Compositions and processes for improving the appearance of the skin

Abstract

Compositions and methods for improving skin appearance. The disclosure relates to compositions, methods, regimens, and necessities for improving skin appearance by applying acetyl trifluoromethylphenyl valylglycine and at least one exfoliating agent to the skin. Figure for abstract: None

Description

Title of the invention: Compositions and methods for improving the appearance of the skin Technical field

[0001] The disclosure relates to compositions for treating skin, methods for treating skin with skin treatment compositions, and kits containing skin treatment compositions. CONTEXT

[0002] Aging can lead to the appearance of wrinkles and other changes in the skin. The aging appearance of the skin is caused, in part, by the disorganization of elastin and collagen fibers, which leads to a loss of elasticity, flexibility, and firmness.

[0003] Desquamation is a natural phenomenon that slows down or reduces the effects of aging on the skin. It is linked to the fact that the epidermis, which constitutes the upper layer of the skin, is constantly regenerating. The epidermis is made up of several cell layers, the deepest of which is the basal layer composed of undifferentiated cells. Over time, these cells will differentiate and migrate to the surface of the epidermis constituting the different layers of the epidermis, until the corneocytes (dead cells) form an outermost layer, the horny layer (also called stratum corneum), or the surface of the epidermis, which are dead cells that are eliminated by desquamation. This loss of surface is compensated by the migration of cells from the basal layer to the surface of the epidermis, which results in a perpetual renewal of the skin.

[0004] Forced removal of the stratum corneum may accelerate desquamation, accelerate skin surface renewal, slow the effects of skin aging, and / or improve the appearance of the skin. It is known that skin exfoliating agents can remove the stratum corneum. The term "exfoliation" conventionally refers to a controlled action of irritating the skin surface with a chemical substance or via a physical process. A surface exfoliating treatment targets the epidermis and relies on attacking the surface of the skin. It affects the epidermis either partially or entirely. A peeling treatment may consist, for example, of applying a chemical substance (a "chemical exfoliating agent") to the skin in order to cause limited and controlled destruction of the epidermis (and in certain embodiments of the upper layers of the dermis).The treatment may require several applications, and the entire procedure can last from one or a few days to several weeks or months.

[0005] There are many types of skin scrub compositions, both in terms of concentration and the specific scrubbing agent (i.e., the active ingredient) used. For example, α-hydroxy acids such as lactic acid, glycolic acid, or others, and β-hydroxy acids such as salicylic acid and its derivatives, are associated with the activation of desquamation. These agents promote the exfoliation of dead surface cells, which occurs less effectively with age, in order to restore the qualities of the skin surface. Home scrubs generally have lower concentrations of active ingredients (e.g., less than 15% by weight of acids), and therefore primarily affect the most superficial layers of the skin. These scrubs are suitable for treating superficial wrinkles, general skin maintenance, or non-serious skin problems.In contrast, professionally administered scrubs are typically more potent, with higher concentrations of active ingredients (e.g., more than 15% by weight of acids). This allows these scrubs to target deeper levels of the dermis and treat moderate to severe wrinkles and other signs of aging.

[0006] There is a continuing need to improve skin treatments that can increase skin peeling and renewal. It has been surprisingly and unexpectedly discovered that acetyl trifluoromethylphenyl valylglycine acts synergistically with chemical peeling agents to increase peeling and improve skin renewal, and thus improve skin appearance. ABSTRACT

[0007] The present disclosure relates to compositions and methods for treating skin, for example, to stimulate, increase, and / or improve skin renewal. For example, the disclosed treatments may act synergistically to encourage or improve desquamation, while helping to reform a mature barrier through keratinization and higher terminal differentiation. According to certain aspects of the disclosure, methods and compositions for treating skin may advantageously improve skin elasticity and / or reduce the appearance of wrinkles.

[0008] In various embodiments, the disclosure relates to methods of treating skin, for example, the skin of the face, neck, chest and / or hands, the methods comprising applying to the skin (a) acetyl trifluoromethylphenyl valylglycine; and (b) at least one exfoliating agent, which is not limited to, and may be selected from, for example, dermabrasion, microdermabrasion, physical exfoliants and / or chemical agents.

[0009] In various embodiments, the methods comprise applying acetyl trifluoromethylphenyl valylglycine in an amount ranging from about 0.01 to about 25% by weight, preferably from about 0.1 to about 20% by weight, so more preferably from about 0.25 to about 15% by weight, more preferably from about 0.5 to about 10% by weight, on the skin, all amounts being relative to the total weight of the composition in which the acetyl trifluoromethylphenyl valylglycine is present.

[0010] In various embodiments, the at least one chemical peeling agent may be selected from α-hydroxy acids, β-hydroxy acids, trichloroacetic acid, or mixtures thereof. For example, in some embodiments, the methods comprise applying at least one α-hydroxy acid to the skin, present in an amount ranging from about 0.1 to about 20% by weight, preferably from about 0.25 to about 15% by weight, more preferably from about 0.5 to about 10% by weight, more preferably from about 1 to about 5% by weight, or from about 2 to about 4% by weight, from about 4 to about 7% by weight, or from about 13 to about 16% by weight, based on the total weight of the composition in which it is present.In some embodiments, the methods comprise applying to the skin a composition comprising from about 0.1 to about 25% by weight, preferably from about 1 to about 20% by weight, more preferably from about 2 to about 16% by weight, more preferably from about 3 to about 15% by weight, or from about 2 to about 4% by weight, from about 4 to about 7% by weight, or from about 13 to about 16% by weight, of glycolic acid, lactic acid, and / or derivatives thereof.

[0011] In other embodiments, the methods comprise applying to the skin a composition comprising at least one β-hydroxy acid, for example present in an amount ranging from about 0.01 to about 2% by weight, preferably from about 0.05 to about 2% by weight, more preferably from about 0.05 to about 1% by weight, most preferably from about 0.05 to about 0.5% by weight, based on the total weight of the composition in which it is present.In other embodiments, the methods comprise applying to the skin a composition comprising salicylic acid or a derivative thereof, for example in an amount of from about 0.01 to about 2% by weight, preferably from about 0.05 to about 2% by weight, more preferably from about 0.05 to about 1% by weight, most preferably from about 0.05 to about 0.5% by weight, based on the total weight of the composition in which it is present. In still further embodiments, the methods comprise applying to the skin a composition comprising trichloroacetic acid, for example in an amount of from about 1 to about 25% by weight, from about 5 to about 22% by weight, from about 7 to about 20% by weight, from about 10 to about 18% by weight, or from about 12 to about 16% by weight, based on the total weight of the composition in which it is present.

[0012] Exemplary methods according to the disclosure comprise applying (a) acetyl trifluoromethylphenyl valylglycine to the skin before and / or after (b) at least one chemical peeling agent, such as, for example, within about 48 hours, within about 24 hours, within about 18 hours, within about 12 hours, within about 6 hours, within about 3 hours, within about 2 hours, within about 1 hour, within about 45 minutes, within about 30 minutes, within about 20 minutes, or within about 10 minutes of each other. Multiple applications of either or both of (a) acetyl trifluoromethylphenyl valylglycine and (b) at least one chemical peeling agent are contemplated.Other methods according to the disclosure include applying (a) acetyl trifluoromethylphenyl valylglycine to the skin before and / or treating the skin with a physical peeling agent, such as, for example, within about 48 hours, within about 24 hours, within about 18 hours, within about 12 hours, within about 6 hours, within about 3 hours, within about 2 hours, within about 1 hour, within about 45 minutes, within about 30 minutes, within about 20 minutes, or within about 10 minutes of each other.

[0013] Some methods according to the disclosure are methods of stimulating skin renewal, wherein (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent are applied to the skin in amounts effective to stimulate skin renewal. Some methods according to the disclosure are methods of stimulating skin peeling, wherein (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent are applied to the skin in amounts effective to stimulate skin peeling. Some methods according to the disclosure are methods of improving skin elasticity, wherein (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent are applied to the skin in amounts effective to improve skin elasticity.Some methods according to the disclosure are methods of reducing elastase activity in skin, wherein (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent are applied to the skin in amounts effective to reduce elastase activity in the skin. Some methods according to the disclosure are methods of treating skin, wherein (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent are applied to the skin in amounts effective to improve the appearance of the skin.

[0014] Compositions comprising (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent are also disclosed. In some In embodiments, the compositions comprise (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent in amounts effective to improve the appearance of the skin, in amounts effective to stimulate skin renewal, in amounts effective to stimulate skin peeling, and / or in amounts effective to improve skin elasticity.

[0015] Kits comprising (a) acetyl trifluoromethylphenyl valylglycine, and (b) at least one chemical peeling agent and / or skin exfoliation implementation are also disclosed. BRIEF DESCRIPTION OF THE FIGURES

[0016] The implementation of the present technology will now be described, by way of example only, with reference to the attached figures, in which:

[0017] [Fig.l] [Fig.l] shows the synergistic inhibition of elastase activity by glycolic acid and / or acetyl trifluoromethylphenyl valylglycine.

[0018] [Fig.2] [Fig.2] shows the synergistic inhibition of elastase activity by lactic acid and / or acetyl trifluoromethylphenyl valylglycine.

[0019] [Fig.3] [Fig.3] shows two-dimensional ex vivo histological sections of a) a skin sample treated with a control vehicle (Control-2 wt% ethanol), b) a skin sample treated with 3 wt% lactic acid and 0.2 wt% salicylic acid (Scrub A), c) a skin sample treated with 3 wt% glycolic acid and 2.4 wt% lactic acid (Scrub B), d) a skin sample treated with a commercially available formulation containing 14.7 wt% glycolic acid and 0.1 wt% salicylic acid (Scrub C), e) a skin sample treated with a commercially available formulation containing 15 wt% trichloroacetic acid and 3 wt% glycolic acid (Scrub D), f) a skin sample treated with 3 wt% lactic acid and 0.2% by weight of salicylic acid (Scrub C), g) a skin sample treated with 3% by weight of lactic acid with 3% by weight of glycolic acid and 2,4% by weight of lactic acid (Scrub B), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, h) a skin sample treated with 14.7% by weight of glycolic acid and 0.1% by weight of salicylic acid (Scrub C), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, and i) a skin sample treated with 15% by weight of trichloroacetic acid and 3% by weight of glycolic acid (Scrub D), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine. The sections are stained for hematoxylin and eosin (H&E) expression. ,

[0020] [Fig.4] [Fig.4] shows two-dimensional ex vivo histological sections of a) a skin sample treated with the control vehicle (2 wt.% ethanol), b) a skin sample treated with 3 wt.% lactic acid and 0.2 wt.% lactic acid salicylic acid (Scrub A), c) a skin sample treated with 3% by weight of glycolic acid and 2.4% by weight of lactic acid (Scrub B), d) a skin sample treated with 14.7% by weight of glycolic acid and 0.1% by weight of salicylic acid (Scrub C), e) a skin sample treated with 15% by weight of trichloroacetic acid and 3% by weight of glycolic acid (Scrub D), f) a skin sample treated with 3% by weight of lactic acid and 0.2% by weight of salicylic acid (Scrub A), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, g) a skin sample treated with 3% by weight of glycolic acid and 2.4% by weight of lactic acid (Scrub B), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, h) a skin sample treated with 14.7% by weight of glycolic acid and 0.1% by weight of salicylic acid (Scrub C), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine,and i) a skin sample treated with 15% by weight of trichloroacetic acid and 3% by weight of glycolic acid (Scrub D), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine. The sections are stained for filaggrin (FLG) expression. ,

[0021] [Fig.5] [Fig.5] shows two-dimensional ex vivo histological sections of a) a skin sample treated with the control vehicle (2% by weight of ethanol), b) a skin sample treated with 3% by weight of lactic acid and 0.2% by weight of salicylic acid (Scrub A), c) a skin sample treated with 3% by weight of glycolic acid and 2.4% by weight of lactic acid (Scrub B), d) a skin sample treated with 14.7% by weight of glycolic acid and 0.1% by weight of salicylic acid (Scrub C), e) a skin sample treated with 15% by weight of trichloroacetic acid and 3% by weight of glycolic acid (Scrub D), f) a skin sample treated with 3% by weight of lactic acid and 0.2% by weight of salicylic acid (Scrub A), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, g) a skin sample treated with 3% by weight of glycolic acid and 2.4% by weight of lactic acid (Scrub B), and 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, h) a skin sample treated with 14,7% by weight glycolic acid and 0.1% by weight salicylic acid (Scrub C), and 0.1% by weight acetyl trifluoromethylphenyl valylglycine, and i) a skin sample treated with 15% by weight trichloroacetic acid and 3% by weight glycolic acid (Scrub D), and 0.1% by weight acetyl trifluoromethylphenyl valylglycine. Sections are stained for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). ,

[0022] [Fig.6] [Fig.6] shows two-dimensional ex vivo histological sections of a) a skin sample treated with a control vehicle (2% by weight of ethanol), b) a skin sample treated with 0.1% by weight of acetyl trifluoromethylphenyl valylglycine, c) a skin sample treated with 15% by weight of trichloroacetic acid and 3% by weight of glycolic acid (Scrub D), and d) a skin sample treated with 0.1 wt% acetyl trifluoromethylphenyl valylglycine, and 15 wt% trichloroacetic acid and 3 wt% glycolic acid (Scrub D). Sections are stained with hematoxylin and eosin. Scale bar = 100 pm.

[0023] [Fig.7] [Fig.7] shows two-dimensional ex vivo histological sections of a) a skin sample treated with the control vehicle (2 wt.% ethanol), b) a skin sample treated with 0.1 wt.% acetyl trifluoromethylphenyl valylglycine, c) a skin sample treated with 15 wt.% trichloroacetic acid and 3 wt.% glycolic acid (Scrub D), and d) a skin sample treated with 0.1 wt.% acetyl trifluoromethylphenyl valylglycine, and 15 wt.% trichloroacetic acid and 3 wt.% glycolic acid (Scrub D). The sections are stained for Filaggrin expression. Arrows point to modified stratum corneum.

