FR3134006A1 - compositions and methods for improving the appearance of the skin - Google Patents

Abstract

compositions and methods for improving the appearance of the skin The disclosure relates to compositions, methods and kits for improving the appearance of the skin by applying to the skin acetyl trifluoromethylphenyl valylglycine, at least one retinoid, and optionally minus an additional skin exfoliating agent. Figure for abstract: figure 4

Description

compositions and methods for improving the appearance of the skin

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

CONTEXT

Aging can lead to the appearance of wrinkles and other skin changes. 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.

Retinol is used to treat aging skin. Once oxidized in the skin to retinoic acid, the biologically active molecule can stimulate the production of new collagen in the dermis, while reducing the activity of matrix metalloproteinase (MMP), inducing epidermal hyperplasia, improving exfoliation and decreasing melanin synthesis. However, using retinol can also cause skin irritation, such as redness, dryness, and inflammation. Additionally, the stability of retinol decreases over time.

Peeling is a natural phenomenon that slows 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 cellular 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 outer layer, the stratum corneum (also called stratum corneum), or the surface of the epidermis, which is made up of dead cells that are removed by desquamation. This surface loss is compensated by the migration of cells from the basal layer towards the surface of the epidermis, which leads to perpetual renewal of the skin.

Forced removal of the stratum corneum can 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 exfoliants can remove the stratum corneum. The term “exfoliation” conventionally refers to a controlled action of irritating the surface of the skin with a chemical substance or via a physical process. A surface exfoliation treatment targets the epidermis and is based on a superficial attack on the skin. It affects the epidermis either partially or entirely. A scrub treatment may consist, for example, of applying a chemical substance (a “chemical scrub agent”) to the skin with the aim of causing limited and controlled destruction of the epidermis (and in certain embodiments of the layers). upper parts of the dermis). The treatment may require multiple applications, and the entire procedure may last from one or a few days to several weeks or months.

Consumers seeking anti-aging treatments want easy-to-use, effective skincare routines that deliver fast visible results with good tolerability and minimal downtime. There is therefore a constant need to improve skin treatments that can increase skin turnover, while reducing the side effects of retinoids and peeling agents, particularly retinoids. It was surprisingly and unexpectedly discovered that acetyl trifluoromethylphenyl valylglycine works synergistically with retinol and optionally with exfoliating agents to improve skin renewal, and thus improve the appearance of the skin, while reducing the Skin irritation associated, for example, with the use of retinoids.

SUMMARY

The present disclosure relates to compositions and methods for treating skin, e.g. stimulating, increasing and/or improving skin regeneration and/or anti-aging benefits. For example, the disclosed treatments may act synergistically to encourage or improve skin renewal, while reducing irritation from retinoids, and conferring greater anti-aging and skin quality benefits to the skin and /or stronger and/or obtaining these benefits with faster kinetics compared to retinol alone or the use of peptides and chemical scrubs alone. According to certain aspects of the disclosure, the skin treatment methods and compositions may advantageously improve the elasticity of the skin and/or reduce the appearance of discoloration/hyperpigmentation and/or wrinkles, such as wrinkles under the skin. eyes, fine lines and/or nasolabial folds.

In various embodiments, the disclosure relates to a two-phase process for treating skin, the process comprising:

a phase (1) comprising application to the skin:

(a) acetyl trifluoromethylphenyl valylglycine at least once a day;

(b) at least one retinoid or derivative thereof at least once every two or three days; And

(c) optionally at least one additional skin exfoliating agent at least once every two or three days,

wherein the (b) at least one retinoid or derivative thereof and the (c) optionally at least one additional skin exfoliating agent are separately applied to the skin for at least about 6 hours, preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

wherein phase (1) lasts for a period of time of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably of at least approximately 28 days; And

a phase (2) comprising application to the skin:

(a) acetyl trifluoromethylphenyl valylglycine at least once a day; And

(b) at least one retinoid or derivative thereof at least once every two or three days; And

wherein phase (2) lasts for a period of time of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably of at least about 14 days.

In other embodiments, the disclosure relates to a two-phase process for treating skin, the process comprising:

a phase (1) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day;

(b) a composition comprising at least one retinoid or a derivative thereof, at least once every two or three days; And

(c) optionally, of a composition comprising at least one additional skin exfoliating agent, at least once every two or three days,

wherein composition (b) comprising at least one retinoid or derivative thereof and optional composition (c) comprising at least one additional skin exfoliating agent are applied to the skin for at least about 6 hours, from preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

wherein phase (1) lasts for a period of time of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably of at least approximately 28 days; And

a phase (2) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day; And

(b) a composition comprising at least one retinoid or a derivative thereof, at least once every two or three days; And

wherein phase (2) lasts for a period of time of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably of at least about 14 days.

In still other embodiments, the disclosure relates to a two-phase process for treating skin, the process comprising:

a phase (1) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day;

(b) a composition comprising at least one retinoid or a derivative thereof and acetyl trifluoromethylphenyl valylglycine, at least once every two or three days; And

(c) optionally a composition comprising at least one additional skin exfoliating agent, at least once every two or three days,

wherein composition (b) comprising at least one retinoid or derivative thereof and acetyl trifluoromethylphenyl valylglycine and optional composition (c) comprising at least one additional skin exfoliating agent are applied to the skin to at least about 6 hours, preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

wherein phase (1) lasts for a period of time of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably of at least approximately 28 days; And

a phase (2) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day; And

(b) a composition comprising at least one retinoid or a derivative thereof and acetyl trifluoromethylphenyl valylglycine, at least once every two or three days; And

wherein phase (2) lasts for a period of time of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably of at least about 14 days.

In yet other embodiments, the disclosure relates to a two-phase process for treating skin, the process comprising:

a phase (1) comprising application to the skin:

(a) from about 0.1 to about 10% by weight of acetyl trifluoromethylphenyl valylglycine, at least once, preferably at least twice, per day;

(b) from about 0.001 to about 10% by weight of at least one retinoid or a derivative thereof, at least once every two or three days; And

(c) optionally, from about 0.1 to about 25% by weight of at least one additional skin exfoliating agent selected from at least α-hydroxy acids, β-hydroxy acids or mixtures thereof once every two or three days,

wherein the (b) at least one retinoid or derivative thereof and the (c) at least one optional additional skin exfoliating agent are separately applied to the skin for at least about 6 hours, preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

wherein phase (1) lasts for a period of time of at least about 10, preferably at least about 14 days, more preferably at least about 21 days, most preferably at least about 21 days, less about 28 days; And

a phase (2) comprising application to the skin:

(a) from about 0.1 to about 10% by weight of acetyl trifluoromethylphenyl valylglycine, at least once, preferably at least twice, per day; And

(b) from about 0.001 to about 10% by weight of at least one retinoid or a derivative thereof, at least once every two or three days; And

wherein phase (2) lasts for a period of time of at least about 5, preferably at least about 7, more preferably at least about 10, most preferably at least about 14 days ;

in which the quantities of all the components are relative to the total weight of the composition in which they are present.

The methods may, for example, be methods for reducing the appearance of nasolabial folds, methods for reducing the appearance of skin wrinkles, methods for improving the appearance of the skin, and/or methods for reducing the appearance of skin discoloration. In other embodiments, the disclosure relates to improving skin tolerance to retinoids and/or retinoid derivatives, comprising applying to the skin acetyl trifluoromethylphenyl valylglycine at least one retinoid or derivative of this one.

The disclosure also relates to compositions comprising acetyl trifluoromethylphenyl valylglycine and either at least one retinoid or derivative thereof, or at least one skin exfoliating agent other than retinoids or derivatives thereof.

The disclosure also relates to kits comprising acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and optionally at least one skin exfoliating agent and/or implementation for exfoliation of the skin. skin.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying drawings, which are incorporated herein and form part of this specification, illustrate exemplary embodiments of the disclosure and, together with the general description given above and the description provided herein, serve to explain the particulars of the disclosure.

