ANTI-AGING EYE CREAM

Abstract

ANTI-AGING EYE CREAM The present invention relates to a stable emulsion-type anti-aging composition in the form of an oil-in-water emulsion that is pleasant to the touch and comprises a mixture of compounds including an elastase reducer, for example a C-glycoside derivative also known as hydroxypropyltetrahydropyrantriol, and two or more compounds selected from the group consisting of cell proliferation agents, for example niacinamide, anti-inflammatory agents, for example an extract of Eperua falcata bark, and collagen-producing agents, for example an extract of Gentiana lutea root, and combinations thereof. Figure for abstract: none

Description

Title of the invention: ANTI-AGING EYE CREAM FIELD OF INVENTION

[0001] The present invention relates to a stable skincare composition containing a combination of active components in sufficient quantities to treat the signs of aging specific to the skin around the eyes. More specifically, the present invention relates to a stable skincare composition in the form of an anti-aging composition for the skin around the eyes, the composition comprising a mixture of compounds including an elastase reducer, for example hydroxypropyltetrahydropyrantriol (commercially available under the name Pro-xylane (TM)), and two or more compounds selected from cell proliferation agents, for example niacinamide, anti-inflammatory agents, for example an extract of Eperua falcata bark (commercially available under the name Eperuline (TM)), and collagen-producing agents, for example an extract of Gentiana lutea root (commercially available under the name Myralys (TM)).CONTEXT OF THE INVENTION.

[0002] The skin is the largest organ of the human body and separates the interior of human beings from the external world. Skin is heterogeneous from the genetic to the tissue level; depending on the anatomical location, the structural components that distinguish the eyelid from other facial skin also vary. In the field of dermatological research, the subtleties of skin care take on increased importance when focusing on the distinct characteristics of the eye contour. The eyelid, characterized by its soft, smooth, and thin skin, stands out due to its unique function and location on the face. Its delicate nature allows for perfect conformity with the essential blinking movement, a crucial mechanism for protecting the eyeball. Despite these unique attributes, a complete understanding of the biophysical characteristics of the eyelid remains more complex compared to other areas of facial skin.

[0003] There is a need to provide an anti-aging skincare composition, including moisturizing and sunscreen embodiments, capable of stably transporting highly effective active ingredients targeting the skin around the eyes, which is also pleasant to the touch for consumers upon application. BRIEF SUMMARY OF THE INVENTION

[0004] In various embodiments, the disclosure proposes a composition that includes an elastase reducer, and one or more compounds selected from the group consisting including cell proliferation agents, anti-inflammatory agents, and collagen production agents.

[0005] In some embodiments, the disclosure proposes a composition that includes an elastase reducer, and two or more compounds selected from the group consisting of cell proliferation agents, anti-inflammatory agents, collagen production agents.

[0006] In some embodiments, the composition includes at least one elastase reducer, at least one cell proliferation agent, at least one anti-inflammatory agent, at least one collagen-producing agent.

[0007] In the various embodiments, the composition may be supplied in one of a variety of formulation types, for example selected from an oil-in-water emulsion, an anhydrous / glycolic formulation which may be free of or substantially free of water (other than as a solvent for a raw material), an aqueous formulation which may be free of or substantially free of oil (other than skin actives such as tocopherol, for example), an aqueous / glycolic formulation which may be free of or substantially free of oil (other than skin actives such as tocopherol), or a glycolic formulation which is free of or substantially free of oil (other than skin actives such as tocopherol) and / or water (other than as a solvent for a raw material).In certain anhydrous and / or glycol-containing embodiments that are free of water, the glycols are present in appropriate amounts to solubilize niacinamide in an otherwise anhydrous form.

[0008] The composition is stable and pleasant to the touch.

[0009] This disclosure also relates to a cosmetic treatment method for keratinous tissues by applying the composition disclosed above to a surface of the keratinous tissue, in particular around the eyes, using an applicator or co-applicator instrument.

[0010] In some embodiments, the disclosure proposes a composition that includes an elastase reducer, for example a C-glycoside derivative also known as hydroxypropyltetrahydropyrantriol, and two or more compounds selected from the group consisting of cell proliferation agents, for example niacinamide, anti-inflammatory agents, for example an extract of Eperua falcata bark and collagen-producing agents, for example an extract of Gentiana lutea root, and combinations thereof.

[0011] In some embodiments, the composition includes at least one elastase reducer comprising hydroxypropyltetrahydropyrantriol, at least one cell proliferation agent comprising niacinamide, and at least one anti-inflammatory agent comprising an extract of Eperua falcata bark.

[0012] In some embodiments, the composition includes at least one elastase reducer comprising hydroxypropyltetrahydropyrantriol, at least one cell proliferation agent comprising niacinamide, and at least one collagen production agent comprising an extract of Gentiana lutea root.

[0013] In some embodiments, the composition includes at least one elastase reducer comprising hydroxypropyltetrahydropyrantriol, at least one cell proliferation agent comprising niacinamide, at least one anti-inflammatory agent comprising an extract of Eperua falcata bark, and at least one collagen-producing agent comprising an extract of Gentiana lutea root.

[0014] In certain embodiments, the present disclosure includes a composition in the form of a stable emulsion-type anti-aging composition. The anti-aging composition, as represented as an oil-in-water emulsion, includes oil and water phases as a carrier system for a mixture of compounds including an elastase reducer, for example, a C-glycoside derivative also known as hydroxypropyltetrahydropyrantriol, and two or more compounds selected from the group consisting of cell proliferation agents, for example, niacinamide, anti-inflammatory agents, for example, an extract of Eperua falcata bark, and collagen-producing agents, for example, an extract of Gentiana lutea root, and combinations thereof. The composition is stable and pleasant to the touch.

[0015] In some embodiments, the disclosure proposes a composition comprising: a. an oil and water carrier system comprising i. of water; ii. at least one surfactant; iii. at least one fatty compound; and iv. at least one thickener; b. an anti-aging system for ocular tissue, comprising i. at least one elastase reducer; and ii. at least two additional agents chosen from the group consisting of: 1. at least one cell proliferation agent; 2. at least one anti-inflammatory agent; and 3. at least one collagen-producing agent.

[0016] In some embodiments, the anti-aging composition is in the form of an oil and water emulsion.

[0017] In certain embodiments, in the anti-aging system for ocular tissue (b): i. at least one elastase reducer is selected from the group consisting of hydroxypropyltetrahydropyrantriol, peptides, for example palmitoyl tripeptide-5, acetyl hexapeptide-8 and palmitoyl tetrapeptide-7, retinol, vitamin C, green tea extract, aloe vera extract, resveratrol, coenzyme Q10, and combinations thereof; ii. when present, at least one cell proliferation agent is chosen from the group consisting of niacinamide, retinol, peptides, growth factors, stem cells, vitamin C, vitamin K, exosomes (for example in Sigma-Aldrich edelfosine (TM) or (Tyr[SO3H]27)cholecystokinin fragment 26-33 amide), and their combinations; iii. when present, at least one anti-inflammatory agent is chosen from the group consisting of Eperua falcata bark extract, aloe vera, calmosensine, alder extract, resargine, Andrographis paniculate extract, Ficus regligiosa bark, Cucuma zeoaria extract, ursolic acid, ectoine, Coptidis chinensis extract, Pongamia pinnata extract, white hibiscus, ectoine, Punica granatum extract, pomegranate extract, ginger root extract, ginkgo biloba extract, witch hazel, exosome, bisabolol (levomenol), green tea extract, zinc oxide, and combinations thereof; and iv. when present, at least one collagen-producing agent is chosen from the group consisting of Gentiana lutea root extract, retinoids, carob seed extract, Saccharomyces cerevisiae extract, panthenol (vitamin B5), carob seed extract, ginger root extract, galactomannans, pullulan, beta-glucan, alpha-glucan, Caesalpinia sphinosa gum,oligosaccharides, oligogalactomannans, wogonin, baicalin, ceramides, sphingolipids, resveratrol and its derivatives, niacinamide and its derivatives, TXA, pomegranate extract, linoleic acid, linolenic acid, olic acid, vitamin C, vitamin E (tocopherols) and its derivatives, polyphenols, flavanols, dihydroflavanols, ellagic acid, flavonoids, collagen and its derivatives, arnica montana extract, carotenoids and their derivatives, triglycerides, soybean oil, oleuropein and its derivatives, phospholipids, beta-carotene, microalgae, chlorella vulgaris extract, dunaliella salina extract, Lactococcus fermentation lysate, Lactobacillus ferment, flaxseed extract, proanthocyanins, anthocyanins, hydroxyacetophenone, lecithin, GHK-Cu peptide, tripeptide-1, peptide copper, GHK-Mn, acetyl tetrapeptides, tripeptide 10, citrulline, palmitoyl hexapeptide-12, palmitoyl tripeptide-1, lipospondin, gexapeptide 11, PKEK, GEKG, SA1-11, tripeptide-3, pentapeptide-18,pentapeptide-3, acetyl octapeptide-1,3, defensins B, cathelicidin, dermcidin, histidine dipeptides, urocanic acid, pyrrolidone carboxylic acid, Pal-KTTKS, peptides, KEK and PKEK, palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, Tropaeolum majus extract, glycoproteins, hyaluronic acid and its derivatives, sh-polypeptide-5, sh-polypeptide-11, sh-oligopeptide-2, sh-polypeptide-6, wheat germ oil, octacosanol, wild yam root extract, bakuchiol, borage oil, geranium oil, Protium heptaphyllum oil, Hamamelis virginiana extract, Citrus medica limonum oil, glutathione, coenzyme Q10, acetylglucosamine disodium phosphate, fermented red ginseng extract, dipeptide diaminobutyroyl benzylamide diacetate, Angelica polymorpha sinensis root extract, sericin, superoxide dismutase, copper peptides, vitamin C, vitamin E, ginseng extract, and their combinations.

[0018] In certain embodiments, in the anti-aging system for eye tissue (b): i. at least one elastase reducer comprises hydroxypropyl tetrahydropyrantriol; ii. when present, at least one cell proliferation agent includes niacinamide; iii. when present, at least one anti-inflammatory agent includes an extract of Eperua falcata bark; and iv. when present, at least one collagen-producing agent includes an extract of Gentiana lutea root.

[0019] In certain embodiments, in the anti-aging system for ocular tissue (b); i. at least one elastase reducer is present from approximately 0.01% to approximately 30%, ii. when present, at least one cell proliferation agent is present from about 0.0001% to about 30%; iii. when present, at least one anti-inflammatory agent is present at a concentration of approximately 0.01% to approximately 10%; and iv. when present, at least one collagen-producing agent is present from approximately 0.01% to approximately 10%.

[0020] In certain embodiments, the anti-aging system for ocular tissue (b) comprises: i. at least one elastase reducer; ii. at least one cell proliferation agent; iii. at least one anti-inflammatory agent; and iv. at least one collagen-producing agent.