[0024] [Fig.8] [Fig.8] shows two-dimensional ex vivo histological sections of a) a skin sample treated with a control vehicle (2 wt% ethanol), b) a skin sample treated with 0.1 wt% acetyl trifluoromethylphenyl valylglycine, c) a skin sample treated with 15 wt% trichloroacetic acid and 3 wt% glycolic acid (Scrub D), and d) a skin sample treated with 0.1 wt% acetyl trifluoromethylphenyl valylglycine, and 15 wt% trichloroacetic acid and 3 wt% glycolic acid (Scrub D). The sections are stained for Desmocollin-1 (DSC1) expression. Arrows point to altered stratum corneum.

[0025] [Fig.9] [Fig.9] shows two-dimensional ex vivo histological sections of a) a skin sample treated with a control vehicle (2 wt% ethanol), b) a skin sample treated with 0.1 wt% acetyl trifluoromethylphenyl valylglycine, c) a skin sample treated with 15 wt% trichloroacetic acid and 3 wt% glycolic acid (Scrub D), and d) a skin sample treated with 0.1 wt% acetyl trifluoromethylphenyl valylglycine, and 15 wt% trichloroacetic acid and 3 wt% glycolic acid (Scrub D). The sections are stained for expression of kallikrein-related peptidase 5 (KLK5) (also known as stratum corneum tryptic enzyme (SCTE)). Arrows point to modified stratum corneum.

[0026] [Fig. 10] [Fig. 10] shows two-dimensional ex vivo histological sections of a) a skin sample treated with a control vehicle (2 wt.% ethanol), b) a skin sample treated with 0.1 wt.% acetyl trifluoromethylphenyl valylglycine, c) a skin sample treated with 15 wt.% trichloroacetic acid and 3 wt.% glycolic acid (Scrub D), and d) a skin sample treated with 0.1 wt.% acetyl trifluoromethylphenyl valylglycine, and 15 wt.% trichloroacetic acid and 3 wt.% glycolic acid (Scrub D). The sections are stained for expression of “terminal deoxynucleotidyl transferase dUTP nick end labeling”.

[0027] [Fig. 11] [Fig. 11] shows the amount of a 2% solution of acetyl trifluoromethylphenyl valylglycine in a) the stratum corneum (SC), b) the epidermis (EP), c) the dermis (D), d) the receptor fluid (RF), and e) the amount that passes through the stratum corneum into the skin (EP + D + RF), after application to skin samples using a Franz horizontal cell clamp system.

[0028] [Fig. 12] [Fig. 12] shows (A) a home care product regimen for 2 study groups (Groups 1-2), and (B) treatment phases for Groups 1 and 2 of Example 4.

[0029] [Fig. 13] [Fig. 13] shows a graph comparing the clinical results of a 2-week, 4-week, 6-week, 10-week, and 12-week regimen described in Example 4 with Group 1 undergoing treatment with 0.3% retinol and Group 2 undergoing treatment with a 2% acetyl trifluoromethylphenyl valylglycine solution and a 0.45% salicylic acid / 11.11% lactic acid home chemical peel. Checkmarks ("V") denote a statistically significant improvement in results for Group 2 over Group 1 or Group 1 over Group 2. Equal signs ("=") denote a statistically insignificant difference in results between Group 1 and Group 2.

[0030] [Fig. 14] [Fig. 14] shows a graph comparing the clinical outcomes of a 2-week, 6-week, and 12-week regimen described in Example 4 with Group 1 undergoing treatment with 0.3% retinol and Group 2 undergoing treatment with a 2% acetyl trifluoromethylphenyl valylglycine solution and a 0.45% salicylic acid / 11.11% lactic acid chemical peel compared to baseline. Boxes with dots denote statistically significant improvements (p < 0.05) in the clinical outcomes of Group 1 or Group 2 compared to baseline. Boxes with solid diagonal lines denote statistically significant and clinically meaningful improvements (p < 0.05) in the outcomes of Group 1 or Group 2 compared to baseline.

[0031] [Fig. 15] [Fig. 15] shows a clinical grading graph for overall fine lines between treatment groups 1 and 2 on the 12-week schedule of Example 4.

[0032] [Fig. 16] [Fig. 16] shows a clinical grading graph of nasolabial folds between treatment groups 1 and 2 on the 12-week regimen of Example 4. An asterisk ("*") denotes a statistically significant difference (p < 0.05) in nasolabial fold wrinkles compared to group 1 at the respective time point.

[0033] [Fig. 17] [Fig. 17] shows a clinical graduation chart for photo- damage between treatment groups 1 and 2 on the 12-week regimen of Example 4. An asterisk ("*") denotes a statistically significant difference (p < 0.05) in photodamage compared to group 1 at the respective time point.

[0034] [Fig. 18] [Fig. 18] shows a graph of clinical gradation of under-eye wrinkles between treatment groups 1 and 2 on the 12-week regimen of Example 4.

[0035] [Fig. 19] [Fig. 19] shows a clinical grading graph of global health appearance between treatment groups 1 and 2 on the 12-week regimen of Example 4. An asterisk ("*") denotes a statistically significant difference (p < 0.05) in global health appearance compared to group 1 at the respective time point.

[0036] It should be understood that the various aspects are not limited to the arrangements and instrumentalities shown in the drawings. detailed description of the disclosure

[0037] The present disclosure relates to compositions, methods and kits for treating skin, for example by increasing, accelerating and / or improving skin renewal, and / or improving the appearance of the skin. The compositions according to various aspects of the disclosure comprise acetyl trifluoromethylphenyl valylglycine and / or at least one chemical peeling agent. The methods according to various aspects of the disclosure comprise applying to the skin, simultaneously or sequentially, acetyl trifluoromethylphenyl valylglycine and at least one chemical peeling agent. The kits according to various aspects of the disclosure comprise acetyl trifluoromethylphenyl valylglycine and at least one chemical peeling agent.

[0038] The compositions and methods according to various aspects of the disclosure may protect against or slow the breakdown of skin elastase, improve skin elasticity, decrease sagging, improve or accelerate skin turnover / sloughing, stimulate or improve epidermal turnover, increase exfoliation, reduce or slow the appearance of skin aging (such as wrinkles), increase skin keratinization or upper terminal differentiation, and / or smooth the skin. For example, methods of treating skin generally include applying acetyl trifluoromethylphenyl valylglycine and at least one chemical peeling agent to the skin to accelerate sloughing and cell turnover in the epidermal layer.Surprisingly, it has been found that in certain embodiments, the skin treatment methods and compositions according to the disclosure inhibit elastase activity.

[0039] In various embodiments, acetyl trifluoromethylphenyl valylglycine and the at least one chemical peeling agent act synergistically to improve the appearance of the skin. For example, the skin treatment methods and compositions disclosed herein may be effective in reducing the appearance of wrinkles by accelerating cell turnover, for example, by keratinization and higher terminal differentiation. As a further example, the skin treatment methods and compositions disclosed herein may be effective in reducing the appearance of wrinkles by inhibiting elastase, thereby allowing the growth of elastin fibers as opposed to their degradation by these enzymes, thereby improving skin elasticity.

[0040] A more detailed description of the skin treatment compositions, methods and kits is provided below. Compositions

[0041] The compositions according to various embodiments of the disclosure comprise acetyl trifluoromethylphenyl valylglycine and / or at least one chemical peeling agent. In some embodiments, the compositions according to the disclosure comprise both acetyl trifluoromethylphenyl valylglycine and at least one chemical peeling agent. In other embodiments, the compositions according to the disclosure comprise acetyl trifluoromethylphenyl valylglycine or at least one chemical peeling agent. Acetyl trifluoromethylphenyl valylglycine

[0042] According to various embodiments, the compositions according to the disclosure comprise at least about 0.01% by weight of acetyl trifluoromethylphenyl valylglycine, for example from about 0.01 to about 25% by weight, based on the total weight of the composition in which it is present. For example, the amount of acetyl trifluoromethylphenyl valylglycine may be from about 0.1 to about 25 wt%, about 0.1 to about 22 wt%, about 0.1 to about 19 wt%, about 0.1 to about 16 wt%, about 0.1 to about 14 wt%, about 0.1 to about 12 wt%, about 0.1 to about 10 wt%, about 0.1 to about 8 wt%, about 0.1 to about 6 wt%, about 0.1 to about 5 wt%, about 0.1 to about 4 wt%, about 0.1 to about 3 wt%, about 0.1 to about 2 wt%, about 0.1 to about 1 wt%;about 0.25 to about 25% by weight, about 0.25 to about 22% by weight, about 0.25 to about 19% by weight, about 0.25 to about 16% by weight, about 0.25 to about 14% by weight, about 0.25 to about 12% by weight, about 0.25 to about 10% by weight, about 0.25 to about 8% by weight, about 0.25 to about 6% by weight, about 0.25 to about 5% by weight, about 0.25 to about 4% by weight, about 0.25 to about 3% by weight, about 0.25 to about 2% by weight, about 0.25 to about 1% by weight; about 0.5 to about 25% by weight, about 0.5 to about 22% by weight, about 0.5 to about 19% by weight, about 0.5 to about 16% by weight, about 0.5 to about 14% by weight, about 0.5 to about 12% by weight, about 0.5 to about 10% by weight; weight, about 0.5 to about 8% by weight, about 0.5 to about 6% by weight, about 0.5 to about 5% by weight, about 0.5 to about 4% by weight, about 0.5 to about 3% by weight, about 0.5 to about 2% by weight, about 0.5 to about 1% by weight; about 0.75 to about 25% by weight, about 0.75 to about 22% by weight, about 0.75 to about 19% by weight, about 0.75 to about 16% by weight, about 0.75 to about 14% by weight, about 0.75 to about 12% by weight, about 0.75 to about 10% by weight, about 0.75 to about 8% by weight, about 0.75 to about 6% by weight, about 0.75 to about 5% by weight, about 0.75 to about 4% by weight, about 0.75 to about 3% by weight, about 0.75 to about 2% by weight;about 1 to about 25% by weight, about 1 to about 22% by weight, about 1 to about 19% by weight, about 1 to about 16% by weight, about 1 to about 14% by weight, about 1 to about 12% by weight, about 1 to about 10% by weight, about 1 to about 8% by weight, about 1 to about 6% by weight, about 1 to about 5% by weight, about 1 to about 4% by weight, about 1 to about 3% by weight, about 1 to about 2% by weight; about 2 to about 25% by weight, about 2 to about 22% by weight, about 2 to about 19% by weight, about 2 to about 16% by weight, about 2 to about 14% by weight, about 2 to about 12% by weight, about 2 to about 10% by weight, about 2 to about 8% by weight, about 2 to about 6% by weight, about 2 to about 5% by weight, about 2 to about 4% by weight, about 2 to about 3% by weight;about 5 to about 25% by weight, about 5 to about 22% by weight, about 5 to about 19% by weight, about 5 to about 16% by weight, about 5 to about 14% by weight, about 5 to about 12% by weight, about 5 to about 10% by weight, about 5 to about 8% by weight; about 7.5 to about 27.5% by weight, about 7.5 to about 22% by weight, about 7.5 to about 19% by weight, about 7.5 to about 16% by weight, about 7.5 to about 14% by weight, about 7.5 to about 12% by weight, about 7.5 to about 10% by weight; about 10 to about 27.5% by weight, about 10 to about 22% by weight, about 10 to about 19% by weight, about 10 to about 16% by weight, about 10 to about 14% by weight, about 10 to about 12% by weight; about 15 to about 27.5% by weight, about 15 to about 22% by weight, about 15 to about 19% by weight;from about 20 to about 27.5% by weight, or from about 20 to about 22% by weight, including intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present.;