There shows two-dimensional ex vivo histological cross-sections of (1) a skin sample treated with vehicle control (control-2 wt% ethanol), (2) a skin sample treated with 0.1 wt% of acetyl trifluoromethylphenyl valylglycine (ATV), (3) a skin sample treated with 0.003% retinol, and (4) a skin sample treated with 0.003% retinol and 0.1% by weight acetyl trifluoromethylphenyl valylglycine. Cross sections are stained for (A) hematoxylin and eosin (H&E) expression, (B) filaggrin (FLG) expression, and (C) desmocollin-1 expression ( DSC). Black scale bars = 100 µm.

There shows the amount of a 2% solution of acetyl trifluoromethylphenyl valylglycine in the stratum corneum (SC), epidermis (Ep), dermis (D), receiving fluid (RF), and the amount passing through the stratum corneum to penetrate the skin (Ep + D + RF), after application to skin samples using a Franz cell with horizontal cell clamp system.

There shows (A) a home care product regimen for 3 study groups (groups 1 to 3), and (B) the treatment phases for groups 2 and 3 of Example 3.

There shows a graph comparing the clinical results of a 2 week, 6 week and 12 week regimen described in Example 3, with group 1 being treated with 0.3% retinol and group 3 being treated with a solution of 2 % acetyl trifluoromethylphenyl valylglycine, 0.3% retinol and a 0.45% salicylic acid/11.11% lactic acid chemical peel. Check marks (“√”) indicate a statistically significant improvement in the results of group 3 compared to group 1. Equal signs (“=”) indicate no statistical difference in the results between group 1 and group 3.

There shows a graph comparing the clinical results of a 2 week, 6 week and 12 week regimen described in Example 3, with group 1 being treated with 0.3% retinol and group 3 being treated with a solution of 2 % acetyl trifluoromethylphenyl valylglycine, 0.3% retinol and a chemical peel with 0.45% salicylic acid and 11.11% lactic acid, compared to the reference base. Empty boxes indicate no statistical difference in clinical outcomes of Group 1 or Group 3 compared to baseline. Boxes with solid diagonal lines indicate a statistically significant (p < 0.05) improvement in clinical outcomes for Group 1 or Group 3 compared to baseline. Boxes with dashed diagonal lines indicate statistically significant and clinically meaningful (p < 0.05) improvements in outcomes for Group 1 or Group 3 compared to baseline.

There shows a clinical grading graph for overall fine lines between all treatment groups (groups 1-3) during the 12-week regimen of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0 .05) in overall fine lines compared to group 1 at the respective time point. A hash mark (“#”) indicates a statistically significant difference (p < 0.05) in overall fine lines compared to Group 2 at the respective time point.

There shows a graph of the clinical ranking of overall fine lines between all treatment groups (groups 1 to 3) during the 12-week regimen of Example 3. An asterisk ("*") indicates a statistically significant difference (p < 0, 05) at the nasolabial folds compared to group 1 at the respective time point.

There shows a clinical grading graph of overall fine lines between all treatment groups (groups 1 to 3) during the 12-week regimen of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0, 05) at the level of photodamage compared to group 1 at the respective time point. A hash mark (“#”) indicates a statistically significant difference (p < 0.05) in photodamage compared to group 2 at the respective time point.

There shows a clinical grading graph for overall fine lines between all treatment groups (groups 1-3) on the 12-week regimen of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0 .05) at the level of wrinkles under the eyes compared to group 1 at the respective time point. A hash mark (“#”) indicates a statistically significant difference (p < 0.05) in under-eye wrinkles compared to Group 2 at the respective time point.

There shows a clinical grading graph of overall fine wrinkles between all treatment groups (groups 1 to 3) during the 12-week regimen of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0.05) in overall healthy appearance compared to group 1 at the respective time point. A hash mark (“#”) indicates a statistically significant difference (p < 0.05) in overall healthy appearance compared to group 2 at the respective time point.

There shows a clinical grading graph for overall fine lines between treatment group 1 (retinol) and group 3 (ATV + scrub + retinol) on the 12-week regimen of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0.05) in overall fine lines compared to group 1 at the respective time point.

There shows a graph of the clinical ranking of overall fine lines between treatment group 1 (retinol) and group 3 (ATV + scrub + retinol) on the 12-week schedule of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0.05) at the nasolabial folds compared to group 1 at the respective time point.

There shows a clinical grading graph for overall fine lines between treatment group 1 (retinol) and group 3 (ATV + scrub + retinol) on the 12-week regimen in Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0.05) in photodamage compared to group 1 at the respective time point.

There shows a clinical grading graph for overall fine lines between treatment group 1 (retinol) and group 3 (ATV + scrub + retinol) on the 12-week regimen in Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0.05) in under-eye wrinkles compared to group 1 at the respective time point.

There shows a clinical grading graph for overall fine lines between treatment group 1 (retinol) and group 3 (ATV + scrub + retinol) on the 12-week regimen of Example 3. An asterisk (“*”) indicates a statistically significant difference (p < 0.05) in overall healthy appearance compared to group 1 at the respective time point.

Detailed description

The disclosure relates to compositions, methods and kits for treating skin, for example by increasing, accelerating and/or improving skin turnover, and/or improving the appearance of skin. The compositions according to various aspects of the disclosure include acetyl trifluoromethylphenyl valylglycine and/or at least one retinoid or derivative thereof, and optionally at least one additional skin exfoliating agent. The methods according to various aspects of the disclosure include applying to the skin, simultaneously or sequentially, acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and optionally at least one agent additional skin scrub. The kits according to various aspects of the disclosure include acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and optionally at least one additional skin exfoliating agent.

The compositions and methods according to various aspects of the disclosure may, in various embodiments, protect against and/or slow the breakdown of skin elastase, improve skin elasticity, decrease sagging, improve or accelerate the skin regeneration/skin peeling, stimulate or improve epidermal renewal, increase exfoliation, reduce or slow the appearance of aging skin (such as wrinkles), improve skin discoloration and/or pigmentation skin, increase skin keratinization or superior terminal differentiation, and/or smooth the skin. For example, methods of treating the skin generally include the application of acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and optionally at least one skin exfoliating agent. additional to the skin to accelerate skin renewal/regeneration and/or anti-aging benefits, while reducing irritation from retinoids. Surprisingly, it has been found that in certain embodiments, the skin treatment methods and compositions according to the disclosure impart greater and/or stronger benefits to the skin in terms of anti-aging effect and skin quality, and/or obtain these benefits with faster kinetics compared to the use of peptides, retinol and/or chemical exfoliation alone.

In various embodiments, the acetyl trifluoromethylphenyl valylglycine, the at least one retinoid or derivative thereof, and the at least one additional skin exfoliating agent act synergistically to improve the appearance of the skin . For example, in various embodiments, the skin treatment methods and compositions disclosed herein may be effective in reducing the appearance of wrinkles through acceleration of cellular regeneration, for example, through keratinization and higher terminal differentiation. In other embodiments, the skin treatment methods and compositions disclosed herein reduce the appearance of wrinkles through inhibition of elastase, thereby allowing the growth of elastin fibers as opposed to their degradation by these. enzymes, improving skin elasticity. In still other embodiments, the skin treatment methods and compositions described herein reduce skin irritation due to retinoids.

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

Compositions

Compositions according to various embodiments of the disclosure include acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and/or at least one additional skin exfoliating agent. In certain embodiments, the compositions according to the disclosure comprise both acetyl trifluoromethylphenyl valylglycine and at least one retinoid or derivative thereof. In other embodiments, the disclosed compositions include acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and at least one additional skin exfoliant.

