SKIN COMPOSITIONS AND PROCESSES

Abstract

SKIN TREATMENT COMPOSITIONS AND PROCESSES The disclosure relates to compositions and processes for improving the appearance of the skin. The processes include treating skin tissue with at least one C-glycoside or one of its derivatives, at least one vitamin B3 or one of its derivatives, and at least one skin-modifying stimulus, and the compositions include at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives. Figure for the abstract: none

Description

Title of the invention: SKIN TREATMENT COMPOSITIONS AND METHODS technical field

[0001] The disclosure relates to compositions and methods for treating the skin, for example, to improve results after an aesthetic skin procedure. The compositions comprise at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives, and the methods comprise treating the skin with at least one C-glycoside or one of its derivatives, at least one vitamin B3 or one of its derivatives, and at least one skin-modifying stimulus. CONTEXT

[0002] Non-surgical cosmetic procedures that remove portions of the epidermis can accelerate skin surface renewal. For example, clinicians may use skin-modifying techniques such as laser treatments and chemical peels to improve skin appearance. Generally, skin treated with such lasers and peels goes through phases of inflammation, granulation, and matrix remodeling during the post-procedure healing process. The inflammation phase begins shortly after injury and lasts several days, and the granulation phase begins approximately 24 hours after injury and lasts one to two weeks. The remodeling phase lasts up to about a year and involves collagen cross-linking and replacement, where a new collagen matrix is ​​formed.

[0003] The prostaglandin E2 (PGE2) signaling pathway is particularly important for skin inflammation. PGE2 has been shown to be present at high levels in fibroblasts stimulated by interleukin-1a (IL-1a). Erythema and hyperpigmentation associated with inflammation caused by lasers and other resurfacing treatments are thought to be caused, in part, by local increases in reactive oxygen species (ROS) concentration, which stimulate mitogen-activated protein kinases (MAPs) and the pro-inflammatory cyclooxygenase-2 (COX2), which in turn increases PGE2 secretion. PGE2 induces acute inflammation by activating mast cells via the EP3 receptor. PGE2 also induces chronic inflammation.

[0004] The release of sulfated glycosaminoglycans (sGAGs) further mediates dermal regeneration, including wound contraction, after such cutaneous procedures. SGAGs stimulate myofibroblasts in granulation tissue to close wounds by strong contraction forces caused in part by α-actin contraction. of smooth muscle (α-SMA). Increased secretion of sGAG, in turn, inhibits neutrophil elastase activity, thus protecting the extracellular matrix (ECM). The Ki-67 protein (also known as MKI67) has also been shown to be present during cell proliferation. Modifying the expression and secretion of these markers has the potential to enhance skin healing.

[0005] Many individuals wish to improve the outcome of their aesthetic procedures. Therefore, there is a continuing need for enhanced skin treatments that mediate these signaling pathways, thereby reducing skin inflammation and discoloration and improving skin healing. The development of enhanced outcomes for aesthetic procedures is important to improve the quality of the results of these treatments and avoid potential undesirable side effects such as skin discoloration.

[0006] It has now been surprisingly discovered that C-glycosides and their derivatives such as proxylane (also known as Pro-xylane™ and hydroxypropyl tetrahydropyrantriol), when combined with at least one vitamin B3 or one of its derivatives such as niacinamide, have an unexpected advantage in strengthening epidermal and dermal renewal, and are particularly effective in providing benefits in managing inflammation and / or pigmentation to the skin, for example following various skin procedures. SUMMARY

[0007] This disclosure relates to methods for improving skin renewal and recovery after an aesthetic procedure and to the compositions used therein. It has been found that the combination of C-glycosides and their derivatives with at least one vitamin B3 or one of its derivatives synergistically improves wound contraction and cell proliferation, and also reduces inflammation associated with melanin production, increases sGAG release and inhibition of elastase activity, and stimulates barrier formation after an aesthetic procedure. Surprisingly, clinical improvements in dyschromia and redness were maintained for up to two months.

[0008] The compositions according to the disclosure include at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives, and the processes according to the disclosure combine the use of at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives with a skin treatment using a skin-modifying stimulus.

[0009] In various embodiments, the disclosure relates to the use of at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives in conjunction with various aesthetic procedures to prevent, reduce, and / or improve the appearance of the skin. In some embodiments, the disclosure relates to processes comprising the application of at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives, simultaneously or separately, before, during, and / or after a skin procedure such as a resurfacing or skin-modifying treatment.

[0010] In various embodiments, the disclosure relates to skin treatment methods, including skin appearance improvement, comprising the application of at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives to the skin in combination with treatment with a skin-modifying stimulus. For example, in some embodiments, the disclosure relates to skin appearance improvement methods, the methods comprising:

[0011] (a) the treatment of the skin with at least one skin-modifying stimulus,

[0012] (b)(l) the application of at least one C-glycoside or one of its derivatives to the skin, and

[0013] (b)(2) the application of at least one vitamin B3 or one of its derivatives to the skin.

[0014] In other embodiments, the disclosure relates to processes of Prevention or reduction of adverse effects of aesthetic skin procedures, such as by improving the outcomes of aesthetic skin procedures, such as skin resurfacing treatments including the application of at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives to the skin tissue prior to skin injury, for example, prior to an aesthetic procedure, in combination with a skin modification stimulation treatment. For example, in some embodiments, the disclosure relates to methods for preventing or reducing skin inflammation, such methods including:

[0015] (a) the treatment of the skin with at least one skin-modifying stimulus,

[0016] (b)(l) the application of at least one C-glycoside or one of its derivatives to the skin, and

[0017] (b)(2) the application of at least one vitamin B3 or one of its derivatives to the skin.

[0018] In another embodiment, the disclosure relates to skin treatment processes to prevent or reduce the formation of skin discoloration after aesthetic procedures, the processes including:

[0019] (a) the treatment of the skin with at least one skin-modifying stimulus,

[0020] (b)(l) the application of at least one C-glycoside or one of its derivatives to the skin, and

[0021] (b)(2) the application of at least one vitamin B3 or one of its derivatives to the skin.

[0022] In various embodiments, at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives may be applied to the skin tissue during treatment with a skin-modifying stimulus. In other embodiments, at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives may be applied to the skin tissue before and / or after treatment with a skin-modifying stimulus, for example, within a few seconds, approximately 1 minute, or approximately 1 hour before and / or after skin treatment with a skin-modifying stimulus, or within approximately 6 hours, approximately 12 hours, approximately 18 hours, or approximately 24 hours before and / or after skin treatment with a skin-modifying procedure.In various embodiments, at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives may be applied to the skin tissue once or more times a day, for example 2 times a day, 3 times a day, or more.In other embodiments, at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives may be applied to the skin tissue at least once a day over a period of one or more consecutive days, for example at least 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, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 or more, or at least once a day over a period of one or more non-consecutive days, for example every other day, about three times a week, about twice a week, about once a week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, or more.In other embodiments, the processes according to the disclosure may be repeated once or more times, for example, every day, every other day, about three times a week, about twice a week, about once a week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, or more often with a home or clinical-grade skin-modifying treatment.

[0023] In still other embodiments, the methods include:

[0024] (a) the treatment of skin tissue with at least one type of modifying stimulus of the skin, for example a laser, radiofrequency, an electrical instrument, heat, low-intensity light, a needle, or an abrasive instrument; and

[0025] (b)(l) the application of a composition comprising C13-D-xylopyranoside-2- hydroxypropane on the modified skin tissue within approximately 6 hours after step (a), in which C13-D-xylopyranoside-2-hydroxypropane is present in the composition in an amount ranging from approximately 0.01% to approximately 50%, from approximately 0.025% to approximately 40%, from approximately 0.05% to approximately 30%, from approximately 0.1% to approximately 20%, from approximately 0.2% to approximately 15%, from approximately 0.3% to approximately 12%, from approximately 0.4% to approximately 11%, from approximately 0.5% to approximately 10%, from approximately 0.6% to approximately 9%, from approximately 0.7% to approximately 8%, from approximately 0.8% to approximately 7%, from approximately 0.9% to approximately 6%, from approximately 1% to approximately 5%, or from approximately 2% to approximately 4%, relative to the total weight of the composition, and

[0026] (b)(2) the application of a composition comprising niacinamide to the skin tissue modified within 6 hours after step (a), wherein niacinamide is present in the composition in an amount ranging from about 0.0001% to about 50%, from about 0.0005% to about 45%, from about 0.001% to about 40%, from about 0.0025% to about 35%, from about 0.005% to about 30%, from about 0.0075% to about 25%, from about 0.01% to about 20%, from about 0.025% to about 15%, from about 0.05% to about 10%, from about 0.075% to about 8%, from about 0.1% to about 7%, from about 0.25% to about 6%, from about 0.5% to about 5%, or from about 1% to about 4% in weight, for example from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to about 13%, from about 8% to about 12%, or from about 9% to about 11%, by weight, relative to the total weight of the composition,

[0027] in which compositions (b)(1) and (b)(2) are applied preferably at least 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, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 times after treatment of the skin tissue in step (a), in which compositions (b)(l) and (b)(2) are applied at least once a day, in which all quantities are by weight, relative to the total weight of the composition in which it is present.

[0028] In various embodiments of the method according to the invention, step (b)(1) of applying at least one C-glycoside or one of its derivatives to the skin and step (b)(2) of applying at least one vitamin B3 or one of its derivatives to the skin take place within approximately 60 days after step (a) of treating the skin with at least one skin-modifying stimulus.

[0029] In various embodiments of the process according to the invention, the C-glycoside(s) and its / their derivatives and the vitamin(s) B3 and its / their derivatives are mixed, and said mixture is applied in step (b) to the skin of step (a). BRIEF DESCRIPTION OF THE FIGURES

[0030] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with drawing(s) Colour copies will be provided by the Office upon request and payment of the necessary fees.

[0031] An implementation of the present technology will now be described, by way of example only, with reference to the attached figures.

