (p<0.05).

[0394] There was also recorded a statistically significant increase in skin elasticity of: [0395] 4% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0396] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0397] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0398] The statistical significance of the values is given below:

TABLE-US-00024 TABLE 20 p value (statistically significant for p < 0.05) T0 T7 T28 T7 7.23E−07 / / T28 7.93E−10 0.000107 / T56 1.56E−10 1.88E−07 0.003712

[0399] The composition of the invention therefore allows elasticity of the epidermis to be significantly improved on and after the first week.

[0400] Regarding skin roughness, the measured values are the following (see FIG. 19):

TABLE-US-00025 TABLE 21 Day of measurement Mean Standard deviation T0 10.9 2.9 T7 10.5 2.7 T28 10.2 2.6 T56 10.0 2.3

[0401] Compared with the base value (TO), skin roughness is improved by: [0402] 3%, after 7 days of use of the product (p<0.05); [0403] 6%, after 28 days of use of the product (p<0.05); and [0404] 8%, after 56 days of use of the product (p<0.05).

[0405] There was also recorded a statistically significant decrease in skin roughness of: [0406] 3% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0407] 5% between the values at T7 (after 7 day's treatment) and T56 (after 56 days' treatment) (p<0.05); and [0408] 7% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0409] The statistical significance of the values is given below:

TABLE-US-00026 TABLE 22 p value (statistically significant for p < 0.05) T0 T7 T28 T7 0.00017 / / T28  4.9E−07 4.26E−05 / T56 1.18E−05 0.000285 0.012686

[0410] Regarding skin roughness, a statistically significant decrease was measured in 25% of volunteers after 7 days of use, in 35% of volunteers after 28 days of use and in 50% of volunteers after 56 days of use.

[0411] Regarding the smooth appearance of the skin, a statistically significant increase was measured in 45% of volunteers after 7 days of use, in 50% of volunteers after 28 days of use and in 70% of volunteers after 56 days of use. The improvement in skin roughness was measured in 45% of volunteers after 56 days of use (p<0.05).

[0412] The composition of the invention therefore allows roughness of the epidermis to be reduced and the smooth appearance thereof to be significantly increased, on and after the first week.

[0413] Regarding wrinkle volume, the measured values are the following (see FIG. 20):

TABLE-US-00027 TABLE 23 Day of measurement Mean Standard deviation T0 4.43 2.18 T7 4.24 1.98 T28 4.19 1.95 T56 4.10 1.89

[0414] Compared with the base value (TO), wrinkle volume was reduced by: [0415] 4%, after 7 days of use of the product (p<0.05); [0416] 5%, after 28 days of use of the product; and [0417] 7%, after 56 days of use of the product (p<0.05).

[0418] There was also recorded a statistically significant reduction in the volume of skin wrinkles of: [0419] 1% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0420] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0421] 2% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0422] The statistical significance of the values is given below:

TABLE-US-00028 TABLE 24 p value (statistically significant for p < 0.05) T0 T7 T28 T7 0.002633 / / T28 0.000705 0.004432 / T56 0.000235 1.07E−05 0.000119

[0423] The composition of the invention therefore allows wrinkles and fine lines to be significantly reduced on and after the first week.

[0424] An increase in skin radiance was measured to be statistically significant in 35% of volunteers after 7 days of use, in 45% of volunteers after 28 days of use and in 60% of volunteers after 56 days of use. Significant even skin tone was measured in 35% of volunteers after 56 days of use.

[0425] The composition of the invention comprising NMN and an extract of Edelweiss therefore allows the signs of ageing to be significantly reduced, and in particular allows a statistically significant improvement in moisturization of the skin, in skin elasticity, skin radiance, the smooth appearance thereof, and significantly reduces skin roughness and wrinkle volume.