[0043] In some embodiments, the composition comprises an amount of acetyl trifluoromethylphenyl valylglycine such that about 0.001 to about 2.5% by weight of acetyl trifluoromethylphenyl valylglycine penetrates through the epidermis and reaches the dermal layer of the skin. For example, the composition may comprise an amount of acetyl trifluoromethylphenyl valylglycine such that about 0.002 to about 2% by weight, about 0.002 to about 1.9% by weight, about 0.002 to about 1.8% by weight, about 0.002 to about 1.7% by weight, about 0.002 to about 1.6% by weight, about 0.002 to about 1.5% by weight, about 0.002 to about 1.4% by weight, about 0.002 to about 1.3% by weight, about 0.002 to about 1.2% by weight, about 0.002 to about 1.1% by weight, about 0.002 to about 1% by weight, about 0.002 to about 0.9% by weight, about 0.002 to about 0.8% by weight, about 0.002 to about 0.7% by weight, about 0.002 to about 0.6% by weight, about 0.002 to about 0.5% by weight, about 0.002 to about 0.4% by weight, about 0.002 to about 0.3% by weight, about 0.002 to about 0.2% by weight, about 0.002 to about 0.1% by weight, about 0.002 to about 0.09% by weight, about 0.002 to about 0.08% by weight, about 0.002 to about 0.07% by weight, about 0.002 to about 0.06% by weight, about 0.002 to about 0.05% by weight, about 0.0042 to about 0.04% by weight, about 0.002 to about 0.03% by weight, about 0,002 to about 0.02 wt. %, about 0.002 to about 0.01 wt. %, about 0.01 to about 2 wt. %, about 0.01 to about 1.9 wt. %, about 0.01 to about 1.8 wt. %, about 0.01 to about 1.7 wt. %, about 0.01 to about 1.6 wt. %, about 0.01 to about 1.5 wt. %, about 0.01 to about 1.4 wt. %, about 0.01 to about 1.3 wt. %, about 0.01 to about 1.2 wt. %, about 0.01 to about 1.1 wt. %, about 0.01 to about 1 wt. %, about 0.01 to about 0.9 wt. %, about 0.01 to about 0.8 wt. %, about 0.01 about 0.7 wt%, about 0.01 to about 0.6 wt%, about 0.01 to about 0.5 wt%, about 0.01 to about 0.4 wt%, about 0.01 to about 0.3 wt%, about 0.01 to about 0.2 wt%, about 0.01 to about 0.1 wt%, about 0.01 to about 0.09 wt%, about 0.01 to about 0.08 wt%, about 0.01 to about 0.07 wt%, about 0.01 to about 0,06% by weight, , about 0.01 to about 0.05% by weight, about 0.01 to about 0.04% by weight, about 0.01 to about 0.03% by weight, about 0.01 to about 0.02% by weight, about 0.01 to about 0.01% by weight, about 0.006 to about 2% by weight, about 0.006 to about 1.9 wt.%, about 0.006 to about 1.8 wt.%, about 0.006 to about 1.7 wt.%, about 0.006 to about 1.6 wt.%, about 0.006 to about 1.5 wt.%, about 0.006 to about 1.4 wt.%, about 0.006 to about 1.3 wt.%, about 0.006 to about 1.2 wt.%, about 0.006 to about 1.1 wt.%, about 0.006 to about 1 wt.%, about 0.006 to about 0.9 wt.%, about 0.006 to about 0.8 wt.%, about 0.006 to about 0.7 wt.%, about 0.006 to about 0.6 wt.%, about 0.006 to about 0.5% by weight, about 0.006 to about 0.4% by weight, about 0.006 to about 0.3% by weight, about 0.006 to about 0.2% by weight, about 0.006 to about 0.1% by weight, about 0.006 to about 0.09% by weight, about 0.006 to about 0.08% by weight, about 0.006 to about 0.07% by weight, about 0.006 to about 0.06% by weight, about 0.006 to about 0.05% by weight, about 0.006 to about 0.04% by weight, about 0.006 to about 0.03% by weight, about 0.006 to about 0.02% by weight, about 0.006 to about 0.01% by weight, about 0.008 to about 2% by weight, about 0.008 to about 1.9% by weight, about 0.008 to about 1.8% by weight, about 0.008 to about 1.7% by weight, about 0.008 to about 1.6% by weight, about 0.008 to about 1.5% by weight, about 0.008 to about 1.4% by weight, about 0.008 to about 1.3% by weight, about 0.008 to about 1.2% by weight, about 0.008 to about 1.1 wt. %, about 0.008 to about 1 wt. %, about 0.008 to about 0.9 wt. %, about 0.008 to about 0.8 wt. %, about 0.008 to about 0.7 wt. %, about 0.008 to about 0.6 wt. %, about 0.008 to about 0.5 wt. %, about 0.008 to about 0.4 wt. %, about 0.008 to about 0.3 wt. %, about 0.008 to about 0.2 wt. %, about 0.008 to about 0.1 wt. %, about 0.008 to about 0.09 wt. %, about 0.008 to about 0.08 wt. %, about 0.008 to about 0.07 wt. %, about 0.008 to about 0.06% by weight, about 0.008 to about 0.05% by weight, about 0.008 to about 0.04% by weight, about 0.008 to about 0.03% by weight, about 0.008 to about 0.02% by weight, about 0.008 to about 0.01% by weight, about 0.01 to about 2% by weight, about 0.01 to about 1.9% by weight, about 0.01 to about 1.8% by weight, about 0.01 to about 1.7% by weight, about 0.01 to about 1.6% by weight,about 0.01 to about 1.5 wt.%, about 0.01 to about 1.4 wt.%, about 0.01 to about 1.3 wt.%, about 0.01 to about 1.2 wt.%, about 0.01 to about 1.1 wt.%, about 0.01 to about 1 wt.%, about 0.01 to about 0.9 wt.%, about 0.01 to about 0.8 wt.%, about 0.01 to about 0.7 wt.%, about 0.01 to about 0.6 wt.%, about 0.01 to about 0.5 wt.%, about 0.01 to about 0.4 wt.%, about 0.01 to about 0.3 wt.%, about 0.01 to about 0.2 wt.%, about 0.01 to about 0.1 wt.%, about 0.01 to about 0.09% by weight, about 0.01 to about 0.08% by weight, , about 0.01 to about 0.07% by weight, about 0.01 to about 0.06% by weight, about 0.01 to about 0.05% by weight, about 0.01 to about 0.04% by weight, about 0.01 to about 0.03% by weight, about 0.01 to about 0.02% by weight, about 0.025 to about 2% by weight, about 0.025 to about 1.9% by weight, about 0.025 to about 1.8% by weight, about 0.025 to about 1.7% by weight, about 0.025 to about 1.6% by weight, about 0.025 to about 1.5% by weight, about 0.025 to about 1.4% by weight, about 0.025 to about 1.3% by weight, about 0.025 to about 1.2% by weight, about 0.025 to about 1.1% by weight, about 0.025 to about 1% by weight, about 0.025 to about 0.9% by weight, about 0.025 to about 0.8% by weight, about 0.025 to about 0.7% by weight, about 0.025 to about 0.6% by weight, about 0.025 to about 0.5% by weight, about 0.025 to about 0.4% by weight, about 0.025 to about 0.3 wt. %, about 0.025 to about 0.2 wt. %, about 0.025 to about 0.1 wt. %, about 0.025 to about 0.09 wt. %, about 0.025 to about 0.08 wt. %, about 0.025 to about 0.07 wt. %, about 0.025 to about 0.06 wt. %, about 0.025 to about 0.05 wt. %, about 0.025 to about 0.04 wt. %, about 0.05 to about 2 wt. %, about 0.05 to about 1.9 wt. %, about 0.05 to about 1.8 wt. %, about 0.05 to about 1.7 wt. %, about 0.05 to about 1.6 wt. %, about 0.05 to about 1.5 wt. %, about 0.05 to about 1.4 wt. %, about 0.05 to about 1.3 wt. %, about 0.05 to about 1.2 wt. %, about 0.05 to about 1.1 wt. %, about 0.05 to about 1 wt. %, about 0.05 to about 0.9 wt. %, about 0.05 to about 0.8 wt. %, about 0.05 to about 0.7 wt. %, about 0.05 to about 0.6 wt. %, about 0.05 to about 0.5 wt.about 0.05 to about 0.4% by weight, about 0.05 to about 0.3% by weight, about 0.05 to about 0.2% by weight, about 0.05 to about 0.1% by weight, about 0.05 to about 0.09% by weight, about 0.05 to about 0.08% by weight, about 0.05 to about 0.07% by weight, about 0.06 to about 2% by weight, about 0.06 to about 1.9% by weight, about 0.06 to about 1.8% by weight, about 0.06 to about 1.7% by weight, about 0.06 to about 1.6% by weight, about 0.06 to about 1.5% by weight, about 0.06 to about 1.4% by weight, about 0.06 to about 1.3% by weight, about 0.06 to about 1.2 wt. %, about 0.06 to about 1.1 wt. %, about 0.06 to about 1 wt. %, about 0.06 to about 0.9 wt. %, about 0.06 to about 0.8 wt. %, about 0.06 to about 0.7 wt. %, about 0.06 to about 0.6 wt. %, about 0.06 to about 0.5 wt. %, about 0.06 to about 0.4 wt. %, about 0.06 to about 0.3 wt. %, about 0.06 to about 0.2% by weight, about 0.06 to about 0.1% by weight, about 0.06 to about 0.09% by weight, about 0.06 to about 0.08% by weight, about 0.06 to about 0.07% by weight, about 0.07 to about 2% by weight, about 0.07 to about 1.9% by weight, about 0.07 to about 1.8% by weight, about 0.07 to about 1.7% by weight, about 0.07 to about 1.6% by weight, about 0.07 to about 1.5% by weight, about 0.07 to about 1.4% by weight, about 0.07 to about 1.3% by weight, about 0.07 to about 1.2% by weight, about 0.07 to about 1.1% by weight, about 0.07 to about 1% by weight weight, about 0.07 to about 0.9 wt%, about 0.07 to about 0.8 wt%, about 0.07 to about 0.7 wt%, about 0.07 to about 0.6 wt%, about 0.07 to about 0.5 wt%, about 0.07 to about 0.4 wt%, about 0.07 to about 0.3 wt%, about 0.07 to about 0.2 wt%, about 0.07 to about 0.1 wt%, about 0.07 to about 0.09 wt%, about 0,07 to about 0.08 wt%, about 0.08 to about 2 wt%, about 0.08 to about 1.9 wt%, about 0.08 to about 1.8 wt%, about 0.08 to about 1.7 wt%, about 0.08 to about 1.6 wt%, about 0.08 to , about 1.5 wt.%, about 0.08 to about 1.4 wt.%, about 0.08 to about 1.3 wt.%, about 0.08 to about 1.2 wt.%, about 0.08 to about 1.1 wt.%, about 0.08 to about 1 wt.%, about 0.08 to about 0.9 wt.%, about 0.08 to about 0.8 wt.%, about 0.08 to about 0.7 wt.%, about 0.08 to about 0.6 wt.%, about 0.08 to about 0.5 wt.%, about 0.08 to about 0.4 wt.%, about 0.08 to about 0.3 wt.%, about 0.08 to about 0.2 wt.%, about 0.08 to about 0.1 wt.%, about 0.08 to about 0.09% by weight, about 0.09 to about 2% by weight, about 0.09 to about 1.9% by weight, about 0.09 to about 1.8% by weight, about 0.09 to about 1.7% by weight, about 0.09 to about 1.6% by weight, about 0.09 to about 1.5% by weight, about 0.09 to about 1.4% by weight, about 0.09 to about 1.3% by weight, about 0.09 to about 1.2% by weight, about 0.09 to about 1.1% by weight,about 0.09 to about 1% by weight, about 0.09 to about 0.9% by weight, about 0.09 to about 0.8% by weight, about 0.09 to about 0.7% by weight, about 0.09 to about 0.6% by weight, about 0.09 to about 0.5% by weight, about 0.09 to about 0.4% by weight, about 0.09 to about 0.3% by weight, about 0.09 to about 0.2% by weight, about 0.09 to about 0.1% by weight, about 0.1 to about 2% by weight, about 0.1 to about 1.9% by weight, about 0.1 to about 1.8% by weight, about 0.1 to about 1.7% by weight, about 0.1 to about 1.6% by weight, about 0.1 to about 1.5% by weight, about 0.1 to about 1.4% by weight, about 0.1 to about 1.3% by weight, about 0.1 to about 1.2% by weight, about 0.1 to about 1.1% by weight, about 0.1 to about 1% by weight, about 0.1 to about 0.9% by weight, about 0.1 to about 0.8% by weight, about 0.1 to about 0.7% by weight, about 0.1 to about 0.6% by weight, about 0.1 to about 0.5% by weight,from about 0.1 to about 0.4% by weight, from about 0.1 to about 0.3% by weight, or from about 0.1 to about 0.2% by weight, including all intermediate ranges and sub-ranges, of acetyl trifluoromethylphenyl valylglycine that penetrates the epidermis and reaches the dermal layer of the skin. In some embodiments, the composition comprises an amount of acetyl trifluoromethylphenyl valylglycine such that from about 0.01 to about 1.5% by weight, preferably from about 0.025 to about 1.3% by weight, more preferably from about 0.5 to about 1.1% by weight, most preferably from about 0.6 to about 1% by weight of acetyl trifluoromethylphenyl valylglycine penetrates the epidermis and reaches the dermal layer of the skin.

[0044] In various embodiments, the compositions according to the disclosure comprise acetyl trifluoromethylphenyl valylglycine but are free or substantially free of chemical peeling agents. Exfoliating agents

[0045] According to various embodiments, the compositions according to the disclosure comprise at least one exfoliating agent, which may be selected from, for example, dermabrasion, microdermabrasion, physical exfoliants and / or chemical exfoliants. Physical exfoliants may include, for example, microbeads or other small particles, or exfoliating pads which may or may not include a chemical exfoliating agent.

[0046] Exemplary and non-limiting chemical exfoliating agents that may be used include chemical agents capable of acting either directly on exfoliation by promoting 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, citric, 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; re-sveratrol; certain jasmonic acid derivatives; resorcinol; phenol; or mixtures thereof.

[0047] Additional exemplary and 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; glycine-type α-amino acid derivatives (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-acetylglucosamine; or mixtures thereof.

[0048] As further exemplary and 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, silicon-containing derivatives of salicylate such as those described in EP 0 796 861, oligofuctases such as those described in EP 0 218 200, agents having effects on transglutaminase as in EP 0 899 330; opuntia indica flower extract such as Exfolactive® from Silab; 8-hexadecene 1,16-dicarboxylic acid; glucose and vitamin F esters; or mixtures thereof.

[0049] The chemical exfoliating agent(s) may, in certain embodiments, be chosen 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-octanoyl-5-salicylic acid; trichloroacetic acid; or mixtures thereof.