[0032] [Fig-1] Fig. 1 shows the secretion of PEG2 in non-fibroblast cultures treated (negative control) and IL-la stimulated fibroblast cultures (positive control) including cultures further treated with dexamethasone (Dex) (positive control), hydroxypropyl tetrahydropyrantriol (PX), niacinamide (Vit B3), or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide.

[0033] [Fig.2] Fig.2 shows the relative expression of α-SMA in untreated fibroblast cultures (negative control) and in fibroblast cultures further treated with a transforming growth factor (TGF-[3]) (positive control), hydroxypropyl tetrahydropyrantriol (PX), niacinamide (NAM) or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide.

[0034] [Fig.3] Fig.3 shows the relative expression of the Ki67 protein (KL67 or MKI67 antigen) in fibroblast cultures (negative control) and in cultures further treated with hydroxypropyl tetrahydropyrantriol (PX), niacinamide (NAM) or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide.

[0035] [Fig.4] Fig.4 shows the relative release of sGAG in the epidermal tissues of the T-Skin Softskin™ daytime model before and after laser ablation, and in tissues further treated with hydroxypropyl tetrahydropyrantriol (PX), niacinamide (NAM) or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide.

[0036] [Fig.5] The [Fig.5] shows a percentage of inhibition of elastase activity in one day in a neutrophil elastase inhibition assay in samples treated with hydroxypropyl tetrahydropyrantriol (PX), niacinamide (NAM) or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide.

[0037] [Fig. 6] [Fig. 6] shows hematoxylin and eosin (H&E), filament aggregation protein (filaggrin), and transglutaminase-1 (TGM-1) stained sections of model epidermal tissues from fresh, defatted, and blood-cleaned normal human skin samples following abdominoplasty that had undergone microneedling (MN) or not (untreated skin). Some tissues were cultured with 0.0009% hydroxypropyl tetrahydropyrantriol and 0.2% niacinamide. Sections were obtained and stained on day 6.

[0038] [Fig. 7] [Fig. 7] shows an overall wrinkle, a fine line, skin dyschromia, skin roughness, and general skin health parameters classified by experts on day 14 (D14), day 28 (D28), and day 56 (D56) after the laser procedure for a subject treated with hydroxypropyl tetrahydropyrantriol (proxylane) and niacinamide.

[0039] [Fig.8] [Fig.8] shows photographs of laser-treated skin immediately after the procedure, and 56 days after the procedure with treatment with hydroxypropyl tetrahydropyrantriol (proxylane) and niacinamide.

[0040] [Fig. 9] [Fig. 9] shows photographs of laser-treated skin immediately after the procedure, and 56 days after the procedure with treatment with hydroxypropyl tetrahydropyrantriol (PX) and niacinamide (NAM) or treatment with Aquafor Healing Ointment (reference).

[0041] [Fig. 10] Fig. 10 shows melanin expression in normal human epidermal melanocytes induced by PGE-2 dark pigment (lot 1981687, passage 3, ThermoFisher, Waltham, MA) (positive control) and in cultures further treated with tranexamic acid (TXA), hydroxypropyl tetrahydropyrantriol (PX), niacinamide (NAM) or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide. DETAILED DESCRIPTION

[0042] The disclosure relates to compositions and methods for treating skin tissue, such as increasing, accelerating, and / or improving the renewal of healthy skin, and / or improving the appearance of the skin. The disclosure also relates to compositions and methods for preventing or minimizing the formation of skin inflammation and skin discoloration before, during, or after a skin injury, for example, before laser treatment or a microdermabrasion procedure.

[0043] The compositions according to various aspects of disclosure include at least one C-glycoside or derivative, for example at least one C-xylopyranoside or derivative, and in at least some embodiments include hydroxypropyl tetrahydropyrantriol with at least one vitamin B3 or one of its derivatives, which may, in at least some embodiments, include niacinamide.

[0044] The methods according to various embodiments include treating skin tissue with at least one skin-modifying stimulus and applying at least one C-glycoside or one of its derivatives, for example, a C-xylopyranoside or one of its derivatives, for example, hydroxypropyl tetrahydropyrantriol, and at least one vitamin B3 or one of its derivatives, for example, niacinamide, to the skin tissue. In other embodiments, the methods include treating undamaged skin with at least one skin-modifying stimulus and applying at least one C-glycoside or one of its derivatives, for example, a C-xylopyranoside or one of its derivatives, for example, hydroxypropyl tetrahydropyrantriol, and at least one vitamin B3 or one of its derivatives, for example niacinamide on the skin, in order to prevent or reduce skin inflammation and / or discoloration after treatment with the skin modification treatment.

[0045] Without intending to be limited by theory, it is understood that C-glycosides or their derivatives when used with vitamin B3 or their derivatives can act synergistically to reduce inflammation and increase skin regeneration after skin modification procedures by reducing PGE2j expression by increasing a-SMA and / or Ki-67 expression, increasing sGAG secretion and / or inhibiting elastase activity.

[0046] In this respect, the compositions and processes according to the disclosure address the problem of skin inflammation and discoloration in a surprising new and previously unknown way, via a mechanism different from that of known processes. By treating the skin tissue with a skin-modifying stimulus and applying at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives to the targeted area, the proliferation of new, normal skin tissue is encouraged, rather than inflamed and / or discolored tissue.

[0047] Surprisingly, it has been found that in some embodiments, the skin treatment and inflammation prevention processes and compositions according to the disclosure confer broader and / or stronger benefits in the treatment and prevention of skin inflammation and hyperpigmentation to resurfaced and otherwise modified skin, with or without enhanced kinetics, compared to known treatments for skin inflammation and hyperpigmentation.

[0048] A more detailed description of the compositions, processes and necessary equipment for the treatment of skin and cutaneous tissue is provided below. I. Compositions

[0049] The compositions according to the disclosure comprise at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives. The compositions may further comprise additional components such as carriers, active ingredients other than C-glycosides or their derivatives and vitamin B3 or its derivatives, and additives typically found in skincare compositions.

[0050] A C-glycoside is a sugar fraction linked via a carbon-carbon bond (CC) to a non-sugar fraction (aglycone). In various embodiments, the C-glycoside can be selected from C13-D-xylopyranoside-n-propan-2-one; Ca-D-xylopyranoside n-propan-2-one; C13-D-xylopyranoside-2-hydroxypropane; Ca-D-xylopyranoside-2-hydroxypropane; l-(C13-D-fucopyranoside)-propan-2-one; l-(Ca-D-fucopyranoside)-propan-2-one; l-(C13-L-fucopyranoside)-propan-2- one ; l-(Ca-L-fucopyranoside)-propane-2-one; 2-one,l-(C13-D-fucopyranoside)-2-hydroxypropane, l-(Ca-D-fucopyranoside)-2-hydroxypropane; 1-(C13-L-fucopyranoside)-2-hydroxypropane; l-(Ca-L-fucopyranoside)-2-hydroxypropane; l-(C13-D-glucopyranosyl)-2-hydroxylpropane; l-(Ca-D-glucopyranosyl)-2-hydroxylpropane; l-(C13-D-galactopyranosyl)-2-hydroxylpropane; l-(Ca-D-galactopyranosyl)-2-hydroxylpropan- l-(C13-D-fucofuranosyl)propan-2-one; 1-(Ca-D-fucofuranosyl)-propan-2-one; l-(C13-L-fucofuranosyl)-propan-2-one; 1-(Ca-L-fucofuranosyl)-propan-2-one; C13-D-maltopyranoside-n-propan-2-one-Ca-D-maltopyranoside-n-propan-2-one-C13-D-maltopyranoside-2-hydroxypropane; Ca-D-maltopyranoside-2-hydroxypropane; and their derivatives or mixtures.

[0051] In various embodiments, at least one C-glycoside is a C-xylopyranoside. In at least some embodiments, the C-glycoside comprises, consists essentially of, or consists of C13-D-xylopyranoside-2-hydroxypropane, Ca-D-xylopyranoside-2-hydroxypropane, or mixtures thereof. In still other embodiments, the C-glycoside comprises, consists essentially of, or consists of C13-D-xylopyranoside-2-hydroxypropane (also known as hydroxypropyl tetrahydropyrantriol or Proxylane). Hydroxypropyl tetrahydropyrantriol corresponds to the formula structure (I) below: OH

[0052] According to various embodiments, the compositions as disclosed may comprise a total amount of C-glycoside and its derivatives of approximately 0.01% to approximately 50%, approximately 0.025% to approximately 40%, approximately 0.05% to approximately 30%, approximately 0.1% to approximately 20%, approximately 0.2% to approximately 15%, approximately 0.3% to approximately 12%, approximately 0.4% to approximately 11%, approximately 0.5% to approximately 10%, approximately 0.6% to approximately 9%, approximately 0.7% to approximately 8%, approximately 0.8% to approximately 7%, approximately 0.9% to approximately 6%, approximately 1% to approximately 5%, or approximately 2% to approximately 4% by weight, including all intermediate ranges and sub-ranges using any of the lower limits disclosed as lower limit and upper limits disclosed as upper limit, in relation to the total weight of the composition in which it is present.For example, the total amount of C-glycoside and its derivatives in the compositions according to the disclosure may be about 0.01%, about 0.05%, about 0.1%, about 0.25%, about 0.5%, about 0.75%, about 1%, about 1.25%, about 1.5%, about 1.75%, about 2%, about 2.25%, about 2.5%, about 2.75%, about 3%, about 3.25%. approximately 3.5%, approximately 3.75%, approximately 5%, approximately 5.25%, approximately 5.5%, approximately 5.75%, approximately 6%, approximately 6.25%, approximately 6.5%, approximately 6.75%, approximately 7%, approximately 7.25%, approximately 7.5%, approximately 7.75%, approximately 8%, approximately 8.25%, approximately 8.5%, approximately 8.75%, approximately 9%, approximately 9.25%, approximately 9.5%, approximately 9.75%, approximately 10%, approximately 10.5%, approximately 11%, approximately 11.5%, approximately 12%, approximately 12.5%, approximately 13%, approximately 13.5%, approximately 14%, approximately 14.5%, approximately 15%, approximately 15.5%, approximately 16%, approximately 16.5%, approximately 17%, approximately 17.5%, approximately 18%, approximately 18.5%, approximately 19% %, approximately 19.5%, approximately 20%, approximately 21%, approximately 22%, approximately 23%, approximately 24%, approximately 25%, approximately 26%, approximately 27%, approximately 28%, approximately 29% or approximately 30% by weight, including all intermediate ranges and sub-ranges, using any of the quantities indicated as the lower or upper limit,relative to the total weight of the composition in which it is present.

