COMPOSITIONS AND METHODS FOR SKIN TREATMENT

Abstract

SKIN TREATMENT COMPOSITIONS AND METHODS The disclosure relates to compositions and methods for improving the appearance of skin. The methods comprise treating skin tissue with at least one C-glycoside or derivative thereof, at least one vitamin B3 or derivative thereof and at least one skin-modifying stimulus, and the compositions comprise at least one C-glycoside or derivative thereof and / or at least one vitamin B3 or derivative thereof. Figure for abstract: none

Description

Title of the invention: COMPOSITIONS AND METHODS FOR TREATING SKIN Technical field

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

[0002] Non-surgical cosmetic procedures that remove portions of the epidermis can accelerate the renewal of the skin's surface. For example, clinicians may use skin-modifying techniques such as laser treatments and chemical peels to improve the appearance of the skin. Typically, skin treated with such lasers and peels undergoes 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 approximately one 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 inflammation-associated hyperpigmentation caused by lasers and other resurfacing treatments are thought to be caused, in part, by local increases in the concentration of reactive oxygen species (ROS), which stimulate mitogen-activated protein (MAP) kinases 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 glycosaminoglycan (sGAG) further mediates dermal regeneration, including wound contraction, after such skin procedures. SGAGs stimulate myofibroblasts in granulated tissue to close wounds by strong contraction forces caused in part by contraction of α-actin smooth muscle (a-SMA). Increased secretion of sGAG in turn inhibits neutrophil elastase activity, signifying protection of the extracellular matrix (ECM). Ki-67 protein (also known as MKI67) has also been shown to be present during cell proliferation. Altering the expression and secretion of these markers has the potential to improve skin healing.

[0005] Many individuals wish to improve the outcome of their aesthetic procedures. Thus, there is a continued need for improved skin treatments that mediate these signaling pathways, thereby reducing skin inflammation and discoloration and improving skin healing. The development of improved outcomes for aesthetic procedures is important to improve the quality of the results of these treatments and avoid potential unwanted 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 benefit in enhancing epidermal and dermal renewal, and are particularly effective in providing benefits in the management of inflammation and / or pigmentation to the skin, for example following various skin procedures. SUMMARY

[0007] The present disclosure relates to methods for improving skin renewal and recovery after an aesthetic procedure and compositions used therein. The combination of C-glycosides and their derivatives and at least one vitamin B3 or derivative thereof has been found to synergistically improve wound contraction and cell proliferation, and also reduce inflammation associated with melanin production, increase sGAG release and inhibition of elastase activity, and stimulate barrier formation after an aesthetic procedure. The clinical improvements in dyschromia and redness were surprisingly maintained for up to 2 months.

[0008] The compositions according to the disclosure comprise at least one C-glycoside or one of its derivatives and at least one vitamin B3 or one of its derivatives, and the methods 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 treatment of the skin using a skin-modifying stimulus.

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

[0010] In various embodiments, the disclosure relates to methods of treating skin, including improving the appearance of skin, comprising applying at least one C-glycoside or derivative thereof and at least one vitamin B3 or derivative thereof to the skin in combination with treatment with a skin-altering stimulus. For example, in some embodiments, the disclosure relates to methods of improving the appearance of skin, the methods comprising:

[0011] (a) treating the skin with at least one skin-altering stimulus,

[0012] (b)(l) applying 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 methods of preventing or reducing adverse effects of aesthetic skin procedures, such as by improving the results of aesthetic skin procedures, such as skin resurfacing treatments comprising applying at least one C-glycoside or derivative thereof and at least one vitamin B3 or derivative thereof to skin tissue prior to skin injury, e.g., prior to an aesthetic procedure, in combination with a skin modification stimulation treatment. For example, in some embodiments, the disclosure relates to methods of preventing or reducing skin inflammation, the methods comprising:

[0015] (a) treating the skin with at least one skin-altering stimulus,

[0016] (b)(l) applying 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 methods of treating skin to prevent or reduce the formation of skin discoloration after cosmetic procedures, the methods comprising:

[0019] (a) treating the skin with at least one skin-altering stimulus,

[0020] (b)(l) applying 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, the at least one C-glycoside or derivative thereof and the at least one vitamin B3 or derivative thereof may be applied to the skin tissue during treatment with a skin-modifying stimulus. In other embodiments, the at least one C-glycoside or derivative thereof and the at least one vitamin B3 or derivative thereof may be applied to the skin tissue before and / or after treatment with a skin-modifying stimulus, for example, within a few seconds, about 1 minute, or about 1 hour before and / or after treatment of the skin with a skin-modifying stimulus, within about 6 hours, about 12 hours, about 18 hours, or about 24 hours before and / or after treatment of the skin with a skin-modifying procedure.In various embodiments, the at least one C-glycoside or derivative thereof and the at least one vitamin B3 or derivative thereof may be applied to the skin tissue one or more times per day, for example 2 times per day, 3 times per day, or more.In other embodiments, the at least one C-glycoside or derivative thereof and the at least one vitamin B3 or derivative thereof may be applied to the skin tissue at least once daily 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 methods of the disclosure may be repeated one or more times, e.g., daily, 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 with an at-home or clinical-grade skin modification treatment.