[0050] The total amount of chemical exfoliating agent(s) present in the composition may range from about 0.01 to about 25% by weight, for example from about 0.1 to about 20% by weight, relative to the total weight of the composition in which it is present. For example, the total amount of chemical peeling agent present in the composition may range from about 0.5 to about 25% by weight, from about 0.5 to about 22% by weight, from about 0.5 to about 19% by weight, from about 0.5 to about 16% by weight, from about 0.5 to about 14% by weight, about 0.5 to about 12% by weight, about 0.5 to about 10% by weight, about 0.5 to about 8% by weight, about 0.5 to about 6% by weight, about 0.5 to about 5% by weight, about 0.5 to about 4% by weight, about 0.5 to about 3% by weight, about 0.5 to about 2% by weight, about 0.5 to about 1% by weight; about 1 to about 25% by weight, about 1 to about 22% by weight, about 1 to about 19% by weight,about 1 to about 16% by weight, about 1 to about 14% by weight, about 1 to about 12% by weight, about 1 to about 10% by weight, about 1 to about 8% by weight, about 1 to about 6% by weight, about 1 to about 5% by weight, about 1 to about 4% by weight, about 1 to about 3% by weight, about 1 to about 2% by weight; about 2 to about 25% by weight, about 2 to about 22% by weight, about 2 to about 19% by weight, about 2 to about 16% by weight, about 2 to about 14% by weight, about 2 to about 12% by weight, about 2 to about 10% by weight, about 2 to about 8% by weight, about 2 to about 6% by weight, about 2 to about 5% by weight, about 2 to about 4% by weight, about 2 to about 3% by weight; about 3 to about 25% by weight, about 3 to about 22% by weight, about 3 to about 19% by weight, about 3 to about 16% by weight, about 3 to about 14% by weight, about 3 to about 12% by weight,about 3 to about 10% by weight, about 3 to about 8% by weight, about 3 to about 6% by weight, about 3 to about 5% by weight, about 3 to about 4% by weight, about 4 to about 25% by weight, about 4 to about 22% by weight, about 4 to about 19% by weight, about 4 to about 16% by weight, about 4 to about 14% by weight, about 4 to about 12% by weight, about 4 to about 10% by weight, about 4 to about 8% by weight, about 4 to about 6% by weight, about 4 to about 5% by weight, about 5 to about 25% by weight, about 5 to about 22% by weight, about 5 to about 19% by weight, about 5 to about 16% by weight, about 5 to about 14% by weight, about 5 to about 12% by weight weight, about 5 to about 10% by weight, about 5 to about 8% by weight; about 7.5 to about 25% by weight, about 7.5 to about 22% by weight, about 7.5 to about 19% by weight, about 7.5 to about 16% by weight, about 7.5 to about 14% by weight, about 7,5 to about 12% by weight, about 7.5 to about 10% by weight, weight; about 10 to about 25% by weight, about 10 to about 22% by weight, about 10 to about 19% by weight, about 10 to about 16% by weight, about 10 to about 14% by weight, about 10 to about 12% by weight; from about 12 to about 25% by weight, from about 12 to about 22% by weight, from about 12 to about 19% by weight, from about 12 to about 16% by weight, from about 12 to about 14% by weight, from about 15 to about 25% by weight, from about 15 to about 22% by weight, from about 15 to about 19% by weight, from about 17 to about 25% by weight, from about 17 to about 22% by weight, or from about 17 to about 19% by weight, including ranges and sub-ranges therebetween, based on the total weight of the composition in which it is present.

[0051] For example, in various embodiments, the compositions according to the disclosure comprise at least one AHA as a chemical peeling agent. In some embodiments, the compositions may comprise a total amount of AHA of between about 1 and about 20 wt.%, about 1 and about 19 wt.%, about 1 and about 18 wt.%, about 1 and about 17 wt.%, about 1 and about 16 wt.%, about 1 and about 15 wt.%, about 1 and about 14 wt.%, about 1 and about 13 wt.%, about 1 to about 12 wt.%, about 1 to about 11 wt.%, about 1 to about 10 wt.%, about 1 to about 9 wt.%, about 1 to about 8 wt.%, about 1 to about 7 wt.%, about 1 to about 6 wt.%, about 1 to about 5 wt.%, about 1 to about 4 wt.%, about 1 to about 3 wt.%, about 1 to about 2 wt.%, about 2 to about 20% by weight, about 2 to about 19% by weight,about 2 to about 18% by weight, about 2 to about 17% by weight, about 2 to about 16% by weight, about 2 to about 15% by weight, about 2 to about 14% by weight, about 2 to about 13% by weight, about 2 to about 12% by weight, about 2 to about 11% by weight, about 2 to about 10% by weight, about 2 to about 9% by weight, about 2 to about 8% by weight, about 2 to about 7% by weight, about 2 to about 6% by weight, about 2 to about 5% by weight, about 2 to about 4% by weight, about 2 to about 3% by weight, about 3 to about 20% by weight, about 3 to about 19% by weight, about 3 to about 18% by weight, about 3 to about 17% by weight, about 3 to about 16% by weight weight, about 3 to about 15% by weight, about 3 to about 14% by weight, about 3 to about 13% by weight, about 3 to about 12% by weight, about 3 to about 11% by weight, about 3 to about 10% by weight, about 3 to about 9% by weight,about 3 to about 8% by weight, about 3 to about 7% by weight, about 3 to about 6% by weight, about 3 to about 5% by weight, about 3 to about 4% by weight, about 10 to about 20% by weight, about 10 to about 19% by weight, about 10 to about 18% by weight, about 10 to about 17% by weight, about 10 to about 16% by weight, about 10 to about 15%, by weight, about 10 to about 14% by weight, about 10 to about 13% by weight, about 10 to about 12% by weight, about 11 to about 20% by weight, about 11 to about 19% by weight, about 11 to about 18% by weight, about 11 to about 17% by weight, about 11 to about 16% by weight, about 11 to about 15% by weight, about 11 to about 14% by weight, about 11 to about 13% by weight, about 12 to about 20% by weight, about 12 to about 19% by weight, about 12 to about 18% by weight, about 12 to about 17% by weight, about 12 to about 16% by weight, about 12 to about 15% by weight, about 12 to about 14% by weight, about 13 to about 20% by weight, about 13 to about 19% by weight, about 13 to about 18% by weight, about 13 to about 17% by weight, about 13 to about 16% by weight, or about 13 to about 15% by weight, including ranges and sub-ranges therebetween, based on the total weight of the composition in which it is present. In some embodiments, the total amount of AHA ranges from about 2 to about 4% by weight, from about 4 to about 7% by weight, or from about 13 to about 16% by weight, based on the total weight of the composition in which it is present.In other embodiments, the total amount of AHA is about 3% by weight, is between 5 and 6% by weight, or is between 14 and 15% by weight, based on the total weight of the composition in which it is present.

[0052] In some embodiments, the compositions according to the disclosure comprise at least one BHA as a chemical peeling agent. For example, the compositions may comprise a total amount of BHA ranging from about 0.01 to about 2 wt.%, from about 0.01 to about 1.9 wt.%, from about 0.01 to about 1.8 wt.%, from about 0.01 to about 1.7 wt.%, from about 0.01 to about 1.6 wt.%, from about 0.01 to about 1.5 wt.%, about 0.01 to about 1.4 wt.%, about 0.01 to about 1.3 wt.%, about 0.01 to about 1.2 wt.%, about 0.01 to about 1.1 wt.%, about 0.01 to about 1.0 wt.%, about 0.01 to about 0.9 wt.%, about 0.01 to about 0.8 wt.%, about 0.01 to about 0.7% by weight, about 0.01 to about 0.6% by weight, about 0.01 to about 0.5% by weight, about 0.01 to about 0.4% by weight, about 0.01 to about 0.3% by weight, about 0.01 to about 0.2% by weight, about 0.01 to about 0,1% by weight, about 0.05 to about 2% by weight, about 0.05 to about 1.9% by weight, about 0.05 to about 1.8% by weight, about 0.05 to about 1.7% by weight, about 0.05 to about 1.6% by weight, about 0.05 to about 1.5% by weight, about 0.05 to about 1.4% by weight, about 0.05 to about 1.3% by weight, about 0.05 to about 1.2% by weight, about 0.05 to about 1.1% by weight, about 0.05 to about 1.0% by weight, about 0.05 to about 0.9% by weight, about 0.05 to about 0.8% by weight, about 0.05 to about 0.7% by weight, about 0.05 to about 0.6% by weight weight, about 0.05 to about 0.5% by weight, about 0.05 to about 0.4%, by weight, about 0.05 to about 0.3% by weight, about 0.05 to about 0.2% by weight, about 0.05 to about 0.1% by weight, about 0.1 to about 2% by weight, about 0.1 to about 1.9% by weight, about 0.1 to about 1.8% by weight, about 0.1 to about 1.7% by weight, about 0.1 to about 1.6% by weight, about 0.1 to about 1.5% by weight, about 0.1 to about 1.4% by weight, about 0.1 to about 1.3% by weight, about 0.1 to about 1.2% by weight, about 0.1 to about 1.1% by weight, about 0.1 to about 1.0% by weight, about 0.1 to about 0.9% by weight, about 0.1 to about 0.8% by weight weight, about 0.1 to about 0.7% by weight, about 0.1 to about 0.6% by weight, about 0.1 to about 0.5% by weight, about 0.1 to about 0.4% by weight, about 0.1 to about 0.3% by weight, or about 0.1 to about 0.2% by weight, including ranges and sub-ranges therebetween, based on the total weight of the composition in which it is present.In some embodiments, the total amount of BHA is about 0.05 wt%, about 0.06 wt%, about 0.07 wt%, about 0.08 wt%, about 0.09 wt%, about 0.1 wt%, about 0.11 wt%, about 0.12 wt%, about 0.13 wt%, about 0.14 wt%, about 0.15 wt%, about 0.16 wt%, about 0.17 wt%, about 0.18 wt%, about 0.19 wt%, about 0.2 wt%, about 0.21 wt%, about 0.22 wt%, about 0.23 wt%, about 0.24 wt%, or about 0.25 wt%, based on the total weight of the composition in which it is present.

[0053] In some embodiments, the compositions according to the disclosure comprise trichloroacetic acid as a chemical peeling agent. For example, the compositions may comprise a total amount of trichloroacetic acid ranging from about 1 to about 25 wt%, from about 1 to about 24 wt%, from about 1 to about 23 wt%, from about 1 to about 22 wt%, from about 1 to about 21 wt%, from about 1 to about 20 wt%, from about 1 to about 19 wt%, from about 1 to about 18 wt%, from about 1 to about 17 wt%, from about 1 to about 16 wt%, about 1 to about 15 wt%, about 1 to about 14 wt%, about 1 to about 13 wt%, about 1 to about 12 wt%, about 1 to about 11 wt%, about 1 to about 10 wt%, about 1 to about 9 wt%, about 1 to about 8% by weight, about 1 to about 7% by weight, about 1 to about 6% by weight,about 1 to about 5% by weight, about 1 to about 4% by weight, about 1 to about 3% by weight, about 1 to about 2% by weight, about 3 to about 25% by weight, about 3 to about 24% by weight, about 3 to about 23% by weight, about 3 to about 22% by weight, about 3 to about 21% by weight, about 3 to about 20% by weight, about 3 to about 19% by weight, about 3 to about 18% by weight, about 3 to about 17% by weight, about 3 to about 16% by weight, about 3 to about 15% by weight, about 3 to , about 14% by weight, about 3 to about 13% by weight, about 3 to about 12% by weight, about 3 to about 11% by weight, about 3 to about 10% by weight, about 3 to about 9% by weight, about 3 to about 8% by weight, about 3 to about 7% by weight, about 3 to about 6% by weight, about 3 to about 5% by weight, 5 to about 25% by weight, about 5 to about 24% by weight, about 5 to about 23% by weight, about 5 to about 22% by weight, about 5 to about 21% by weight, about 5 to about 20% by weight, about 5 to about 19% by weight, about 5 to about 18% by weight, about 5 to about 17% by weight, about 5 to about 16% by weight, about 5 to about 15% by weight, about 5 to about 14% by weight, about 5 to about 13% by weight, about 5 to about 12% by weight, about 5 to about 11% by weight, about 5 to about 10% by weight, about 5 to about 9% by weight, about 5 to about 8% by weight, about 5 to about 7% by weight,8 to about 25% by weight, about 8 to about 24% by weight, about 8 to about 23% by weight, about 8 to about 22% by weight, about 8 to about 21% by weight, about 8 to about 20% by weight, about 8 to about 19% by weight, about 8 to about 18% by weight, about 8 to about 17% by weight, about 8 to about 16% by weight, about 8 to about 15% by weight, about 8 to about 14% by weight, about 8 to about 13% by weight, about 8 to about 12% by weight, about 8 to about 11% by weight, about 8 to about 10% by weight, about 10 to about 25% by weight, about 10 to about 24% by weight, about 10 to about 23% by weight, about 10 to about 22% by weight, about 10 to about 21% by weight, about 10 to about 20% by weight, about 10 to about 19% by weight, about 10 to about 18% by weight, about 10 to about 17% by weight, about 10 to about 16% by weight, about 10 to about 15% by weight, about 10 to about 14% by weight,about 10 to about 13% by weight, about 10 to about 12% by weight, about 12 to about 25% by weight, about 12 to about 24% by weight, about 12 to about 23% by weight, about 12 to about 22% by weight, about 12 to about 21% by weight, about 12 to about 20% by weight, about 12 to about 19% by weight, about 12 to about 18% by weight, about 12 to about 17% by weight, about 12 to about 16% by weight, about 12 to about 15% by weight, or about 12 to about 14% by weight, based on the total weight of the composition in which it is present.

[0054] Optionally, the compositions may comprise more than one exfoliating agent, such as, for example, at least two exfoliating agents, at least three exfoliating agents, at least four exfoliating agents, and so on. For example, the compositions may comprise two or more AHAs, may comprise two or more BHAs, may comprise a combination of one or more AHAs and one or more BHAs, and so on. By way of non-limiting example only, the compositions may comprise glycolic acid and lactic acid, may include glycolic acid and salicylic acid, may include lactic acid and salicylic acid, may include glycolic acid and trichloroacetic acid, may include lactic acid and trichloroacetic acid, may include salicylic acid and trichloroacetic acid, may include glycolic acid, lactic acid and trichloroacetic acid, may include glycolic acid, salicylic acid and trichloroacetic acid, and so on.