Acetyl trifluoromethylphenyl valylglycine

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, relative to the total weight of the composition in which it is present. For example, the amount of acetyl trifluoromethylphenyl valylglycine may range 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% by weight, about 0.1 to about 14% by weight, about 0.1 to about 12% by weight, about 0.1 to about 10% by weight, about 0.1 to about 8% by weight weight, about 0.1 to about 6% by weight, about 0.1 to about 5% by weight, about 0.1 to about 4% by weight, about 0.1 to about 3% by weight, about 0.1 at about 2% by weight, about 0.1 to about 1% by weight; about 0.25 to about 25 wt.%, about 0.25 to about 22 wt.%, about 0.25 to about 19 wt.%, about 0.25 to about 16 wt.%, 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 wt.%, about 0.25 to about 4 wt.%, about 0.25 to about 3 wt.%, about 0.25 to about 2 wt.%, about 0.25 to about 1 % in weight ; about 0.5 to about 25 wt.%, about 0.5 to about 22 wt.%, about 0.5 to about 19 wt.%, about 0.5 to about 16 wt.%, 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 % in weight ; about 0.75 to about 25 wt.%, about 0.75 to about 22 wt.%, about 0.75 to about 19 wt.%, about 0.75 to about 16 wt.%, 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 wt.%, about 0.75 to about 4 wt.%, about 0.75 to about 3 wt.%, about 0.75 to about 2 wt.%; about 1 to about 25 wt.%, about 1 to about 22 wt.%, about 1 to about 19 wt.%, about 1 to about 16 wt.%, about 1 to about 14 wt.%, 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 wt.%, about 2 to about 22 wt.%, about 2 to about 19 wt.%, about 2 to about 16 wt.%, about 2 to about 14 wt.%, 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 wt.%, about 5 to about 22 wt.%, about 5 to about 19 wt.%, about 5 to about 16 wt.%, about 5 to about 14 wt.%, 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 wt.%, about 7.5 to about 22 wt.%, about 7.5 to about 19 wt.%, about 7.5 to about 16 wt.%, about 7.5 at 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 approximately 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; about 20 to about 27.5% by weight, or about 20 to about 22% by weight, including intermediate ranges and subranges, based on the total weight of the composition in which it is present.

In some embodiments, the composition includes an amount of acetyl trifluoromethylphenyl valylglycine such that about 0.001 to about 2.5 weight percent of acetyl trifluoromethylphenyl valylglycine penetrates through the epidermis and reaches the dermal layer of the skin. For example, the compositions may include an amount of acetyl trifluoromethylphenyl valylglycine such as about 0.002 to about 2 wt.%, about 0.002 to about 1.9 wt.%, about 0.002 to about 1.8 wt.%, 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 weight percent, about 0.002 to about 1.1 weight percent, about 0.002 to about 1 weight percent, about 0.002 to about 0.9 weight percent, about 0.002 to about 0 .8% by weight, approximately 0.002 to approximately 0.7% by weight, approximately 0.002 to approximately 0.6% by weight, approximately 0.002 to approximately 0.5% by weight, approximately 0.002 to approximately 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% by weight, about 0.002 to about 0.01% by weight, about 0.01 to about 2% by weight, about 0.01 to about 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% by weight, about 0.01 to about 0.2% by weight, about 0.01 to about 0.1% by weight, 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 0.01 to about 0.01% by weight, about 0.006 to about 2% by weight, about 0.006 to about 1.9% by weight, about 0.006 to about 1.8% by weight, about 0.006 to about 1.7% by weight, 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 % by weight, about 0.006 to about 1.1% by weight, about 0.006 to about 1% by weight, about 0.006 to about 0.9% by weight, about 0.006 to about 0.8% by weight, about 0.006 to about 0.7% by weight, about 0.006 to about 0.6% by weight, 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 wt.%, about 0.006 to about 0.1 wt.%, about 0.006 to about 0.09 wt.%, about 0.006 to about 0.08 wt.%, 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 wt.%, about 0.006 to about 0.01 wt.%, about 0.008 to about 2 wt.%, about 0.008 to about 1.9 wt.%, about 0.008 to about 1.8% by weight, about 0.008 to about 1.7 weight percent, about 0.008 to about 1.6 weight percent, about 0.008 to about 1.5 weight percent, about 0.008 to about 1.4 weight percent, about 0.008 to about about 1.3% by weight, about 0.008 to about 1.2% by weight, about 0.008 to about 1.1% by weight, about 0.008 to about 1% by weight, about 0.008 to about 0.9% by weight, about 0.008 to about 0.8% by weight, about 0.008 to about 0.7% by weight, about 0.008 to about 0.6% by weight, about 0.008 to about 0.5% by weight, about 0.008 to about 0, 4% by weight, about 0.008 to about 0.3% by weight, about 0.008 to about 0.2% by weight, about 0.008 to about 0.1% by weight, about 0.008 to about 0.09% by weight, about 0.008 to about 0.08 wt.%, about 0.008 to about 0.07 wt.%, about 0.008 to about 0.06 wt.%, about 0.008 to about 0.05 wt.%, 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% by weight, about 0.01 to about 1.4% by weight, about 0.01 to about 1.3% by weight, about 0.01 to about 1.2% by weight weight, about 0.01 to about 1.1% by weight, about 0.01 to about 1% by weight, about 0.01 to about 0.9% by weight, about 0.01 to about 0.8% by weight weight, about 0.01 to about 0.7 weight percent, about 0.01 to about 0.6 weight percent, about 0.01 to about 0.5 weight percent, 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 0.01 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% by weight, about 0.025 to about 0.2% by weight weight, about 0.025 to about 0.1% by weight, about 0.025 to about 0.09% by weight, about 0.025 to about 0.08% by weight, about 0.025 to about 0.07% by weight, about 0.025 to about 0.06% by weight, about 0.025 to about 0.05% by weight, about 0.025 to about 0.04% 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% 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, 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 0.05 to about 0.09% by weight, about 0 .05 to about 0.08 wt.%, about 0.05 to about 0.07 wt.%, about 0.06 to about 2 wt.%, about 0.06 to about 1.9 wt.%, 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% by weight, about 0.06 to about 1.1% by weight weight, about 0.06 to about 1% by weight, about 0.06 to about 0.9% by weight, about 0.06 to about 0.8% by weight, about 0.06 to about 0.7% by weight weight, about 0.06 to about 0.6% by weight, about 0.06 to about 0.5% by weight, about 0.06 to about 0.4% by weight, about 0.06 to about 0.3 % by weight, 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 wt.%, about 0.06 to about 0.07 wt.%, about 0.07 to about 2 wt.%, about 0.07 to about 1.9 wt.%, about 0.07 to about 1 .8% by weight, approximately 0.07 to approximately 1.7% by weight, approximately 0.07 to approximately 1.6% by weight, approximately 0.07 to approximately 1.5% by weight, approximately 0.07 to approximately 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, about 0.07 to about 0.9% by weight, about 0.07 to about 0.8% by weight, about 0.07 to about 0.7% by weight, about 0, 07 to about 0.6% by weight, about 0.07 to about 0.5% by weight, about 0.07 to about 0.4% by weight, about 0.07 to about 0.3% by weight, 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% by weight, about 0.08 to about 1.9% by weight, about 0.08 to about 1.8% by weight, about 0.08 to about 1.7% by weight , 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% by weight, 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% by weight, about 0.08 to about 0.8% by weight, about 0.08 to about 0.7% by weight, about 0.08 to about 0.6% by weight, about 0.08 to about 0, 5% by weight, about 0.08 to about 0.4% by weight, about 0.08 to about 0.3% by weight, about 0.08 to about 0.2% by weight, about 0.08 to about 0.1% by weight, 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 wt.%, about 0.09 to about 1.3 wt.%, about 0.09 to about 1.2 wt.%, about 0.09 to about 1.1 wt.%, about 0 .09 to about 1 wt.%, about 0.09 to about 0.9 wt.%, about 0.09 to about 0.8 wt.%, about 0.09 to about 0.7 wt.%, 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 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, 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 of acetyl trifluoromethylphenyl valylglycine penetrates the epidermis and reaches the dermal layer of the skin.

In some embodiments, the compositions include an amount of acetyl trifluoromethylphenyl valylglycine such as about 0.01 to about 1.5 weight percent, preferably about 0.025 to about 1.3 weight percent, more preferably about 0.5 to about 1.1% by weight, most preferably about 0.6 to about 1% by weight of acetyl trifluoromethylphenyl valylglycine penetrates the epidermis and reaches the dermal layer of the skin.