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

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

[0025] (b)(l) applying a composition comprising C13-D-xylopyranoside-2- hydroxypropane on the modified skin tissue within about 6 hours after step (a), wherein C13-D-xylopyranoside-2-hydroxypropane is present in the composition in an amount of 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%, based on the total weight of the composition, and

[0026] (b)(2) applying a composition comprising niacianmide to skin tissue modified within 6 hours of step (a), wherein the niacinamide is present in the composition in an amount of 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, based on the total weight of the composition,

[0027] in which compositions (b)(l) and (b)(2) are preferably applied 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), wherein compositions (b)(l) and (b)(2) are applied at least once a day, wherein all amounts 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)(l) 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 a period of approximately 60 days after step (a) of treating the skin with at least one skin-modifying stimulus.

[0029] In various embodiments of the method 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) in color will be provided by the Office upon request and upon 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 accompanying figures.

[0032] [Fig-1] [Fig.l] shows the secretion of PEG2 in non-fibroblast cultures treated (negative control) and IL-1α-stimulated fibroblast cultures (positive control) including cultures additionally 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 a-SMA in untreated fibroblast cultures (negative control) and fibroblast cultures and in cultures additionally treated with 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 Ki67 protein (KL67 or MKI67 antigen) in fibroblast cultures (negative control) and in cultures additionally 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 epidermal tissues of the T-Skin Softskin™ model day before and after laser ablation, and in tissues additionally treated with hydroxypropyl tetrahydropyrantriol (PX), niacinamide (NAM), or a combination of hydroxypropyl tetrahydropyrantriol and niacinamide.

[0036] [Fig.5] [Fig.5] shows a percentage 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 of fresh, defatted, and blood-free normal human skin samples after abdominoplasty that were subjected to microneedling (“microneedling” or “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 overall wrinkle, fine line, skin dyschromia, skin roughness and general skin health parameters classified by experts at day 14 (D14), day 28 (D28) and day 56 (D56) after the laser procedure for a subject treated with hydroxypropyl tetrahydropyrantriol (proxylan) and niacinamide.

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

[0040] [Fig.9] [Fig.9] shows photographs of laser-treated skin immediately after surgery, and 56 days after surgery with hydroxypropyl tetrahydropyrantriol (PX) and niacinamide (NAM) treatment or Aquafor Healing Ointment treatment (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 additionally 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 enhancing 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 skin injury, for example before a laser treatment or microdermabrasion procedure.

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

[0044] The methods according to various embodiments comprise treating skin tissue with at least one skin-altering stimulus and applying at least one C-glycoside or a derivative thereof, e.g., a C-xylopyranoside or a derivative thereof, e.g., hydroxypropyl tetrahydropyrantriol, and at least one vitamin B3 or a derivative thereof, e.g., niacinamide to the skin tissue. In other embodiments, the methods comprise treating uninjured skin with at least one skin-altering stimulus and applying at least one C-glycoside or a derivative thereof, e.g., a C-xylopyranoside or a derivative thereof, e.g., hydroxypropyl tetrahydropyrantriol, and at least one vitamin B3 or one of its derivatives, e.g., niacinamide on the skin, to prevent or reduce inflammation and / or discoloration of the skin after treatment with the skin modifying 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 may 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] As such, the compositions and methods of the disclosure surprisingly address the problem of skin inflammation and discoloration in a new and previously unknown manner, via a mechanism different from that of known methods. By treating skin tissue with a skin-altering stimulus and applying at least one C-glycoside or derivative thereof and at least one vitamin B3 or derivative thereof to the targeted area, the proliferation of new normal skin tissue, rather than inflamed and / or discolored tissue, is encouraged.

[0047] Surprisingly, it has been found that in certain embodiments, the disclosed skin treatment and inflammation prevention methods and compositions provide broader and / or stronger benefits in treating and preventing 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, methods and kits for treating skin and skin 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 vitamins B3 or their derivatives, and additives typically found in skin care compositions.

[0050] A C-glycoside is a sugar moiety linked via a carbon-carbon (CC) bond to a non-sugar moiety (aglycone). In various embodiments, the C-glycoside may 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; as well as their derivatives or mixtures.