[0053] In various embodiments, at least one vitamin B3 or one of its derivatives is selected from niacin (nicotinic acid), niacinamide (nicotinamide), nicotinamide riboside, their derivatives, or mixtures thereof. In various embodiments, at least one vitamin B3 is niacinamide.

[0054] According to various embodiments, the compositions according to the disclosure may comprise a total amount of vitamin B3 and its derivatives of approximately 0.0001% to approximately 50%, approximately 0.0005% to approximately 45%, approximately 0.001% to approximately 40%, approximately 0.0025% to approximately 35%, approximately 0.005% to approximately 30%, approximately 0.0075% to approximately 25%, approximately 0.01% to approximately 20%, approximately 0.025% to approximately 15%, approximately 0.05% to approximately 10%, approximately 0.075% to approximately 8%, approximately 0.1% to approximately 7%, approximately 0.25% to approximately 6%, approximately 0.5% to approximately 5%, or approximately 1% to approximately 4% by weight, for example from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to about 13%, from about 8% to about 12%, or from about 9% to about 11% by weight,including all intermediate ranges and subranges using any of the disclosed lower limits as the lower limit and the disclosed upper limits as the upper limit, relative to the total weight of the composition in which it is present. For example, the total amount of vitamin B3 and its derivatives in compositions according to the disclosure may be approximately 0.0001%, approximately 0.0005%, approximately 0.001%, approximately 0.0025%, approximately 0.005%, approximately 0.0075%, approximately 0.01%, approximately 0.025%, approximately 0.05%, approximately 0.075%, approximately 0.1%, approximately 0.25%, approximately 0.5%, approximately 0.75%, approximately 1%, approximately 2%, approximately 3%, approximately 4%, approximately 5%, approximately 6%, approximately 7%, approximately 8%, approximately 9%, approximately 10%, approximately 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%, including all intermediate ranges and sub-ranges, using any of the quantities indicated as a lower or upper limit, relative to the total weight of the composition in which it is present.

[0055] In some embodiments, the compositions according to the disclosure include at least one C-glycoside and at least one vitamin B3.

[0056] The compositions will generally comprise one or more cosmetically acceptable carriers, including, but not limited to, water and / or non-aqueous solvents. Examples of non-aqueous solvents include glycerin; glycols, such as ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polyethylene glycol, caprylyl glycol, and hexylene glycol;glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-propyl ether, ethylene glycol mono-isopropyl ether, diethylene glycol mono-isopropyl ether, ethylene glycol mono-n-butyl ether, ethylene glycol mono-t-butyl ether, diethylene glycol mono-t-butyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol mono-t-butyl ether, propylene glycol mono-n-propyl ether, propylene glycol mono-isopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol mono-n-propyl ether and dipropylene glycol mono-isopropyl ether;and alcohols such as ethanol, propanol, isopropanol, butanol, pentanol, hexanol, octanol, decanol, dodecanol, hexadecanol, octadecanol, eicosadecanol, 2-propanol, 2-methyl-1-propanol, 2-methyl-2-butanol, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, and cyclohexanol. Mixtures of two or more non-aqueous solvents may also be chosen, and it is envisaged that in various embodiments, the carrier comprises water and at least one non-aqueous solvent.

[0057] The compositions may optionally include one or more active ingredients other than C-glycosides or their derivatives and vitamin B3 and its derivatives, such as, for example, active ingredients that can modulate inflammation (including, but not limited to, carotenoids, curcumin, steroids, cannabinoids, glycoproteins, essential oils, flavonoids and flavonoid derivatives, phenolic acids, ascorbic acid, polyphenols, marine and algae extracts), active ingredients that can strengthen the skin barrier (e.g., including, but not limited to, pantothenic acid, ceramides, pseudo-ceramides such as 2-oleyl-l,3-octadecanediol, niacinamides, niacinamide derivatives, carob seed extracts, oligogalactomannan, colloidal oatmeal, hyaluronic acids, probiotics and [3-glucan]) and / or actives that may modulate skin fibrosis (including, but not limited to, TNF inhibitors, TGF-[3] inhibitors, mTOR pathway inhibitors and kynurenic acid and its derivatives).

[0058] The compositions may optionally contain one or more additives such as those typically found in skin care compositions, including, but not limited to, oils, waxes or other fatty substances; gelling and / or thickening agents; emulsifiers; moisturizing agents; emollients; sunscreens; hydrophilic or lipophilic active agents, such as ceramides; free radical scavengers; bactericides; sequestering agents; preservatives; pH adjusters; skin penetration enhancers; perfumes; surfactants; fillers; natural products or their extracts, such as aloe or green tea; vitamins; and / or coloring materials.The quantity of these additives, if any, will vary according to the intended use and / or the properties of the composition and the desired effect, but, individually or in combination, will typically vary from about 0.0001% to about 20%, such as from about 0.001% to about 15%, from about 0.01% to about 10%, from about 0.1% to about 7.5%, from about 0.5% to about 5%, or from about 1% to about 3% by weight, relative to the total weight of the composition.

[0059] Additives may also include, but are not limited to, 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,extract of dunaliella salina), 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, tripeptide 10, citrulline, palmitoyl-12 hexapeptide, palmitoyl-1 tripeptide, lipospondin, gexapeptide 11, PKEK, GEKG, SA1-11, tripeptide-3, pentapeptide-18, pentapeptide-3, acetyl-1,3 octapeptide, antimicrobial peptides (including, but not limited to, phosphenins, 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, witch hazel 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.

[0060] The form of the compositions according to the disclosure is not limited and may include, for example, liquids, emulsions, suspensions, lotions, creams, gels (including hydrogels), balms, pastes, serums, ointments, foams or the like.

[0061] The compositions are generally applied topically and can, in various embodiments, be applied by the consumer as a home formulation, or by a professional, for example in a clinical setting as part of an aesthetic procedure.

[0062] A non-limiting example of a composition according to the disclosure includes a carrier, for example water and / or at least one non-aqueous solvent, optionally at least one active ingredient other than C-glycosides or their derivatives and / or at least one additive, and a total amount of C-glycosides and their derivatives ranging from about 0.01% to about 50%, from about 0.025% to about 40%, from about 0.05% to about 30%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11%, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1% to about 5%, or from about 2% to about 4% by weight, including all intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present.Another non-limiting example of a composition according to the disclosure includes a carrier comprising water and optionally at least one non-aqueous solvent, optionally at least one active ingredient other than C-glycosides or their derivatives and / or at least one additive, and hydroxypropyl tetrahydropyrantriol present. in an amount ranging from about 0.01% to about 50%, from about 0.025% to about 40%, from about 0.05% to about 30%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11%, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1% to about 5%, or from about 2% to about 4% by weight, including all intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present.

[0063] Another non-limiting example of a composition according to the disclosure includes a carrier, for example water and / or at least one non-aqueous solvent, optionally at least one active ingredient other than vitamin B3 or its derivatives and / or at least one additive, and a total amount of vitamin B3 and its derivatives ranging from about 0.0001% to about 50%, from about 0.0005% to about 45%, from about 0.001% to about 40%, from about 0.0025% to about 35%, from about 0.005% to about 30%, from about 0.0075% to about 25%, from about 0.01% to about 20%, from about 0.025% to about 15%, from about 0.05% to about 10%, from about 0.075% to about 8%, from about 0.1% to about 7%, from about 0.25% to about 6%, from about 0.5% to about 5%, or from about 1% to about 4% by weight, for example from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example from about 4% to about 16%, from about 5% to about 15%,from about 6% to about 14%, from about 7% to about 13%, from about 8% to about 12%, or from about 9% to about 11% by weight, including all intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present. Another non-limiting example of a composition according to the disclosure includes a carrier comprising water and optionally at least one non-aqueous solvent, optionally at least one active ingredient other than niacinamide or its derivatives and / or at least one additive, and niacinamide present in an amount ranging from approximately 0.0001% to approximately 50%, from approximately 0.0005% to approximately 45%, from approximately 0.001% to approximately 40%, from approximately 0.0025% to approximately 35%, from approximately 0.005% to approximately 30%, from approximately 0.0075% to approximately 25%, from approximately 0.01% to approximately 20%, from approximately 0.025% to approximately 15%, from approximately 0.05% to approximately 10%, from approximately 0.075% to approximately 8%, from approximately 0.1% to approximately 7%, from approximately 0.25% to approximately 6%,from about 0.5% to about 5%, or from about 1% to about 4% by weight, for example from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to about 13%, from about 8% to about 12%, or from about 9% to about 11% by weight, including all intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present.

[0064] In another embodiment, a composition according to the disclosure includes a carrier, for example water and / or at least one non-aqueous solvent, optionally at least one active ingredient other than C-glycosides or their derivatives and vitamin B3 and its derivatives, and / or at least one additive, a total amount of C-glycosides and their derivatives ranging from about 0.01% to about 50%, from about 0.025% to about 40%, from about 0.05% to about 30%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11%, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1% to about 5%, or from about 2% to about 4%, and a total amount of vitamin B3 and its derivatives ranging from about 0.0001% to about 50%, from about 0.0005% to about 45%, from about 0.001% to about 40%, from about 0,0.025% to about 35%, from about 0.005% to about 30%, from about 0.0075% to about 25%, from about 0.01% to about 20%, from about 0.025% to about 15%, from about 0.05% to about 10%, from about 0.075% to about 8%, from about 0.1% to about 7%, from about 0.25% to about 6%, from about 0.5% to about 5%, or from about 1% to about 4% by weight, for example, from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example, from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to about 13%, from approximately 8% to approximately 12%, or from approximately 9% to approximately 11% by weight, including all intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present. The weight ratio between the total amount of the C-glycoside(s) and its / their derivatives and the total amount of vitamin B3 and its derivatives applied to the skin can range from approximately 0,001:1 to approximately 10:1, from approximately 0.005:1 to approximately 8:1, from approximately 0.01:1 to approximately 6:1, from approximately 0.05:1 to approximately 4:1, from approximately 0.1:1 to approximately 2:1, or from approximately 0.5:1 to approximately 1.5:1. II. Processes

[0065] In various embodiments, the disclosure relates to methods for treating skin tissue to improve the appearance of the skin. In other embodiments, the disclosure relates to methods for reducing skin inflammation after skin modification treatment. In still other embodiments, the disclosure relates to methods for reducing prostaglandin E2 secretion in modified skin tissue, reducing alpha-actin secretion from smooth muscle in modified skin tissue, increasing cell proliferation in modified skin tissue, reducing melanin secretion in modified skin tissue, and / or increasing the secretion of at least one sulfated glycosaminoglycan in modified skin tissue.