Retinoids

According to various embodiments, the compositions according to the disclosure comprise at least one retinoid or a derivative thereof. As used herein, a “retinoid” refers to a compound that comprises a four-isoprenoid unit. Non-limiting examples of retinoids or derivatives thereof that may be used include retinol (vitamin A), retinal, retiferol, tretinoin (all-trans-retinoic acid, e.g. retinoic acid, Retin-A), isotretinoin, alitretinoin (9-cis-retinoic acid), etretinate, acitretin, tazarotene, bexarotene, adapalene, N,N-diethylaminoethyl 13-cis-retinoate, 13-cis-retinoic acid, all-trans-N,N-diethylaminoethyl retinoate, Retinyl N,N-dimethyl-2-aminoacetate, retinyl palmitate, retinoid metabolites, or agents that can be metabolized to a retinoid or retinoid metabolite.

According to various embodiments, the compositions according to the disclosure comprise at least approximately 0.00001% by weight of the at least one retinoid or a derivative thereof, for example from approximately 0.0001 to approximately 10%. by weight, relative to the total weight of the composition in which it is present. For example, the amount of the at least one retinoid or a derivative thereof may range from about 0.0003 to about 9.5 wt.%, from about 0.0005 to about 9 wt.% , from about 0.0007 to about 8.5% by weight, from about 0.0009 to about 8% by weight, from about 0.001 to about 7% by weight, including all intermediate ranges and subranges, relative to the total weight of the composition in which it is present.

In various embodiments, acetyl trifluoromethylphenyl valylglycine and at least one retinoid or derivative may be present in the same composition, or may be present in separate compositions. The compositions comprising acetyl trifluoromethylphenyl valylglycine and/or at least one retinoid or a derivative may be, for example, composition(s) for topical treatment of the skin. The topical skin treatment composition(s) may be formulated in the form of a cream, lotion, serum, gel or 'an 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-water emulsions, silicone, or combinations thereof. In one embodiment, acetyl trifluoromethylphenyl valylglycine and optionally the at least one retinoid or derivative thereof are present in an emulsion, such as an oil-in-water emulsion. For example, the emulsion may be an oil/silicone-in-water emulsion. In some embodiments, the emulsion includes a silicone oil such as dimethicone. The emulsion may also optionally include emulsifiers, such as octyldodecyl xyloside and/or polysorbate.

Additional skin exfoliating agents

According to various embodiments, the compositions according to the disclosure optionally comprise at least one additional physical and/or chemical skin exfoliation agent. In various embodiments, the compositions may include one or more physical exfoliants, such as microbeads or other small particles. In other embodiments, the compositions may include one or more chemical exfoliating agents.

Chemical skin exfoliants which may be used include, but are not limited to, β-hydroxy acids (BHAs), e.g. salicylic acid and derivatives thereof (including 5-n-octanoyl acid). salicylic acid, also known as capryloyl salicylic acid (INCI name)); α-hydroxy acids (AHA), such as glycolic, citric, lactic, tartaric, malic or mandelic acids; 8-hexadecene-1,16-dicarboxylic acid, or 9-octadecene dioic acid; urea and derivatives thereof; trichloroacetic acid; gentisic acid and derivatives thereof; oligofuctoses; cinnamic acid; Saphora japonica extract; resveratrol; certain derivatives of jasmonic acid; resorcinol; phenol; or mixtures thereof.

Other exemplary and non-limiting chemical skin exfoliation agents which may be used include compounds involved in exfoliation or degradation of corneodesmosomes, such as aminosulfonic compounds, e.g. 4-(2-hydroxyethyl)piperazine acid. -1-propanesulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine) and derivatives thereof; glycine-type α-amino acid derivatives (as described in document 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.

As other exemplary and non-limiting chemical exfoliating agents for the skin, suitable for use in the compositions according to the disclosure, EDTA and derivatives thereof, kelp extracts, O-linoleyl-6-D-gluocose are mentioned. ; (3-hydroxy-2-pentylcyclopentyl) acetic acid, glycerol trilactate, S carboxymethyl cysteine, silica-containing derivatives of salicylate such as those described in patent EP 0 796 861, oligofuctases such as those described in patent EP 0 218 200, agents having effects on transglutaminase as in patent EP 0 899 330; F icus opuntia indica flower extract such as Exfolactive ^® from Silab; 8-hexadecene 1,16-dicarboxylic acid; esters of glucose and vitamin F; or mixtures thereof.

The chemical agent(s) for exfoliating the skin may, in certain embodiments, be chosen from α-hydroxy acids such as citric, lactic, glycolic, malic, tartaric or mandelic; β-hydroxy acids such as salicylic acid or derivatives thereof, for example n-octanoyl-5-salicylic acid; trichloroacetic acid; or mixtures thereof. In at least some embodiments, the compositions include lactic acid, salicylic acid or mixtures thereof, and in a preferred embodiment, the compositions include lactic acid and optionally l salicylic acid as additional skin exfoliating agents.

The total amount of additional skin exfoliating chemical agent(s) present in the composition may range from about 0.01 to about 25% by weight, such as about 0. 1 to approximately 20% by weight, relative to the total weight of the composition in which it(s) is(are) present(s). For example, the total amount of chemical exfoliant present in the composition may range from about 0.5 to about 25 weight percent, about 0.5 to about 22 weight percent, about 0.5 to about 19 weight percent. 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, 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 weight, about 0.5 to about 2% by weight, about 0.5 to about 1% by weight; about 1 to about 25 wt.%, about 1 to about 22 wt.%, about 1 to about 19 wt.%, about 1 to about 16 wt.%, about 1 to about 14 wt.%, 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 wt.%, about 2 to about 22 wt.%, about 2 to about 19 wt.%, about 2 to about 16 wt.%, about 2 to about 14 wt.%, 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 wt.%, about 3 to about 22 wt.%, about 3 to about 19 wt.%, about 3 to about 16 wt.%, about 3 to about 14 wt.%, 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 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 weight, about 5 to about 8% by weight; about 7.5 to about 25 wt.%, about 7.5 to about 22 wt.%, about 7.5 to about 19 wt.%, about 7.5 to about 16 wt.%, 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 25 wt.%, about 10 to about 22 wt.%, about 10 to about 19 wt.%, about 10 to about 16 wt.%, about 10 to about 14 wt.%, about 10 to about 12 % in weight ; about 12 to about 25 wt.%, about 12 to about 22 wt.%, about 12 to about 19 wt.%, about 12 to about 16 wt.%, about 12 to about 14 wt.%, about 15 to about 25 % by weight, about 15 to about 22% by weight, about 15 to about 19% by weight, about 17 to about 25% by weight, about 17 to about 22% by weight, or about 17 to about 19% by weight, including intermediate ranges and sub-ranges, relative to the total weight of the composition in which it is present.

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 include a total amount of AHA ranging from about 1 to about 20 wt.%, about 1 to about 19 wt.%, about 1 to about 18 wt.%, about 1 to about 17% by weight, about 1 to about 16% by weight, about 1 to about 15% by weight, about 1 to about 14% by weight, about 1 to about 13% by weight, about 1 to about 12% by weight, 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 % 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 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 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 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 about 17% by weight, about 13 to about 16% by weight, or about 13 to about 15% by weight, including intermediate ranges and subranges, based on the total weight of the composition in which they are present . In some embodiments, the total amount of AHA is from about 2 to about 4 weight percent, about 4 to about 7 weight percent, or about 13 to about 16 weight percent, based on the total weight of the AHA. composition in which they are 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 they are present.