[0051] In various embodiments, the 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-xylopyranoside2-hydroxypropane (also known as hydroxypropyl tetrahydropyrantriol or Proxylane). Hydroxypropyl tetrahydropyrantriol has the structure of formula (I) below: OH

[0052] According to various embodiments, the compositions according to the disclosure may comprise a total amount of C-glycoside and its derivatives of 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 subranges using any of the lower limits disclosed as the lower limit and the upper limits disclosed as the upper limit, based on 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%. about 3.5%, about 3.75%, about 5%, about 5.25%, about 5.5%, about 5.75%, about 6%, about 6.25%, about 6.5%, about 6.75%, about 7%, about 7.25%, about 7.5%, about 7.75%, about 8%, about 8.25%, about 8.5%, about 8.75%, about 9%, about 9.25%, about 9.5%, about 9.75%, about 10%, about 10.5%, about 11%, about 11.5%, about 12%, about 12.5%, about 13%, about 13.5%, about 14%, about 14.5%, about 15%, about 15.5%, about 16%, about 16.5%, about 17%, about 17.5%, about 18%, about 18.5%, about 19%, about 19.5%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29% or about 30% by weight, including all intermediate ranges and sub-ranges, using any of the amounts indicated as a lower or upper limit,relative to the total weight of the composition in which it is present.

[0053] In various embodiments, the at least one vitamin B3 or one of its derivatives is selected from niacin (nicotinic acid), niacinamide (nicotinamide), nicotinamide riboside, their derivatives or their mixtures. In various embodiments, the 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 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 using any of the disclosed lower limits as the lower limit and the disclosed upper limits as the upper limit, based on the total weight of the composition in which it is present. For example, the total amount of vitamin B3 and its derivatives in the compositions according to the disclosure may be about 0.0001%, about 0.0005%, about 0.001%, about 0.0025%, about 0.005%, about 0.0075%, about 0.01%, about 0.025%, about 0.05%, about 0.075%, about 0.1%, about 0.25%, about 0.5%, about 0.75%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 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 amounts indicated as a lower limit or an upper limit, based on the total weight of the composition in which it is present.

[0055] In some embodiments, the compositions according to the disclosure comprise 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-iso-propyl ether, diethylene glycol mono-iso-propyl 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-iso-propyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol mono-n-propyl ether and dipropylene glycol mono-iso-propyl 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 selected, and it is contemplated that in various embodiments, the carrier comprises water and at least one non-aqueous solvent. ;

[0057] The compositions may optionally comprise one or more active ingredients other than C-glycosides or their derivatives and vitamin B3 and its derivatives, such as, for 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 including, but not limited to, pantothenic acid, ceramides, pseudoceramides 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; fragrances; surfactants; fillers; natural products or extracts thereof, such as aloe or green tea; vitamins; and / or coloring matters.The amount of such additives, if any, will vary depending on the intended use and / or properties of the composition and the desired effect, but, in individual or combined amounts, 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, based on 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, oligo-galactomannans), 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, oil soy, oleuropeins and their derivatives, phospholipids, beta-carotene, microalgae and algae extracts (including, but not limited to, chlorella vulgaris extract,Dunaliella salina extract), pre- / pro- / postbiotics (including but not limited to Lactococcus fermentation lysate, Lactobacillus ferment), flax seed extract, proanthocyanins, anthocyanins, hydroxyacetophenone, lecithin, GHK-Cu peptide, tripeptide-1, copper peptide, GHK-Mn, acetyl tetrapeptides, tripeptide 10, citrulline, palmitoyl hexapeptide-12, palmitoyl tripeptide-1, lipospondin, gexapeptide 11, PKEK, GEKG, SA1-11, tripeptide-3, pentapeptide-18, pentapeptide-3, acetyl octapeptide-1,3, 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 tetrapeptide-7, palmitoyl pentapeptide-4, tropaeolum majus extract, glycoproteins, hyaluronic acid and its derivatives, sh-polypeptide-5, sh-polypeptide-11, sh-oligopeptide-2, sh-polypeptide-6, wheat germ oil, octacosanol, wild yam root extract, bakuchiol, borage oil, geranium oil, protium heptaphyllum oil, hamamelis virginiana extract, citrus medica limonum oil, glutathione, coenzyme Q10, 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, mousses or the like.

[0061] The compositions are generally applied topically and may, in various embodiments, be applied by the consumer as an at-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, based on 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 of 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, based on 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, based on 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 the niacinamide present 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% 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, based on 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 10%, from about 0.9% to about 10%, from about 10 ... % 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 0,0025% 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. The weight ratio of the total amount of the C-glycoside(s) and its derivatives to the total amount of vitamin B3 and its derivatives applied to the skin may range 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. , II. Procedures

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

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

[0067] In methods according to the disclosure, useful skin-altering stimuli include those used in the field of skin care to alter or damage the skin to encourage new growth, generally in a controlled manner. These treatments typically damage the outermost layers of skin tissue to a relatively slight degree, thereby setting in motion the body's natural healing process. These treatments may also stimulate collagen production. Thus, any known method or device for altering or damaging skin tissue may be used in the methods according to the disclosure.For example, in various embodiments, the skin-altering 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 herein, "altered skin tissue" is skin tissue that has been altered or damaged by one or more skin-altering stimuli, and that heals from treatment with the skin-altering stimulus.