[0066] Typically, the methods include applying at least one C-glycoside or one of its derivatives, for example, a C-xylopyranoside or one of its derivatives, for example, niacinamide, to an area to be treated (collectively referred to herein in some cases as the "target area"), before, during, and / or after treatment of the skin with a skin-modifying stimulus (interchangeably referred to herein as the "skin-modifying stimulus"). In various methods, the C-glycoside or one of its derivatives comprises, consists essentially of, or consists of C-xylopyranosides and / or their derivatives, and in other methods, the C-glycoside or one of its derivatives comprises, consists essentially of, or consists of hydroxypropyl tetrahydropyrantriol. In various methods, vitamin B3 or one of its derivatives comprises, consists essentially of, or consists of niacinamide (nicotinamide).

[0067] In processes according to the disclosure, useful skin-modifying stimuli include those used in skincare to alter or damage the skin in order to encourage new growth, generally in a controlled manner. These treatments typically damage the outermost layers of skin tissue to a relatively mild degree, thereby setting in motion the body's natural healing process. These treatments may also stimulate collagen production. Thus, any known process or device for altering or damaging skin tissue may be used in the processes according to the disclosure.For example, in various embodiments, the skin-modifying stimulus may alter or damage skin tissue by cutting, burning, chemically damaging, ablating, micro-ablating, coagulating, or otherwise affecting the stratum corneum and subcutaneous tissue of the target area. Therefore, as used here, "modified skin tissue" is skin tissue that has been altered or damaged by one or more skin-modifying stimuli, and that heals from treatment with the skin-modifying stimulus.

[0068] The skin-modifying stimulus used in the processes according to the disclosure may, in various embodiments, be invasive or non-invasive. By way of non-limiting example, the skin-modifying stimulus may be a laser, plasma, radiofrequency, high-intensity focused ultrasound, an electric field, heat, a low-intensity light device, a needle, a microneedle, an abrasive element, a chemical agent such as a chemical exfoliating agent, or the like, and the skin-modifying stimulus treatment may be a laser procedure, a microneedling procedure, a high-intensity focused ultrasound procedure, an electroporation procedure, a dermabrasion procedure, a microdermabrasion procedure, a plasma skin rejuvenation procedure, a chemical exfoliation procedure, or the like.

[0069] Any variety of cosmetic lasers, distinguished by their wavelength and laser delivery method, can be used. In various embodiments, the target area can be treated with ablative or non-ablative lasers. Ablative lasers may include, for example, carbon dioxide or erbium lasers. Non-ablative lasers may include, for example, pulsed light, pulsed dye, and fractional lasers. Lasers can also be modified when combined with other elements, such as gases, gemstones, and metals. Non-limiting examples include Clear +Brilliant® lasers, fractional photothermolysis lasers, alexandrite lasers, carbon dioxide (CO2) lasers, erbium (Er:YAG) lasers, intense pulsed light (IPL) lasers, Nd:YAG lasers, pulsed dye lasers, triggered lasers, picosecond lasers, etc.

[0070] In various embodiments, the target area can be treated with mechanical microneedling, which uses a motorized pen with tiny, fine needles to create thousands of channels up to 2.5 millimeters deep. These channels disrupt the undamaged skin tissue to allow the growth of new skin. Non-limiting examples of mechanical microneedling devices that can be used include SkinPen Precision, MDpen, Skin Stylus, etc.

[0071] In some embodiments, the target area can be treated with fractional radiofrequency (RF) microneedling, which is a heat-based therapy that uses thicker needles to deliver heat deep into the skin. RF microneedling thermally coagulates the tissue to stimulate collagen denaturation and renewal. RF microneedling generates fewer microchannels than mechanical needling. In one embodiment, the target area can be treated with standard or short-pulse RF microneedling. Non-limiting examples of RF devices that can be used include Scarlet SRF, Agnes RF, Endymed Intensive, Secret RF, Vivace, Virtue RF, Morpheus8, etc.

[0072] The target area can also be treated with ultrasound, for example by ultratherapy. Ultrasound can loosen, stretch, and thermally reorient collagen tissue. Ultrasound acts mechanically on the skin tissue like a micromassage and produces microscopic droplets of oxygen (cavitation) from the vibrations.

[0073] Electroporation mesotherapy can also be used with the disclosed methods. Electroporation uses electricity to increase the permeability of the skin tissue membrane by creating microscopic channels that open pathways deep into the skin, thereby disrupting the skin tissue.

[0074] Dermabrasion, including microdermabrasion, can also be used to treat the target area in certain embodiments. Dermabrasion involves the controlled, deeper abrasion of the upper to middle layers of undamaged skin tissue with a variety of powerful abrasive devices such as a wire brush, a diamond grinding wheel (or burr), or a toothed wheel. Examples of embodiments may include crystal microdermabrasion or diamond microdermabrasion.

[0075] In other embodiments, plasma skin rejuvenation can be used in the disclosed processes. Plasma skin regeneration can be used to deliver energy in the form of plasma to the target area, resembling a thermal device and a dry scrub.

[0076] In some embodiments, a chemical agent such as a chemical exfoliating or scrubbing agent (also known as chemical exfoliation or derma-scrubbing) may be used as a skin-modifying stimulus.Examples of non-limiting chemical agents that can be used to treat the target area include chemical agents capable of acting either directly on the scrub by encouraging exfoliation, such as 3-hydroxy acids (BHAs), for example salicylic acid and its derivatives (including n-octanoyl 5-salicylic acid, also known as capryloyl salicylic acid (INCI name)); α-hydroxy acids (AHAs), such as glycolic, lactic, tartaric, malic, or mandelic acids; 8-hexadecene-1,16-dicarboxylic acid or 9-octadecene dioic acid; urea and its derivatives; trichloroacetic acid; gentisic acid and its derivatives; oligofuctoses; cinnamic acid; saphora japonica extract; resveratrol; resorcinol; carbolic acid (phenol); or mixtures thereof.

[0077] Other examples of non-limiting chemical scrubbing agents that may be used include compounds involved in scrubbing or degrading comeodesmosomes, such as aminosulfonic compounds, for example 4-(2-hydroxyethyl)piperazine-l-propanesulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine) and its derivatives; α-amino acid derivatives of the glycine type (as described in EP-0 852 949) as well as sodium methylglycine diacetate sold by BASF under the trade name Trilon M; honey; sugar derivatives such as O-octanoyl-6-D-maltose and N-acetyl glucosamine; or mixtures thereof.

[0078] Other examples of non-limiting chemical scrubbing agents suitable for use in compositions according to disclosure include EDTA and its derivatives, kelp extracts, O-linoleyl-6-D-glucose; (3-hydroxy-2-pentylcyclopentyl)acetic acid, glycerol trilactate, S-carboxymethyl cysteine, silica-containing salicylate derivatives such as those described in patent EP 0 796 861, oligofuctases such as those described in patent EP 0 218 200, agents having effects on transglutaminase such as in patent EP 0 899 330; the extract of the ficus opuntia flower indicated by Silab's Exfolactive®; 8-hexadecene 1,16-dicarboxylic acid; glucose and vitamin F esters; or mixtures thereof.

[0079] In certain embodiments, the chemical agent(s) may be chosen from among α-hydroxy acids such as citric, lactic, glycolic, malic, tartaric or mandelic acids; α-hydroxy acids such as salicylic acid or its derivatives, for example n-octanoy 1-5-salicylic acid, trichloroacetic acid, phenols, croton oil scrubs; or mixtures thereof.

[0080] The C-glycoside or one of its derivatives will typically remain on the skin, which may or may not be modified skin tissue, for a sufficient period to achieve the desired benefits. Thus, it may be preferable to leave the C-glycoside or one of its derivatives on the skin until it is absorbed or removed during routine personal hygiene, for example, the next time the skin is washed.For example, in some embodiments, at least one C-glycoside or one of its derivatives is left on the skin for a desired period of time, for example at least 10 seconds, at least 20 seconds, at least 30 seconds, at least 40 seconds, at least 50 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 25 minutes, at least 30 minutes, at least 35 minutes, at least 40 minutes, at least 45 minutes, at least 1 hour, at least 2 hours, at least 5 hours, at least 8 hours, at least 10 hours, at least 15 hours, at least 20 hours, at least 24 hours, at least 36 hours or at least 48 hours before being removed, such as, for example, by wiping or rinsing the skin.For example, at least one C-glycoside or one of its derivatives may be left on the skin for a period ranging from 5 to 60 minutes, such as 5 to 50 minutes, 5 to 40 minutes, 5 to 35 minutes, 5 to 30 minutes, 5 to 25 minutes, 5 to 20 minutes, 5 to 15 minutes, or 5 to 10 minutes. As a further example, at least one C-glycoside or one of its derivatives may be left on the skin for a period ranging from 10 to 60 minutes, such as 10 to 50 minutes, 10 to 40 minutes, 10 to 35 minutes, 10 to 30 minutes, 10 to 25 minutes, 10 to 20 minutes, or 10 to 15 minutes.