[0055] In various embodiments, the compositions according to the disclosure comprise at least one exfoliating agent but are free or substantially free of acetyl trifluoromethylphenyl valylglycine.

[0056] By way of non-limiting example only, compositions comprising at least one exfoliating agent that are free or substantially free of acetyl trifluoromethylphenyl valylglycine may comprise additional components and amounts thereof typically used in exfoliating compositions, such as, for example, at least one solvent, at least one oil, and additional optional components. These compositions may, in some embodiments, have a pH of not less than about 3.0, such as, for example, not less than about 3.5.The pH may be corrected to the desired value by the addition of a base (organic or inorganic) to the composition, for example ammonia or a primary, secondary or tertiary (poly)amine, such as monoethanolamine, diethanolamine, triethanolamine, isopropanolamine or 1,3-propanediamine, or alternatively by the addition of an inorganic or organic acid such as a carboxylic acid, for example citric acid.

[0057] For example, compositions comprising at least one exfoliating agent that are free or substantially free of acetyl trifluoromethylphenyl valylglycine may comprise at least one solvent selected from water and organic solvents. For example, the compositions may comprise water in an amount of at least about 15% by weight, such as, for example, from about 20% by weight to about 70% by weight, from about 25% by weight to about 60% by weight, from about 30% by weight to about 50% by weight, or from about 35% by weight to about 40% by weight, including all intermediate ranges and sub-ranges.

[0058] In other embodiments, compositions comprising at least one exfoliating agent which are free or substantially free of acetyl trifluoromethylphenyl valylglycine include one or more organic solvents such as monoalcohols and polyols, for example ethyl alcohol, isopropyl alcohol, propyl alcohol, benzyl alcohol and phenylethyl alcohol, or glycols or glycol ethers such as, for example, monomethyl, monoethyl and monobutyl ethers of ethylene glycol, propylene glycol or their ethers such as, for example, monomethyl ether of propylene glycol, butylene glycol, hexylene glycol, dipropylene glycol as well as diethylene glycol alkyl ethers, for example, diethylene glycol monoethyl ether or diethylene glycol monobutyl ether. In some embodiments, the alcoholic solvent is selected from ethanol, isopropyl alcohol, ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, pro-panediol, glycerin, or mixtures thereof. Optionally, in some embodiments, the organic solvent(s) may be present in amounts of up to about 20% by weight, for example, from about 0.1 to about 20% by weight, from about 1 to about 20% by weight, from about 5 to about 20% by weight, or from about 10 to about 15% by weight, based on the weight of the composition.

[0059] In various embodiments, compositions comprising at least one exfoliating agent that are free or substantially free of acetyl trifluoromethylphenyl valylglycine include one or more oils. Optionally, the at least one oil may be immiscible in water. For example, the at least one oil may be selected from hydrocarbons, silicones, fatty alcohols, glycols, and vegetable oils. The at least one oil may include one or a combination of polar and non-polar oils. In some embodiments, the oil may be selected from hydrocarbon oils of plant or vegetable origin, mineral oils, ester oils, fatty alcohols containing from 12 to 26 carbon atoms, fatty acids containing from 12 to 26 carbon atoms, and vinylpyrrolidone copolymers, and mixtures thereof. In certain particular embodiments, an oil may be selected from purcellin oil (cetostearyl octanoate),squalane, hemisqualane, isonyl isononanoate, a C12-C15 alkyl benzoate, 2-ethylhexyl palmitate, isodecyl neopentanoate, tridecyl neopentanoate, octyldodecyl neopentanoate, 2-octyldodecyl stearate, 2-octyldodecyl erucate, oleyl erucate, isostearyl isostearate, 2-octyldodecyl benzoate, alcohol or polyalcohol octanoates, decanoates or ricinoleates, isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, 2-ethylhexyl palmitate, 2-hexyldecyl laurate, 2-octyldecyl palmitate, 2-Octyldodecyl Myristate and 2-Diethylhexyl Succinate, Coco-Glyceride, Cyclomethicone, Dimethicone, Dicaprylyl Carbonate, Dicaprylyl Maleate, Caprylic / Capric Triglyceride, Isopropyl Myristate, Octyl Stearate, Isostearyl Linoleate, Lanolin Oil, Coconut Oil, Cocoa Butter, Olive Oil, Avocado Oil, Aloe Barbadensis Leaf Extract, Jojoba Oil, Castor Oil, Fatty Acid, Oleic Acid, Stearic Acid,fatty alcohol, cetyl alcohol, hexadecyl alcohol, diisopropyl adipate, hydroxybenzoate esters, benzoic acid esters of C9-C15 alcohols, alkanes, mineral oil, silicone, dimethyl polysiloxane, ether, polyoxypropylene butyl ether, polyoxypropylene cetyl ether, C12-C15 alkyl benzoate, arylalkyl benzoate, isopropyl lauroyl sarcosinate, and any combination thereof.

[0060] In some embodiments, the oil is selected from C 13-15 alkanes (hemisqualane), dicaprylyl carbonate, isonyl isononanoate, isopropyl myristate, dimethicone, squalane, mineral oil, or mixtures thereof. In an exemplary and non-limiting embodiment, the oil comprises a C 13-15 alkane (hemisqualane) or a combination of C 13-15 alkane, dicaprylyl carbonate, isononyl isononanoate, isopropyl myristate, dimethicone, squalane, and mineral oil. In some embodiments, the oil includes isopropyl myristate.

[0061] According to the various embodiments, the amount of at least one oil present in the compositions comprising at least one exfoliating agent that are free or substantially free of acetyl trifluoromethylphenyl valylglycine is at least about 5% by weight, at least about 10% by weight, at least about 15% by weight, or at least about 20% by weight, for example, may range from about 5% by weight to about 70% by weight, from about 10% by weight to about 65% by weight, from about 15% by weight to about 60% by weight, or from about 20% by weight to about 55% by weight, including all intermediate ranges and sub-ranges, based on the weight of the composition. In one embodiment, the total amount of oil is between about 20% by weight and about 60% by weight of the composition.

[0062] Compositions comprising at least one exfoliating agent which are free or substantially free of acetyl trifluoromethylphenyl valylglycine may also comprise one or more optional additional components typically used in chemical exfoliating compositions, for example one or more additives selected from citric acid, sodium chloride, chelating agents, antimicrobial agents, neutralizing agents, vitamins (e.g. tocopherol), perfumes, pearlizing agents, odor absorbers, colorants, essential oils, fruit extracts or combinations thereof.

[0063] In various embodiments, the optional additional components may include one or a combination of antimicrobial agents and their salts, selected from, for example, chlorphenesin, caprylyl glycol, phenoxyethanol, caprylhydroxamic acid, benzoic acid, salicylic acid, benzyl alcohol, phenethyl alcohol, benzalkonium chloride, 4-hydroxyacetophenone, piroctone olamine, hexylglycerin, ethylhexylglycerin, octylglycerin, benzylglycerin, 3-heptoyl-2,2-propandiol, 1,2-hexandiol, pentylene glycol, or mixtures thereof.

[0064] In various embodiments, the amount of one or more additional optional components, alone or in combination, may be present in the compositions comprising at least one chemical peeling agent which are free or substantially free of acetyl trifluoromethylphenyl valylglycine in an amount ranging from about 0.001 wt% to about 20 wt%, for example from about 0.005 wt% to about 0.01 wt%, from about 0.01 wt% to about 0.1% by weight, from about 0.15% by weight to about 5% by weight, from about 0.40% by weight to about 4% by weight, from about 0.5% by weight to about 2.5% by weight, or from about 1% by weight to about 2% by weight, including all intermediate ranges and sub-ranges, based on the weight of the composition. Processes

[0065] The methods according to the disclosure comprise applying (a) acetyl trifluoromethylphenyl valylglycine and (b) at least one exfoliating agent to the skin. The skin may be on the face, neck, chest, or hands. In various embodiments, the acetyl trifluoromethylphenyl valylglycine and at least one exfoliating agent may be applied to the skin simultaneously (e.g., when both are present in one composition or when both are present in two compositions that are mixed at or near the time of use), or consecutively (e.g., when each is present in a separate composition, which are applied sequentially to the skin, or when a non-chemical exfoliating agent is used).

[0066] In some embodiments, the methods comprise applying an amount of the at least one chemical peeling agent such that about 0.1 grams or more of the at least one chemical peeling agent is applied to the skin. For example, the skin treatment composition may be applied such that about 0.05 grams per decimeter (g / dm2) or more, such as about 0.06 g / dm2 or more, such as about 0.07 g / dm2 or more, such as about 0.08 g / dm2 or more, such as about 0.09 g / dm2 or more, such as about 0.1 g / dm2 or more, such as about 0.15 g / dm2 or more, about 0.2 g / dm2 or more, about 0.3 g / dm2 or more, about 0.4 g / dm2 or more, about 0.5 g / dm2 or more, about 0.75 g / dm2 or more, about 1 g / dm2 or more, about 1.5 g / dm2 or more, about 2 g / dm2 or more, about 2.5 g / dm2 or more, or about 3 g / dm2 or more of at least one chemical peeling agent is applied to the skin.In some embodiments, the composition is applied such that about 0.05 to about 10 g / dm2, about 0.06 to about 9 g / dm2, about 0.07 to about 8 g / dm2, about 0.08 to about 7 g / dm2, about 0.09 to about 6 g / dm2, about 0.1 to about 5 g / dm2, about 0.15 to about 4 g / dm2, about 0.2 to about 3 g / dm2, about 0.3 to about 2 g / dm2, about 0.4 to about 1 g / dm2; about 0.5 to about 10 grams per decimeter (g / dm2), about 0.5 to about 9 g / dm 2, about 0.5 to about 8 g / dm2, about 0.5 to about 7 g / dm2, about 0.5 to about 6 g / dm2, about 0.5 to about 5 g / dm2, about 0.5 to about 4 g / dm2, about 0.5 to about 3 g / dm2, about 0.5 to about 2 g / dm2, about 0.5 to about 1 g / dm2; or about 1 to about 10 grams per decimeter (g / dm2), about 1 to about 9 g / dm2, about 1 to about 8 g / dm2, about 1 to about 7 g / dm2, about 1 to about 6 g / dm2, about 1 to about 5 g / dm2, about 1 to about 4 g / dm2, about 1 to about 3 g / dm2, . or about 1 to about 2 g / dm2 of at least one chemical peeling agent is applied to the skin.

[0067] In some embodiments, the methods comprise applying an amount of acetyl trifluoromethylphenyl valylglycine such that about 0.1 grams or more of acetyl trifluoromethylphenyl valylglycine is applied to the skin. For example, the skin treatment composition may be applied such that about 0.05 grams per decimeter (g / dm2) or more, such as about 0.06 g / dm2 or more, such as about 0.07 g / dm2 or more, such as about 0.08 g / dm2 or more, such as about 0.09 g / dm2 or more, such as about 0.1 g / dm2 or more, such as about 0.15 g / dm2 or more, such as about 0.2 g / dm2 or more, about 0.3 g / dm2 or more, about 0.4 g / dm2 or more, about 0.5 g / dm2 or more, about 0.75 g / dm2 or more, about 1 g / dm2 or more, about 1.5 g / dm2 or more, about 2 g / dm2 or more, or plus, about 2.5 g / dm2 or more, or about 3 g / dm2 or more of acetyl trifluoromethylphenyl valylglycine is applied to the skin. In some embodiments,the composition is applied such that about 0.05 to about 10 g / dm2, about 0.06 to about 9 g / dm2, about 0.07 to about 8 g / dm2, about 0.08 to about 7 g / dm2, about 0.09 to about 6 g / dm2, about 0.1 to about 5 g / dm2, about 0.15 to about 4 g / dm2, about 0.2 to about 3 g / dm2, about 0.3 to about 2 g / dm2, about 0.4 to about 1 g / dm2; about 0.5 to about 10 grams per decimeter (g / dm2), about 0.5 to about 9 g / dm2, about 0.5 to about 8 g / dm2, about 0.5 to about 7 g / dm2, about 0.5 to about 6 g / dm2, about 0.5 to about 5 g / dm2, about 0.5 to about 4 g / dm2, about 0.5 to about 3 g / dm2, about 0.5 to about 2 g / dm2, about 0.5 to about 1 g / dm2; or about 1 to about 10 grams per decimeter (g / dm2), about 1 to about 9 g / dm2, about 1 to about 8 g / dm2, about 1 to about 7 g / dm2, about 1 to about 6 g / dm2, about 1 to about 5 g / dm2, about 1 to about 4 g / dm2, about 1 to about 3 g / dm2,or about 1 to about 2 g / dm2 of acetyl trifluoromethylphenyl valylglycine.,

[0068] In one embodiment, at least one chemical scrub may be left on the skin for 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, for example, between 10 seconds and 48 hours, before the at least one chemical scrub is removed, such as, for example, by rinsing. In one embodiment, the at least one chemical scrub is not removed before applying one or more other skin compositions, such as, for example, a composition comprising acetyl trifluoromethylphenyl valylglycine, moisturizers, sunscreen, or other anti-aging treatments.

[0069] The at least one exfoliating agent may be applied to the skin at least once a day, for example at least twice a day.