[0068] The skin-altering stimulus used in the methods of the disclosure may, in various embodiments, be invasive or non-invasive. By way of non-limiting example, the skin-altering 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-altering 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, may be used. In various embodiments, the target area may 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. The lasers may 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 may 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 uninjured skin tissue to allow new skin growth. Non-limiting examples of mechanical microneedling devices that may be used include SkinPen Precision, MDpen, Skin Stylus, etc.

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

[0072] The target area can also be treated with ultrasound, for example, 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 may also be employed with the disclosed methods. Electroporation uses electricity to intensify the permeability of the skin tissue membrane by creating microscopic channels that open pathways deep within the skin, thereby disrupting the skin tissue.

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

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

[0076] In some embodiments, a chemical agent such as a chemical exfoliation or peeling agent (also known as chemical exfoliation or derma-peel) may be used as a skin-altering stimulus.Examples of non-limiting chemical agents that may be used to treat the target area include chemical agents capable of acting either directly on the peeling 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 exfoliating agents that may be used include compounds involved in exfoliation or degradation of comeodesmosomes, such as aminosulfonic compounds, e.g., 4-(2-hydroxyethyl)piperazine-1-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] As other examples of non-limiting chemical exfoliating agents suitable for use in the compositions according to the disclosure, mention may be made of EDTA and its derivatives, laminaria extracts, O-linoleyl-6-D-gluocose; (3-hydroxy-2-pentylcyclopentyl) acetic acid, glycerol trilactate, S carboxymethyl cysteine, silica-containing salicylate derivatives such as those described in EP 0 796 861, oligofuctases such as those described in EP 0 218 200, agents having effects on transglutaminase such as in patent EP 0 899 330; the extract of the flower of ficus opuntia indica such as Exfolactive® from Silab; 8-hexadecene 1,16-dicarboxylic acid; esters of glucose and vitamin F; or mixtures thereof.

[0079] In some embodiments, the chemical agent(s) may be selected from α-hydroxy acids such as citric, lactic, glycolic, malic, tartaric or mandelic acids; β-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 a derivative thereof will typically remain on the skin, which may or may not be modified skin tissue, for a sufficient period of time to achieve the desired benefits. Thus, it may be preferable to leave the C-glycoside or a derivative thereof on the skin until it penetrates the skin or is removed during ordinary personal hygiene, such as the next time the skin is washed.For example, in some embodiments, the at least one C-glycoside or derivative thereof is left on the skin for a desired period of time, e.g., 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, the at least one C-glycoside or derivative thereof may be left on the skin for a period of time ranging from 5 minutes to 60 minutes, such as 5 minutes to 50 minutes, 5 minutes to 40 minutes, 5 minutes to 35 minutes, 5 minutes to 30 minutes, 5 minutes to 25 minutes, 5 minutes to 20 minutes, 5 minutes to 15 minutes, or 5 minutes to 10 minutes. As a further example, the at least one C-glycoside or derivative thereof may be left on the skin for a period of time ranging from 10 minutes to 60 minutes, such as 10 minutes to 50 minutes, 10 minutes to 40 minutes, 10 minutes to 35 minutes, 10 minutes to 30 minutes, 10 minutes to 25 minutes, 10 minutes to 20 minutes, or 10 minutes to 15 minutes. .

[0081] Vitamin B3 or a derivative thereof will also typically remain on the skin, which may or may not be modified skin tissue, for a sufficient period of time to achieve the desired benefits. Thus, it may be preferable to leave vitamin B3 or a derivative thereof on the skin until it penetrates the skin or is removed during ordinary personal hygiene, such as the next time the skin is washed. For example, in some embodiments, the at least one vitamin B3 or derivative thereof is left on the skin for a desired period of time, e.g., 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, the at least one vitamin B3 or derivative thereof may be left on the skin for a period of time ranging from 5 minutes to 60 minutes, such as 5 minutes to 50 minutes, 5 minutes to 40 minutes, 5 minutes to 35 minutes, 5 minutes to 30 minutes, 5 minutes to 25 minutes, 5 minutes to 20 minutes, 5 minutes to 15 minutes, or 5 minutes to 10 minutes. As a further example, the at least one vitamin B3 or derivative thereof may be left on the skin for a period of time ranging from 10 minutes to 60 minutes, such as 10 minutes to 50 minutes, 10 minutes to 40 minutes, 10 minutes to 35 minutes, 10 minutes to 30 minutes, 10 minutes to 25 minutes, 10 minutes to 20 minutes, or 10 minutes to 15 minutes.