Example 2—Eye Contour Serum

[0426] An example of a cosmetic composition of the invention formulated as an eye contour serum was tested in 20 women aged between 45 and 60 years. The formulation of the composition of the invention is given in the Table below:

TABLE-US-00029 TABLE 25 Eye contour serum Ingredients CAS Weight (INCI name) number Role percent Aqua 7732-18-5 Solvent q.s. to 100% Glycerin 56-81-5 Humectant, 7.658800 solvent Nicotinamide 1094-61-7 Active cosmetic 2.0 Mononucleotide substance Pentylene Glycol 5343-92-0 Solvent, emollient 2.0 Squalane 111-01-3 Emollient 1.5 C14-C22 alcohols / / 1.185000 Hydroxyethyl 111286- Emulsion 0.8 Acrylate/Sodium 86-3 stabilising, Acryloyldimethyl Taurate viscosity Copolymer controlling Polyacrylate / Emulsion 0.8 Crosspolymer-6 stabilising, viscosity controlling Glyceryl Stearate SE 11099-07-3 Emulsifying, 0.5 emollient Dicaprylyl Carbonate 1680-31-5 Emollient, 0.499813 Fagus Sylvatica Bud 85251-65-6 Astringent 0.35 Extract Glyceryl Caprylate 26402-26-6 Emollient, 0.30 emulsifying C12-20 Alkyl / Emulsifying, 0.285 Glucoside surfactant Allantoin 97-59-6 Lipid-replenishing, 0.20 skin protecting Diethylhexyl 444811-29-4 Skin protecting 0.18 Syringylidenemalonate Sodium Hydroxide 1310-73-2 Buffering 0.13950 Ethylhexylglycerin 70445-33-9 Emollient 0.09990 Benzyl Alcohol 100-51-6 Fragrance, 0.060 preserving, viscosity controlling, solvent Polysorbate 60 9005-67-8 Chelating/ 0.060 buffering Sorbitan Isostearate 71902-01-7 Emulsifying 0.060 Leontopodium Alpinum / Antioxidant, 0.04 Callus Culture Extract humectant Chlorella Vulgaris 223749- Emollient 0.0225 Extract 83-5 Caprylic/Capric 73398-61-5 Emollient, solvent, 2.0 Triglyceride fragrance, lipid- replenishing Glucose 50-99-7 Humectant 0.015 Palmaria Palmata 223751- Skin protecting 0.01 Extract 74-4 Hydrolyzed Linseed / Emollient 0.00950 Extract Sodium Benzoate 532-32-1 Preserving agent 0.0075 Citric Acid 77-92-9 Antioxidant 0.0061 Benzoic Acid 65-85-0 Preserving agent 0.004 Xanthan Gum 6132-04-3 Binder, 0.000600 emulsifying, surfactant, viscosity controlling, gelling, lipid- replenishing Tocopherol 10191-41-0 Antioxidant, 0.000288 59-02-9 Emollient

[0427] Different signs of ageing were assessed in the participants and in particular skin roughness via fringe projection (see FIG. 5), skin firmness and skin elasticity via Cutometry®, skin density via DermaScan® ultrasound, swelling of the lower eyelid also known as bags under the eyes, dark circles under the eye and tired appearance of the skin via clinical evaluation by an expert. These parameters were measured in the patients at Day 0 at the time of inclusion in the study and before any treatment, at Day 28 in the middle of the study, and at Day 56 at the end of the study. The different parameters were also compared between the different dates of measurement to assess continuity of improvement. Wrinkle volume and assessment of skin roughness were evaluated with Antera 3D® software. The results were analysed with a Student's test on EXCEL software (Microsoft) and SAS 9.4.

[0428] Regarding moisturization, the measured values are the following (see FIG. 21):

TABLE-US-00030 TABLE 26 Day of measurement Mean Standard deviation T0 52.2 3.0 T7 55.8 2.0 T28 57.5 2.1 T56 59.8 2.6

[0429] Compared with the base value (TO), moisturizing of the skin increased by: [0430] 7%, after 7 days of use of the product (p<0.05); [0431] 10%, after 28 days of use of the product (p<0.05); and [0432] 15%, after 56 days of use of the product (p<0.05).

[0433] There was also recorded a statistically significant increase in skin moisturization of: [0434] 3% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); and [0435] 7% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0436] 4% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0437] The statistical significance of the values is given below:

TABLE-US-00031 TABLE 27 p value (statistically significant for p < 0.05) T0 T7 T28 T7 4.287E−08 / / T28 1.621E−08 0.00027348 / T56  1.71E−10 3.3914E−08 2.63669E−05

[0438] The composition of the invention therefore allows moisturizing of the epidermis to be significantly improved on and after the first week.