[0021] In certain embodiments, the anti-aging system for ocular tissue (b) comprises: i. at least one elastase reducer; ii. at least one cell proliferation agent; and iii. at least one anti-inflammatory agent.

[0022] In certain embodiments, the anti-aging system for ocular tissue (b) comprises: i. at least one elastase reducer; ii. at least one cell proliferation agent; and iii. at least one collagen-producing agent.

[0023] In certain embodiments, in the anti-aging system for ocular tissue (b); i. at least one elastase reducer is present from approximately 0.01% to approximately 30% ii. at least one cell proliferation agent is present from approximately 0.0001% to approximately 30% iii. at least one anti-inflammatory agent is present from approximately 0.01% to approximately 10% iv. at least one collagen-producing agent is present from approximately 0.01% to approximately 10%

[0024] In certain embodiments, in the anti-aging system for eye tissue (b): i. at least one elastase reducer comprises hydroxypropyl tetrahydropyrantriol; ii. at least one cell proliferation agent includes niacinamide; iii. at least one anti-inflammatory agent includes a bark extract of Eperua falcata; and iv. at least one collagen-producing agent comprises an extract of Gentiana lutea root.

[0025] In certain embodiments, in the anti-aging system for ocular tissue (b): i. Hydroxypropyltetrahydropyrantriol is present from about 0.01% to about 30%; ii. Niacinamide is present from approximately 0.0001% to approximately 30%; iii. The bark extract of Eperua falcata is present from approximately 0.01% to approximately 10%; and iv. Gentiana lutea root extract is present from approximately 0.01% to approximately 10%.

[0026] In certain embodiments, in the anti-aging system for ocular tissue (b): i. Hydroxypropyltetrahydropyrantriol is present at approximately 10%; ii. Niacinamide is present at approximately 3%; iii. The bark extract of Eperua falcata is present at approximately 0.1%; and iv. Gentiana lutea root extract is present at approximately 0.015%.

[0027] In certain embodiments, in the oil-in-water carrier system (a), at least one surfactant is selected from the group consisting of steareth-100, cetearyl alcohol (and) cetearyl glucoside, behenyl alcohol, C14-22 alcohols (and) C12-20 alkyl glucoside, and combinations thereof; at least one fatty compound is selected from the group consisting of dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, squalane, coco caprylate / caprate, one or more ceramides selected from Ceramide EOP, Ceramide AS, Ceramide AP, Ceramide NS, Ceramide NP, Ceramide NH, Ceramide AH, Ceramide EOH, Ceramide EOS, Ceramide AdS, Ceramide NdS, Ceramide EOdS, Phytosphingosine, Sphingosine, 2-Oleyl-1,3-octadecanediol, ceramide precursors, fatty acids, fatty alcohols, cholesterol, cholesterol sulfate and their combinations, at least one thickener is chosen from the group consisting of Zea mays (maize) starch,C10-30 alkyl polyacrylate, ammonium acryloyldimethyltaurate / VP copolymer and combinations thereof, and comprising at least one additive selected from the group consisting of citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin, trisodium ethylenediamine disuccinate, and dextrin, propanediol, pentylene glycol and propylene glycol, and combinations thereof.

[0028] In some embodiments, in the oil-in-water carrier system (a): i. water is present in a range of about 5% to about 90%; ii. at least one surfactant is present in a range of approximately 1% to approximately 15%; iii. at least one fatty compound is present in a range of approximately 2% to approximately 20%; and iv. at least one thickener is present in a range of approximately 0.5% to approximately 10%,

[0029] all quantities being in weight, relative to the total weight of the composition.

[0030] In certain embodiments, in the oil-in-water carrier system (a): i. Water is present at approximately 60%; ii. at least one surfactant is present at approximately 2.5%; iii. at least one fatty compound is present at approximately 10%; and iv. at least one thickener is present at approximately 2.25%

[0031] all quantities being in weight, relative to the total weight of the composition.

[0032] In certain embodiments, in the oil-in-water carrier system (a): i. Water is present at approximately 60%; ii. at least one surfactant is present at approximately 2.5% and comprises steareth-100, cetearyl alcohol (and) cetearyl glucoside, behenyl alcohol and C14-22 alcohols (and) a C12-20 alkyl glucoside; iii. at least one fatty compound is present at approximately 10% and includes dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, squalane, and coconut caprylate / caprate; and iv. At least one thickener is present at approximately 2.25% and comprises Zea mays (maize) starch, a C10-30 alkyl polyacrylate, an ammonium acryloyldimethyltaurate / VP copolymer,

[0033] wherein the composition also includes glycerin present at approximately 7%, and one or more additives selected from the group consisting of citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin, trisodium ethylenediamine disuccinate and dextrin, propanediol, pentylene glycol and propylene glycol,

[0034] all amounts being by weight, relative to the total weight of the composition.

[0035] In one embodiment, the disclosure proposes an anti-aging composition comprising:

[0036] an anti-aging system (a) for ocular tissue comprising i. of hydroxypropyltetrahydropyrantriol present at approximately 10%; ii. of niacinamide present at approximately 3%; iii. an extract of Eperua falcata bark present at approximately 0.1%; iv. an extract of Gentiana lutea root present at approximately 0.015%

[0037] all quantities being in weight, relative to the total weight of the composition.

[0038] In some embodiments, the anti-aging composition includes a carrier system (b) comprising: i. of water present in a range of about 5% to about 90%; ii. at least one surfactant is present in a range of approximately 1% to approximately 15%; iii. at least one fatty compound is present in a range of approximately 2% to approximately 20%; and iv. at least one thickener is present in a range of approximately 0.5% to approximately 10%,

[0039] In some embodiments, at least one surfactant is present at approximately 2.5% and comprises steareth-100, cetearyl alcohol (and) cetearyl glucoside, behenyl alcohol, C14-22 alcohols (and) a C12-20 alkyl glucoside; at least one fatty compound is present at approximately 10% and comprises dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, squalane, and coco caprylate / caprate; and at least one thickener is present at approximately 2.25% and comprises Zea mays (maize) starch, a Cl0-30 alkyl polyacrylate, and an acryloyldimethyltaurate copolymer. of ammonium / VP, and wherein the composition also includes glycerin present at about 7% and one or more additives selected from the group consisting of citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin, trisodium ethylenediamine disuccinate, and dextrin, propanediol, pentylene glycol and propylene glycol, all quantities being by weight, relative to the total weight of the composition.

[0040] In certain embodiments, the disclosure proposes a method for minimizing the signs of aging of the tissue around the eyes, the method comprising: A. The provision of a composition comprising a plurality of agents to minimize the effects of mitophagy and sarcopenia on skeletal muscles, increase sGAG release and inhibit elastase activity, and increase skin cell proliferation in the tissues around the eyes, the plurality of agents comprising at least three agents selected from the group consisting of B. at least one elastase reducer includes hydroxypropyltetrahydropyrantriol; and C. at least two additional agents chosen from the group consisting of: i. at least one cell proliferation agent is chosen from the group consisting of niacinamide, retinol, peptides, growth factors, stem cells, vitamin C, vitamin K, exosomes and their combinations; ii. at least one anti-inflammatory agent is selected from the group consisting of Eperua falcata bark extract, aloe vera, hamamelis, exosome, bisabolol (levomenol), green tea extract, zinc oxide, and combinations thereof; and iii. at least one collagen-producing agent is selected from the group consisting of Gentiana lutea root extract, retinoids, copper peptides, vitamin C, vitamin E, ginseng extract, and combinations thereof, D. the application of the composition preferably to the skin above and below the user's eye; and E. following a regimen of repeated application of the composition for a period of at least thirty days.

[0041] In certain embodiments, the method includes making available one or more of a professional device or a device for domestic use, or a combination thereof, the professional device being chosen from the group consisting of a microdermabrasion machine, a microneedling machine, an LED light therapy device, a high-frequency machine, a radiofrequency device, an ultrasound device, a cryotherapy machine, a laser device and combinations thereof, and the home-use device being selected from the group consisting of LED masks, microdermabrasion devices, microneedling devices, ultrasonic skin scrubbers, facial steamers, IPL skin rejuvenation devices, sonic eye massagers, fractional laser devices, cold laser therapy devices, microcurrent, and combinations thereof.

[0042] In certain embodiments, the disclosure proposes a system for minimizing the signs of aging of the tissue around the eyes, the system comprising: a. a composition according to any one of the preceding compositions, b.a device chosen from the group consisting of one or more of a professional device or a home-use device, or a combination thereof, the professional device being chosen from the group consisting of a microdermabrasion machine, a microneedling machine, an LED light therapy device, a high-frequency machine, a radiofrequency device, an ultrasound device, a cryotherapy machine, a laser device and combinations thereof, and the home-use device being chosen from the group consisting of LED masks, microdermabrasion devices, microneedling devices, ultrasonic skin scrubbers, facial steamers, IPL skin rejuvenation devices, sonic eye massagers, fractional laser devices, cold laser therapy devices, microcurrent, and combinations thereof.

[0043] In some embodiments, the composition comprises: i. at least one elastase reducer including hydroxypropyltetrahydropyrantriol; ii. at least one cell proliferation agent selected from the group consisting of niacinamide, retinol, peptides, growth factors, stem cells, vitamin C, vitamin K, exosomes and their combinations; iii. at least one anti-inflammatory agent selected from the group consisting of Eperua falcata bark extract, aloe vera, hamamelis, exosome, bisabolol (levomenol), green tea extract, zinc oxide, and combinations thereof; and iv. at least one collagen-producing agent selected from the group consisting of Gentiana lutea root extract, retinoids, copper peptides, vitamin C, vitamin E, ginseng extract, and combinations thereof,

[0044] wherein in the oil-in-water carrier system (a), at least one surfactant is selected from the group consisting of steareth-100, cetearyl alcohol (and) cetearyl glucoside, behenyl alcohol, C14-22 alcohols (and) C12-20 alkyl glucoside, and combinations thereof, at least one fatty compound is selected from the group consisting of dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, squalane, coco caprylate / caprate, and combinations thereof, at least one thickener is selected from the group consisting of Zea mays starch (maize), C10-30 alkyl polyacrylate, ammonium acryloyldimethyltaurate / VP copolymer and their combinations,and comprising at least one additive selected from the group consisting of citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin, trisodium ethylenediamine disuccinate, and dextrin, propanediol, pentylene glycol and propylene glycol, and combinations thereof.