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

[0083] The step of applying a C-glycoside or derivative thereof may comprise 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 comprise applying at least one C-glycoside or derivative thereof to the target area at least once before, at least once during, and / or at least once after treatment with the skin-altering stimulus. For example, the at least one C-glycoside or derivative thereof may be applied to the target area at least once before, at least once during, and at least once after treatment with the skin-altering stimulus treatment.As another example, the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least twice before, at least twice during, and / or at least twice after treatment with the skin-altering stimulus. As yet another example, the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least once, such as at least twice, before treatment with the skin-altering stimulus, and at least once, such as at least twice, after treatment with the stimulus. skin modification. As another further example, the methods comprise applying at least one C-glycoside or derivative thereof to the target area at least once, e.g., at least twice, after treatment with the skin modification stimulus.

[0084] The step of applying a vitamin B3 or derivative thereof may also comprise 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 comprise applying at least one vitamin B3 or derivative thereof to the target area at least once before, at least once during, and / or at least once after treatment with the skin-altering stimulus. For example, the at least one vitamin B3 or derivative thereof may be applied to the target area at least once before, at least once during, and at least once after treatment with the skin-altering stimulus treatment.As another example, the methods comprise applying at least one vitamin B3 or a derivative thereof to the target area at least twice before, at least twice during, and / or at least twice after treatment with the skin-altering stimulus. As yet another further example, the methods comprise applying at least one vitamin B3 or a derivative thereof to the target area at least once, such as at least twice, before treatment with the skin-altering stimulus, and at least once, such as at least twice, after treatment with the skin-altering stimulus. As another further example, the methods comprise applying at least one vitamin B3 or a derivative thereof to the target area at least once, such as at least twice, after treatment with the skin-altering stimulus.

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

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

[0087] In various embodiments, the methods according to the disclosure may 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 any of the above as upper and lower limits to that range of time periods.

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

[0089] In various methods according to the disclosure, the application of at least one C-glycoside or a derivative thereof is accomplished by applying a composition comprising at least one C-glycoside or a derivative thereof, for example, a composition comprising at least one C-xylopyranoside or a derivative thereof, 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 a derivative thereof is accomplished by applying a composition comprising at least one vitamin B3 or a derivative thereof, 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, the at least one C-glycoside or a of its derivatives and the at least one vitamin B3 are combined in a composition and applied simultaneously using methods of the disclosure.

[0090] In at least some embodiments, treatments with the skin-altering stimulus are performed with home devices. As non-limiting examples, microneedling and microdermabrasion may be accomplished with home devices. Such home devices may be sold in kits with compositions comprising at least one C-glycoside or derivative thereof, at least one vitamin B3 or derivative thereof, or combinations thereof, for example, a first composition comprising at least one C-xylopyranoside or derivative thereof, for example, hydroxypropyl tetrahydropyrantriol, and a second composition comprising a vitamin B3 or derivative thereof, for example, niacinamide. Such home devices may be sold in kits with a composition comprising at least one C-glycoside or derivative thereof and at least one vitamin B3 or derivative thereof.

[0091] The methods of the disclosure treat the skin using the skin-altering stimuli according to typical known procedures. Thus, while it is possible to do so, it is not necessary to vary the length, intensity, or other parameters of treatments with the skin-altering stimuli from those currently performed in order to achieve the surprising and unexpected benefits of reducing inflammation and / or improving or reducing skin discoloration of the disclosure. For example, in a typical microdermabrasion procedure, a device having exfoliating crystals is moved over the skin with gentle pressure for a period of about 30 minutes.In a method according to the disclosure where an abrasive element is chosen as the skin modifying stimulus, the same microdermabrasion procedure may be performed and the at least one C-glycoside or derivative thereof and the 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 comprise treating skin tissue by applying at least one C-glycoside or derivative thereof and at least one niacinamide to the skin tissue in connection with treating the skin tissue with a skin-altering stimulus. In various embodiments, the methods comprise:

[0093] (a) treating skin tissue with at least one skin-modifying stimulus skin,

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

[0095] (b)(2) applying 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 occurs before the steps of (b)(1) applying at least one C-glycoside or derivative thereof to the skin tissue, such that the at least one C-glycoside or derivative thereof is applied to the modified skin tissue, and (b)(2) applying at least one vitamin B3 or derivative thereof to the skin tissue, such that the at least one vitamin B3 or derivative thereof is applied to the modified skin tissue. In some embodiments, the step of (b)(l) applying at least one C-glycoside or one of its derivatives to the skin tissue comprises applying a composition comprising at least one C-glycoside 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 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, based on the total weight of the composition. In some embodiments, the step of (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 0.0025% 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% at about 13%, from about 8% to about 12%, or from about 9% to about 11% by weight, based on the total weight of the composition.