[0081] Vitamin B3 or one of its derivatives will also typically remain on the skin, which may or may not be modified skin tissue, for a sufficient period to achieve the desired benefits. Thus, it may be preferable to leave vitamin B3 or one of its derivatives on the skin until it is absorbed or removed during ordinary personal hygiene, for example, the next time the skin is washed off. For example, in some embodiments, at least one vitamin B3 or one of its derivatives is left on the skin for a desired period of time, for example at least 10 seconds, at least 20 seconds, at least 30 seconds, at least 40 seconds, at least 50 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 25 minutes, at least 30 minutes, at least 35 minutes, at least 40 minutes, at least 45 minutes, at least 1 hour, at least 2 hours, at least 5 hours, at least 8 hours, at least 10 hours, at least 15 hours, at least 20 hours, at least 24 hours, at least 36 hours or at least 48 hours before being removed, such as, for example, by wiping or rinsing the skin.For example, at least one vitamin B3 or one of its derivatives can be left on the skin for a period ranging from 5 to 60 minutes, such as 5 to 50 minutes, 5 to 40 minutes, 5 to 35 minutes, 5 to 30 minutes, 5 to 25 minutes, 5 to 20 minutes, 5 to 15 minutes, or 5 to 10 minutes. As a further example, at least one vitamin B3 or one of its derivatives can be left on the skin for a period ranging from 10 to 60 minutes, such as 10 to 50 minutes, 10 to 40 minutes, 10 to 35 minutes, 10 to 30 minutes, 10 to 25 minutes, 10 to 20 minutes, or 10 to 15 minutes. .

[0082] The application steps of a C-glycoside or one of its derivatives and of a vitamin B3 or one of its derivatives may take place separately or simultaneously.

[0083] The application step of a C-glycoside or one of its derivatives may include one or more applications, such as two or more applications, three or more applications, etc., to the target area. Thus, in various embodiments, the methods include applying at least one C-glycoside or one of its derivatives to the target area at least once before, at least once during, and / or at least once after treatment with the skin-modifying stimulus. For example, at least one C-glycoside or one of its derivatives may be applied to the target area at least once before, at least once during, and at least once after treatment with the skin-modifying stimulus.As another example, the methods include applying at least one C-glycoside or one of its derivatives to the target area at least twice before, at least twice during, and / or at least twice after treatment with the skin-modifying stimulus. As yet another example, the methods include applying at least one C-glycoside or one of its derivatives to the target area at least once, such as at least twice, before treatment with the skin-modifying stimulus, and at least once, such as at least twice, after treatment with the stimulus. of skin modification. As a further example, the processes include the application of at least one C-glycoside or one of its derivatives to the target area at least once, for example at least twice, after treatment with the skin modification stimulus.

[0084] The step of applying vitamin B3 or one of its derivatives may also include one or more applications, such as two or more applications, three or more applications, etc., to the target area. Thus, in various embodiments, the methods include applying at least one vitamin B3 or one of its derivatives to the target area at least once before, at least once during, and / or at least once after treatment with the skin-modifying stimulus. For example, at least one vitamin B3 or one of its derivatives may be applied to the target area at least once before, at least once during, and at least once after treatment with the skin-modifying stimulus.As another example, the methods include applying at least one vitamin B3 or one of its derivatives to the target area at least twice before, at least twice during, and / or at least twice after treatment with the skin-modifying stimulus. As a further example, the methods include applying at least one vitamin B3 or one of its derivatives to the target area at least once, such as at least twice, before treatment with the skin-modifying stimulus, and at least once, such as at least twice, after treatment with the skin-modifying stimulus. As yet another example, the methods include applying at least one vitamin B3 or one of its derivatives to the target area at least once, such as at least twice, after treatment with the skin-modifying stimulus.

[0085] In various embodiments, at least one C-glycoside or one of its derivatives may be applied to the target area at least once a day, at least twice a day, or at least three times a day, such as one to five times a day, one to four times a day, one to three times a day, or one to two times a day, for example, once a day, before and / or after treatment with the skin-modifying stimulus. At least one C-glycoside or one of its derivatives may be applied to the target area at least once a day for at least approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, approximately 7, approximately 8, approximately 9, approximately 10, approximately 11, approximately 12, approximately 13, approximately 14, approximately 15, approximately 16, approximately 17, approximately 18, approximately 19, approximately 20, approximately 21, approximately 22, approximately 23, approximately 24, approximately 25, approximately 26, approximately 27, approximately 28, approximately 29, approximately 30, approximately 31, approximately 32, approximately 33, approximately 34, approximately 35, approximately 36, approximately 37, approximately 38, approximately 39, approximately 40, approximately 41, approximately 42, approximately 43, approximately 44, approximately 45, approximately 46, approximately 47, approximately 48, approximately 49, approximately 50, approximately 51, approximately 52, approximately 53, approximately 54, approximately 55, approximately 56, approximately 57, approximately 58, approximately 59, or approximately 60 consecutive or non-consecutive days, before and / or after treatment with the skin-modifying stimulus. At least one C-glycoside or one of its derivatives may be applied to the target area at least once daily, for at least approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, or approximately 7 days per week. For example, at least one C-glycoside or one of its derivatives may be applied to the target area at least twice daily, in which the second or subsequent application occurs at least approximately 6 hours, for example, at least approximately 8 hours, at least approximately 10 hours, at least approximately 12 hours, or at least approximately 15 hours after the previous application.

[0086] Similarly, at least one vitamin B3 or one of its derivatives can be applied to the target area at least once a day, at least twice a day, or at least three times a day, such as one to five times a day, one to four times a day, one to three times a day, or one to two times a day, for example, once a day, before and / or after treatment with the skin-modifying stimulus. At least one vitamin B3 or one of its derivatives can be applied to the target area at least once a day, for at least approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, approximately 7, approximately 8, approximately 9, approximately 10, approximately 11, approximately 12, approximately 13, approximately 14, approximately 15, approximately 16, approximately 17, approximately 18, approximately 19, approximately 20, approximately 21, approximately 22, approximately 23, approximately 24, approximately 25, approximately 26, approximately 27, approximately 28, approximately 29, approximately 30, approximately 31, approximately 32, approximately 33, approximately 34, approximately 35, approximately 36, approximately 37, approximately 38, approximately 39, approximately 40, approximately 41, approximately 42, approximately 43, approximately 44, approximately 45, approximately 46, approximately 47, approximately 48, approximately 49, approximately 50, approximately 51, approximately 52, approximately 53, approximately 54, approximately 55, approximately 56, approximately 57, approximately 58, approximately 59, or approximately 60 consecutive or non-consecutive days before and / or after treatment with the skin-modifying stimulus. At least one vitamin B3 or one of its derivatives may be applied to the target area at least once daily for at least approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, or approximately 7 days per week. For example, at least one vitamin B3 or one of its derivatives may be applied to the target area at least twice daily, where the second or subsequent application occurs at least approximately 6 hours, for example, at least approximately 8 hours, at least approximately 10 hours, at least approximately 12 hours, or at least approximately 15 hours after the previous application.

[0087] In various embodiments, the processes according to the disclosure can be carried out as described herein for at least one month or more, for example for 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, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 consecutive or non-consecutive months, or for any period of time using one of the above proposals as upper and lower limits to that range of time periods.

[0088] In various embodiments, at least one C-glycoside or one of its derivatives is applied to the target area within approximately 1 minute, such as within approximately 5 minutes, within approximately 10 minutes, within approximately 15 minutes, within approximately 20 minutes, within approximately 30 minutes, within approximately 45 minutes, within approximately 60 minutes, within approximately 90 minutes, within approximately 2 hours, within approximately 3 hours, within approximately 4 hours, within approximately 5 hours, within approximately 6 hours, within approximately 8 hours, within approximately 10 hours, within approximately 12 hours, within approximately 18 hours, within approximately 24 hours, within approximately 36 hours, or within approximately 48 hours before and / or after treatment of skin tissue with a skin-modifying stimulus treatment.In other embodiments, at least one vitamin B3 or one of its derivatives is applied to the target area within approximately 1 minute, such as within approximately 5 minutes, within approximately 10 minutes, within approximately 15 minutes, within approximately 20 minutes, within approximately 30 minutes, within approximately 45 minutes, within approximately 60 minutes, within approximately 90 minutes, within approximately 2 hours, within approximately 3 hours, within approximately 4 hours, within approximately 5 hours, within approximately 6 hours, within approximately 8 hours, within approximately 10 hours, within approximately 12 hours, within approximately 18 hours, within approximately 24 hours, within approximately 36 hours, or within a period approximately 48 hours before and / or after treatment of the skin tissue with a skin-modifying stimulus treatment.

[0089] In various methods according to the disclosure, the application of at least one C-glycoside or one of its derivatives is accomplished by applying a composition comprising at least one C-glycoside or one of its derivatives, for example, a composition comprising at least one C-xylopyranoside or one of its derivatives, for example, hydroxypropyl tetrahydropyrantriol, to the target area before, during, and / or after treatment of the skin tissue with a skin-modifying stimulus. In other methods according to the disclosure, the application of at least one vitamin B3 or one of its derivatives is accomplished by applying a composition comprising at least one vitamin B3 or one of its derivatives, for example, a composition comprising niacinamide, to the target area before, during, and / or after treatment of the skin tissue with a skin-modifying stimulus. In one embodiment, at least one C-glycoside or a of its derivatives and at least one vitamin B3 are combined in a composition and applied simultaneously using disclosure processes.

[0090] In at least some embodiments, treatments with the skin-modifying stimulus are performed using at-home devices. By way of non-limiting example, microneedling and microdermabrasion can be performed with at-home devices. These at-home devices may be sold in kits with compositions comprising at least one C-glycoside or one of its derivatives, at least one vitamin B3 or one of its derivatives, or combinations thereof, for example, a first composition comprising at least one C-xylopyranoside or one of its derivatives, for example, hydroxypropyl tetrahydropyrantriol, and a second composition comprising one vitamin B3 or one of its derivatives, for example, niacinamide. Such at-home devices may be sold in kits with a composition comprising at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives.