[0045] Other features and advantages of the present invention will become apparent from the following more detailed description of the preferred embodiment which illustrates, by way of example, the principles of the invention. DESCRIPTION OF THE DRAWINGS

[0046] Fig. 1 shows the significant structural difference between the skin around the eyes and the skin on the face;

[0047] [Fig.2] represents a graph of histological analysis of the skin of the upper eyelids and the skin of the face;

[0048] [Fig.3] presents the results of the analysis of changes in gene expression in skin samples;

[0049] [Fig.4] presents the results of the analysis of changes in gene expression in skin samples;

[0050] [Fig.5] presents the results of changes in gene expression;

[0051] [Fig.6] presents the results of changes in gene expression;

[0052] Figure 7 presents the data obtained with hydroxypropyltetrahydropyra ntriol;

[0053] [Fig.8] presents the data obtained with hydroxypropyltetrahydropyrantriol and niacinamide;

[0054] [Fig.9] presents the data obtained with hydroxypropyltetrahydropyrantriol and niacinamide;

[0055] [Fig. 10] presents the data obtained with hydroxypropyltetrahydropyrantriol and niacinamide;

[0056] Figure 11 presents the data obtained with the root extract of Gentiana Lutea on collagen expression; and

[0057] [Fig. 12] presents the data obtained by micropuncture and the addition of an extract of Eperua Falcata bark.

[0058] It should be understood that the preceding and following descriptions are given solely by way of example and explanation, and are not intended to restrict any claimed subject matter. DETAILED DESCRIPTION OF THE INVENTION

[0059] According to the disclosure, the inventors sought to bridge the knowledge gap regarding the distinctions between the aging of skin around the eyes and other facial skin, by providing information on the distinctive qualities of the eye contour and highlighting the importance of personalized skincare practices. Through a multi-level review and methodological exploration, the inventors provide knowledge that shapes effective skincare strategies to maintain the health and vitality of the eye contour.Through digital data analysis (RNA sequencing) to understand changes in the genes of ocular skin tissue in subjects ranging from middle-aged (38 to 60 years) to elderly (62 to 85 years), the inventors gained specific information on gene activity in the skin around the eyes and developed an eye-specific anti-aging composition with key active ingredients designed to address age-related changes around the eyes. As a result, the anti-aging eye cream composition includes at least one elastase reducer, at least one cell proliferation agent, at least one anti-inflammatory agent, and at least one collagen-promoting agent.In one embodiment of the anti-aging composition, at least one elastase reducer includes hydroxypropyltetrahydropyrantriol, at least one cell proliferation agent includes niacinamide, at least one anti-inflammatory agent includes an extract of Eperua falcata bark, and at least one collagen-producing agent includes an extract of Gentiana lutea root.

[0060] Digital data analysis by RNA sequencing conducted by the inventors surprisingly revealed that the skin of the eyes is clearly more affected by aging factors than general facial tissue. By evaluating facial tissue in middle-aged (43 to 60 years) and elderly (62 to 70 years) subjects, the inventors also surprisingly discovered that ocular tissue exhibits marked changes in the expression of genes that have not been previously described in association with aging, particularly aging of ocular tissue.

[0061] The inventors have shown, in aged ocular tissue (62 to 70 years), downregulation (reduced expression compared to middle-aged ocular tissue of 43 to 60 years or younger) of genes associated with the extracellular matrix, including elastic fibers / elastase, GAGs, and collagen, and with cell migration motility, differentiation, and proliferation, and upregulation of genes associated with skeletal muscle. These data show that differentially expressed gene changes increase with age at a faster rate in ocular tissue compared to general facial tissue.The aggregate effect on ocular tissue is greater given the greater number of genes shown to have altered expression, particularly an abundance of downregulated genes, with a greater magnitude of change, in the tissue around the eyes compared to other facial tissues in aged skin compared to younger skin.

[0062] Without being bound by any theory, it is postulated that the presence of skeletal muscle tissue near the surface in the eye contour promotes aging around the eyes. Some explanations include the decline in mitophagy within skeletal tissue, whereby cells are less able to remove and recycle damaged mitochondria to regulate the biogenesis of new, fully functional, healthy mitochondria, as well as sarcopenia, a loss of muscle function caused by oxidative stress and inflammation associated with the accumulation of ROS (reactive oxygen species), inflammatory and pro-inflammatory cytokines, and damage to lipids, DNA, and proteins.

[0063] Based on new gene expression data, the inventors have identified four key categories of active ingredients which are combined in an anti-aging composition for the eyes, targeting key changes in ocular tissue to enhance underlying cellular processes and at least reduce the signs of skin aging.

[0064] Data obtained with combined ingredients of the composition of the invention (hydroxypropyltetrahydropyrantriol and niacinamide) demonstrate that the combined actives can increase the release of sGAG and inhibit elastase activity, and significantly increase skin cell proliferation, in which the data show that 0.004% and 0.012% of niacinamide significantly increase proliferation and that the combinations of 0.017% of hydroxypropyltetrahydropyrantriol + 0.004% of niacinamide and of 0.05% of hydroxypropyltetrahydropyrantriol + 0.012% of niacinamide significantly increase proliferation.

[0065] The data also confirm the antioxidant effects of Eperua falcata bark extract and the improvement of collagen expression by Gentiana lutea root extract.

[0066] Gene analysis data show that eye contour tissue is not equivalent to facial tissue, and that eye contour tissue requires different anti-aging solutions due to anatomical differences that affect eye contour tissue more strongly than other facial tissues tested.

[0067] Composition:

[0068] To treat the signs of aging of the skin around the eyes (i.e., the eyelid tissue above the eye and the tissue below and at the outer edges of the eye), the inventors propose a composition comprising a combination of active ingredients, in one embodiment including rhydroxypropyltetrahydropyrantriol, niacinamide, an extract of Eperua falcata bark, and an extract of Gentiana lutea root, as a unique combination to provide anti-aging benefits to the tissue around the eyes. This combination treats age-related eye problems, such as wrinkles, sagging, and roughness of the skin.

[0069] In various embodiments, the anti-aging composition developed to combat aging in the eye contour tissue includes a mixture of compounds comprising an elastase reducer, for example a C-glycoside derivative also known as hydroxypropyltetrahydropyrantriol, and two or more compounds selected from the group consisting of cell proliferation agents, for example niacinamide, anti-inflammatory agents, for example an extract of Eperua falcata bark, and collagen-producing agents, for example an extract of Gentiana lutea root, and combinations thereof. In some embodiments, the anti-aging composition is in the form of an oil-and-water emulsion.

[0070] The anti-aging composition according to the present disclosure finds application in a wide variety of treatments, particularly cosmetic treatments of keratinous tissue, such as the skin, and more specifically the skin around the eye. It will be understood that although the composition of the invention is particularly suited for use on the skin around the eyes, it may be beneficial for use on other areas of the skin of the face and body, for example, on the skin of the lips, neck, hands, abdomen, and on the hair, including the scalp.

[0071] As described herein, in certain embodiments, the anti-aging composition can be used according to a monthly treatment regimen, or can be used for daily application over a shorter or longer period of time. Furthermore, the anti-aging composition can be used in conjunction with one or more applicators and instruments and, optionally, as part of a more extensive treatment regimen that includes the use of compositions containing other active ingredients and / or the use of one or more applicators and instruments.

[0072] In certain embodiments, the anti-aging composition can be used with one or more of a professional device or a home device, or a combination thereof, the professional device being chosen from the group consisting of a microdermabrasion machine, a microneedling machine, an LED light therapy device, a high-frequency machine, a radiofrequency device, an ultrasound device, a cryotherapy machine, a laser device and combinations thereof, and the home device being chosen from the group consisting of LED masks, microdermabrasion devices, microneedling devices, ultrasonic skin scrubbers, facial steamers, IPL skin rejuvenation devices, sonic eye massagers, fractional laser devices, cold laser therapy devices, microcurrent, and combinations thereof.

[0073] Elastase reducer:

[0074] In various embodiments, the composition includes at least one elastase reducer selected from the group consisting of hydroxypropyltetrahydropyrantriol, peptides, for example palmitoyl tripeptide-5, acetyl hexapeptide-8 and palmitoyl tetrapeptide-7, retinol, vitamin C, green tea extract, aloe vera extract, resveratrol, coenzyme Q10, and combinations thereof. Other examples of elastase reducers include: peptides, for example palmitoyl tripeptide-5, acetyl hexapeptide-8, palmitoyl tetrapeptide-7, retinol, vitamin C, green tea extract, aloe vera extract, resveratrol, coenzyme Q10, etc.

[0075] In some embodiments, at least one elastase reducer includes hydroxypropyltetrahydropyrantriol.

[0076] In some embodiments, the anti-aging composition is in the form of an oil and water emulsion.

[0077] C-glycoside / hydroxypropyltetrahydropyrantriol derivative;

[0078] In various embodiments, the anti-aging composition includes at least one elastase reducer comprising a C-glycoside derivative. Generally, suitable C-glycoside derivatives can be found among those described in EP 1 345 919. In some particular embodiments, a suitable C-glycoside derivative is C-[3-D-xylopyranoside-2-hydroxypropane sold by Chimex under the name Mexoryl SBB(R) (TM), and also called C-beta-D-xylopyranoside-2-hydroxypropane, hydroxypropyltetrahydropyrantriol and Pro-xylane (TM).

[0079] Hydroxypropyltetrahydropyrantriol is a sugar-protein hybrid made from xylose and can effectively activate the synthesis of GAGs (glycosamineoglycans), promote the production of hyaluronic acid, collagen synthesis, adhesion between the dermis and epidermis, synthesis of the components of the structure of the epidermis, regeneration of damaged tissues and maintenance of skin elasticity.

[0080] When present, the amount of hydroxypropyltetrahydropyrantriol in the anti-aging composition will vary, but in various embodiments, it is from approximately 0.01% to approximately 30%, or from approximately 5% to approximately 15%, or any appropriate combination, subcombination, range, or subrange of these values ​​by weight, relative to the weight of the anti-aging composition. A person skilled in the art will understand, however, that other ranges fall within the scope of the invention.

[0081] Thus, at least one elastase reducer, for example comprising a C-glycoside derivative, is present, by weight, relative to the total weight of the anti-aging composition, of approximately 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.20, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 0.90, 1.0, 2, 3, 4.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, at approximately 30 percent by weight, including increments and intermediate ranges.

[0082] Cell proliferation agent:

[0083] In various embodiments, the composition includes at least one cell proliferation agent selected from the group consisting of niacinamide, retinol, peptides, growth factors, stem cells, vitamin C, vitamin K, exosomes (for example in Sigma-Aldrich edelfosine (TM) or (Tyr[SO3H]27)cholecystokinin fragment 26-33 amide), and combinations thereof.

[0084] In some embodiments, at least one cell proliferation agent includes niacinamide.

[0085] In some embodiments, the anti-aging composition is in the form of an oil and water emulsion.

[0086] Niacinamide;

[0087] In various embodiments, the anti-aging composition includes at least one cell proliferation agent. In some embodiments, the at least one cell proliferation agent comprises niacinamide. Niacinamide improves cell motility / proliferation and increases cellular energy.