In certain embodiments, the compositions according to the disclosure comprise at least one BHA as a chemical exfoliating agent. For example, the compositions may include a total amount of BHA ranging from 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, weight, about 0.01 to about 1.7 weight percent, about 0.01 to about 1.6 weight percent, about 0.01 to about 1.5 weight percent, about 0.01 to about 1.4 % by weight, about 0.01 to about 1.3% by weight, about 0.01 to about 1.2% by weight, about 0.01 to about 1.1% by weight, about 0.01 to about 1 .0% by weight, about 0.01 to about 0.9% by weight, about 0.01 to about 0.8% by weight, 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 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 1.0% 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, 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, about 0 .1 to approximately 0.7% by weight, approximately 0.1 to approximately 0.6% by weight, approximately 0.1 to approximately 0.5% by weight, approximately 0.1 to approximately 0.4% by weight, about 0.1 to about 0.3% by weight, or about 0.1 to about 0.2% by weight, including intermediate ranges and subranges, based on the total weight of the composition in which they are present. In some embodiments, the total amount of BHAs is about 0.05 wt%, about 0.06 wt%, about 0.07 wt%, about 0.08 wt% weight, about 0.09% by weight, about 0.1% by weight, about 0.11% by weight, about 0.12% by weight, about 0.13% by weight weight, approximately 0.14% by weight, approximately 0.15% by weight, approximately 0.16% by weight, approximately 0.17% by weight, approximately 0.18% by weight, approximately 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% by weight, relative to the total weight of the composition in which they are present.

In some embodiments, the compositions according to the disclosure include trichloroacetic acid as a chemical peeling agent. For example, the compositions may include a total amount of trichloroacetic acid ranging from about 1 to about 25 weight percent, about 1 to about 24 weight percent, about 1 to about 23 weight percent, about 1 to about 22 weight percent. by weight, about 1 to about 21 weight percent, about 1 to about 20 weight percent, about 1 to about 19 weight percent, about 1 to about 18 weight percent, about 1 to about 17 weight percent, about 1 to about 16% by weight, about 1 to about 15% by weight, about 1 to about 14% by weight, about 1 to about 13% by weight, about 1 to about 12% by weight, about 1 to about 11% by weight weight, about 1 to about 10% by weight, about 1 to about 9% by weight, 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 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 wt.%, about 3 to about 11 wt.%, about 3 to about 10 wt.%, about 3 to about 9 wt.%, about 3 to about 8 wt.%, 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 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 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 wt.%, about 8 to about 23 wt.%, about 8 to about 22 wt.%, about 8 to about 21 wt.%, about 8 to about 20 wt.%, 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 weight percent, about 10 to about 22 weight percent, about 10 to about 21 weight percent, about 10 to about 20 weight percent, about 10 to about 19 weight percent, about 10 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 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 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, relative to the total weight of the composition in which it is present.

Optionally, the compositions may include more than one skin exfoliating agent, such as, for example, at least two skin exfoliating agents, at least three skin exfoliating agents, at least four skin exfoliating agents, skin, and so on. For example, the compositions may include two or more AHAs, may include two or more BHAs, may include a combination of one or more AHAs and one or more BHAs, etc. By way of non-limiting example only, the compositions may include 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.

In various embodiments, the compositions useful in the methods and/or kits according to the disclosure comprise at least one skin exfoliating agent but are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or retinoids or a derived from these.

By way of non-limiting example only, the compositions comprising at least one skin exfoliation agent may comprise additional components and their quantities typically used in chemical exfoliation compositions, such as, for example, at least one solvent, at least one solvent. minus an oil, and other 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 can be adjusted 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.

For example, compositions comprising at least one skin exfoliating agent which are free or substantially free of acetyl trifluoromethylphenyl valylglycine may comprise at least one solvent chosen from water and organic solvents. By way of example, the compositions may include 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 ranges and subranges thereof. this.

In other embodiments, compositions comprising at least one skin exfoliant that are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or retinoids or a derivative thereof include one or more solvents organic 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, ethylene glycol monomethyl, monoethyl and monobutyl ethers , propylene glycol or ethers thereof such as, for example, monomethyl ether of propylene glycol, butylene glycol, hexylene glycol, dipropylene glycol as well as alkyl ethers of diethylene glycol, for example monoethyl ether or ether monobutyl diethylene glycol. In some embodiments, the alcohol solvent is selected from ethanol, isopropyl alcohol, ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, propanediol, glycerin, or mixtures thereof. Optionally, in some embodiments, the organic solvent(s) may be present in amounts up to about 20% by weight, e.g. from about 0.1 to about 20% by weight, about 1 to about 20% by weight, about 5 to about 20% by weight, or about 10 to about 15% by weight, based on the weight of the composition.

In various embodiments, compositions comprising at least one skin exfoliant that are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or retinoids or a derivative thereof include one or more oils. Optionally, the at least one oil may be immiscible in water. For example, the at least one oil can be chosen 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 certain embodiments, the oil can be chosen from hydrocarbon-based oils from plants or vegetable origin, mineral oils, ester oils, fatty alcohols containing 12 to 26 carbon atoms, fatty acids containing of 12 to 26 carbon atoms and vinylpyrrolidone copolymers, and mixtures thereof. In some embodiments, an oil may be chosen from purcellin oil (ketostearyl octanoate), squalane, hemisqualane, isononyl isononanoate, C ₁₂ to C ₁₅ alkyl benzoate, 2-ethylhexyl palmitate, neopentanoate isodecyl, tridecyl neopentanoate, octyldecyl 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, cocoglyceride, cyclomethicone, dimethicone, dicaprylyl carbonate, dicapryl maleate, caprylic/capric triglyceride, isopropyl myristate, octyl stearate, isostearyl linoleate, lanolin oil, coconut oil, cocoa butter, coconut oil olive, avocado oil, aloe extracts, jojoba oil, castor oil, fatty acid, oleic acid, stearic acid, fatty alcohol, cetyl alcohol, hexadecyl alcohol, diisopropyl adipate, hydroxybenzoate esters, esters of C ₉ -C ₁₅ alcohols benzoic acid, alkanes, mineral oil, silicone, dimethyl polysiloxane, ether, polyoxypropylene butyl ether, polyoxypropylene cetyl ether, C ₁₂ -C ₁₅ alkyl benzoate, arylalkyl benzoate , isopropyl lauroyl sarcosinate, and any combination thereof.

In some embodiments, the oil is selected from C _13-15 alkanes (hemisqualane), dicaprylyl carbonate, isononyl isononanoate, isopropyl myristate, dimethicone, squalane, mineral oil, or mixtures thereof. this. In an exemplary and non-limiting embodiment, the oil comprises one of or a combination of C _13-15 alkane (hemisqualane), dicaprylyl carbonate, isononyl isononanoate, isopropyl myristate , dimethicone, squalane and mineral oil. In some embodiments, the oil includes isopropyl myristate.

In various embodiments, the total amount of an oil present in compositions comprising at least one skin exfoliant that are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or retinoids or a derivative thereof -this 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, can range from about 5% by weight to approximately 70% by weight, from approximately 10% by weight to approximately 65% by weight, from approximately 15% by weight to approximately 60% by weight, or from approximately 20% by weight to approximately 55% by weight, including all ranges and sub-ranges thereof, relative to the weight of the composition. In one embodiment, the total amount of oil ranges from about 20% by weight to about 60% by weight of the composition.

Compositions comprising at least one skin exfoliating agent that are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or retinoids or a derivative thereof may also include one or more optional additional components typically used in chemical exfoliation compositions, for example one or more additives chosen from citric acid, sodium chloride, chelating agents, antimicrobial agents, neutralizing agents, vitamins (e.g. tocopherol), perfumes, pearly agents, odor absorbers, dyes, essential oils , fruit extracts or combinations thereof.

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

In various embodiments, the amount of one or more additional optional components, alone or in combination, may be present in compositions comprising at least one skin exfoliant that are free or substantially free of acetyl trifluoromethylphenyl valylglycine and /or retinoids or a derivative thereof in an amount ranging from approximately 0.001% by weight to approximately 20% by weight, for example from approximately 0.005% by weight to approximately 0.01% by weight, d 'about 0.01% by weight 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, d 'about 0.5% by weight to about 2.5% by weight, or from about 1% by weight to about 2% by weight, including all ranges and subranges thereof, based on the weight of the composition.

Processes

The methods according to the disclosure comprise applying to the skin (a) acetyl trifluoromethylphenyl valylglycine and (b) at least one retinoid or a derivative thereof, and optionally (c) at least one additional skin exfoliation agent. The at least one additional skin exfoliation agent is not limited, and may be chosen from, for example, dermabrasion, microdermabrasion, physical exfoliants, and/or chemical agents. The methods may be, for example, methods for reducing the appearance of nasolabial folds, methods for reducing the appearance of skin wrinkles, methods for improving the appearance of the skin, and/or methods for reducing the appearance of skin discoloration.