[0091] The processes according to the disclosure treat the skin using skin-modifying stimuli according to known typical procedures. Thus, although it is possible to do so, it is not necessary to vary the length, intensity, or other parameters of treatments with skin-modifying stimuli compared to those currently performed in order to obtain the surprising and unexpected benefits of reducing inflammation and / or improving or reducing skin discoloration according to the disclosure. For example, in a typical microdermabrasion procedure, a device having exfoliating crystals is moved over the skin with light pressure for a period of approximately 30 minutes.In a disclosure procedure where an abrasive element is chosen as the skin-modifying stimulus, the same microdermabrasion procedure may be performed and at least one C-glycoside or one of its derivatives and at least one vitamin B3 may be applied to the target area before, during and / or after the procedure.

[0092] According to various embodiments of the disclosure, the methods include treating skin tissue by applying at least one C-glycoside or one of its derivatives and at least one niacinamide to the skin tissue in connection with treating the skin tissue with a skin-modifying stimulus. In various embodiments, the methods include:

[0093] (a) the treatment of skin tissue with at least one modifying stimulus skin,

[0094] (b)(l) the application of at least one C-glycoside or one of its derivatives to the tissue cutaneous, and

[0095] (b)(2) the application of at least one vitamin B3 or one of its derivatives to the tissue cutaneous.

[0096] In some embodiments, the step of (a) treating the skin tissue with at least one skin-modifying stimulus takes place before the steps of (b)(1) applying at least one C-glycoside or one of its derivatives to the skin tissue, so that at least one C-glycoside or one of its derivatives is applied to the modified skin tissue, and (b)(2) applying at least one vitamin B3 or one of its derivatives to the skin tissue, so that at least one vitamin B3 or one of its derivatives is applied to the modified skin tissue. In some embodiments, step (b)(l) applying at least one C-glycoside or one of its derivatives to the skin tissue includes applying a composition comprising at least one C-glycoside or one of its derivatives and at least one vector to the skin tissue before and / or after step (a), wherein the total amount of C-glycosides and their derivatives present in the composition ranges from about 0.01% to about 50%,from about 0.025% to about 40%, from about 0.05% to about 30%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11%, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1% to about 5%, or from about 2% to about 4% by weight, relative to the total weight of the composition. In some embodiments, step (b)(2) applying at least one vitamin B3 or one of its derivatives to the skin tissue comprises applying a composition comprising at least one vitamin B3 or one of its derivatives and at least one carrier to the skin tissue before and / or after step (a), wherein the total amount of vitamin B3 and its derivatives present in the composition ranges from about 0.0001% to about 50%, from about 0.0005% to about 45%, from about 0.001% to about 40%, from about 0,0.025% to about 35%, from about 0.005% to about 30%, from about 0.0075% to about 25%, from about 0.01% to about 20%, from about 0.025% to about 15%, from about 0.05% to about 10%, from about 0.075% to about 8%, from about 0.1% to about 7%, from about 0.25% to about 6%, from about 0.5% to about 5%, or from about 1% to about 4% by weight, for example, from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example, from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to about 13%, from approximately 8% to approximately 12%, or from approximately 9% to approximately 11% by weight, relative to the total weight of the composition.

[0097] According to other embodiments of the disclosure, the methods include applying at least one C-glycoside or one of its derivatives to the skin before a skin injury, and / or applying at least one vitamin B3 and one of its derivatives to the skin before a skin injury, for example before a surgical procedure related to skin treatment with a skin-modifying stimulus. In various embodiments, the methods include:

[0098] (a) treatment of undamaged skin with at least one modifying stimulus skin,

[0099] (b)(l) the application of at least one C-glycoside or one of its derivatives to the skin, and

[0100] (b)(2) the application of at least one vitamin B3 or one of its derivatives to the skin.

[0101] In some embodiments, step (a) of treating the undamaged skin with at least one skin-modifying stimulus takes place before step (b)(1) of applying at least one C-glycoside or one of its derivatives to the undamaged skin, so that at least one C-glycoside or one of its derivatives is applied to modified skin tissue and / or step (b)(2) of applying at least one vitamin B3 or one of its derivatives to the undamaged skin, so that at least one vitamin B3 or one of its derivatives is applied to modified skin tissue. In some embodiments, the step of (b)(l) applying at least one C-glycoside or one of its derivatives to undamaged skin includes applying a composition comprising at least one C-glycoside or one of its derivatives and at least one vector to undamaged skin before and / or after step (a), wherein the total amount of C-glycosides and their derivatives present in the composition ranges from approximately 0,0.1% to about 50%, from about 0.025% to about 40%, from about 0.05% to about 30%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11%, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, from about 1% to about 5%, or from about 2% to about 4% by weight, relative to the total weight of the composition. In some embodiments, step (b)(2) applying at least one vitamin B3 or one of its derivatives to unbroken skin comprises applying a composition comprising at least one vitamin B3 or one of its derivatives and at least one carrier to unbroken skin before and / or after step (a), wherein the total amount of vitamin B3 and its derivatives present in the composition ranges from about 0.0001% to about 50%, from about 0.0005% to about 45%, from about 0.001% to about 40%,from about 0.0025% to about 35%, from about 0.005% to about 30%, from about 0.0075% to about 25%, from about 0.01% to about 20%, from about 0.025% to about 15%, from about 0.05% to about 10%, from about 0.075% to about 8%, from about 0.1% to about 7%, from about 0.25% to about 6%, from about 0.5% to about 5%, or from about 1% to about 4% by weight, for example from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, for example from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to approximately 13%, of about 8% to about 12%, or about 9% to about 11% by weight, relative to the total weight of the composition.

[0102] Optionally, in certain embodiments, one or more additional active agents (other than C-glycosides or their derivatives and vitamin B3 and its derivatives) may be applied to the skin either as part of a composition comprising at least one C-glycoside or one of its derivatives and / or vitamin B3 and its derivatives, or separately, including, by way of example, actives that can modulate inflammation (including, but not limited to, carotenoids, curcumin, steroids, cannabinoids, glycoproteins, essential oils, flavonoids and flavonoid derivatives, phenolic acids, ascorbic acid, polyphenols, marine and algae extracts), actives that can strengthen the skin barrier (including, but not limited to, pantothenic acid, ceramides, pseudo-ceramides such as 2-Oleyl-1,3-Octadecanediol, niacinamides, niacinamide derivatives,carob seed extract, oligogalactomannan, colloidal oatmeal, hyaluronic acids, probiotics, and [3-glucan]) and / or active ingredients that can modulate skin fibrosis (including, but not limited to, TNF inhibitors, TGF-[3] inhibitors, mTOR pathway inhibitors, and kynurenic acid and its derivatives). The additional active ingredient(s) may be applied to the target area before, during, and / or after treatment of undamaged skin tissue with a skin-modifying stimulus, and / or before, during, and / or after application of at least one C-glycoside or one of its derivatives to the target area.

[0103] In some embodiments, at least one additional composition, such as, for example, a moisturizer, a sunscreen, and / or anti-aging compositions, may be applied to the target area before and / or after the application of at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives. In various embodiments, at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives are first applied to the target area and are not removed before the application of at least one additional skin composition. In another embodiment, at least one additional skin composition is first applied to the target area and is not removed before the application of at least one C-glycoside or one of its derivatives or at least one vitamin B3 and one of its derivatives.

[0104] If desired, any of the disclosed steps or processes may be repeated one or more times, using the same or a different skin-modifying stimulus, and / or the same C-glycoside or one of its derivatives and / or vitamin B3 and one or a different derivative. In case of difference, the Treatment with a skin-modifying stimulus can vary in any way; for example, it can use different skin-modifying stimuli, it can use the same stimulus but for a different duration, etc. Similarly, the application of a C-glycoside or derivative can vary in any way; for example, it can use different C-glycosides, it can use the same C-glycoside but at different concentrations, etc. Likewise, the application of vitamin B3 or one of its derivatives can vary in any way; for example, it can use different vitamin B3s, it can use the same vitamin B3 but at different concentrations, etc.

[0105] For example, a method may include repeating the treatment with the skin-modifying stimulus once or more before and / or after applying at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives to the target area, where the treatments with the skin-modifying stimulus may be identical or different. Another example of a method may include the repeated application of at least one C-glycoside or one of its derivatives and / or at least one vitamin B3 or one of its derivatives to the target area once or more before and / or after the treatment with the skin-modifying stimulus, where the C-glycoside or derivative may be identical or different and / or the vitamin B3 or derivative may be identical or different.

[0106] By way of further, non-limiting example, a first skin-modifying stimulus may be a laser, where the first treatment is a 1470 nm Sciton Halo laser procedure, and a second skin-modifying stimulus may be an abrasive element, where the second treatment is a microdermabrasion procedure. As yet another, non-limiting example, a first skin-modifying stimulus may be a laser, where the first treatment is a Clear+Brilliant® laser procedure, and a second treatment may be a second Clear+Brilliant® laser procedure.

[0107] In yet another example, a first step of applying at least one C-glycoside or one of its derivatives to the skin of an individual before surgery, before, during, and / or after treatment of the skin with at least one skin-modifying stimulus; then, after the individual's surgical wound has healed for 7 days, a second step of applying at least one C-glycoside or one of its derivatives to the skin tissue formed at the wound site before, during, and / or after treatment of the skin tissue with at least one skin-modifying stimulus, wherein one or both of the C-glycoside or one of its derivatives and the skin-modifying stimulus in the first and second steps are the same or different. Similarly, in yet another example, a first step of applying at least one vitamin B3 or one of its derivatives to the skin of an individual before surgery, before, during and / or after treatment of the skin with at least one skin-modifying stimulus; then, after the individual's surgical wound has healed for 7 days, a second step of applying at least one vitamin B3 or one of its derivatives to the skin tissue formed at the wound site before, during and / or after treatment of the skin tissue with at least one skin-modifying stimulus, in which either one of the vitamin B3 or one of its derivatives and the skin-modifying stimulus or both in the first and second steps are the same or different.