[0097] According to other embodiments of the disclosure, the methods comprise applying at least one C-glycoside or one of its derivatives to the skin prior to skin injury, and / or applying at least one vitamin B3 and one of its derivatives to the skin prior to skin injury, for example prior to a surgical procedure. in relation to treating skin with a skin-altering stimulus. In various embodiments, the methods comprise:

[0098] (a) treating uninjured skin with at least one skin-altering stimulus skin,

[0099] (b)(l) applying 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 uninjured skin with at least one skin-modifying stimulus occurs before step (b)(l) of applying at least one C-glycoside or derivative thereof to the uninjured skin, such that the at least one C-glycoside or derivative thereof is applied to modified skin tissue and / or step (b)(2) of applying at least one vitamin B3 or derivative thereof to the uninjured skin, such that the at least one vitamin B3 or derivative thereof 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 the uninjured skin comprises applying a composition comprising at least one C-glycoside or one of its derivatives and at least one carrier to the uninjured skin 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, based on the total weight of the composition. In some embodiments, the step of (b)(2) applying at least one vitamin B3 or one of its derivatives to the uninjured skin comprises applying a composition comprising at least one vitamin B3 or one of its derivatives and at least one carrier to the uninjured 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 about 13%, from about 8% to about 12%, or from about 9% to about 11% by weight, based on the total weight of the composition.

[0102] Optionally, in some embodiments, one or more additional active agents (other than C-glycosides or derivatives thereof and vitamin B3 and derivatives thereof) may be applied to the skin either as part of a composition comprising the at least one C-glycoside or derivative thereof and / or vitamin B3 and derivatives thereof, or separately, including by way of example actives that may 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 may 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 extracts, oligogalactomannan, colloidal oatmeal, hyaluronic acids, probiotics and [3-glucan) and / or actives that can modulate skin fibrosis (including, but not limited to, TNF inhibitors, TGF-[3 inhibitors, mTOR pathway inhibitors and kynurenic acid and derivatives thereof). The additional active agent(s) may be applied to the target area before, during and / or after treatment of the uninjured skin tissue with a skin-modifying stimulus, and / or before, during and / or after application of the at least one C-glycoside or derivative thereof to the target area.

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

[0104] If desired, any of the disclosed steps or methods may be repeated one or more times, using the same or a different skin-modifying stimulus, and / or the same or a different C-glycoside or derivative thereof and / or vitamin B3 and one or a different derivative thereof. In case of difference, the treatment with a skin-modifying stimulus may be different in any way, e.g., it may use different skin-modifying stimuli, it may use the same stimulus but for a different duration, etc. Similarly, if there is a difference, the application of a C-glycoside or derivative may be different in any way, e.g., it may be different C-glycosides, it may be the same C-glycoside but at different concentrations, etc. Similarly, if there is a difference, the application of a vitamin B3 or one of its derivatives may be different in any way, e.g., it may be different B3 vitamins, it may be the same vitamin B3 but at different concentrations, etc.

[0105] For example, a method may comprise repeating the treatment with the skin-modifying stimulus one or more times before and / or after applying the at least one C-glycoside or derivative thereof and / or the at least one vitamin B3 or derivative thereof to the target area, wherein the treatments with the skin-modifying stimulus may be the same or different. Another example method may comprise repeatedly applying at least one C-glycoside or derivative thereof and / or the at least one vitamin B3 or derivative thereof to the target area one or more times before and / or after the treatment with the skin-modifying stimulus, wherein the C-glycoside or derivative may be the same or different and / or the vitamin B3 or derivative may be the same or different.

[0106] As another non-limiting example, a first skin-altering stimulus may be a laser, where the first treatment is a 1470 nm Sciton Halo laser procedure, and a second skin-altering stimulus may be an abrasive element, where the second treatment is a microdermabrasion procedure. As yet another non-limiting example, a first skin-altering 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 a derivative thereof 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 a derivative thereof 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 either or both of the C-glycoside or a derivative thereof 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 a derivative thereof 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, wherein either or both of the vitamin B 3 or one of its derivatives and the skin-modifying stimulus in the first and second steps are the same or different.

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

[0109] Those skilled in the art will appreciate, based on the foregoing, that many additional variations of the treatment regimens according to the disclosure are contemplated as falling within the scope of the disclosure.

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

[0111] The term "and / or" is to be understood to include both the conjunctive and the disjunctive and expressly covers instances of either. For example, application of a C-glycoside or a derivative thereof to a target area "before and / or after" treatment with a skin-altering stimulus includes application of a C-glycoside or a derivative thereof to a target area before treatment with a skin-altering stimulus and after treatment with a skin-altering stimulus. the skin, as well as the application of a C-glycoside or a derivative thereof to a target area before treatment with a skin-modifying stimulus or after treatment with a skin-modifying stimulus.