In various embodiments, acetyl trifluoromethylphenyl valylglycine and at least one retinoid or derivative thereof may be applied to the skin simultaneously (e.g., when both are present in a composition or when each is present in compositions which are mixed at or near the time of use) or consecutively (for example, when each is present in separate compositions which are applied sequentially to the skin). The skin may be on the face, neck, chest or hands.

In some embodiments, the methods include applying an amount of a composition comprising acetyl trifluoromethylphenyl valylglycine to the skin such that about 0.1 grams or more of acetyl trifluoromethylphenyl valylglycine is applied on the skin. For example, the composition may be applied such that about 0.05 grams per decimeter (g/dm ² ) or more, such as about 0.06 g/dm ² or more, such as about 0.07 g/dm ² or more, such as about 0.08 g/dm ² or more, such as about 0.09 g/dm ² or more, such as about 0.1 g/dm ² or more, such than about 0.15 g/dm ² or more, about 0.2 g/dm ² or more, about 0.3 g/dm ² or more, about 0.4 g/dm ² or more, about 0.5 g/dm ² or more, about 0.75 g/dm ² or more, about 1 g/dm ² or more, about 1.5 g/dm ² or more, about 2 g/dm ² or more, about 2, 5 g/dm ² or more, or about 3 g/dm ² 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/dm ² , about 0.06 to about 9 g/dm ² , about 0.07 to about 8 g/dm ² , approximately 0.08 to approximately 7 g/dm ² , approximately 0.09 to approximately 6 g/dm ² , approximately 0.1 to approximately 5 g/dm ² , approximately 0.15 to approximately 4 g/dm ² , approximately 0.2 to approximately 3 g/dm ² , approximately 0.3 to approximately 2 g/dm ² , approximately 0.4 to approximately 1 g/dm ² ; approximately 0.5 to approximately 10 g/dm ² , approximately 0.5 to approximately 9 g/dm ² , approximately 0.5 to approximately 8 g/dm ² , approximately 0.5 to approximately 7 g/dm ² , approximately 0 .5 to approximately 6 g/dm ² , approximately 0.5 to approximately 5 g/dm ² , approximately 0.5 to approximately 4 g/dm ² , approximately 0.5 to approximately 3 g/dm ² , approximately 0.5 at approximately 2 g/dm ² , approximately 0.5 to approximately 1 g/dm ² ; or about 1 to about 10 g/dm ² , about 1 to about 9 g/dm ² , about 1 to about 8 g/dm ² , about 1 to about 7 g/dm ² , about 1 to about 6 g/dm ² , about 1 to about 5 g/dm ² , about 1 to about 4 g/dm ² , about 1 to about 3 g/dm ² , or about 1 to about 2 g/dm ² of acetyl trifluoromethylphenyl valylglycine is applied to the skin.

In some embodiments, acetyl trifluoromethylphenyl valylglycine 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 least 48 hours, for example between 10 seconds and 48 hours. In one embodiment, the acetyl trifluoromethylphenyl valylglycine is not removed before the application of one or more other compositions for the skin, such as, for example, a composition comprising at least one retinoid or a derivative, a composition Extra skin scrub, moisturizers, sunscreen, other anti-aging treatments, etc.

In some embodiments, the at least one retinoid or derivative thereof 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. In one embodiment, the at least one retinoid or derivative thereof is not removed before applying one or more other compositions for the skin, such as, for example, a composition comprising acetyl trifluoromethylphenyl valylglycine, additional skin scrub composition, moisturizers, sunscreen, other anti-aging treatments, etc.

In some embodiments, the methods include applying an amount of a composition comprising at least one additional chemical skin exfoliating agent such as about 0.1 grams or more of the at least one exfoliating agent. Skin scrub is applied to the skin. For example, the composition may be applied such that about 0.05 g/dm ² or more, such as about 0.06 g/dm ² or more, such as about 0.07 g/dm ² or more, such as about 0.08 g/dm ² or more, such as about 0.09 g/dm ² or more, like about 0.1 g/dm ² or more, like about 0.15 g/dm ² or more, about 0.2 g/dm ² or more, about 0.3 g/dm ² or more, about 0.4 g/dm ² or more, about 0.5 g/dm ² or more, about 0.75 g/dm ² or more , about 1 g/dm ² or more, about 1.5 g/dm ² or more, about 2 g/dm ² or more, about 2.5 g/dm ² or more, or about 3 g/dm ² or more of the at least one skin exfoliating agent is applied to the skin. In some embodiments, the composition is applied such that about 0.05 to about 10 g/dm ² , about 0.06 to about 9 g/dm ² , about 0.07 to about 8 g/dm ² , approximately 0.08 to approximately 7 g/dm ² , approximately 0.09 to approximately 6 g/dm ² , approximately 0.1 to approximately 5 g/dm ² , approximately 0.15 to approximately 4 g/dm ² , approximately 0.2 to approximately 3 g/dm ² , approximately 0.3 to approximately 2 g/dm ² , approximately 0.4 to approximately 1 g/dm ² ; approximately 0.5 to approximately 10 g/dm ² , approximately 0.5 to approximately 9 g/dm ² , approximately 0.5 to approximately 8 g/dm ² , approximately 0.5 to approximately 7 g/dm ² , approximately 0 .5 to approximately 6 g/dm ² , approximately 0.5 to approximately 5 g/dm ² , approximately 0.5 to approximately 4 g/dm ² , approximately 0.5 to approximately 3 g/dm ² , approximately 0.5 at approximately 2 g/dm ² , approximately 0.5 to approximately 1 g/dm ² ; or about 1 to about 10 g/dm ² , about 1 to about 9 g/dm ² , about 1 to about 8 g/dm ² , about 1 to about 7 g/dm ² , about 1 to about 6 g/dm ² , about 1 to about 5 g/dm ² , about 1 to about 4 g/dm ² , about 1 to about 3 g/dm ² , or about 1 to about 2 g/dm ² of the at least one exfoliating agent Additional chemical peel is applied to the skin.

In some embodiments, the at least one additional chemical skin exfoliant 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 compositions for the skin, such as, for example, a composition comprising acetyl trifluoromethylphenyl valylglycine, a composition comprising a retinoid or derivative thereof, moisturizers, sunscreen, other anti-aging treatments, etc.

The at least one chemical scrub can be applied in any known manner. For example, it can be applied directly to the skin (for example with the fingers) or using a device such as a ball or pad particularly suitable for wiping a surface. The pad may include an absorbent core having the ability to absorb and retain liquids, and a liner layer in contact with the absorbent core and covering at least one side thereof. The liner layer has the ability to retain and release liquid through the liner layer. The pad may be made from any practical material, suitable materials of interest including, but not limited to, cellulosic materials, polymeric materials, etc. The wipe can be formed from a substrate based on paper, cotton or textile. In some cases, the material of the absorbent pad is made of hydrophilic materials. In other embodiments, the absorbent pads are selected from the group consisting of gauzes, cellulose pads, agarose gels, acrylamide gels or hydrogels.

The ball or pad can be soaked with approximately 0.5 mL to approximately 10 mL of a composition comprising the at least one chemical scrub, such as approximately 0.7 mL to approximately 9 mL, approximately 0.9 mL to approximately 8 mL, approximately 1 mL to approximately 7 mL, approximately 1.5 mL to approximately 6 mL, approximately 2 mL to approximately 5 mL, approximately 2 mL to approximately 4 mL, approximately 2 mL to approximately 3 mL, approximately 3 mL to approximately 5 mL, or approximately 4 mL to approximately 5 mL of a composition comprising at least one chemical scrub. When using a pad or a ball, the at least one chemical scrub can be applied by making at least one pass of the ball or pad on the skin, such as at least 2 passes, at least once. 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, or at least 10 passes, such as from 1 to 10 passes, 1 to 9 passes, 1 to 8 passes, 1 to 7 passes, 1 to 6 passes, 1 to 5 passes, 1 to 4 passes, 1 to 3 passes, or 1 to 2 passes.