[0070] The at least one scrub may be applied in any known manner, and will vary depending on the type of scrubbing agent chosen. For example, it may be applied directly to the skin (e.g., with the fingers) or using an instrument such as a ball or pad particularly suited to wiping surfaces. The pad may include an absorbent core having the ability to absorb and retain liquid, and a coating layer in contact with the absorbent core and covering at least one side of the absorbent core. The coating layer has the ability to retain and wick liquid through the coating layer. The pad may be made from any suitable material, with suitable materials of interest including, but not limited to, cellulosic materials, polymeric materials, etc. The wipe may be formed from a paper-, cotton-, or textile-based substrate.In some instances, the absorbent pad material is comprised of hydrophilic materials. In other embodiments, absorbent pads are selected from the group consisting of gauzes, cellulose pads, agarose gels, acrylamide gels, or hydrogels.

[0071] The at least one chemical scrub may be applied directly to the skin or using a device such as a ball or pad, such as a cotton ball or cotton swab. The ball or pad may be soaked with about 0.5 mL to about 10 mL of a composition comprising the at least one chemical scrub, such as about 0.7 mL to about 9 mL, about 0.9 mL to about 8 mL, about 1 mL to about 7 mL, about 1.5 mL to about 6 mL, about 2 mL to about 5 mL, about 2 mL to about 4 mL, about 2 mL to about 3 mL, about 3 mL to about 5 mL, or about 4 mL to about 5 mL of a composition comprising at least one chemical scrub.When using a pad or ball, the at least one chemical peel may be applied by making at least one pass of the ball or pad over the skin, for example, at least 2 passes, at least 3 passes, at least 4 passes, at least 5 passes, at least 6 passes, at least 7 passes, at least 8 passes, at least 9 passes, at least 10 passes, for example, between 1 and 10 passes, 1 and 9 passes, 1 and 8 passes, 1 and 7 passes, 1 and 6 passes, 1 and 5 passes, 1 and 4 passes, 1 and 3 passes, and 1 and 2 passes.

[0072] If (a) acetyl trifluoromethylphenyl valylglycine and (b) at least one peeling agent are applied consecutively, the methods disclosed herein may include, in various embodiments, applying acetyl trifluoromethylphenyl valylglycine to the skin within about 48 hours before or after applying at least a peeling agent on the skin. For example, in some embodiments, acetyl trifluoromethylphenyl valylglycine may be applied within about 24 hours, about 20 hours, about 16 hours, about 12 hours, about 10 hours, about 8 hours, about 6 hours, about 4 hours, about 2 hours, about 1 hour, about 30 minutes, about 20 minutes, about 10 minutes, about 5 minutes, or about 1 minute after applying at least one peeling agent to the skin.In other embodiments, the acetyl trifluoromethylphenyl valylglycine may be applied within about 24 hours, about 20 hours, about 16 hours, about 12 hours, about 10 hours, about 8 hours, about 6 hours, about 4 hours, about 2 hours, about 1 hour, about 30 minutes, about 20 minutes, about 10 minutes, about 5 minutes, or about 1 minute before applying at least one exfoliating agent to the skin.

[0073] In one embodiment, the acetyl trifluoromethylphenyl valylglycine may be left on the skin for no more than 10 seconds, no more than 20 seconds, no more than 30 seconds, no more than 40 seconds, no more than 50 seconds, no more than 1 minute, no more than 2 minutes, no more than 3 minutes, no more than 5 minutes, no more than 10 minutes, no more than 15 minutes, no more than 20 minutes, no more than 25 minutes, no more than 30 minutes, no more than 35 minutes, no more than 40 minutes, no more than 45 minutes, no more than 1 hour, no more than 2 hours, no more than 5 hours, no more than 8 hours, no more than 10 hours, no more than 15 hours, no more than 20 hours, no more than 24 hours, no more than 36 hours, or no more than 48 hours before the acetyl trifluoromethylphenyl valylglycine is removed, such as, e.g., by rinsing.In one embodiment, the acetyl trifluoromethylphenyl valylglycine is not removed prior to the application of other skin compositions, such as, for example, a composition comprising a peeling agent, moisturizers, sunscreen, or other anti-aging treatments.

[0074] Acetyl trifluoromethylphenyl valylglycine may be applied at least once a day, at least twice a day, at least three times a day, at least four times a day, or at least five times a day, for example 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.

[0075] In one embodiment, the at least one chemical peeling agent is left on the skin for 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 the at least one chemical exfoliating agent is removed, e.g., by rinsing. In one embodiment, the at least one chemical peeling agent is left on the skin for at most 10 seconds, at most 20 seconds, at most 30 seconds, at most 40 seconds, at most 50 seconds, at most 1 minute, at most 2 minutes, at most 3 minutes, at most 5 minutes, at most 10 minutes, at most 15 minutes, at most 20 minutes, at most 25 minutes, at most 30 minutes, at most 35 minutes, at most 40 minutes, at most 45 minutes, at most 1 hour, at most 2 hours, at most 5 hours, at most 8 hours, at most 10 hours, at most 15 hours, at most 20 hours, at most 24 hours, at most 36 hours, or at most 48 hours before the at least one chemical peeling agent is removed, such as by rinsing.For example, the at least one chemical peeling agent may be left on the skin for a time range of 5 minutes to 60 minutes, e.g., 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 before the at least one chemical peeling agent is removed. In another example, the at least one chemical peeling agent may be left on the skin for a period of time ranging from 10 minutes to 60 minutes, e.g., 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 before the at least one chemical peeling agent is removed.

[0076] The methods may, in some embodiments, include applying the acetyl trifluoromethylphenyl valylglycine to the skin more than once, e.g., before and after applying at least one exfoliating agent to the skin. The methods may, in some embodiments, include applying the at least one exfoliating agent to the skin more than once, e.g., before and after applying the acetyl trifluoromethylphenyl valylglycine to the skin. In some cases, the method may be repeated to achieve optimal results.

[0077] In case of simultaneous application, the acetyl trifluoromethylphenyl valylglycine and the exfoliating agent(s) may optionally be present in a single composition. Alternatively, the acetyl trifluoromethylphenyl valylglycine and the exfoliating agent(s) may optionally be present in separate compositions, for example two or more compositions, three or more compositions, etc. which are mixed at or near the time of use.

[0078] The compositions comprising acetyl trifluoromethylphenyl valylglycine and / or at least one exfoliating agent may be, for example, one or more topical skin treatment compositions. The one or more topical skin treatment compositions may be formulated as a cream, lotion, serum, gel, or ampoule, or in any other topically suitable form. For example, the skin treatment compositions may be in the form of water-in-oil emulsions, oil-in-water emulsions, silicone-in-water emulsions, water-in-silicone emulsions, or combinations thereof. The skin treatment compositions may be used in methods for increasing or improving skin renewal.

[0079] Acetyl trifluoromethylphenyl valylglycine may be applied to the skin at least once a day, for at least 1, 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, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83 or 84 consecutive or non-consecutive days, preferably consecutive days. Acetyl trifluoromethylphenyl valylglycine may be applied to the skin at least once a day, for at least 1, 2, 3, 4, 5, 6 or 7 days a week, preferably at least 2 times a day. For example, acetyl trifluoromethylphenyl valylglycine may be applied to the skin at least twice a day, with the second application being at least about 6 hours, preferably at least about 8 hours, more preferably at least about 10 hours, most preferably at least about 12 hours after the first application.

[0080] The at least one exfoliating agent, for example a physical or chemical exfoliating agent, may be applied to the skin at least once a day for at least 1, 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 or 28 consecutive or non-consecutive days, preferably non-consecutive days. The at least one exfoliating agent may be applied to the skin at least once a day for at least 1, 2, 3, 4, 5, 6 or 7 days per week. For example, the at least one exfoliating agent may be applied to the skin at least every other day.

[0081] The at least one exfoliating agent may be applied to the skin at least every other day for a period of at least 1, 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 or 28 days, followed by a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days during which the exfoliating agent is not applied.

[0082] Alternatively, acetyl trifluoromethylphenyl valylglycine may be present in a composition and the skin may be treated with acetyl trifluoromethylphenyl valylglycine and a non-chemical peeling agent sequentially, as described herein for treatment with acetyl trifluoromethylphenyl valylglycine and chemical peeling agents.

[0083] It has been surprisingly and unexpectedly discovered that the use of acetyl trifluo- romethylphenyl valylglycine with at least one peeling agent improved skin renewal. Therefore, in various exemplary and non-limiting embodiments, the methods relate to improving skin renewal, comprising applying acetyl trifluoromethylphenyl valylglycine and at least one chemical peeling agent simultaneously or sequentially, as described above.

[0084] In exemplary and non-limiting embodiments, the methods disclosed herein may comprise a regimen comprising applying to the skin:

[0085] (a) acetyl trifluoromethylphenyl valylglycine at least once a day; and

[0086] (b) at least one exfoliating agent at least once every two or three days,

[0087] wherein the regimen lasts for a period of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably at least about 28 days.

[0088] In other exemplary and non-limiting embodiments, the methods disclosed herein may comprise a skin treatment regimen, the regimen comprising applying to the skin:

[0089] (a) of a composition comprising acetyl trifluoromethylphenyl valylglycine, at at least once a day; and

[0090] (b) a composition comprising at least one exfoliating agent, at least once every few days,

[0091] wherein the regimen lasts for a period of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably at least about 28 days.

[0092] In still other exemplary and non-limiting embodiments, the methods disclosed herein may comprise a skin treatment regimen, the regimen comprising applying to the skin:

[0093] (a) a composition comprising acetyl trifluoromethylphenyl valylglycine; and

[0094] (c) of a composition comprising at least one exfoliating agent, at least once every few days,

[0095] wherein the regimen lasts for a period of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably at least about 28 days.

[0096] In still other exemplary and non-limiting embodiments, the methods disclosed herein may comprise a skin treatment regimen, the regimen comprising applying to the skin:

[0097] (a) from about 0.1 to about 10% by weight of acetyl trifluoromethylphenyl va lylglycine, at least once, preferably at least twice, per day; and

[0098] (b) optionally, from about 0.1 to about 25% by weight of at least one chemical exfoliation chosen from α-hydroxy acids, β-hydroxy acids or their mixtures, at least once every two or three days,

[0099] wherein the regimen lasts for a period of at least about 10, preferably at least about 14 days, more preferably at least about 21 days, most preferably at least about 28 days. Necessary

[0100] The disclosure also relates to kits comprising acetyl trifluoromethylphenyl valylglycine and at least one exfoliating agent. In other embodiments, the kits comprise acetyl trifluoromethylphenyl valylglycine and at least one exfoliating instrument, such as, for example, a skin exfoliating pad which may or may not comprise a chemical exfoliating agent.

[0101] The kits may comprise at least two containers or compartments, wherein a first container or compartment comprises (a) a composition comprising acetyl trifluoromethylphenyl valylglycine, and a second container or compartment comprises (b) a composition comprising at least one chemical exfoliating agent or at least one exfoliating instrument. The kits may optionally further comprise at least one additional container or compartment.

[0102] By way of non-limiting example only, the kits may be in the form of a two-chamber container with a dispenser. The first and second chambers may be separated such that compositions (a) and (b) are separated from each other prior to use. The two-chamber container may optionally include a metering device for mixing and dispensing amounts of compositions (a) and (b) such that compositions (a) and (b) are dispensed as a single composition comprising the desired amounts of acetyl trifluoromethylphenyl valylglycine and chemical peeling agent(s) for use in various methods according to the disclosure.

[0103] As a further non-limiting example, the kits may comprise a first container with a dispenser, wherein the first container comprises (a) a composition comprising acetyl trifluoromethylphenyl valylglycine, and a second container with a dispenser, wherein the second container comprises (b) a composition comprising at least one chemical peeling agent. Optionally, the kits may also comprise instructions providing the dosage, order and timing of application, etc., of compositions (a) and (b) for use in various methods according to the disclosure.

[0104] Having described in detail the various embodiments of the present disclosure, it will be apparent that modifications and variations thereof are possible without departing from the scope of the disclosure. Furthermore, it should be appreciated that all Examples of the present disclosure, while illustrating embodiments of the disclosure, are provided as non-limiting examples and should therefore not be construed as limiting the various aspects thus illustrated. It is understood that all definitions given herein are solely for the purposes of the present disclosure.

[0105] The terms "comprising", "having" and "including" (or "comprise", "have" and "include") are used in their open and non-limiting sense. The expression "consisting essentially of" limits the scope of a claim to the specified materials or steps and to those which do not materially affect the fundamental and novel characteristics of the compositions.

[0106] In this application, the use of the singular includes the plural, unless otherwise indicated. The singular forms "a", "an", "the", "the" and "at least one" are understood to encompass the plural as well as the singular, unless the context clearly indicates otherwise, and these expressions, as well as the expression "one or more" which means "at least one", are expressly intended to include the individual components as well as mixtures / combinations thereof. Thus, where the disclosure refers to an element "selected from A, B, C, D, E, F and / or mixtures thereof", this indicates that any of A, B, C, D and F may be included (e.g., only A, only B, only C, etc.), or that a mixture of any two of A, B, C, D, E and F may be included (e.g., a mixture of A and B, a mixture of A and C, a mixture of C, D and E, etc.).

[0107] As used herein, the phrases "and mixtures thereof," "and a mixture thereof," "and combinations thereof," "and a combination thereof," "or mixtures thereof," "or a mixture thereof," "or combinations thereof," "or a combination thereof," and variations thereof are used interchangeably to indicate that the list of components immediately preceding the phrase, such as "A, B, C, D, or mixtures thereof," means that the component(s) may be selected from A, B, C, D, A+B, A+B+C, A+D, A+C+D, etc., without limitation of variations thereof. Thus, the components may be used individually or in any combination thereof.

[0108] Unless otherwise indicated, all percentages indicated herein are by weight, relative to the total weight of the composition.

[0109] All percentages, parts and ratios set forth herein are based on the total weight of the compositions of the present disclosure, unless otherwise indicated.