[0088] When present, the amount of niacinamide in the anti-aging composition will vary, but in various embodiments, it is from approximately 0.0001% to approximately 30%, or from approximately 1% to approximately 5%, or any appropriate combination, sub-combination, range, or sub-range of these values ​​by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0089] Thus, at least one cell proliferation agent, for example comprising niacinamide, is present, by weight, relative to the total weight of the anti-composition age, approximately 0.0001, 0.0005, 0.0009, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.20, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 0.90, 1.0, 2, 3, 4.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, at approximately 30 percent by weight, including increments and intermediate ranges.

[0090] Anti-inflammatory agents:

[0091] In various embodiments, the composition includes at least one anti-inflammatory agent selected from the group consisting of Eperua falcata bark extract, aloe vera, calmosensine, alder extract, resargine, Andrographis paniculate extract, Ficus regligiosa bark, Cucuma Zeoaria extract, ursolic acid, ectoine, Coptidis chinensis, Pongamia pinnata extract, white hibiscus, ectoine, Punica granatum, pomegranate extract, ginger root extract, ginkgo biloba extract, hamamelis, exosome, bisabolol (levomenol), green tea extract, zinc oxide, and combinations thereof.

[0092] In some embodiments, at least one anti-inflammatory includes an extract of Eperua falcata bark.

[0093] In some embodiments, the anti-aging composition is in the form of an oil and water emulsion.

[0094] Extract of Eperua falcata bark;

[0095] In various embodiments, the anti-aging composition includes at least one anti-inflammatory agent. In some embodiments, the at least one anti-inflammatory agent comprises an extract of Eperua falcata bark. The Eperua falcata bark extract reduces ROS, reduces inflammation, and improves mitophagy in skeletal muscle.

[0096] When present, the amount of at least one anti-inflammatory agent, for example, an extract of Eperua falcata bark, in the anti-aging composition will vary, but in various embodiments, it is from about 0.01% to about 10%, or from about 0.01% to about 0.02%, or any appropriate combination, sub-combination, range, or sub-range of these values ​​by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0097] Thus, at least one anti-inflammatory agent, for example comprising an extract of Eperua falcata bark, is present, by weight, relative to the total weight of the anti-aging composition, from about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.90, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9 to about 10 percent by weight, including increments and intermediate ranges.

[0098] Collagen-producing agents:

[0099] In various embodiments, the composition includes at least one collagen-producing agent selected from the group consisting of Gentiana lutea root extract, retinoids, carob seed extract, Saccharomyces cerevisiae extract, panthenol (vitamin B5), carob seed extract, ginger root extract, polysaccharides (including, but not limited to, galactomannans, pullulan, beta-glucan, alpha-glucan, Caesalpinia sphinosa gum), oligosaccharides (including, but not limited to, oligogalactomannans), wogonin, baicalin, ceramides / sphingolipids and their derivatives, resveratrol and its derivatives, niacinamide and its derivatives, TXA, pomegranate extract, linoleic acid, linolenic acid, olic acid, vitamin C, vitamin E / tocopherols and their derivatives, polyphenols, flavanols, dihydroflavanols, ellagic acid, flavonoids, collagen and its derivatives, arnica montana extract, carotenoids and their derivatives, triglycerides,soybean oil, oleuropeins and their derivatives, phospholipids, beta-carotene, microalgae and algae extracts (including, but not limited to, chlorella vulgaris extract, dunaliella salina extract), pre- / pro- / postbiotics (including, but not limited to, Lactococcus fermentation lysate, lactobacillus ferment), flaxseed extract, proanthocyanins, anthocyanins, hydroxyacetophenone, lecithin, GHK-Cu peptide, tripeptide-1, copper peptide, GHK-Mn, acetyl tetrapeptides, citrulline tripeptide-10, palmitoyl hexapeptide-12, palmitoyl tripeptide-1, lipospondin, gexapeptide-11, PKEK, GEKG, SA1-11, tripeptide-3, pentapeptide-18, pentapeptide-3, acetyl-1,3 octapeptide, antimicrobial peptides (including, but not limited to, phosphenines, cactylcyline, dermin), NMF-derived peptides (including, but not limited to, histidine dipeptides, urocanic acid, pyrrolidone carboxylic acid),Pal-KTTKS and other acyl peptides, KEK and PKEK peptides, palmitoyl-7 tetrapeptide, palmitoyl-4 pentapeptide, Tropaeolum majus extract, glycoproteins, hyaluronic acid and its derivatives, sh-polypeptide-5, sh-polypeptide-11, sh-oligopeptide-2, sh-polypeptide-6, wheat germ oil, octacosanol, wild yam root extract, bakuchiol, borage oil, geranium oil, Protium heptaphyllum oil, Hamamelis virginiana extract, Citrus medica limonum oil, glutathione, coenzyme Q10, disodium acetylglucosamine phosphate, fermented red ginseng extract, dipeptide diaminobutyroyl benzylamide diacetate, Angelica polymorpha sinensis root extract, sericin, superoxide dismutase, peptides copper, vitamin C, vitamin E, ginseng extract, and combinations thereof.

[0100] In some embodiments, at least one collagen-producing agent includes an extract of Gentiana lutea root.

[0101] In some embodiments, the anti-aging composition is in the form of an oil and water emulsion.

[0102] Gentiana lutea root extract;

[0103] In various embodiments, the anti-aging composition includes at least one collagen-producing agent. In some embodiments, the at least one collagen-producing agent comprises an extract of Gentiana lutea root.

[0104] When present, the amount of at least one collagen-producing agent, for example, Gentiana lutea root extract, in the anti-aging composition will vary, but in various embodiments, it is from about 0.01% to about 10%, or from about 0.01% to about 0.02%, or any appropriate combination, sub-combination, range, or sub-range of these values ​​by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0105] Thus, at least one collagen-producing agent, for example comprising an extract of Gentiana lutea root, is present, by weight, relative to the total weight of the anti-aging composition, from about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.90, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9 to about 10 percent by weight, including increments and intermediate ranges.

[0106] Surfactant:

[0107] In various embodiments, the anti-aging composition comprises at least one surfactant. In some embodiments, the anti-aging composition may include, or alternatively may be substantially free from, or exclude one or more non-ionic, cationic, or anionic surfactants.

[0108] In some embodiments, the composition may include at least one surfactant selected from the group consisting of steareth-100, cetearyl alcohol (and) cetearyl glucoside, behenyl alcohol, and C14-22 alcohols (and) C12-20 alkyl glucoside.

[0109] When present, at least one surfactant is present in the anti-aging composition at a concentration of approximately 0.1% to approximately 15%, or approximately 2% to approximately 12%, or approximately 5% to approximately 10%, or approximately 0.2% to approximately 1.5%, or any appropriate combination, sub-combination, range, or sub-range of these values ​​by weight relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0110] Thus, the at least one surfactant, when present, is present, by weight, relative to the total weight of the anti-aging composition, from about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, to about 15 percent by weight, including increments and intermediate ranges.

[0111] Fatty compounds and ceramides:

[0112] In various embodiments, the composition also includes one or more fatty compounds.

[0113] In some embodiments, the composition may include at least one fatty compound selected from the group consisting of dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, squalane, coco caprylate / caprate, one or more ceramides selected from Ceramide EOP, Ceramide AS, Ceramide AP, Ceramide NS, Ceramide NP, Ceramide NH, Ceramide AH, Ceramide EOH, Ceramide EOS, Ceramide AdS, Ceramide NdS, Ceramide EOdS, Phytosphingosine, Sphingosine, 2-Oleyl-1,3-octadecanediol, ceramide precursors, fatty acids, fatty alcohols, cholesterol, cholesterol sulfate and their combinations.

[0114] In some embodiments, the composition may include at least one fatty compound selected from the group consisting of dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, squalane, coco caprylate / caprate and their combinations. In a preferred embodiment, at least one fatty compound may include one or more ceramides, for example one or more ceramides selected from Ceramide EOP, Ceramide AS, Ceramide AP, Ceramide NS, Ceramide NP, Ceramide NH, Ceramide AH, Ceramide EOH, Ceramide EOS, Ceramide AdS, Ceramide NdS, Ceramide EOdS, Phytosphingosine, Sphingosine, 2-Oleyl-1,3-octadecanediol, ceramide precursors, fatty acids, fatty alcohols, cholesterol, cholesterol sulfate or combinations thereof.

[0115] When present, at least one fatty compound is present in the anti-aging composition at a concentration of approximately 0.1% to approximately 20%, or approximately 2% to approximately 18%, or approximately 5% to approximately 15%, or approximately 8% to approximately 12%, or approximately 2% to approximately 6%, or any appropriate combination, sub-combination, range, or sub-range by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0116] Thus, at least one fatty compound, when present, is present, by weight, relative to the total weight of the anti-aging composition, from about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 to about 20 percent by weight, including increments and intermediate ranges.

[0117] Cosmetically acceptable solvent:

[0118] Embodiments of the anti-aging composition according to the disclosure contain at least one cosmetically acceptable solvent. In various embodiments, the cosmetically acceptable solvent may be selected from water.

[0119] Water:

[0120] According to the various embodiments, water is present in the anti-aging composition in a range of approximately 10% to approximately 90%, or approximately 20% to approximately 75%, or approximately 25% to approximately 70%, or approximately 30% to approximately 65%, or any suitable combination, sub-combination, range, or sub-range of these values ​​by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0121] Thus, water may be present by weight, relative to the total weight of the anti-aging composition, from approximately 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, to approximately 60 percent by weight, including the intermediate increments and ranges.

[0122] The water used may be sterile demineralized water and / or floral water such as rose water, cornflower water, chamomile water or linden water, and / or natural thermal or mineral water such as, for example: Vittel water, Vichy basin water, Uriage water, La Roche-Posay water, La Bourboule water, Enghien-les-Bains water, Saint-Gervais-les-Bains water, Néris-les-Bains water, Allevar-les-Bains water, Digne water, Maizières water, Neyrac-les-Bains water, Lons-le-Saunier water, Eaux-Bonnes water, Rochefort water, Saint-Christau water, Les Fumades, Tercis-les-Bains water or Avène water.

[0123] The aqueous phase may also include reconstituted thermal water, i.e. water including trace elements such as zinc, copper, magnesium etc., reconstituting the characteristics of thermal water.

[0124] The anti-aging composition has a pH of approximately 4 to approximately 7.

[0125] The pH can be corrected to the desired value by adding a base (organic or inorganic), for example sodium hydroxide, potassium hydroxide or another suitable base, or combinations thereof. Water-soluble solvents

[0126] According to certain embodiments, the anti-aging composition includes at least one water-soluble solvent. The term "water-soluble solvent" is interchangeable with the term "water-miscible solvent" and refers to a compound that is liquid at 25°C and atmospheric pressure (760 mmHg), and that has a solubility of at least 50% in water under these conditions. In some cases, the water-soluble solvent has a solubility of at least 60%, 70%, 80%, or 90% in water under these conditions.