[0108] By way of further non-limiting example, a method may be a method for treating skin tissue to improve the appearance of the skin, wherein a first skin-modifying stimulus is a laser and the first treatment is a Clear+Brilliant® laser procedure, and a second skin-modifying stimulus is an abrasive element where the second treatment is a microdermabrasion procedure, with application of at least one C-glycoside or one of its derivatives to the target area before, between, during, and / or after the first and second treatments, where the C-glycoside or one of its derivatives in each application is the same or different, and with application of at least one vitamin B3 or one of its derivatives to the target area before, between, during, and / or after the first and second treatments, where the vitamin B3 or one of its derivatives in each application is the same or different.

[0109] A person skilled in the art will appreciate, on the basis of the foregoing, that many additional variations of the treatment regimes according to the disclosure are envisaged as falling within the scope of the disclosure.

[0110] In this application, the use of the singular includes the plural, unless specifically stated otherwise. Thus, the terms "a," "an," "the," and "the" are understood to mean both singular and plural; therefore, "a skin-modifying stimulus" is to be understood as "at least one skin-modifying stimulus," unless expressly stated otherwise. In this application, the use of "or" means "and / or" unless otherwise stated. Furthermore, the use of the term "including," as well as other forms such as "includes" and "included," is not restrictive. Similarly, terms such as "element" or "component" encompass both elements and components comprising a single unit and elements and components comprising more than one unit, unless specifically stated otherwise.

[0111] The term “and / or” should be understood as including both connective and disconnective and expressly covers cases of either. For example, the application of a C-glycoside or one of its derivatives to a target area “before and / or after” treatment with a skin-modifying stimulus includes the application of a C-glycoside or one of its derivatives to a target area before treatment with a skin-modifying stimulus and after treatment with a skin-modifying stimulus. the skin, as well as the application of a C-glycoside or one of its derivatives to a target area before treatment with a skin-modifying stimulus or after treatment with a skin-modifying stimulus.

[0112] As used herein, the expression "at least one" means one or more and thus includes individual components as well as mixtures / combinations.

[0113] 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 given that would be reasonably deduced based on ordinary competence 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. Thus, a range of "1% to 10%, such as 2% to 8%, such as 3% to 5%", is intended to encompass ranges of "1% to 8%", "1% to 5%", "2% to 10%", and so on.All figures, quantities, ranges, etc., are assumed to be modified by the term "approximately," whether or not it is explicitly stated. Similarly, a given range of "approximately 1% to 10%" is assumed to have its bounds of both 1% and 10% modified by the term "approximately." The term "approximately" 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%, + / - 1%, + / - 0.5%, + / - 0.1%, or + / - 0.01%.

[0114] As used herein, the expressions "ranging from" and "between" include the bounds of the range(s) cited.

[0115] As used herein, all ranges provided are intended to include each specific range within the given ranges, as well as a combination of intermediate subranges. Thus, a range from 1 to 5 specifically includes 1, 2, 3, 4, and 5, as well as subranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc. All ranges and values ​​disclosed herein are inclusive and combinable. For example, any value or point described herein that lies within a range described herein may serve as a minimum or maximum value for deducing a subrange, etc.

[0116] The term "comprising" (and its grammatical variations) as used here is used in the inclusive sense of "having" or "including" and not in the exclusive sense of "consisting solely of".

[0117] As used herein, "topical application" (and its grammatical variations) refers to the application of the disclosure compositions to keratinous substrates such as skin.

[0118] As used herein, "reduce" or "improve" the appearance of the skin means that the skin would show more signs of aging than in the absence of treatment according to processes disclosed herein.

[0119] As used herein, "reduce" inflammation means that, although inflammation may occur, its appearance to the naked eye is less visible or noticeable than after treatment with a skin modification technique in the absence of treatment according to the processes disclosed herein, or that the presence of inflammatory markers is less than it would have been after treatment with a skin modification technique in the absence of treatment according to the processes disclosed herein.

[0120] Unless expressly stated otherwise, no process presented herein is intended to be interpreted as requiring its steps to be performed in a specific order. Accordingly, where a process claim does not expressly state that its steps must be followed in any particular order, 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.

[0121] The compositions and processes of the present invention may include, consist of, or consist essentially of the essential elements and limitations of the disclosure described herein, together with any additional or optional ingredients, components or limitations described herein or otherwise useful.

[0122] As several embodiments have been described above, disclosure may be better understood by reference to examples. The following examples are provided by way of illustration only and should in no way be construed as limiting. EXAMPLES

[0123] The following examples are intended to be non-limiting and explanatory in nature only.

[0124] Example 1: Cell cultures

[0125] Surgical skin samples were taken from adults and subjected to the 0.25% trypsin dermis / epidermis separation procedure described in Rheinwald to obtain suspensions of normal human epidermal keratinocytes (NHK) and dermal fibroblasts. See Rheinwald JG, Green H.: Serial cultivation of strains of human epidermal keratinocytes: The formation of keratinizing colonies from single cells. Cell. 6(3):331-43. 1975. The separated normal human dermal fibroblasts were cultured in DMEM + 10% fetal bovine serum. The fibroblasts were cast onto a lower layer of proto-SoftSkin gel. ™. NHEK cell cultures were initiated using the 3T3 feeder layer technique described in Rheinwald JG, Green H.: Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature 265:421-424 (1977). Example 2#: Inflammation model

[0126] Fibroblasts as disclosed in Example 1 were stimulated with FIL-la and treated with proxylane (1 mM, 3 mM) and niacinamide (vitamin B3) (0.3 mM and 1 mM) alone and in combination to simulate in vitro inflammation. The amount of PGE2 secreted was quantified. The results are shown in [Fig. 1]. It can be observed that 1 mM vitamin B3 and 3 mM proxylane synergistically reduce PGE2 secretion in inflamed cell cultures, compared to vitamin B3 or proxylane alone, and to a similar degree to the anti-inflammatory drug dexamethasone (30 pM). Example 3#: aSMA expression

[0127] Fibroblasts as disclosed in Example 1 were treated with proxylane (0.005%, 0.017%, 0.05%) and niacinamide (0.0012%, 0.004%, and 0.012%) alone and in combination and stained for α-SMA by in situ immunostaining. Expression was quantified by image analysis. The results are shown in [Fig. 2]. It can be observed that vitamin B3 and proxylane synergistically increase α-SMA expression in fibroblast cells, compared to vitamin B3 or proxylane alone. The results demonstrate the ability of vitamin B3 and proxylane to stimulate the expression of a-SMA in fibroblasts, and thus the combination demonstrates the benefits of wound contraction and the ability to increase the differentiation of fibroblasts into myofibroblasts in the tissue regeneration process. Example 4#: Proliferation

[0128] NHEKs as disclosed in Example 1 were treated with proxylane (0.005%, 0.017%, and 0.05%) and niacinamide (0.0012%, 0.004%, and 0.012%) alone and in combination. Keratinocytes were stained with Ki67, and expression was quantified. The results are shown in [Fig. 3]. Vitamin B3 and proxylane have been shown to stimulate keratinocyte cell proliferation alone or in combination. It can be observed that 0.012% vitamin B3 and 0.05% proxylane synergistically increase α-SMA expression in keratinocytes. Example 5#: Releasing sGAG

[0129] The entire thickness of the reconstructed skin (Episkin T-Skin) as disclosed in Example 1 was systematically treated with proxylane (3 mM) and niacinamide (200 µM) alone and in combination. The release of SGAG into the supernatant was quantified. The results are shown in [Fig. 4]. It can be observed that proxylane alone and in combination with vitamin B3 significantly increases sGAG secretion in fibroblasts. Example 6#:

[0130] PGE-2-induced inflammation and melanin synthesis

[0131] Normal human epidermal melanocytes - dark pigment (lot 1981687, passage 3, ThermoFisher, Waltham, MA) were seeded in 6-well plates at a density of 100,000 cells per well. The cells were incubated in culture medium supplemented with Gibo Human Melanocyte Growth Supplement-2 (ThermoFisher, Waltham, MA). Once 70–80% confluence was achieved, the cell culture medium was removed and replaced with a medium containing processing conditions as shown below: • Untreated control • 30 nM of PGE2 • 30 nM of PGE2+ 6 mM of TXA (positive control) • 30 nM PGE2 + 10 mM (0.12%) niacinamide • 30 nM of PGE2+ 10 mM (0.19%) of Proxylan • 30 nM of PGE2+ 10 mM (0.12%) of Niacinamide + 10 uM (0.19%) of Proxylane

[0132] Cells were cultured for 10 days with treatment, with the treatment medium being renewed every two days except on weekends. After 10 days, the cells were trypsinized, and melanin was isolated using NaOH. A standard curve using commercially available melanin was used to calculate the mean cellular melanin content using the optical density recorded from the isolated melanin with a microplate reader. The mean cellular melanin content was normalized to the total protein content. The results in [Fig. 10] demonstrate that vitamin B3 alone and in combination with proxylane significantly decreases melanin production, demonstrating the efficacy of the ingredients in preventing inflammation-induced melanogenesis in PGE2-stimulated melanocytes. Example 7#: Neutrophil elastase inhibition assay

[0133] A neutrophil elastase inhibition assay was performed according to the manufacturer's instructions (MAK213, Sigma-Aldrich, MO). A 4x sample inhibitor solution (test compounds) was prepared, as well as inhibitor control, enzyme control (PBS), neutrophil elastase, and substrate solutions. The test compounds (proxylan, vitamin B3, and proxylane + vitamin B3), controls, and neutrophil elastase were added to a 96-well plate, protected from light, and incubated at 37 °C for 5 minutes. The substrate was then added, and fluorescence (FLU, Xex = 400 nm, Xem = 505 nm) was recorded every minute for thirty minutes at 37 °C. The slope of the trace (time versus FLU) was recorded. The relative inhibition was calculated as follows: % d mndEHtim! re / atîw = | t—-— -----------------x 1ÛO

[0134] The results are shown in [Fig. 5]. The results demonstrate that vitamin B3 and proxylane, alone and in combination, inhibit elastase activity. It can be observed that vitamin B3 and proxylane synergistically inhibit elastase, compared to vitamin B3 or proxylane alone. Example 8#: Ex Vivo microneedling model

[0135] Fresh samples of normal human skin following abdominoplasty were obtained from BioIVT Inc. (Westbury, NY). The tissue was degreased and cleaned of residual blood. The tissue was then subjected to 5 passes using a microneedling pen (36-pin needles, Dr. Pen A6 Cartridge Tips, Dr. Pen Inc., San Jose, CA, USA) with a needle length of 1.5 mm. Following treatment, 1.2 cm diameter skin biopsies were created and cultured at the air-liquid interface. Skin expiants not subjected to microneedling served as an untreated control group. Control and microneedle control samples were cultured in Dulbecco's modified Eagle medium (650 pL per well, DMEM with 10% fetal bovine serum and 1% penicillin-streptomycin) at 37°C and 5% CO2.Treated microneedle samples (MN+Proxylane / Niacinamide) were cultured in DMEM with 10% fetal bovine serum, 1% penicillin-streptomycin, 0.0009% proxylane, and 0.2% niacinamide. The medium was changed every two days except on weekends. Following a 6-day culture period, all biopsies were processed for histological and immunohistochemical analysis. Skin expiants were processed for hematoxylin and eosin (H&E) staining and immunohistochemical staining for filaggrin and TGM1 according to the standard protocol (Histowiz, Brooklyn, NY).