The at least one pad particularly suitable for surface wiping may comprise a composition comprising at least one skin exfoliation agent. The wipe may also contain routine skin permeation activators known in the art. In one embodiment, the wipe is soaked in agents such as water, phosphate buffered saline, soap, surfactant, inorganic or organic solvents such as water, ethanol, isopropanol or a combination of these. An exemplary formulation of the agent contains 30-95% isopropanol in water and the wiping material is gauze. The at least one skin exfoliating agent is typically applied to the target skin area by massaging, wiping, dabbing, rubbing or any other method to cleanse the target skin site and increase porosity.

When (a) acetyl trifluoromethylphenyl valylglycine and (b) at least one retinoid or derivative thereof are applied consecutively, the methods disclosed herein may include, in various embodiments, applying acetyl trifluoromethylphenyl valylglycine to the skin within approximately 24 hours before or after application to the skin of the at least one retinoid or a derivative thereof. For example, in some embodiments, acetyl trifluoromethylphenyl valylglycine can be applied within about 20 hours, about 16 hours, about 12 hours, about 10 hours, about 8 hours, approximately 6 hours, approximately 4 hours, approximately 2 hours, approximately 1 hour, approximately 30 minutes, approximately 20 minutes, approximately 10 minutes, approximately 5 minutes or approximately 1 minute after application of the at least one retinoid or a derivative thereof to the skin. In other embodiments, acetyl trifluoromethylphenyl valylglycine may be applied within 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 retinoid or a derivative thereof to the skin.

When (a) acetyl trifluoromethylphenyl valylglycine and (b) at least one additional skin exfoliating agent are applied consecutively, the methods disclosed herein may include, in various embodiments, applying acetyl trifluoromethylphenyl valylglycine to the skin. skin within approximately 48 hours before or after application to the skin of the at least one skin exfoliating agent. For example, in some embodiments, acetyl trifluoromethylphenyl valylglycine can 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, approximately 5 minutes or approximately 1 minute after applying the at least one additional skin exfoliating 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 approximately 1 minute before application to the skin of at least one additional skin exfoliating agent.

In some embodiments, the composition comprising acetyl trifluoromethylphenyl valylglycine may be left on the skin for up to 10 seconds, up to 20 seconds, up to 30 seconds, up to 40 seconds, up to 50 seconds, up to 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 acetyl trifluoromethylphenyl valylglycine is eliminated, for example, by rinsing. In one embodiment, the composition comprising acetyl trifluoromethylphenyl valylglycine is not removed prior to the application of other compositions for the skin, such as, for example, a composition comprising a retinoid or a derivative thereof , a composition comprising an additional skin exfoliating agent for the skin, moisturizers, sunscreen, other anti-aging treatments, etc.

Acetyl trifluoromethylphenyl valylglycine may, in various embodiments, 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.

In some embodiments, the composition comprising at least one retinoid or a derivative thereof 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 it is removed, such as, for example, by rinsing. In one embodiment, the composition comprising at least one retinoid or a derivative thereof 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 it is removed, such as, for example, by rinsing. For example, the composition comprising at least one retinoid or a derivative thereof can be left on the skin for a time range ranging from 5 minutes to 60 minutes, such as from 5 minutes to 50 minutes, from 5 minutes to 40 minutes. 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. In another example, the composition comprising at least one retinoid or a derivative thereof can be left on the skin for a time range ranging from 10 minutes to 60 minutes, such as from 10 minutes to 50 minutes, from 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.

In some embodiments, the composition comprising at least one additional skin exfoliating 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 it is removed, such as by rinsing. In one embodiment, the composition comprising at least one additional skin exfoliating 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. For example, compositions comprising the at least one additional skin exfoliating agent may be left on the skin for a time range of 5 minutes to 60 minutes, such as 5 minutes to 50 minutes, 5 minutes to 40 minutes, 5 minutes to 35 minutes, 5 minutes to 30 minutes, 5 minutes to 25 minutes, 5 minutes to 20 minutes, 5 minutes to 15 minutes, or 5 minutes to 10 minutes. In another example, the composition comprising at least one additional skin exfoliating agent may be left on the skin for a time range of 10 minutes to 60 minutes, such as 10 minutes to 50 minutes, 10 minutes to 40 minutes. minutes, from 10 minutes to 35 minutes, from 10 minutes to 30 minutes, from 10 minutes to 25 minutes, from 10 minutes to 20 minutes, or from 10 minutes to 15 minutes.

The methods may, in some embodiments, include applying a composition comprising acetyl trifluoromethylphenyl valylglycine to the skin more than once, e.g. before and after applying to the skin the at least a retinol and/or at least one skin exfoliating agent. In some embodiments, the methods may include applying the at least one retinol to the skin more than once, for example before and after applying the acetyl trifluoromethylphenyl valylglycine and/or the at minus a chemical scrub on the skin. In some cases, the process can be repeated to achieve optimal results. The methods may, in some embodiments, include applying the at least one skin exfoliating agent to the skin more than once, e.g. before and after applying the acetyl trifluoromethylphenyl valylglycine and /or at least one retinol on the skin. In some cases, the process can be repeated to achieve optimal results.

If applied simultaneously, acetyl trifluoromethylphenyl valylglycine and the retinoid(s) or derivative(s) may optionally be present in a single composition. Alternatively, acetyl trifluoromethylphenyl valylglycine and the retinoid(s) or derivative(s) may optionally be present in separate compositions, e.g. two or more compositions, three compositions or more, etc. which may be mixed at or near the time of use.

If applied simultaneously, the acetyl trifluoromethylphenyl valylglycine and the skin exfoliating agent(s) may optionally be present in a single composition. Alternatively, the acetyl trifluoromethylphenyl valylglycine and the skin exfoliating agent(s) may optionally be present in separate compositions, e.g. two or more compositions, three or more compositions, etc. which may be mixed at or near the time of use.

The skin treatment compositions may be used in methods to increase or improve skin renewal/regeneration, and/or improve the appearance of the skin. Non-limiting examples of such methods include methods of treating fine lines, methods of treating wrinkles under the eyes, and/or methods of treating nasolabial folds.

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 days or not, preferably consecutive days. Acetyl trifluoromethylphenyl valylglycine can 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 daily, wherein the second application is 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.

The at least one retinoid or derivative thereof 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 or 42 consecutive days or not, preferably non-consecutive days. The retinoid can be applied to the skin at least once a day for at least 1, 2, 3, 4, 5, 6, or 7 times a week. For example, the at least one retinoid or derivative thereof may be applied to the skin at least every other day.

The at least one additional skin exfoliating agent can 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 additional skin exfoliating agent may be applied to the skin at least once per day for at least 1, 2, 3, 4, 5, 6 or 7 days per week. For example, the at least one additional skin exfoliating agent may be applied to the skin at least every other day.

The additional skin 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 additional skin exfoliating agent is not applied.

In some embodiments, the at least one retinoid or derivative thereof and the at least one additional skin exfoliating agent are not applied to the skin on the same day.

In various embodiments, the methods include two phases for treating the skin, including:

a phase (1) comprising application to the skin:

(a) acetyl trifluoromethylphenyl valylglycine at least once a day;

(b) at least one retinoid or derivative thereof at least once every two or three days; And

(c) optionally at least one additional skin exfoliating agent at least once every two or three days,

wherein the (b) at least one retinoid or derivative thereof and the (c) optionally at least one additional skin exfoliating agent are separately applied to the skin for at least about 6 hours, preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

in which phase (1) lasts for a period of time of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably of at least approximately 28 days; And

a phase (2) comprising application to the skin:

(a) acetyl trifluoromethylphenyl valylglycine at least once a day; And

(b) at least one retinoid or derivative thereof at least once every two or three days; And

in which phase (2) lasts for a period of time of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably of at least about 14 days.