[0127] In certain particular embodiments, the water-soluble solvent includes glycerin present from about 1% to about 15%, or from about 5% to about 10%, by weight of the anti-aging composition.

[0128] By way of example of organic solvents, one may mention, without limitation, ethyl alcohol, isopropyl alcohol, propyl alcohol, benzyl alcohol and phenylethyl alcohol, or glycols or glycol ethers such as, for example, Monomethyl-, monoethyl-, and monobutyl ethers of ethylene glycol, propylene glycol, or their ethers, such as, for example, monomethyl ether of propylene glycol, butylene glycol, hexylene glycol, and dipropylene glycol, as well as alkyl ethers of diethylene glycol, for example, diethylene glycol monoethyl ether or monobutyl ether. Organic solvents may be volatile or non-volatile compounds.

[0129] Other non-limiting examples of water-soluble solvents include alkanols (polyhydric alcohols, glycols, and polyols) such as glycerin, 1,2,6-hexanetriol, trimethylolpropane, ethylene glycol, propylene glycol, diethylene glycol, butylene glycol, hexylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, dipropylene glycol, 1,3-butanediol, 2,3-butanediol, 1,4-butanediol, 3-methyl-1,3-butanediol, 1,5-pentanediol, tetraethylene glycol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, polyethylene glycol, 1,2,4-butanetriol, 1,2,6-hexanetriol, 2-butene-l,4-diol, 2-ethyl-l,3-hexanediol, 2-methyl-2,4-pentanediol, 1,2-hexanediol, 1,2-pentanediol and 4-methyl-l,2-pentanediol.

[0130] Other non-limiting examples of water-soluble solvents include alkyl alcohols having 1 to 4 carbon atoms such as ethanol, methanol, butanol, propanol and isopropanol;glycol ethers such as monomethyl ethylene glycol ether, monoethyl ethylene glycol ether, monobutyl ethylene glycol ether, ethylene glycol acetate monomethyl ether, monomethyl diethylene glycol ether, monoethyl diethylene glycol ether, mono-n-propyl diethylene glycol ether, mono-isopropyl ethylene glycol ether, mono-isopropyl diethylene glycol ether, mono-n-butyl ethylene glycol ether, mono-t-butyl ethylene glycol ether, mono-t-butyl diethylene glycol ether, 1-methyl-l-methoxybutanol, monomethyl propylene glycol ether, monoethyl propylene glycol ether, mono-t-butyl propylene glycol ether, mono-n-propyl propylene glycol ether, mono-isopropyl propylene glycol ether, monomethyl dipropylene glycol ether, monoethyl dipropylene ether glycol, mono-n-propyl dipropylene glycol ether and mono-iso-propyl dipropylene glycol ether;2-pyrrolidone, N-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, formamide, acetamide, dimethyl sulfoxide, sorbitol, sorbitan, acetin, diacetinate, triacetin, sulfolane, or a mixture thereof.

[0131] According to the various embodiments, the quantity of at least one water-soluble solvent is from approximately 0.1% to approximately 25%, or from approximately 0.1% to approximately 2%, or from approximately 0.1% to approximately 1%, or from approximately 0.1% to approximately 0.8%, or from approximately 0.1% to approximately 0.5%, or from approximately 1% to approximately 20%, or from approximately 1% to approximately 10%, or from approximately 2% to approximately 8%, or any appropriate combination, subcombination, range or subrange of these values ​​by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0132] In some embodiments, the anti-aging composition includes more than one water-soluble solvent, each water-soluble solvent being present in an amount such as indicated above, in which each different water-soluble solvent may be present in one of the ranges selected from the ranges indicated above.

[0133] Thus, each water-soluble solvent or combination of water-soluble solvents may be present by weight, relative to the total weight of the anti-aging composition, from about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 to about 25 percent by weight, including intermediate increments and ranges. Thickeners

[0134] In various embodiments, the anti-aging composition may include at least one thickener. The thickener may be thickening polymers.Non-limiting examples include sclerotium gum, xanthan gum, carrageenan, acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, sodium alginate, calcium carrageenan, camitin, carrageenan, dextrin, gelatin, gellan gum, guar gum, tragacanth gum, acacia gum, gum arabic, hydroxypropyltrimonium guar chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, carrageenan, propylene glycol acrylate, sodium carboxymethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, modified xanthan gum, gum of biosaccharides, chitin, levan, elsinan, collagen, gelatin, zein, gluten, soy protein, casein and mixtures thereof.

[0135] According to some embodiments, the anti-aging composition comprises one or more of Zea mays (maize) starch, C10-30 alkyl polyacrylate, ammonium acryloyldimethyltaurate / VP copolymer, or a combination thereof, present in a range of about 0.01% to about 10%.

[0136] According to some embodiments, the anti-aging composition comprises each of Zea mays (maize) starch, C10-30 alkyl polyacrylate, ammonium acryloyldimethyltaurate / VP copolymer, as a thickener.

[0137] The at least one thickener, when present, is present in the anti-aging composition at a concentration of approximately 0.01% to approximately 10%, or approximately 0.2% to approximately 3%, or approximately 0.5% to approximately 2%, or approximately 1%, or any appropriate combination, sub-combination, range, or sub-range of these values ​​by weight, relative to the weight of the anti-aging composition. However, a person skilled in the art will understand that other ranges fall within the scope of the invention.

[0138] Thus, a thickener or a combination of thickeners may be present, by weight, relative to the total weight of the anti-aging composition, from about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.90, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9 to about 10% by weight, including intermediate increments and ranges.

[0139] Optional additives:

[0140] In certain embodiments, there may be one or more optional active ingredients or other ingredients (here, "additives") present in the anti-aging composition, the one or more additives being optionally selected from: antimicrobials; chelating agents; oils; fatty alcohols; fatty amides; alkylene carbonates; glycols; lower alcohols (e.g., ethanol; propanediol); anti-elastase and anti-collagenase agents; peptides; fatty acid derivatives; steroids; trace elements; algae and plankton extracts; enzymes and coenzymes; alpha- or beta-hydroxy acids and mixtures thereof; cationic polymers such as naturally occurring polymers such as chitosan and a polylysine, and polyquaternium compounds; fillers; clays; penetrants; sequestrants; perfumes; dispersants;skin care actives such as ceramides, for example sodium lauroyl lactylate (and) ceramide NP (and) ceramide AP (and) phytosphingosine (and) cholesterol (and) xanthan gum (and) carbomer (and) ceramide EOP; opacifiers; alpha-hydroxy acids; organic and inorganic UV filters; citric acid; phenylethyl resorcinol; hydroxyacetophenone;Antioxidants, including but not limited to phenolic compounds such as chalcones, flavones, flavanones, flavanols, flavonols, dihydroflavonols, isoflavonoids, neoflavonoids, catechins, anthocyanins, tannins, lignans, aurones, stylbenoids, curcuminoids, alkylphenols, betacyanins, capsacinoids, hydroxybenzoketones, methoxyphenols, naphthoquinones, and phenolic terpenes, resveratrol or resveratrol glucoside, curcumin, pinoresinol, ferrulic acid, hydroxytyrosol, cinnamic acid, caffeic acid, p-coumaric acid, baicalin (Scutellaria baicalensis root extract), an extract pine bark (Pinus Pinaster bark / bud extract), ellagic acid; hyaluronic acid and its derivatives;escin (also known as Aescin, a mixture of saponins with anti-inflammatory, vasoconstrictive, and vasoprotective effects found in Aesculus hippocastanum); retinol; niacinamide; jasmonic acid; 2-acetyl-3-trifluoromethylphenylamino-3-methylbutyrylaminoacetic acid; phloretin; acetyltrifluoromethylphenylvalylglycine; hesperidin or neohesperidin; biocellulose; vitamins and vitamin derivatives, such as vitamin C, ethylvitamin C, vitamin E (tocopherol); and their combinations.

[0141] Although the aforementioned optional additives are given by way of example, it will be understood that other optional components compatible with cosmetic applications known in the art may be used. And of course, one of the aforementioned additives may be excluded.

[0142] In some embodiments, the anti-aging composition includes at least one additive selected from the group consisting of citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin, trisodium ethylenediamine disuccinate, and dextrin, propanediol, pentylene glycol and propylene glycol, and combinations thereof.

[0143] In some embodiments, the anti-aging composition includes additives comprising citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin and trisodium ethylenediamine disuccinate.

[0144] According to the different embodiments, the quantities of additives, for example active ingredients and other components, which may be present in the anti-aging composition, may range from about 0.001% to about 50%, or from about 0.5% to about 30%, or from about 1.5% to about 20%, and from about 5% to about 15%, or any appropriate combination, sub-combination, range or sub-range of these values ​​by weight, relative to the weight of the anti-aging composition.

[0145] Thus, an additive or a combination of additives may be present in the anti-aging composition, by weight, relative to the weight of the anti-aging composition, each additive or combination being present in approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.20, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 0.90, 1.0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 at approximately 50 percent by weight, including increments and intermediate ranges.

[0146] Of course, a person skilled in the art will take care to select this or these additional optional compounds in such a way that the advantageous properties intrinsically associated with the composition according to this disclosure are not, or substantially not, adversely affected by the contemplated addition or additions.

[0147] It goes without saying that a person skilled in the art will take care to select this / these optional additional additive(s), and / or its / their quantity, so that the advantageous properties of the composition according to this disclosure are not, or are not substantially, adversely affected by the contemplated addition.

[0148] Stability: 3 months stable at 45 °C

[0149] The embodiments of the anti-aging composition according to the disclosure are considered to be a stable composition despite the high quantities of assets when it is demonstrated that they have retained an aesthetically homogeneous phase, in which there are no visually perceptible signs of phase separation, that they do not exhibit a granular texture and / or become non-homogeneous over a period of 8 weeks in a storage temperature range of 4°C to 45°C, without significant changes in appearance, pH, viscosity and color.

[0150] Pleasant to the touch:

[0151] Embodiments of the anti-aging composition according to the disclosure include a pleasant tactile sensation. By "pleasant tactile sensation" and its grammatical variations, it is understood that embodiments of the anti-aging composition have a texture that is pleasant to the consumer and is substantially free from a rough, sticky or tacky feeling, and from skin safety issues.

[0152] Packaging:

[0153] The anti-aging composition can be assembled in a kit or system including the anti-aging composition and at least one co-treatment device or device.The device or co-treatment device may include one or more of a professional device or a home-use device, or a combination thereof, the professional device being chosen from the group consisting of a microdermabrasion machine, a microneedling machine, an LED light therapy device, a high-frequency machine, a radiofrequency device, an ultrasound device, a cryotherapy machine, a laser device and combinations thereof, and the home-use device being chosen from the group consisting of LED masks, microdermabrasion devices, microneedling devices, ultrasonic skin scrubbers, facial steamers, IPL skin rejuvenation devices, sonic eye massagers, fractional laser devices, cold laser therapy devices, microcurrent, and combinations thereof.