[0112] As used herein, the term "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, to provide a more concise description, some of the quantitative expressions given herein are not qualified with the term "about." It is understood that, whether the term "about" is used explicitly or not, each quantity given herein is intended to refer to the actual value given, and it is also intended to refer to the approximation to that given value that would be reasonably deduced based on ordinary skill in the art, including approximations due to experimental and / or measurement conditions for that given value. All ranges and quantities given herein are intended to include sub-ranges 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 intended to be modified by the term "approximately," whether or not expressly stated. Similarly, a given range of "approximately 1% to 10%" is intended to have both its 1% and 10% limits modified by the term "approximately." The term "approximately" is used here to indicate a difference of up to + / - 10% of 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 cited range(s).

[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 sub-ranges. Thus, a range of 1-5 specifically includes 1, 2, 3, 4, and 5, as well as sub-ranges 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 falls within a range described herein may serve as a minimum or maximum value to infer a sub-range, etc.

[0116] The term "comprising" (and its grammatical variations) as used herein 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 compositions of the disclosure to keratinous substrates such as the 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 methods disclosed herein.

[0119] As used herein, "reducing" 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 methods 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 methods disclosed herein.

[0120] Unless otherwise expressly stated, it is not intended that any method disclosed herein be construed as requiring that its steps be performed in any specific order. Accordingly, where a method claim does not expressly reciting that an order be followed by its steps or it is not specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is not intended that any particular order be inferred therefrom.

[0121] The compositions and methods of the present invention may comprise, consist of, or consist essentially of the essential elements and limitations of the disclosure described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful.

[0122] Since several embodiments have been described above, the disclosure may be better understood by reference to examples. The following examples are provided for illustration purposes only and should not be construed as limiting in any way. 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 ofhuman 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 calf serum. The fibroblasts were cast on a bottom 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-1a and treated with proxylan (1 mM, 3 mM) and niacinamide (vitamin B3) (0.3 mM and 1 mM) alone and in combination to simulate inflammation in vitro. 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 proxylan synergistically reduce PGE2 secretion in inflamed cell cultures, compared to vitamin B3 or proxylan alone, and to a similar extent as the anti-inflammatory drug dexamethasone (30 μM). Example 3#: Expression of aSMA

[0127] Fibroblasts as disclosed in Example 1 were treated with proxylan (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 proxylan synergistically increase the expression of α-SMA in fibroblast cells, compared to vitamin B3 or proxylan alone. The results demonstrate the ability of vitamin B3 and proxylan 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 proxylan (0.005%, 0.017% and 0.05%) and niacinamide (0.0012%, 0.004% and 0.012%) alone and in combination. Keratinocytes were stained for KI67 and the expression was quantified. The results are shown in [Fig.3]. It was demonstrated that vitamin B3 and proxylan were able to stimulate cell proliferation of keratinocytes alone or in combination. It can be observed that 0.012% vitamin B3 and 0.05% proxylan synergistically increase the expression of a-SMA in keratinocytes. Example 5#: Release of sGAG

[0129] The full 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 the secretion of sGAG 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 into 6-well plates at a density of 100,000 cells per well. The cells were grown in culture medium supplemented with Gibo Human Melanocyte Growth Supplement-2 (ThermoFisher, Waltham, MA). Once 70-80% confluence was reached, the cell medium was removed and replaced with medium containing treatment conditions as demonstrated below: • Untreated witness • 30 nM of PGE2 • 30 nM PGE2+ 6 mM 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 Proxylan

[0132] The cells were cultured for 10 days with treatment with renewal of the treatment medium every other day except 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 average cellular melanin content using the recorded optical density of the isolated melanin using a microplate reader. The average cellular melanin content was normalized to the total protein content. The results in [Fig. 10] demonstrate that vitamin B3 alone and in combination with proxylan significantly decreases melanin production, demonstrating the effectiveness 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, along with the inhibitor control, enzyme control (PBS), neutrophil elastase, and substrate solutions. The test compounds (proxylan, vitamin B3, and proxylan+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 the fluorescence (FLU, Xex = 400 nm, Xem = 505 nm) was recorded every minute for thirty minutes at 37°C. The slope of the plot (time versus FLU) was recorded. 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 proxylan alone and in combination inhibit elastase activity. It can be observed that vitamin B3 and proxylan synergistically inhibit elastase, compared to vitamin B3 or proxylan alone. Example 8#: Ex Vivo Micro-Needling Model

[0135] Fresh samples of normal human skin after abdominoplasty were obtained from BioIVT Inc. (Westbury, NY). The tissue was defatted and cleaned of blood residue. The tissue was then subjected to 5 passes using a microneedling pen (36-pin needles, Dr. Pen A6 Cartridges Tips, Dr. Pen Inc, San Jose, CA, USA) with a needle length of 1.5 mm. Following treatment, skin biopsies of 1.2 cm in diameter were created and cultured at the air-liquid interface. The skin explants not subjected to microneedling served as an untreated control group. Control and microneedle control samples were cultured in Dulbecco's modified Eagle's 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% proxylan, and 0.2% niacinamide. The medium was replaced every other day except for weekends. Following a 6-day culture period, all biopsies were processed for histological and immunohistochemical analysis. Skin explants 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 proxylan increase the expression of filaggrin and TGM1 after microneedling procedures. Thus, the results demonstrate that vitamin B3 and proxylan increase barrier regeneration and renewal and accelerate epidermal renewal and differentiation. Example 9#: Non-ablative laser study