[0136] The results are shown in [Fig. 6]. It can be observed that vitamin B3 and proxylane increase the expression of filaggrin and TGM1 after microneedling procedures. Thus, the results demonstrate that vitamin B3 and proxylane increase barrier regeneration and renewal and accelerate epidermal renewal and differentiation. Example 9#: Non-ablative laser study

[0137] An 8-week, controlled, randomized, double-blind, half-face study was conducted to evaluate skin repair and anti-aging efficacy of the disclosed topical compositions compared to a reference after non-ablative whole-face laser treatment.Healthy subjects with (a) mild to severe global facial skin dyschromia (dark spots / sun spots on the face) (score of 3.5 to 8 on a modified Griffith scale of 0 to 9), with a difference < 1 between the left and right sides of the face, (b) mild to severe visual roughness of the skin (score of 3.5 to 8 on an internal scale of 0 to 9), with a difference < 1 between the left and right sides of the face, and (c) mild to severe crow's feet wrinkles (score of 2 to 5.6 on the L'Oréal Atlas of Signs of Aging scale of 0 to 6, Caucasian or Asian) on both sides of the face, with a difference < 1 between the left and right sides of the face, were included in the study.

[0138] A laser specialist under the supervision of a Board-certified dermatologist performed full-face non-ablative fractional laser treatment on the test subjects, as well as post-laser assessments. Composition A, disclosed in Table 1 below, and Composition B, Aquafor Healing Ointment, were applied randomly to different sides of the face in a double-blind manner immediately after laser treatment. The compositions were applied twice daily for 56 days following laser treatment.

[0139] [Tables 1] Concentration % NIACINAMIDE 3 SODIUM HYALURONATE 0.02 PEG-100 STEARATE 0.4 SODIUM POLYACRYLATE 0.8 GLYCERYL STEARATE 0.4 BEESWAX / CERA ALBA 2.73 BEHENYL ALCOHOL 0.6 DIMETHICONE 2.5 ARACHIDYL ALCOHOL 1.1 ISONONYL ISONONANOATE 1.0 ADENOSINE 0.04 STEARIC ACID 0.795 PALMITIC ACID 0.66 MYRISTIC ACID 0.045 HYDROXYPROPYL TETRAHYDROPYRANTRIOL 10.01 ARACHIDYL GLUCOSIDE 0.3 ADDITIVES (thickeners, preservatives, vitamins, oils, hydrating agents, ceramides, pH adjusters, emulsifiers, sunscreens, chelating agents, etc.) < 10 SOLVENTS (water and non-aqueous solvents) Qs per 100 Composition A

[0140] Following the 56-day trial period, experts evaluated and rated the efficacy of the topical compositions in promoting skin repair and improving skin dyschromia and signs of aging, as well as maintaining resurfacing effects when used after non-ablative fractional laser facial resurfacing treatment on healthy subjects through clinical evaluation. Figure 7 shows clinical assessments of the skin healing process (Days 14, 28, and 56) separately on each side of the face (left, right) using the following objective anti-aging efficacy parameters: overall wrinkles, overall healthy appearance, skin radiance, skin roughness, overall skin dyschromia, and overall fine lines. The combination of vitamin B3 and proxylane significantly improved overall wrinkles, fine lines, skin dyschromia, skin roughness, and overall skin health.The combined treatment also demonstrated efficacy in improving skin redness. Furthermore, the non-ablative laser routine with proxylane and vitamin B3 provided faster and better laser treatment benefits compared to laser alone. Figures 8 and 9 show VISIA digital facial photographs of each subject (JO and J56) (left 45, right 45) demonstrating improvements in overall wrinkles, fine lines, skin dyschromia, skin roughness, and overall skin health in the skin treated with vitamin B3 and proxylane.

Claims

Demands

1. Combination of at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives for use in improving the appearance of the skin, the application of the combination following treatment of the skin with at least one skin-modifying stimulus

2. Combination for its use according to claim 1, wherein the application of the combination takes place within approximately 60 days after treatment of the skin with at least one skin-modifying stimulus.

3. Combination for use according to any one of the preceding claims, wherein at least one C-glycoside is selected from C13-D-xylopyranoside-n-propan-2-one; Ca-D-xylopyranoside n-propan-2-one; C13-D-xylopyranoside-2-hydroxypropane; Ca-D-xylopyranoside-2-hydroxypropane; 1-(C13-D-fucopyranoside)-propane-2-one; 1-(Ca-D-fucopyranoside)-propan-2-one; 1-(C13-L-fucopyranoside)-propan-2-one; 1-(Ca-L-fucopyranoside)-propane-2-one; 2-one, 1-(C13-D-fucopyranoside)-2-hydroxypropane; l-(Ca-D-fucopyranoside)-2-hydroxypropane; l-(C13-L-fucopyranoside)-2-hydroxypropane; l-(Ca-L-fucopyranoside)-2-hydroxypropane; l-(C13-D-glucopyranosyl)-2-hydroxypropane; l-(Ca-D-glucopyranosyl)-2-hydroxypropane; l-(C13-D-galactopyranosyl)-2-hydroxypropane; l-(Ca-D-galactopyranosyl)-2-hydroxypropane-l-(C13-D-fucofuranosyl)propan-2-one; l-(Ca-D-fucofuranosyl)-propan-2-one; 1-(C13-L-fucofuranosyl)-propan-2-one; l-(Ca-L-fucofuranosyl)-propan-2-one;C13-D-maltopyranoside-n-propan-2-one-Ca-D-maltopyranoside-n-propan-2-one-C13-D-maltopyranoside-2-hydroxypropane; Ca-D-maltopyranoside-2-hydroxypropane; their derivatives, or combinations thereof.

4. Combination for use according to any one of the preceding claims, wherein at least one vitamin B3 comprises niacin (nicotinic acid), niacinamide (nicotinamide), nicotinamide riboside, or combinations thereof.

5. Combination for use according to any one of the preceding claims, wherein at least one vitamin B3 comprises niacinamide.

6. Combination for use according to any one of the preceding claims, wherein the composition comprising at least one C-glycoside or one of its derivatives and the composition comprising at least one vitamin B3 or one of its derivatives are applied simultaneously.

7. Combination for use according to any one of the preceding claims, wherein the C-glycoside(s) and its / their derivatives and the vitamin(s) B3 and its / their derivatives are mixed, and wherein said mixture is applied to skin treated with at least one skin-modifying stimulus.

8. Combination for use according to any one of the preceding claims, wherein the weight ratio between the total amount of the C-glycoside(s) and its / their derivatives and the total amount of vitamin B3 and its derivatives applied to the skin ranges from about 0.001:1 to about 10:1, from about 0.005:1 to about 8:1, from about 0.01:1 to about 6:1, from about 0.05:1 to about 4:1, from about 0.1:1 to about 2:1 or from about 0.5:1 to about 1.5:1 in the mixture.

9. Composition comprising: (i) at least one C-glycoside or one of its derivatives, wherein the total amount of C-glycosides and their derivatives present in the composition ranges from about 0.01% to about 50%, preferably from about 0.025% to about 40%, from about 0.05% to about 30%, from about 0.1% to about 20%, from about 0.2% to about 15%, from about 0.3% to about 12%, from about 0.4% to about 11%, from about 0.5% to about 10%, from about 0.6% to about 9%, from about 0.7% to about 8%, from about 0.8% to about 7%, from about 0.9% to about 6%, or from about 1% to about 5%, most preferably from about 2% to about 4% in weight, relative to the total weight of the composition, (ii) at least one vitamin B3 or one of its derivatives, in which the total amount of vitamin B3 and its derivatives present in the composition ranges from about 0.0001% to about 50%, preferably from about 0.0005% to about 45%, or from about 0.001% to about 40%from approximately 0.0025% to approximately 35%, from approximately 0.005% to approximately 30%, from approximately 0.0075% to approximately 25%, from approximately 0.01% to approximately 20%, from approximately 0.025% to approximately 15%, from approximately 0.05% to approximately 10%, from approximately 0.075% to approximately 8%, from approximately 0.1% % to about 7%, about 0.25% to about 6%, about 0.5% to about 5%, or about 1% to about 4% by weight, such as about 1% to about 19%, about 2% to about 18%, about 3% to about 17%, such as about 4% to about 16%, about 5% to about 15%, about 6% to about 14%, about 7% to about 13%, or about 8% to about 12%, most preferably about 9% to about 11% by weight, relative to the total weight of the composition, (iii) panthenol, and (iv) at least one vector.

10. Composition according to claim 9, wherein the weight ratio between the total amount of C-glycosides and their derivatives and the total amount of vitamin B3 and its derivatives ranges from about 0.001:1 to about 10:1, from about 0.005:1 to about 8:1, from about 0.01:1 to about 6:1, from about 0.05:1 to about 4:1, from about 0.1:1 to about 2:1, or from about 0.5:1 to about 1.5:1.

Images