[0154] Definitions and terms:

[0155] The transitional terms “comprising,” “consisting essentially of,” and “consisting of,” when used in the appended claims, in their original and amended forms, define the scope of the claims with respect to any additional unmentioned elements or steps of claims that are excluded from the scope of the claim(s). As used herein, the terms “comprising,” “having,” and “including” (or “comprise,” “have,” and “include”) are used in their open, non-limiting sense. The term “comprising” is intended to be inclusive or broad and does not exclude any additional, unmentioned element, process, step, or material.

[0156] The expression "consisting of" excludes any element, step or material other than those specified in the claims and, in the latter case, impurities ordinarily associated with the specified material or materials.

[0157] The expression "consisting essentially of" limits the scope of a claim to the specified elements, steps, or material(s) and to those that do not materially affect the fundamental and innovative feature(s) of the claimed invention. All the processes and materials described herein that incorporate the present invention can, in alternative embodiments, be defined more specifically by any of the transitional expressions "comprising," "consisting essentially of," and "consisting of."

[0158] As used herein, the expressions "and their mixtures", "and one of their mixtures", "and their combinations", "and one of their combinations", "or their mixtures", "or one of their mixtures", "or their combinations", and "or one of their combinations" are used interchangeably to indicate that the list of components immediately preceding the expression, such as "A, B, C, D, or their mixtures", means that the component(s) may be chosen from A, B, C, D, from A + B, from A + B + C, from A + D, from A + C + D, etc., without limitation as to their variations. Thus, the components may be used individually or in any combination thereof.

[0159] For the purposes of this disclosure, it should be noted that, for the sake of brevity, some of the quantitative expressions given herein are not qualified with the term "approximately." It is understood that, whether the term "approximately" is used explicitly or implicitly, each quantity given herein is intended to refer to the actual value given, and is also intended to refer to the approximation of that value that would be reasonably deduced by a person skilled in the art, including approximations due to the experimental and / or measurement conditions for that value. All ranges and quantities indicated herein are intended to include subranges and quantities using any disclosed point as a bound.

[0160] A given range of "about 3% to 7%" is understood to have its bounds at both 3% and 7% modified by the term "about". The term "about" is used here to indicate a difference of up to + / - 10% from the stated number, such as + / - 9%, + / - 8%, + / - 7%, + / - 6%, + / - 5%, + / - 4%, + / - 3%, + / - 2%, or + / - 1%. Similarly, all bounds of the ranges are understood to be disclosed individually, such that, for example, a range of 1:2 to 2:1 is understood to disclose a ratio of 1:2 and 2:1.

[0161] “Active substance”, as used herein in relation to the percentage of a ingredient or raw material, refers to 100% of the activity of the ingredient or raw material. All quantities indicated here refer to the quantity of active ingredient, unless otherwise stated.

[0162] All percentages, parts and ratios herein are based on the total weight of embodiments of the anti-aging composition of this disclosure, unless otherwise stated.

[0163] As used herein, the term "surfactants", as well as any specifically identified surfactant, includes salts of surfactants, even if not explicitly stated.

[0164] As used herein, the term "synthetic" refers to a material that is not of natural origin. The term "natural" and the expressions "of natural source" and "of natural origin" refer to a material of natural origin, such as derived from plants, which also cannot be subsequently chemically or physically modified. "Of plant origin" means that the material comes from a plant.

[0165] Unless expressly stated otherwise, no process described herein is intended to be interpreted as requiring that its steps be performed in a specific order. Accordingly, where a process claim does not expressly state an order to be followed by its steps, or where it is not specifically stated in the claims or descriptions that the steps must be limited to a specific order, no particular order is to be inferred therefrom.

[0166] As used herein, the expressions "substantially free" or "essentially free" mean that the specific material may be present in small quantities that do not materially affect the basic and innovative characteristics of the embodiments of the anti-aging compositions as disclosed, or that the material may be absent. For example, there may be less than 2% by weight of a specific material added to a composition, relative to the total weight of the compositions (provided that an amount less than 2% by weight does not materially affect the basic and innovative characteristics of the embodiments of the anti-aging compositions as disclosed). Similarly, the compositions may include less than 2%, less than 1.5%, less than 1%, less than 0.5%, less than 0.1%, less than 0.05%, or less than 0.01%, or not include any (0%) of the specified material.Furthermore, all components positively presented in this disclosure may be negatively excluded from the claims; for example, a claimed composition may be "free," "substantially free" (or "substantially free") of one or more components that are positively presented in this disclosure. The expression "substantially free" or "substantially free" as used herein may also mean that the specific material is not added to the composition. the composition, but that it can still be present in a raw material included in the composition. Examples

[0167] The following examples are intended to be non-limiting and explanatory only. In the examples, quantities are expressed as a percentage by weight (% by weight) of active materials, relative to the total weight of the composition. Example 1#: Raw materials

[0168] The percentages of each ingredient as given by way of example in the following composition examples are indicated in quantity of active ingredients, the raw materials containing the active ingredient being able to be present in an amount equal to the amount of active ingredient, or if the raw material has a concentration of active ingredient less than 100%, then the cosmetic composition includes the raw material which includes the active ingredient and a suitable solvent, the concentration of active ingredient in the raw material being indicated here below in Table 1. When referring to the examples of the invention and comparatives, it should be assumed that each ingredient as indicated in the compositions given by way of example is the final amount of active ingredient, unless otherwise indicated.

[0169] Select raw materials (including raw materials with active ingredient concentrations below 100%)

[0170] [Tables] MP ~% active ingredients in the MP Hydroxypropyl tetrahydropyrantriol 14.3 Dextrin (and) Eperua falcata bark extract 1 Taraxacum Officinale (bedstrawberry) root / rhizome extract 2 Gentiana lutea root extract 0.5 Steareth-100 0.125 Example 2#: Compositions of the invention

[0171] One embodiment of the anti-aging composition of the invention according to the disclosure includes water, hydroxypropyl tetrahydropyrantriol and two or more of niacinamide, dextrin (and) an extract of Eperua Falcata bark, and an extract of Gentiana Lutea root.

[0172] In some embodiments, the composition also includes one or more surfactants, for example selected from the group consisting of steareth-100, cetearyl alcohol (and) cetearyl glucoside, behenyl alcohol, C14-22 alcohols (and) C12-20 alkyl glucoside, and one or more fatty compounds, for example selected in the group consisting of dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cocoa (cocoa) seed butter, squalane, coco caprylate / caprate, and one or more thickeners, for example selected from the group consisting of Zea mays (maize) starch, C10-30 alkyl polyacrylate, ammonium acryloyldimethyltaurate / VP copolymer, and one or more additives, for example selected from the group consisting of citric acid, sodium hydroxide, tocopherol, Taraxacum Officinale (dandelion) rhizome / root extract, phenoxyethanol, glycerin, chlorphenesin, trisodium ethylenediamine disuccinate, and dextrin, propanediol, pentylene glycol and propylene glycol as solvents / carriers with active ingredients. Composition of the invention

[0173] [Tables2] Ingredients Range % by weight* Hydroxypropyl tetrahydropyrantriol 0.01% - 30% Gentiana lutea root extract 0.01% - 10% Niacinamide 0.0001% - 30% Eperua falcata bark extract 0.01% - 10% Additives (e.g., chlorphenesin, phenoxyethanol, sodium hydroxide, trisodium ethylenediamine disuccinate, tocopherol, Taraxacum officinale (dandelion) rhizome / root extract, citric acid) 0% - 2% Fatty compound (e.g., squalane, dicaprylyl carbonate, Butyrospermum parkii (shea) butter, Theobroma cacao (cocoa) seed butter, coconut caprylate / caprate) 0.1% - 20% Thickener (e.g., polyacrylate) C10-30 alkyl, ammonium acryloyldimethyltaurate / VP copolymer, Zea mays (maize) starch) 0.1% - 10% Surfactant (e.g., C14-22 (and) (C12-20 alkyl) alcohols glucoside, cetearyl glucoside, behenyl alcohol, cetearyl alcohol, steareth-1000,1% - 15% Glycerin 0% - 20% Propanediol 0% - 10% Pentylene glycol 0% - 10% Propylene glycol 0% - 10% Dextrin 0% - 10% Water 5% - 90%

[0174] *each ingredient or combination

[0175] A composition of the invention shown in Table 2 was prepared according to the following embodiment of the invention:

[0176] In one embodiment, a composition according to the disclosure includes water (~61%), hydroxypropyltetrahydropyrantriol (-10%), niacinamide (-3%), dextrin (and) Eperua Falcata bark extract (-0.1%) (including dextrin (-0.9% as a solvent for the active ingredient)), Gentiane Lutea root extract (-0.015%), surfactants including steareth-100 (-0.12%), cetearyl alcohol (and) cetearyl glucoside (-1.4%), behenyl alcohol (-0.5%), C14-22 alcohols (and) C12-20 alkyl glucoside (-0.3%), fatty compounds including dicaprylyl carbonate (-3%), butter Butyrospermum parkii (shea) (-2%), Theobroma cacao (cocoa) seed butter (-1%), squalane (-2%), coconut caprylate / caprate (-2%), thickeners including Zea mays (maize) starch (-2%), a C10-30 alkyl polyacrylate (-0.25%),an ammonium acryloyldimethyltaurate / VP copolymer (-1%) and additives including Taraxacum Officinale (dandelion) rhizome / root extract (-0.09%), tocopherol (-0.0002%), phenoxyethanol (-0.7%), glycerin (-7%), chlorphenesin (-0.2%), trisodium ethylenediamine disuccinate (-0.11%), citric acid (-0.00002%), and also including propanediol (-0.24% as a solvent for an active ingredient), pentylene glycol (-0.2% as a solvent for an active ingredient) and propylene glycol (-1.14% as a solvent for an active ingredient).

[0177] The embodiments of the anti-aging composition according to the disclosure are considered stable when evaluated for an aesthetic texture that is pleasant upon application, and when applied to the skin, they do not exhibit a rough, sticky, or tacky sensation. The stability of the formulation is evident when supplied as an emulsion, in which the composition does not separate or release oily droplets, and when supplied in any form, it does not exhibit precipitation or separation into discernible layers.