[0439] Regarding elasticity, the measured values are the following (see FIG. 22):

TABLE-US-00032 TABLE 28 Day of measurement Mean Standard deviation T0 0.570 0.058 T7 0.600 0.060 T28 0.612 0.051 T56 0.624 0.049

[0440] Compared with the base value (TO), skin elasticity was increased by: [0441] 5%, after 7 days of use of the product (p<0.05); [0442] 7%, after 28 days of use of the product (p<0.05); and [0443] 9%, after 56 days of use of the product (p<0.05).

[0444] There was also recorded a statistically significant increase in skin elasticity of: [0445] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); and [0446] 4% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0447] 2% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0448] The statistical significance of the values is given below:

TABLE-US-00033 TABLE 29 p value (statistically significant for p < 0.05) T0 T7 T28 T7 9.14E−07 / / T28 1.84E−08 0.010169 / T56 1.29E−09 3.71E−05 0.00083

[0449] The composition of the invention therefore allows elasticity of the epidermis to be significantly improved on and after the first week.

[0450] Regarding skin roughness, the measured values are the following (see FIG. 23):

TABLE-US-00034 TABLE 30 Day of measurement Mean Standard deviation T0 12.4 2.0 T7 12.0 1.9 T28 11.7 1.8 T56 11.5 1.7

[0451] Compare with the base value (T0), skin roughness was reduced by: [0452] 3%, after 7 days of use of the product (p<0.05); [0453] 6%, after 28 days of use of the product (p<0.05); and [0454] 7%, after 56 days of use of the product (p<0.05).

[0455] There was also recorded a statistically significant decrease in skin roughness, of: [0456] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0457] 4% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0458] 2% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0459] The statistical significance of the values is given below:

TABLE-US-00035 TABLE 31 p value (statistically significant for p < 0.05) T0 T7 T28 T7 5.77E−05 / / T28 3.41E−08 0.000731 / T56 8.47E−09 8.46E−07 2.14E−05

[0460] Regarding the smooth appearance of the skin, a statistically significant increase was measured in 45% of volunteers after 7 days of use, in 60% of volunteers after 28 days of use and in 75% of volunteers after 56 days of use. The reduction in skin roughness was measured in 50% of volunteers after 28 days of use and in 55% of volunteers after 56 days of use (p<0.05).

[0461] The composition of the invention therefore allows roughness of the epidermis at the eye contour to be reduced, and allows significant improvement in the smooth appearance thereof on and after the first week.

[0462] Regarding wrinkle volume, the measured values are the following (see FIG. 24):

TABLE-US-00036 TABLE 32 Day of measurement Mean Standard deviation T0 3.29 1.47 T7 3.15 1.40 T28 3.08 1.35 T56 3.03 1.34

[0463] Compared with the base value (TO), the volume of skin wrinkles was improved by: [0464] 4%, after 7 days of use of the product (p<0.05); [0465] 4%, after 28 days of use of the product (p<0.05); and [0466] 5%, after 56 days of use of the product (p<0.05).

[0467] There was also recorded a statistically significant reduction in the volume of skin wrinkles, of: [0468] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0469] 4% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0470] 2% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0471] The statistical significance of the values is given below:

TABLE-US-00037 TABLE 33 p value (statistically significant for p < 0.05) T0 T7 T28 T7 0.000603 / / T28 7.16E−06 0.007166 / T56 1.27E−06 0.000159 0.000371

[0472] The composition of the invention therefore allows the volume of wrinkles and fine lines to be significantly reduced, on and after the first week.

[0473] An increase in skin radiance was measured to be statistically significant in 40% of volunteers after 7 days of use, in 60% of volunteers after 28 days of use and in 75% of volunteers after 56 days of use.

[0474] Even skin tone was measured to be significant in 35% of volunteers after 28 days of use and in 50% of volunteers after 56 days of use.