[0110] As used herein, the term "treat" (and its grammatical variations, such as "treat") refers to the application of the compositions of the present disclosure to the surface of the skin. By "treating" the skin according to the disclosure, the appearance of various signs of aging such as fine lines, wrinkles under the eyes, and / or discoloration, etc. is diminished.

[0111] As used herein, the terms "skin renewal", "epidermal renewal", are used interchangeably to refer to the process of skin cell renewal, including the formation of new cells and / or the removal of old cells.

[0112] The terms "substantially free" or "essentially free" as used herein mean that the specific material may be used in a manufacturing process in small amounts that do not materially affect the fundamental and novel characteristics of the compositions according to the disclosure. These terms may also mean that the specific material is not used in a manufacturing process but may still be present in a starting material that is included in the composition.

[0113] As used herein, the term "substantially free" or "essentially free" means that the specific material may be present in small amounts that do not materially affect the fundamental and novel characteristics of the compositions according to the disclosure. For example, there may be less than 2% by weight of a specific material added to a composition, based on the total weight of the compositions (provided that an amount less than 2% by weight does not materially affect the fundamental and novel characteristics of the compositions according to the disclosure). Similarly, the compositions may include less than 2% by weight, less than 1.5% by weight, less than 1% by weight, less than 0.5% by weight, less than 0.1% by weight, less than 0.05% by weight, or less than 0.01% by weight, or none of the specified materials.Furthermore, any components that are positively presented in the present disclosure may be negatively excluded from the claims, e.g., a claimed composition may be "free," "essentially free" (or "substantially free") of one or more components that are positively presented in the present disclosure. The term "substantially free" or "essentially free" as used herein may also mean that the specific material is not added to the composition but may still be present in a starting material that is included in the composition.

[0114] For the purposes of this disclosure, it should be noted that for the purpose of providing a more concise description, some of the quantitative expressions given herein are not qualified by 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 of that given value. All ranges and quantities given as used herein are intended to include subranges and quantities using any point disclosed as an endpoint. Thus, a range of “1 wt% to 10 wt%, such as 2 wt% to 8 wt%, such as 3 wt% to 5 wt%” is intended to encompass ranges of “1 wt% to 8 wt%,” “1 wt% to 5 wt%,” “2 wt% to 10 wt%,” etc. All numbers, quantities, ranges, etc., are intended to be modified by the term “about,” whether or not expressly stated. Similarly, a given range of “about 1 wt% to 10 wt%” is intended to be such that the term “about” modifies both the 1 wt% and 10 wt% bounds. The term "about" is used herein to indicate a difference of up to + / - 10% by weight from the stated number, such as + / - 9% by weight, + / - 8% by weight, + / - 7% by weight, + / - 6% by weight, + / - 5% by weight, + / - 4% by weight, + / - 3% by weight, + / - 2% by weight or + / - 1% by weight.Similarly, all bounds of the ranges are understood to be individually disclosed, so that, for example, a range of 1:2 to 2:1 is understood to disclose a ratio of both 1:2 and 2:1.

[0115] Unless otherwise expressly stated, it is in no way 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 state an order for its steps to be followed or it is not specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is in no way intended that any particular order be inferred. EXAMPLES

[0116] An implementation of the present disclosure is given by means of the following examples. The examples serve to illustrate the technology without being limiting in nature. Example 1 - Effect on Elastase Activity

[0117] The ability of acetyl trifluoromethylphenyl valylglycine ("ATV"), glycolic acid, and / or lactic acid to inhibit the hydrolyzing effect of elastase on elastin was evaluated in a one-tube neutrophil elastase (NE) inhibition assay (MAK213, Sigma-Aldrich, MO). Neutrophil elastase activity was measured by hydrolyzing the substrate to yield a fluorescent product (Xex = 400 / Xem = 505 nm) proportional to the enzyme activity present.

[0118] A 4x sample inhibitor solution of each test chemical peeling agent and acetyl trifluoromethylphenyl valylglycine, and each combination shown in Figures 1 and 2 was prepared. The inhibitor / positive control (elastase inhibitor, SPCK, AG Scientific), enzyme / negative control (contains elastase), neutrophil elastase, and substrate solutions were prepared. The test, control, and neutrophil elastase compounds were added to a 96-well plate, protected from light, and incubated at 37°C for 5 minutes. The elastin substrate was

[0119]

[0120]

[0121] was then added to each well and the fluorescence (FLU, Xex= 400 nm, Xem = 505 nm) was measured every minute for thirty minutes at 37°C. The slope of the graph (time versus FLU) was taken. The relative inhibition was calculated as follows: % Relative inhibition = ( ) x 100 \ * Enzyme Téw / The results are summarized in Figures 1 and 2, and in Tables 1 and 2 below. [Table 1] - Glycolic acid Mean Inhibition (%) Standard Deviation Positive Control (SPCK) 100.0109 7.137924 Negative Control (PBS) 0 1.995331 0.125 wt% glycolic acid 15.8949 1.471364 0.625 wt% glycolic acid 23.894386 1.4483291 0.0125 wt% ATV 12.48963 2.027787 0.025 wt% ATV 14.96986 2.009879 0.0625 wt% ATV 18.35813 2.03135 0.0125 wt% ATV + 0.125 wt% glycolic acid 29.23064 2.068951 0.025 wt% ATV + 0.125 wt% glycolic acid 52.44359 2.078497 0.0625 wt% ATV + 0.125 wt% glycolic acid 64.94714 2.163293 0.0125 wt% ATV + 0.625 wt% glycolic acid 29.1853 2.074465 0.025 wt% ATV + 0.625 wt% glycolic acid 51.42889 2.079239 0.0625 wt% ATV + 0.625 wt% glycolic acid 59.62986 2,11721 [Table 2] - Lactic acid

[0122] Mean inhibition (%) standard deviation Positive control (SPCK) 100.0808112 0.853338449 Negative control (PBS) 0 0.950033704 0.125 wt% lactic acid 8.507005217 0.741461688 0.625 wt% lactic acid 24.09473075 0.844732585 0.0125 wt% ATV 4.929862841 0.985914248 0.025 wt% ATV 9.310938342 0.963233445 0.0625 wt% ATV 11.95944762 0.96476709 0.0125 wt% ATV + 0.125 wt% lactic acid 14.81134343 1.122736831 0.025 wt% ATV + 0.125 wt% lactic acid 34.31431883 1.09021311 0.0625 wt% ATV + 0.125 wt% lactic acid 47.25971545 1.077350254 0.0125 wt% ATV + 0.625 wt% lactic acid 7.208154235 1.136390847 0.025 wt% ATV + 0.625 wt% lactic acid 29.76463436 1.08205185 0.0625 wt% ATV + 0.625% by weight of lactic acid 46.44821182 1.091261707 Positive control (SPCK) 100.0808112 0.853338449

[0123] Acetyl trifluoromethylphenyl valylglycine in combination with glycolic acid or lactic acid was found to inhibit elastin hydrolysis by elastase at all concentrations tested in a dose-dependent manner, suggesting that acetyl trifluoromethylphenyl valylglycine can be combined with AHAs such as lactic acid and / or glycolic acid to synergistically reduce elastin dissociation in the skin and further improve skin elasticity.

[0124] Example 2 - Effect on skin renewal

[0125] The effect of acetyl trifluoromethylphenyl valylglycine and / or chemical peels on skin turnover / desquamation, filaggrin expression, desmocollin-1 expression, kallikrein-related peptidase 5 expression and terminal deoxynucleotidyl transferase dUTP nick end labeling was evaluated in an ex vivo skin model.

[0126] Fresh normal human skin samples after abdominoplasty (3 batches, age 36-59 years, Hispanic / Caucasian / African American, female) were purchased from BioIVT Inc. (Westbury, NY). Tissues were degreased and cleaned of residues of blood. Explant samples were then created using a 12 mm biopsy punch. The explants were subjected to two separate 5 μL treatments of chemical scrub formulations (Scrub AD, see Figures 3-10), which were applied to the stratum corneum with a sterile cotton-tipped applicator for 10 minutes on day 1 and day 4 of culture. Untreated skin biopsies served as controls. Scrub A in the figures contained 3 wt% lactic acid and 0.2 wt% salicylic acid. Scrub B in the figures contained 3 wt% glycolic acid and 2.4 wt% lactic acid.Scrub C in the figures is a commercially available formulation containing 14.7% by weight glycolic acid and 0.1% by weight salicylic acid (Scrub C - Ingredients on the label: Water, Glycolic Acid, Dicaprylyl Carbonate, Di-methicone, Sodium Hydroxide, Butylene Glycol, Propanediol, Glycerin, Phytic Acid, Cetyl PEG / PPG-10 / 1 Dimethicone, Aluminum Starch Octenylsuccinate, Nylon-12, Polyglyceryl-4 Isostearate, Magnesium Sulfate, Jojoba Esters, Phenoxyethanol, Helianthus Annuus Seed Cera / Sunflower Seed Wax, Caprylyl Glycol, Disodium EDTA, Salicylic Acid, Acacia Decurrens Flower Cera / Acacia Decurrens Flower Wax, Polyglycerin-3, Tocopherol, Pentaerythrityl Tetra-di-t-butyl Hydroxyhydrocinnamate).Scrub D in the figures is a commercially available formulation containing 15% by weight trichloroacetic acid and 3% by weight glycolic acid (Scrub D-Ingredients on the label: Water, Trichloroacetic Acid, Glycolic Acid, Sodium Lauryl Sulfate, Citric Acid).

[0127] After this period, the samples were cleaned with sterile phosphate-buffered saline (“PBS”). Skin explants were maintained at the air-liquid interface at 37 °C and 5 wt% CO2 in two different treatment groups (n = 3 per medium type): 1) Dulbecco's modified Eagle's medium (DMEM) with 10 wt% fetal bovine serum, 1 wt% penicillin-streptomycin, and 2 wt% ethanol serving as vehicle control; and 2) Dulbecco's modified Eagle's medium with 10 wt% fetal bovine serum, 1 wt% penicillin-streptomycin, and 0.1 wt% ATV in 2 wt% ethanol serving as treatment group. Fresh medium was renewed every other day, except on weekends. After a 7-day culture period, samples from all explants were collected for histological and immunohistochemical analyses.The remaining biopsy punches were used for corneocyte maturation analysis.

[0128] Skin explants were processed for hematoxylin and eosin, TUNEL, and immunohistochemical staining (Reveal Biosciences, CA). H&E and TUNEL staining were performed according to the standard protocol (Reveal Biosciences, CA).

[0129] Immunohistochemical staining was performed using an immunostainer automated Leica Bond (Reveal Biosciences, CA). Heat-induced antigen retrieval was performed and nonspecific antibody binding was blocked. Sections were incubated with the primary antibodies mouse monoclonal anti-filaggrin (MA5-13441, Thermofisher, MA), rabbit polyclonal anti-kallikrein 5 (LS-B15516-50, LS Bio, WA), or rabbit polyclonal anti-desmocollin 1 (HPA075379, Sigma, MO). Primary staining was followed by rabbit anti-mouse IgG or Poly-HRP-anti-rabbit IgG, respectively, and was detected using the Bond Polymer Refine Detection Kit (DS9800, Leica Biosystems, RU). All sections were then counterstained with hematoxylin nuclear stain. Tissue samples were then embedded as formalin-fixed paraffin (FFPE) blocks and imaged with an inverted microscope (Leica DM500, Germany).

[0130] Figures 3-10 disclose the images of the stained explants on day 7 of culture following the application of different chemical scrubs with or without acetyl trifluoromethylphenyl valylglycine. Tissue structure and integrity after the chemical scrub treatments were observed among the hematoxylin and eosin stained tissues and immunohistochemically stained tissues in Figures 3-10. The tissues treated with 2 wt% ethanol in the culture medium in the figures serve as negative controls that demonstrate what untreated 2D ex vivo histological sections would look like, with no significant changes in tissue health or biomarkers assessed. Scrub D is a commercially available professional grade scrub that is included in Figures 3-5 for comparison with the home use scrubs (Scrubs A-C).The images are representative of the skin renewal process after treatment with the corresponding chemical peels and / or ATV.

[0131] Several observations were made:

[0132] - Treatment with chemical scrubs for domestic use + acetyl trifluoro methylphenyl valylglycine (Scrubs BC in [Fig. 3]) resulted in a change in the appearance of the stratum corneum compared to vehicle control tissues and tissues that were not treated with acetyl trifluoromethylphenyl valylglycine in H&E-stained tissues, indicating an increase in epidermal turnover compared to treatments that did not include ATV. Scrub C further showed some evidence of vacuole formation in the upper epidermis. Treatment with a commercially available professional chemical scrub + acetyl trifluoromethylphenyl valylglycine (Scrub D in [Fig. 4]) resulted in a change in the cohesion of the stratum corneum compared to vehicle control tissues and tissues not treated with acetyl trifluoromethylphenyl valylglycine in H&E-stained tissues, indicating an increase in epidermal turnover the epidermis after ATV treatment + professional scrub.

[0133] - Treatment with chemical scrubs + acetyl trifluoromethylphenyl va- lylglycine (scrubs BC in [Fig.4] and D in [Fig.7]) resulted in increased FLG expression in FLG-stained tissues compared to vehicle control tissue and tissues that were not treated with acetyl trifluoromethylphenyl valylglycine, indicating increased epidermal turnover compared to scrub treatments that did not include ATV.

[0134] - Treatment with a professional chemical peel available in the commercial + acetyl trifluoromethylphenyl valylglycine (Scrub D in [Fig.8]) resulted in a reduction in DSC1 expression, which may help facilitate cell turnover, compared to vehicle control tissues and tissues that were not treated with acetyl trifluoromethylphenyl valylglycine, indicating an increase in skin cell turnover following treatment with ATV + the professional scrub.