[0137] An 8-week, randomized, double-blind, controlled half-face study was conducted to evaluate the skin repair and anti-aging efficacy of the disclosed topical compositions versus a reference following full-face non-ablative laser treatment.Healthy subjects with (a) mild to severe overall facial skin dyschromia (dark patches / sunspots on the face) (rating 3.5–8 on a modified Griffith scale of 0–9), with a difference < 1 between the left and right sides of the face, (b) mild to severe visual roughness of the skin (rating 3.5–8 on an internal scale of 0–9), with a difference < 1 between the left and right sides of the face, and (c) mild to severe crow's feet wrinkles (rating 2–5.6 on the L'Oréal Atlas of Signs of Aging scale of 0–6, 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 a full-face non-ablative fractional laser treatment on the test subjects, as well as post-laser evaluations. Composition A, disclosed in Table 1 below, and Composition B, Aquafor Healing Ointment, were applied to different sides of the face in a randomized, double-blind manner immediately after the laser treatment. The compositions were applied twice daily for 56 days after the 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, moisturizers, ceramides, pH adjusters, emulsifiers, sunscreen agents, chelators, 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 discoloration and signs of aging, as well as maintaining resurfacing effects when used after non-ablative fractional laser facial resurfacing treatment on healthy subjects by clinical evaluation. [Fig.7] shows clinical evaluations of the skin healing process (D14, D28, and D56) separately on each side of the face (left, right) using the following objective anti-aging efficacy parameters: overall wrinkles, overall healthy appearance, skin brightness, skin roughness, overall skin discoloration, and overall fine lines. The combination of vitamin B3 and proxylane significantly improved overall wrinkles, fine lines, skin discoloration, skin roughness, and overall skin health.The combination treatment also demonstrated efficacy in improving skin redness. In addition, the non-ablative laser routine with proxylane and vitamin B3 conferred faster and better laser treatment benefits compared to laser alone. Figures 8 and 9 show VISIA digital photographs of each subject's face (JO and J56) (left 45 , right 45 ) demonstrating improvements in overall wrinkles, fine lines, skin discoloration, skin roughness, and overall skin health in skin treated with vitamin B3 and proxylane.

Claims

Claims

1. Combination of at least one C-glycoside or one of its derivatives and at least one vitamin B 3 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. A combination for use according to claim 1, wherein the application of the combination takes place within about 60 days after treatment of the skin with at least one skin-modifying stimulus.

3. A combination for use according to any one of the preceding claims, wherein the 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)-propan-2-one; l-(Ca-D-fucopyranoside)-propan-2-one; l-(C13-L-fucopyranoside)-propan-2-one; 2-one,l-(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-hydroxylpropane; l-(Ca-D-glucopyranosyl)-2-hydroxylpropane; l-(C13-D-galactopyranosyl)-2-hydroxylpropane; l-(Ca-D-galactopyranosyl)-2-hydroxylpropane-l-(C13-D-fucofuranosyl)pro pan-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. A combination for use according to any preceding claim, wherein the at least one vitamin B 3 comprises niacin (nicotinic acid), niacinamide (nicotinamide), nicotinamide riboside, or combinations thereof.

5. A combination for use according to any preceding claim, wherein the 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. A combination for use according to any preceding claim, wherein the C-glycoside(s) and its derivative(s) and vitamin B3 and its derivative(s) are mixed, and wherein said mixture is applied to the treated skin with at least one skin-modifying stimulus.

8. A combination for use according to any preceding claim, wherein the weight ratio of the total amount of the C-glycoside(s) and its derivatives to the total amount of vitamin B3 and its derivatives applied to the skin is 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. A composition comprising: (i) at least one C-glycoside or derivative thereof, wherein the total amount of C-glycosides and derivatives thereof present in the composition is 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% by weight, relative to the total weight of the composition, (ii) at least one vitamin B3 or one of its derivatives, wherein 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%, 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, such as from about 1% to about 19%, from about 2% to about 18%, from about 3% to about 17%, such as from about 4% to about 16%, from about 5% to about 15%, from about 6% to about 14%, from about 7% to about 13%, or from about 8% to about 12%, most preferably from about 9% to about 11% by weight, based on the total weight of the composition, (iii) panthenol, and (iv) at least one carrier.

10. The composition of claim 9, wherein the weight ratio of the total amount of the C-glycoside(s) and derivatives thereof to the total amount of vitamin B3 and derivatives thereof is 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.

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