[0178] Embodiments of the anti-aging composition according to the disclosure are considered to be a stable composition despite the high quantities of active ingredients when it is demonstrated that they have maintained an aesthetically homogeneous phase, in which there are no visually perceptible signs of phase separation, that they do not exhibit a granular texture and / or become non-homogeneous on a 8-week period in a storage temperature range of 4°C to 45°C, without significant changes in appearance, pH, viscosity and color. Example 3#: Genetic Analysis Ex Vivo Tissue Sampling

[0179] The inventors used ex vivo skin tissue obtained from freshly harvested samples for the purpose of digital data analysis. Regarding donor information, a total of 21 donors were included for the eyelid skin analysis. Of these, 10 donors were in the middle-aged group (38 to 60 years), while 11 donors were in the elderly group (62 to 85 years). All donors were of Caucasian origin. For the middle-aged facial skin tissue, a total of 10 donors in the 43 to 60-year age range were included, one donor being of Hispanic origin and the others being Caucasian. To include an elderly group for the facial skin analysis, a total of seven donors aged 62 to 70 years were selected.One day after a blepharoplasty or rhytidectomy procedure (BioIVT, Westbury, NY, USA), with informed consent from all donors and authorization from the WCG IRB (IRB tracking number: 20180798), the hypodermis was removed and the tissue was washed twice with phosphate-buffered saline (PBS) to remove residual blood. The tissue was then cut into 12 mm diameter biopsies.

[0180] Analysis of RNA sequences - NGS (Next Generation Sequencing)

[0181] RNA Extraction: Samples were mechanically homogenized using a pestle, and total RNA was extracted from each sample using TriPure Isolation Reagent™ according to the manufacturer's instructions. RNA quality was assessed by capillary electrophoresis (Bioanalyzer 2100, Agilent Technologies). RNA quantity was assessed using a spectrophotometer (Synergy Hl, BioTek Instruments). RNA quality controls are provided to the DDRB group. All RNA samples were then sent to BGI Genomics for analysis.

[0182] TRNA Sequencing: The RNA was processed according to the manufacturer's protocol to convert it into cDNA and libraries ready for final sequencing: mRNA fragmentation, cDNA synthesis with random primers, adapter ligation, and adapter-specific PCR amplification. The final libraries were sequenced on the NextSeq 500 (Illumina) with 40 bp paired-end reads, and 30 million reads were obtained for each sample. After quality control and cross-checking, the reads were mapped to the human genome, and gene abundance was estimated. All condition types were compared pairwise. with control conditions to test for the presence of differentially expressed genes (determination of significant difference factor).

[0183] Histological and immunohistochemical staining: Ex vivo skin tissues underwent hematoxylin and eosin (H&E) staining using a standard protocol at the Histowiz laboratory in Brooklyn, NY. Tissue samples were first fixed in 10% formalin, then processed and embedded in paraffin wax. For smooth muscle α-actin (α-SMA), immunohistochemistry was performed on a Leica Biosystems Bond Rx automated stainer (Buffalo Grove, IL, USA) with heat-induced antigen recovery at pH 6 using standard protocols. Sections stained against a-SMA were incubated with a primary anti-a-SMA antibody (rabbit polyclonal, 1 / 1000 dilution, Cat# ab5694, Abcam, Cambridge, UK) with heat-induced antigen recovery at pH 9 using standard protocols.All sections were counterstained with hematoxylin nuclear stain, then dehydrated and covered with film using Sakura TissueTek-Prisma and Coverslipper. Finally, a full scan of the slides (40x) was performed on an Aperio AT2 (Leica Biosystems, Buffalo Grove, IL, USA).

[0184] Data management: Raw data were analyzed using Microsoft Excel and Matlab software. Intergroup comparisons were performed using one-way ANOVA with Graphpad.

[0185] To highlight the significant structural difference between the skin around the eyes, as shown in [Fig. 1], and the skin of the face, the inventors performed a tissue-level examination using H&E and IHC staining. The inventors also performed high-throughput RNA sequencing on skin samples obtained from the upper eyelids and cheek area of ​​individuals who had undergone plastic surgery. The aim was to identify the disparities between the skin around the eyes and the rest of the face.

[0186] Referring again to the drawings, [Fig. 2] presents the histological analysis of the upper eyelid skin and facial skin, (a) H&E staining of the upper eyelid skin, showing the cellular composition and tissue structure, (c) H&E staining of the facial skin, providing a comparison with the upper eyelid skin, (b) Immunostaining for anti-actin α of smooth muscle, highlighting the higher expression of muscle cells in the upper eyelid skin compared to (d) facial skin tissue

[0187] Looking again at the drawings, [Fig. 3] presents the analysis of changes in gene expression in biopsies collected during aging. Principal Component Analysis (PCA) describing the correlation between the first two main components of the RNA sequencing data. Looking again at [Fig.3], the results revealed a distinct demarcation between middle-aged and aged skin, indicating genetic changes associated with the aging process.

[0188] By applying a minimum change factor threshold > 2 (p < 0.05), the inventors identified a total of 912 differentially expressed genes (DEG) between middle-aged and elderly eyelid skin out of the 17,387 genes analyzed. With reference to [Fig. 4].

[0189] Among these DEGs, with reference to [Fig. 5], 701 genes were downregulated. It should be noted that these downregulated genes play vital roles in various biological pathways, including the extracellular matrix, blood vessel development, cell migration, and regulation of cell population proliferation, all of which are influenced by the aging process.

[0190] In addition, pathways associated with muscle tissue, particularly the downregulation of smooth muscle cell migration, were also affected. When comparing facial skin with eyelid skin, the inventors observed a total of 1195 differentially expressed genes, with the most significant differences occurring in muscle-associated pathways, as shown in [Fig. 6]. This finding is consistent with observations of smooth muscle actin expression at the tissue level. This underscores the importance of incorporating not only traditional targets found in most facial moisturizers or anti-aging creams, but also factors such as muscle autophagy and cellular senescence into an eye skincare routine.

[0191] Furthermore, when comparing middle-aged facial skin with middle-aged eyelid skin, the inventors identified a total of 223 genes that showed significant changes, with the majority of differences observed in pathways associated with muscle function. However, when comparing aged eyelid skin with aged facial skin, the inventors found 40 differentially expressed genes, and the pathways showing significant differences underwent a dramatic change. This underscores the importance of prioritizing muscle-related anti-aging interventions, reducing oxidative stress and inflammation associated with the accumulation of ROS (reactive oxygen species), as well as inflammatory and pro-inflammatory cytokines, to achieve overall longevity and healthy eye skin. Example 4#: Releasing sGAG

[0192] A reconstructed full-thickness skin (T-Skin, Episkin) was systemically treated with hydroxypropyltetrahydropyrantriol (PX, 0.02% and 0.06%) based on the T-skin evaluation assay. Tissues are received on the medium on day 11 and stored at 37°C (95% humidity and 5% CO2) until the end of treatment on day 18. Tissues received medium and medium + hydroxypropyltetrahydropyrantriol from day 11 to day 15 (n=3). On day 15, the medium supernatant was collected for measurement using the sulfated glycosaminoglycan assay kit (ab289846, Abcam). For the analysis, sGAG release from the supernatant was quantified according to the manufacturer's protocol. Referring to [Fig. 7], the data obtained with hydroxypropyltetrahydropyrantriol demonstrate that the active ingredient can increase sGAG release. Example 5#: Elastase Inhibition

[0193] For elastase (neutrophil elastase inhibition assay, MAK213, Sigma-Aldrich, MO) (collagenase activity colorimetric assay kit, Cat # MAK293-1KT, Sigma-Aldrich, MO), the experiments were performed according to the manufacturer's instructions. In brief, neutrophil elastase hydrolyzes a specific fluorescent substrate to release the fluorescent group, which can be detected at Ex / Em = 400 / 505 nm. This assay evaluates the ability of hydroxypropyltetrahydropyrantriol (PX, 1% and 5%), niacinamide (1% and 5%), and a combination of hydroxypropyltetrahydropyrantriol and niacinamide to inhibit neutrophil elastase-induced hydrolysis. With reference to [Fig.8], data obtained with hydroxypropyltetrahydropyrantriol and niacinamide demonstrate that the combination can inhibit elastase activity. Example 6#: Stimulating cell proliferation

[0194] Normal adult human epidermal keratinocytes (NHEK-Ad, Cat# 00192627, Lonza, Switzerland) were maintained in a basal growth medium (KGM Gold Keratinocyte Growth Medium Bulletkit, Cat# 00192060) until the initiation of the proliferation experiment. The keratinocytes were seeded at a concentration of 1 x 10³ / 24 wells and allowed to equilibrate overnight (n=3 / group). The cell culture medium was replaced with fresh growth medium containing different concentrations of hydroxypropyltetrahydropyrantriol (0.005%, 0.017%, and 0.05%), NAM (0.0012%, 0.004%, and 0.012%) alone, and a combination of hydroxypropyltetrahydropyrantriol + niacinamide (PX / NAM). The cells were incubated for 48 hours and the keratinocytes were stained against the primary antibody KI67 (anti-Ki67 antibody, Cat# abl5580, Abcam) and the secondary goat anti-rabbit IgG Alexa Fluor@488 antibody (Cat#150077, Abcam).The fluorescent signals of Ki67 and DAPI were captured using a fluorescence microscope (DMi8, Leica). Ki67 expression was quantified relative to total cell nucleus staining (DAPI staining solution, ab228549, Abcam) to calculate the number of proliferating cells relative to the total number of cells. With reference to [Fig.9] and [Fig.10], the data obtained with hydroxypropyltetrahydropyrantriol and niacinamide demonstrate that the combined actives significantly increase skin cell proliferation, in which the data show that 0.004% and 0.012% of niacinamide significantly increase proliferation and that the combinations of 0.017% hydroxypropyltetrahydropyrantriol + 0.004% niacinamide and 0.05% hydroxypropyltetrahydropyrantriol + 0.012% niacinamide significantly increase proliferation, which indicates a synergy between the two actives that improves collagen expression. Example 7#: Collagen Expression

[0195] Primary human fibroblasts (normal, adult human, PCS-201-012, ATCC) were obtained and cultured in a fibroblast base medium (PCS-201-030, ATCC). For the experiment, cells were seeded at a concentration of 1 x 10⁵ / 6 wells and allowed to equilibrate overnight (n=3 / group). In this experiment, the cells were then processed in fresh medium supplemented with varying concentrations of Gentiana lutea root extract (0.1%, 0.25%, 0.5%, 1%, and 2%). After 3 days of culture, total RNA was extracted using TRIZOL reagent (Invitrogen, Thermo Fisher Scientific, Inc.) according to the manufacturer's instructions. Total RNA was reverse-transcribed to cDNA using the ProtoScript First Strand cDNA Synthesis Kit (New England Biolabs, Inc.) according to the manufacturer's instructions.Collagen I mRNA expression levels were assessed using the 5x HOT FIREPOL EvaGreen qPCR mixture (Solis BioDyne), a StepOnePlus RTPCR system (Applied Biosystems), and gene-specific primers. The Cq value for collagen I was normalized to the expression of the beta-actin housekeeping gene, and the 2AAcq method was used to calculate the relative expression level. Referring to [Fig. 11], data obtained with Gentiana Lutea root extract on collagen expression, where aged fibroblasts were treated with various concentrations for 3 days to assess the agent's ability to stimulate callus formation, demonstrate that 0.1% of Gentiana Lutea root extract stimulates callus formation. At the end of day 3, cells were collected and harvested for RTPCR of the Collagen I gene.