[0135] Treatment with a commercially available professional chemical scrub + acetyl trifluoromethylphenyl valylglycine (Scrub D in [Fig.9]) resulted in increased expression of KLK5 (an enzyme that regulates desquamation) and increased signs of exfoliation compared to vehicle control tissues and tissues that were not treated with acetyl trifluoromethylphenyl valylglycine, indicating increased desquamation after ATV + professional scrub treatment.

[0136] - None of the fabrics treated with chemical peeling and / or acetyl trifluoromethane Thylphenyl valylglycine did not show evidence of increased TUNEL expression (Figures 3-10) compared to vehicle control-treated tissues, suggesting that treated skin cells do not undergo increased rates of DNA degradation as might occur during the later stages of apoptosis.

[0137] Thus, the results of the ex vivo skin model demonstrate that acetyl trifluoromethylphenyl valylglycine can be synergistically combined with chemical scrubs having various components and their amounts to increase or improve skin renewal. Example 3 - Penetration into the skin

[0138] Human skin samples were obtained during abdominal surgery. Excess subcutaneous fat was removed, if necessary. The skin samples were excised and cut into pieces of approximately 2 cm x 2 cm. The thickness was measured and the transepidermal water loss (TEWL) was measured. Human skin was included in the study if the TEWL was between 0.5 and 13 g / m2 / h for abdominal skin. The 2 cm2 skin samples were kept in a static cell in a diffusion chamber in a Franz horizontal cell clamp system (Crown Glass, Inc.) and maintained at a constant temperature of 32°C ± 1°C. Static cells consist of a donor chamber and a receiver chamber with a 7 mL receiver fluid compartment separated by the skin.

[0139] The cells were placed on a magnetic stirrer integrated into a fixed temperature water bath maintained so as to have 32°C ± 1°C at the skin surface. The receiving compartment of each cell was filled with the receptor fluid (PB S) and was continuously stirred. The skin samples were placed on the receiving compartment. The donor compartment was then placed on the skin samples. After confirming the absence of air bubbles, a clamp was placed to connect the two compartments. Stirring of the receptor fluid began.

[0140] A composition containing 2% by weight of acetyl trifluoromethylphenyl valylglycine was applied to the skin sample at a rate of 10 mg / cell using a volumetric pipette and the exact amount applied was determined by weight and then recorded (Sartorius Entris II Essential analytical balance, Thermo-Fisher).

[0141] The experiment began immediately after application of the preparation to the skin surface and ended 16 hours after application. The preparation was washed off the skin samples 16 hours after application.

[0142] The skin was then stripped with a constant weight and application time. A maximum of 20 strippings were performed on each skin sample and the strippings were grouped by 5. The stripping samples were stored with the solvent (methanol) at -20°C for a maximum of 5 days before being analyzed. Using a scalpel blade, the epidermis (E) and dermis (D) corresponding to the application area were cut and then separated by heating. The epidermis (E) and dermis (D) were weighed. The remaining skin (RS) was cut into four parts. The RS bottles were stored with solvent (methanol) at -20°C for a maximum of 7 days before being analyzed. The dermis and epidermis samples were stored with solvent at -20°C for a maximum of 7 days before being analyzed. The receiving fluid was collected 16 hours after application and the samples were analyzed.

[0143] Recipient fluid samples were stored at -20°C for up to 6 days before analysis. The donor compartment, upper seal, and scalpel blade (LM) were placed in a vial with methanol and shaken for 2 hours. Samples were stored at -20°C for up to 5 days before analysis.

[0144] The final extract was analyzed by LC-MS / MS. The results are provided in [Fig. 11]. The skin penetration level (EP + D + RF in [Fig.l 1]) of acetyl trifluoromethylphenyl valylglycine was calculated to be approximately 4% by weight of the pre preparation of 2% by weight acetyl trifluoromethylphenyl valylglycine. Thus, about 0.08% by weight of acetyl trifluoromethylphenyl valylglycine penetrated through the stratum corneum. Thus, the dermal dose of the 2% by weight acetyl trifluoromethylphenyl valylglycine preparation based on in vitro functionality and penetration level was calculated to be at least about 0.08% by weight.

[0145] Thus, application of the 2% acetyl trifluoromethylphenyl valylglycine composition to the skin allowed approximately 0.8% to penetrate beyond the stratum corneum barrier and into the epidermis, dermis, and receptor fluid fractions. The level of penetration of acetyl trifluoromethylphenyl valylglycine correlates with the approximate level of acetyl trifluoromethylphenyl valylglycine assayed in the elastase (Example 1) and ex vivo skin (Example 2) experiments above. Example 4 - Clinical studies

[0146] A single-center, full-face, randomized, double-blind study was conducted to evaluate the clinical efficacy and consumer perception of three home skincare regimens for improving facial dyschromia and signs of aging in healthy Caucasian women. Eighty-six (86) healthy Caucasian women, aged 40 to 65 years (mean age: 57.85 years), with mild to moderate signs of aging and Fitzpatrick skin phototype II-III were included in this study. Pregnant or breastfeeding women who had used retinol or a related product and / or had received treatment for chemical peeling, laser, photofacial, dermabrasion, botulinum toxin, injectable fillers, or other skin tightening treatments within 6 months prior to the study start date were excluded. Once enrolled, subjects were asked to discontinue their usual skincare regimen.Subjects in Table 1 were trained in self-application of all test products prior to the start of the study.

[0147] [Tables3] Demographics of enrolled subjects Group 1: Retinol product Group 2: ATV and Home Scrub N = 46 Mean age (years): 58.6 Retinol-naive users: 38; retinol users: 8 N = 40 19 Fitz II and 21 Fitz III Retinol-naive users: 33; retinol users: 7

[0148] The study consisted of a 7-day washout period, followed by 12 weeks of treatment. Subjects were provided with ancillary products (cleanser, moisturizer, and SPF 30 sunscreen) for use during the washout period. The cleanser and sunscreen were also used during the 12 weeks of treatment. After the washout period, subjects were randomly divided into two home care groups, as illustrated in [Fig. 12] (A). The regimens are described below:

[0149] Regimen 1 consisted of a moisturizer, applied every morning; a retinol-containing product, applied every third night during the post-washout period of the first week, then every other day during the second week, and then applied every night for the remainder of the study duration.

[0150] Regimen 2 consisted of a 2% acetyl trifluoromethylphenyl va-lylglycine composition, applied daily morning and evening, and a 0.45% salicylic acid / 11.11% lactic acid chemical peel, applied three times a week in the evening.

[0151] Regimen group 1 used the same product routine during the 12 weeks of treatment. For regimen group 2, the 12-week treatment periods were divided into two phases, performed twice ([Fig. 12] (B)): 4 weeks of using the home chemical peel in combination with all topical products (week 1 to week 4 and week 7 to week 10), followed by 2 weeks of using the topical products, but not the chemical peel treatment (week 5 to week 6 and week 11 to week 12).

[0152] Clinical efficacy and tolerability of subjects were assessed at baseline and at weeks 2, 4, 6, 10, and 12. Photoaging parameters were assessed globally using a modified Griffith 10-point scale with the following numerical definition (half-point scores were used if necessary for accuracy): 0=none, 1-3=mild, 4-6=moderate, and 7-9=severe. Crow's feet and nasolabial fold lines were assessed globally using the Caucasian Skin Aging Atlas Volume 1 scales, ranging from 0 to 5 (scores of 0.4 and 0.6 were used if necessary for accuracy). Tolerability was assessed objectively at each visit by the investigator by evaluating signs of erythema, dryness, scaling, and peeling.In addition, subjects' self-assessment of the degree of burning, stinging, itching, dryness, tightness, or tingling of the facial skin was also recorded. Both clinical grading and subjective assessments of tolerability were measured using a 3-point scale (half-point scores were used if necessary for accuracy): where 0 = none; 1 = mild; 2 = moderate; and 3 = severe.

[0153] Self-assessment questionnaires were given to the subjects to assess their perception of facial skin condition, product efficacy and sensory appearance at baseline, weeks 4, 6 and 12, according to the following system: completely agree, somewhat agree, neither agree nor disagree, somewhat disagree and completely disagree.

[0154] For clinical evaluation of efficacy and safety parameters, a frequentist and Bayesian linear mixed model was used to analyze the mean difference in change from baseline with baseline, treatment, time, and treatment-time interaction as fixed effects and subject as random effect to obtain differences in treatment and time effects. Both effect size and p-values ​​were used to interpret significant differences (p-values ​​<0.05 were considered statistically significant and effect size classes).

[0155] Tolerability results:

[0156] Table 2 below shows the mean scores on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe).

[0157] [Tables4] Skin tolerance grading (mean score) in home care regimen groups Week 6 Week 12 Parameters Group 1 (n = 32 reactions) Group 2 (n = 15 reactions) Group 1 (n = 16 reactions) Group 2 (n = 9 reactions) Objective assessment (Investigator) Erythema 1 (n = 25) 1 (n = 12) 1 (n = 15) 1.2 Peeling 1.3 (n = 4) l(n=l) 1 (n = 1) 0 Dryness 1.5 (n = 2) l(n=l) 0 0 Edema 1.5 (n = 1) 0 0 0 Subjective assessment (subject reported) Stinging / burning / itching 1 (n = 1) 0 0 0 Tingling 0 0 0 0 Tightness 0 0 0 0

[0158] More subjects in group 1 than in group 2 experienced mild to moderate local intolerances at week 6, with signs of erythema as the determining factor. One subject also reported stinging, burning, and itching. At week 12, only mild erythematous reactions were clinically observed. Approximately half of the subjects in group 2 experienced mild to moderate local intolerances at week 12, compared with group 1.

[0159] Adverse events:

[0160] Overall, 8 subjects experienced a total of 8 non-serious adverse events (AEs) that were considered unrelated to the product regimen, and all were resolved without sequelae. These subjects were withdrawn from the study by the investigator.

[0161] Efficacy evaluations:

[0162] Clinical evaluation of anti-aging parameters demonstrated significant improvement from baseline for both treatment groups at weeks 2 and 4 for overall fine lines ([Fig. 15]). At week 6, group 2, which included chemical peeling, showed significant improvement in photodamage and nasolabial fold wrinkle appearance compared to baseline (Figures 16 and 17). At week 12, all treatment groups demonstrated significant improvement in all parameters assessed compared to baseline, as illustrated in Figures 15 to 19.

[0163] Treatment comparisons in the figures demonstrated that group (chemical peel and acetyl trifluoromethylphenyl valylglycine), was significantly better at improving nasolabial folds than group 1 (retinol-containing product) in week 4, and photodamage in week 7. Group 2 significantly outperformed group 1 in week 12 for all anti-aging parameters evaluated (figures 15 to 19).

[0164] The anti-aging routine containing acetyl trifluoromethylphenyl valylglycine + chemical peel treatment provides superior anti-aging and skin quality benefits in a kinetically accelerated manner, compared to the use of retinol alone.

Claims

Claims

1. A two-phase method for treating skin, the method comprising: a phase (1) comprising applying to the skin: (a) a composition comprising from about 0.01 to about 10% by weight, of acetyl trifluoromethylphenyl valylglycine at least once, preferably at least twice, per day; (b) a composition comprising at least one chemical skin peeling agent selected from α-hydroxy acids, β-hydroxy acids, or mixtures thereof, at least once every two or three days, wherein phase (1) lasts for a period of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably at least about 28 days; and a phase (2) comprising the application to the skin: (a) a composition comprising from about 0.01 to about 10% by weight of acetyl trifluoromethylphenyl valylglycine at least once daily, wherein phase (2) lasts for a period of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably at least about 14 days; wherein the amount of each component is relative to the total weight of the composition in which it is present; and wherein composition (a) comprising acetyl trifluoromethylphenyl valylglycine in phase (1), phase (2), or both, is optionally an oil-in-water emulsion or a silicone-in-water emulsion.

2. The method of claim 1, wherein step (1) comprises applying (b) a composition comprising at least one α-hydroxy acid to the skin, wherein the total amount of α-hydroxy acids in the composition is between about 0.1 and about 25% by weight, preferably between about 0.25 and about 20% by weight, more preferably between about 0.5 and about 15% by weight, most preferably between about 1 and about 12% by weight, based on the total weight of the composition in which he is present.

3. A method according to claim 1, wherein step (1) comprises applying (b) a composition comprising at least one β-hydroxy acid to the skin, wherein the total amount of β-hydroxy acids in the composition is between about 0.01 and about 2% by weight, preferably between about 0.05 and about 2% by weight, more preferably between about 0.05 and about 1% by weight, most preferably between about 0.05 and about 0.5% by weight, relative to the total weight of the composition in which it is present.

4. A method according to any one of claims 1 to 3, wherein step (1) comprises applying (b) a composition comprising (i) at least one α-hydroxy acid selected from lactic acid, glycolic acid, citric acid, malic acid, tartaric acid, mandelic acid, their derivatives or their mixtures, preferably lactic acid, and (ii) at least one β-hydroxy acid selected from salicylic acid, their derivatives or their mixtures, preferably salicylic acid, to the skin.

5. A method according to any one of claims 1 to 4, wherein the skin is on the face, neck, chest or hands.

6. A method according to any one of claims 1 to 5, wherein the method is a method for stimulating skin renewal, a method for stimulating skin exfoliation, a method for reducing the appearance of nasolabial folds, a method for reducing the appearance of wrinkles, a method for reducing the appearance of skin discoloration, or a method for improving the appearance of skin.

7. A kit comprising: (i) a first container comprising a composition comprising from about 0.01 to about 10% by weight of acetyl trifluoromethylphenyl valylglycine, based on the total weight of the composition; and (ii) a second container comprising a composition comprising at least one chemical skin exfoliating agent selected from α-hydroxy acids, β-hydroxy acids, or mixtures thereof.

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