[0475] Regarding the volume of under-eye bags, the measured values are the following (see FIG. 25):

TABLE-US-00038 TABLE 34 Day of measurement Mean Standard deviation T0 22.1 4.6 T7 21.4 4.1 T28 21.0 4.0 T56 20.7 3.9

[0476] Compared with the base value (TO), the volume of under-eye bags was improved by: [0477] 3%, after 7 days of use of the product (p<0.05); [0478] 5%, after 28 days of use of the product (p<0.05); and [0479] 7%, after 56 days of use of the product (p<0.05).

[0480] There was also recorded a statistically significant reduction in the volume of under-eye bags: [0481] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0482] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0483] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0484] The statistical significance of the values is given below:

TABLE-US-00039 TABLE 35 p value (statistically significant for p < 0.05) T0 T7 T28 T7 0.0107571 / / T28 0.000539  5.6059E−05 / T56 0.0001048 1.63605E−06 2.74E−06

[0485] A reduction in the visibility of under-eye bags was measured to be statistically significant in 40% of volunteers after 28 days of use, and in 55% of volunteers after 56 days of use.

[0486] The composition of the invention therefore allows the volume of bags under the eyes to be significantly reduced on and after the first week.

[0487] Regarding erythema under the eyes, assessed using a Mexameter® MX 18 following the manufacturer's instructions, the measured values are the following (see FIG. 26):

TABLE-US-00040 TABLE 36 Day of measurement Mean Standard deviation T0 349.3 58.5 T7 326.3 49.6 T28 320.2 50.0 T56 316.5 49.6

[0488] Compared with the base value (TO), erythema of dark circles was improved by: [0489] 7%, after 7 days of use of the product (p<0.05); [0490] 8%, after 28 days of use of the product (p<0.05); and [0491] 9%, after 56 days of use of the product (p<0.05).

[0492] There was also recorded a statistically significant reduction in skin erythema, of: [0493] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0494] 3% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0495] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0496] The statistical significance of the values is given below:

TABLE-US-00041 TABLE 37 p value (statistically significant for p < 0.05) T0 T7 T28 T7   9E−05 / / T28 2.87E−07 0.046357 / T56 1.94E−07 0.008644 0.004654

[0497] The composition of the invention therefore allows a significant reduction in erythema of under-eye bags, on and after the first week.

[0498] Regarding the melanin content of dark circles reflecting the colouring thereof, as assessed with the use of a Mexameter® MX 18 following the manufacturer's instructions, the measured values are the following (see FIG. 27):

TABLE-US-00042 TABLE 38 Day of measurement Mean Standard deviation T0 174 25 T7 166 24 T28 163 22 T56 160 22

[0499] Compared with the base value (TO), colouring of dark circles was reduced by: [0500] 4%, after 7 days of use of the product (p<0.05); [0501] 6%, after 28 days of use of the product (p<0.05); and [0502] 8%, after 56 days of use of the product (p<0.05).

[0503] There was also recorded a statistically significant reduction in the volume of skin wrinkles, of: [0504] 2% between the values at T7 (after 7 days' treatment) and T28 (after 28 days' treatment) (p<0.05); [0505] 4% between the values at T7 (after 7 days' treatment) and T56 (after 56 days' treatment) (p<0.05); and [0506] 1% between the values at T28 (after 28 days' treatment) and T56 (after 56 days' treatment) (p<0.05).

[0507] The statistical significance of the values is given below:

TABLE-US-00043 TABLE 39 p value (statistically significant for p < 0.05) T0 T7 T28 T7 0.002475 / / T28  1.1E−06 0.018411 / T56 4.19E−08 0.000848 0.001489

[0508] The composition of the invention therefore allows a significant reduction in erythema of under-eye bags, on and after the first week.

[0509] A reduction in the visibility of dark circles was measured to be statistically significant in 35% of volunteers after 7 days of use, in 45% of volunteers after 28 days of use, and in 55% of volunteers after 56 days of use. A significant increase in even skin tone was measured in 35% of volunteers after 56 days of use.

[0510] The composition of the invention therefore allows the signs of ageing to be significantly reduced, and in particular allows a statistically significant improvement in skin moisturization, skin elasticity, skin radiance, the smooth appearance thereof, and significantly reduces skin roughness, wrinkle volume, the volume of under-eye bags and the colouring of dark circles.