[0196] Evaluation of reactive oxygen species:

[0197] Primary human fibroblasts (normal, adult human, PCS-201-012, ATCC) were obtained and cultured in a basal fibroblast medium (PCS-201-030, ATCC) until the start of the experiment. The fibroblasts were pretreated for 48 hours with two concentrations of Eperua Falcata bark extract (0.1% and 0.01%) in a basal medium before exposing the cells to UVA irradiation of 20 J / cm². For this experiment, all cells received irradiation 20 J / cm² UVA was applied using a MAX-303 Xenon Light Source 300W lamp (Asahi Spectra). Twenty-four hours after irradiation, cells were harvested and measured for the HM0X1 gene by RTPCR. In short, total RNA was extracted using TRIZOL reagent (Invitrogen, Thermo Fisher Scientific, Inc.) according to the manufacturer's instructions. The total RNA was reverse-transcribed to cDNA using the ProtoScript First-Strand cDNA Synthesis Kit (New England Biolabs, Inc.) according to the manufacturer's instructions. Collagen 1 mRNA expression levels were assessed using the 5x HOT FIREPOL EvaGreen qPCR mixture (Solis BioDyne), a StepOnePlus RTPCR system (Applied Biosystems), and gene-specific primers. The Cq value for HM0X1 was normalized to the expression of the beta-actin housekeeping gene and the 2-AAcq method was used to calculate the relative expression level.The bark extract of Eperua Falcata showed a significant reduction in UVA-triggered HM0X1. HM0X1 (heme oxygenase) is triggered as a protective mechanism by cells in response to oxidative stress; the bark extract of Eperua Falcata showed a protective effect by lowering the level of UVA-triggered HM0X1. Example 8#: Anti-inflammatory effect

[0198] Fresh ex vivo skin (3 donors aged 37 to 64 years, female) was acquired one day after an abdominoplasty procedure (BioIVT, Westbury, NY, USA). Upon receipt, the hypodermis was removed, and the tissue was subjected to two washes with phosphate-buffered saline (PBS) to remove residual blood. The tissue was then treated with a microneedling pen (36-pin needles, Dr. Pen A6 Cartridge Tips, Dr. Pen Inc., San Jose, CA, USA) with a 1.5 mm needle length. The tissue underwent 5 microneedling passes. After treatment, 1.2 cm diameter skin biopsies were created (a minimum of N = 3 per condition) and cultured at the air-liquid interface. Skin expellees not subjected to microneedling served as the untreated control group.Samples were cultured in Dulbecco Modified Eagle Medium (650 µl per well, DMEM with 10% fetal bovine serum and 1% penicillin-streptomycin) at 37°C and 5% CO2. The medium was changed every two days except on weekends. During the 6-day culture period, the supernatant was collected to measure the level of the pro-inflammatory cytokine using the DueSet ELISA kit for human IL-1 alpha (R&D Systems). 1TL1A was shown to be triggered by micropuncture, and the addition of an extract of Eperua falcata bark was effective in reducing the level of inflammation, as shown in [Fig. 12]. It is postulated that the use of anti-inflammatory agents, such as Eperua Falcata bark extract, will affect ROS and inflammation in a skeletal muscle model, resulting in benefits for the muscles. skeletal, especially when used in an anti-aging composition according to the disclosure for the treatment of the skin around the eyes. Example 9#: Clinical Assessment

[0199] Although the invention has been described with reference to a preferred embodiment, a person skilled in the art will understand that various changes can be made and equivalents can replace elements of it without departing from the scope of the invention. Furthermore, numerous modifications can be made to adapt a particular situation or subject matter to the teachings of the invention without departing from its essential scope. Accordingly, the invention is not limited to the particular embodiment disclosed as being the best envisaged embodiment for implementing the present invention, but the invention will include all embodiments within the scope of the appended claims.

Claims

Demands

1. Composition, in an oil and water emulsion, comprising: a) an oil and water carrier system comprising i. water; ii. at least one surfactant; iii. at least one fatty compound; and iv. at least one thickener; b) an anti-aging system for eye tissue, comprising i. at least one elastase reducer; and ii. at least two additional agents selected from the group consisting of: (1) at least one cell proliferation agent; (2) at least one anti-inflammatory agent; and (3) at least one collagen-producing agent.

2. Composition according to claim 1, wherein in the anti-aging system for eye tissue (b): i. at least one elastase reducer is selected from the group consisting of hydroxypropyltetrahydropyrantriol, peptides, for example palmitoyl tripeptide-5, acetyl hexapeptide-8 and palmitoyl tetrapeptide-7, retinol, vitamin C, green tea extract, aloe vera extract, resveratrol, coenzyme Q10, and combinations thereof; ii. when present, at least one cell proliferation agent is chosen from the group consisting of niacinamide, retinol, peptides, growth factors, stem cells, vitamin C, vitamin K, exosomes (e.g. in Sigma-Aldrich edelfosine (TM) or (Tyr[SO3H]27)cholecystokinin fragment 26-33 amide), and their combinations; iii.when present, at least one anti-inflammatory agent is chosen from the group consisting of Eperua falcata bark extract, aloe vera, calmosensine, alder extract, resargine, Andrographis paniculate extract, Ficus regligiosa bark, Cucuma zeoaria extract, ursolic acid, ectoine, Coptidis chinensis extract, Pongamia pinnata extract, white hibiscus, ectoine, Punica granatum extract, pomegranate extract, ginger root extract, ginkgo biloba extract, witch hazel, exosome, bisabolol (levomenol), green tea extract, zinc oxide, and combinations thereof; and.

3. iv. When present, at least one collagen-producing agent is selected from the group consisting of Gentiana lutea root extract, retinoids, carob seed extract, Saccharomyces cerevisiae extract, panthenol (vitamin B5), carob seed extract, ginger root extract, galactomannans, pullulan, beta-glucan, alpha-glucan, Caesalpinia sphinosa gum, oligosaccharides, oligogalactomannans, wogonin, baicalin, ceramides, sphingolipids, resveratrol and its derivatives, niacinamide and its derivatives, TXA, pomegranate extract, linoleic acid, linolenic acid, olic acid, vitamin C, vitamin E (tocopherols) and its derivatives, polyphenols, flavanols, dihydroflavanols, ellagic acid, flavonoids, collagen and its derivatives, arnica montana extract, carotenoids and their derivatives, triglycerides, soybean oil, oleuropeins and their derivatives, phospholipids, beta-carotene, microalgae, chlorella vulgaris extract, dunaliella salina extract,Lactococcus fermentation lysate, Lactobacillus ferment, flaxseed extract, proanthocyanins, anthocyanins, hydroxyacetophenone, lecithin, GHK-Cu peptide, tripeptide-1, copper peptide, GHK-Mn, acetyl tetrapeptides, tripeptide-10, citrulline, palmitoyl hexapeptide-12, palmitoyl tripeptide-1, lipospondin, gexapeptide-11, PKEK, GEKG, SA1-11, tripeptide-3, pentapeptide-18, pentapeptide-3, acetyl octapeptide-1,3, defensins B, cathelicidin, dermcidin, histidine dipeptides, urocanic acid, pyrrolidone carboxylic acid, Pal-KTTKS, KEK and PKEK peptides, palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, extract Tropaeolum majus, glycoproteins, hyaluronic acid and its derivatives, sh-polypeptide-5, sh-polypeptide-11, sh-oligopeptide-2, sh-polypeptide-6, wheat germ oil, octacosanol, wild yam root extract, bakuchiol, borage oil, geranium oil, Protium heptaphyllum oil, Hamamelis virginiana extract,Citrus medica limonum oil, glutathione, coenzyme Q10, disodium acetylglucosamine phosphate, fermented red ginseng extract, dipeptide diaminobutyroyl benzylamide diacetate, angelica polymorpha sinensis root extract, sericin, superoxide dismutase, copper peptides, vitamin C, vitamin E, ginseng extract, and combinations thereof. Composition according to any one of the preceding claims, wherein, in the anti-aging system for ocular tissue (b): i. at least one elastase reducer comprises hydroxypropyl tetrahydropyrantriol; ii. when present, at least one cell proliferation agent comprises niacinamide; iii. when present, at least one anti-inflammatory agent comprises an extract of Eperua falcata bark; and iv. when present, at least one collagen-producing agent comprises an extract of Gentiana lutea root.

4. Composition according to claim 1, wherein, in the ocular tissue anti-aging system (b); i. at least one elastase reducer is present from about 0.01% to about 30%, ii. when present, at least one cell proliferation agent is present from about 0.0001% to about 30%; iii. when present, at least one anti-inflammatory agent is present from about 0.01% to about 10%; and iv. when present, at least one collagen-producing agent is present from about 0.01% to about 10%.

5. Composition according to claim 1, wherein the anti-aging system for ocular tissue (b) comprises: i. at least one elastase reducer; ii. at least one cell proliferation agent; iii. at least one anti-inflammatory agent; and iv. at least one collagen-producing agent.

6. Composition according to claim 5, wherein, in the ocular tissue anti-aging system (b): i. at least one elastase reducer is present from about 0.01% to about 30% ii. at least one cell proliferation agent is present from about 0.0001% to about 30% iii. at least one anti-inflammatory agent is present from about 0.01% to about 10% iv. at least one collagen-producing agent is present from about 0.01% to about 10%

7. Composition according to claim 5, wherein, in the anti-aging system for eye tissue (b): i. at least one elastase reducer comprises hydroxypropyl tetrahydropyrantriol; ii. at least one cell proliferation agent includes niacinamide; iii. at least one anti-inflammatory agent includes an extract of Eperua falcata bark; and iv. at least one collagen production agent includes an extract of Gentiana lutea root.

8. Composition according to claim 7, wherein, in the anti-aging eye tissue system (b): i. hydroxypropyltetrahydropyrantriol is present from about 0.01% to about 30%; ii. niacinamide is present from about 0.0001% to about 30%; iii. Eperua falcata bark extract is present from about 0.01% to about 10%; and iv. Gentiana lutea root extract is present from about 0.01% to about 10%.

9. Composition according to claim 7, wherein, in the anti-aging eye tissue system (b): i. hydroxypropyltetrahydropyrantriol is present at approximately 10%; ii. niacinamide is present at approximately 3%; iii. Eperua falcata bark extract is present at approximately 0.1%; and iv. Gentiana lutea root extract is present at approximately 0.015%.

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