In other embodiments, the methods include two phases for treating the skin, including:

a phase (1) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day;

(b) a composition comprising at least one retinoid or a derivative thereof, at least once every two or three days; And

(c) optionally, of a composition comprising at least one additional skin exfoliating agent, at least once every two or three days,

wherein composition (b) comprising at least one retinoid or derivative thereof and optional composition (c) comprising at least one additional skin exfoliating agent are applied to the skin for at least about 6 hours, from preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

in which phase (1) lasts for a period of time of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably of at least approximately 28 days; And

a phase (2) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day; And

(b) a composition comprising at least one retinoid or a derivative thereof, at least once every two or three days; And

in which phase (2) lasts for a period of time of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably of at least about 14 days.

In still other embodiments, the methods include two phases for treating the skin, including:

a phase (1) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day;

(b) a composition comprising at least one retinoid or a derivative thereof and acetyl trifluoromethylphenyl valylglycine, at least once every two or three days; And

(c) optionally a composition comprising at least one additional skin exfoliating agent, at least once every two or three days,

wherein composition (b) comprising at least one retinoid or derivative thereof and acetyl trifluoromethylphenyl valylglycine and optional composition (c) comprising at least one additional skin exfoliating agent are applied to the skin to at least about 6 hours, preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

in which phase (1) lasts for a period of time of at least about 10 days, preferably at least about 14 days, more preferably at least about 21 days, most preferably of at least approximately 28 days; And

a phase (2) comprising separate application to the skin:

(a) a composition comprising acetyl trifluoromethylphenyl valylglycine, at least once a day; And

(b) a composition comprising at least one retinoid or a derivative thereof and acetyl trifluoromethylphenyl valylglycine, at least once every two or three days; And

in which phase (2) lasts for a period of time of at least about 5 days, preferably at least about 7 days, more preferably at least about 10 days, most preferably of at least about 14 days.

In still other embodiments, the methods include two phases for treating the skin, including:

a phase (1) comprising application to the skin:

(a) from about 0.1 to about 10% by weight of acetyl trifluoromethylphenyl valylglycine, at least once, preferably at least twice, per day;

(b) from about 0.001 to about 10% by weight of at least one retinoid or a derivative thereof, at least once every two or three days; And

(c) optionally, from about 0.1 to about 25% by weight of at least one additional skin exfoliating agent selected from at least α-hydroxy acids, β-hydroxy acids or mixtures thereof once every two or three days,

wherein the (b) at least one retinoid or derivative thereof and the (c) at least one optional additional skin exfoliating agent are separately applied to the skin for at least about 6 hours, preferably at least about 12 hours, more preferably at least about 18 hours, most preferably at least about 24 hours apart; And

in which phase (1) lasts for a period of time of at least about 10, preferably at least about 14 days, more preferably at least about 21 days, most preferably at less about 28 days; And

a phase (2) comprising application to the skin:

(a) from about 0.1 to about 10% by weight of acetyl trifluoromethylphenyl valylglycine, at least once, preferably at least twice, per day; And

(b) from about 0.001 to about 10% by weight of at least one retinoid or a derivative thereof, at least once every two or three days; And

wherein phase (2) lasts for a period of time of at least about 5, preferably at least about 7, more preferably at least about 10, most preferably at least about 14 days ;

in which the quantities of all the components are relative to the total weight of the composition in which they are present.

It was also surprisingly and unexpectedly discovered that the use of acetyl trifluoromethylphenyl valylglycine reduces skin irritation, redness, etc. typically observed with the use of retinoids and derivatives thereof. Therefore, in other embodiments, the methods relate to improving skin tolerance to retinoids and/or derivatives thereof, comprising the application of acetyl trifluoromethylphenyl valylglycine and at least a retinoid or a derivative thereof simultaneously or sequentially, as described above.

Required

The disclosure also relates to kits comprising acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and optionally at least one skin exfoliating agent. In other embodiments, the kits include acetyl trifluoromethylphenyl valylglycine, at least one retinoid or derivative thereof, and/or at least one exfoliating implementation, such as, for example, a pad for exfoliate the skin which may or may not include a chemical exfoliating agent.

In some embodiments, the kits include at least two or three separate containers. In other embodiments, the kits include one or more containers, wherein at least one container includes at least two separate compartments.

In some embodiments, the kits include a first container or compartment that comprises (a) a composition comprising acetyl trifluoromethylphenyl valylglycine, a second container or compartment that comprises (b) a composition comprising at least one retinoid or a derivative of this, and optionally a third container or compartment which comprises (c) a composition comprising at least one additional skin exfoliating agent. In other embodiments, the kits include a first container or compartment that includes (a) a composition comprising acetyl-trifluoromethylphenyl-valylglycine and (b) a composition comprising at least one retinoid or derivative thereof , and optionally a second container or compartment which comprises (c) a composition comprising at least one additional skin exfoliating agent. The kits may optionally further include at least one additional container or compartment.

As a non-limiting example only, the kits may be in the form of a container with two or three chambers. The first, second and/or third chambers may be separated such that the compositions (a), (b) and/or (c) are separated from each other before use. The two-chamber container may optionally include an operation for mixing and/or dispensing quantities of compositions (a), (b) and/or (c) such that the compositions (a), (b) and/or (c) are dispensed as a single composition comprising desired amounts of acetyl trifluoromethylphenyl valylglycine, retinoid(s) or derivatives thereof, and/or skin exfoliating agent(s) additional(s) for use in various processes according to the disclosure.

As a further non-limiting example, the kits may include a first container with a dispenser, wherein the first container comprises (a) a composition comprising acetyl trifluoromethylphenyl valylglycine, a second container with a dispenser, wherein the second container comprises (b) a composition comprising at least one retinoid or a derivative thereof, and/or a third container with a dispenser, wherein the third container comprises (c) a composition comprising at least one additional skin exfoliating agent the skin. Optionally, the kits may further include instructions providing the dosage, order and timing of application, etc., of compositions (a) and (b), (a)/(b) and (c), (a), (b) and (c), etc. for use in various processes according to the disclosure. The kits according to the disclosure may also include implementation for exfoliating the skin in addition to or instead of a composition comprising a chemical exfoliating agent, for example a pad for exfoliating the skin which may or may not comprise a exfoliating agent. chemical.

In some embodiments, the kits according to the disclosure include a first container comprising a composition comprising acetyl trifluoromethylphenyl valylglycine and at least one retinoid or derivative thereof, and optionally a second container comprising at least one exfoliating agent additional skin or at least an exfoliating application. In other embodiments, the kits according to the disclosure include a first container comprising a composition comprising acetyl trifluoromethylphenyl valylglycine, a second container comprising at least one retinoid or derivative thereof, and optionally a third container comprising at least one additional skin exfoliating agent or at least one exfoliating application.

In other embodiments, the kits according to the disclosure include a first container comprising a composition comprising acetyl trifluoromethylphenyl valylglycine and at least one additional peeling agent, and optionally a second container comprising at least one retinoid or derivative of this one.

In other embodiments, the kits disclosed include a first container comprising (a) compositions comprising acetyl trifluoromethylphenyl valylglycine that are free or substantially free of retinoids or derivatives thereof and/or additional skin exfoliating agents; a second container comprising (b) compositions comprising retinoids or derivatives thereof which are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or additional skin exfoliating agents; and/or a third container comprising (c) compositions comprising one or more skin exfoliating agents that are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or retinoids or derivatives thereof. In still further embodiments, the kits disclosed include a first container comprising (a) compositions comprising acetyl trifluoromethylphenyl valylglycine that are free or substantially free of retinoids or derivatives thereof and/or d additional skin exfoliation agents; a second container comprising (b) compositions comprising retinoids or derivatives thereof which are free or substantially free of acetyl trifluoromethylphenyl valylglycine and/or additional skin exfoliating agents; and/or at least one exfoliating application.

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 in the present disclosure, while illustrating embodiments of the disclosure, are provided as non-limiting examples and therefore should not be considered to limit the various aspects thus illustrated. It is understood that all definitions given herein are for the purposes of this disclosure only.

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

Thus, when the disclosure refers to an element "selected from A, B, C, D, E, F and/or mixtures thereof", it indicates that one of the elements 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.)

As used herein, the expressions "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 which immediately precedes the sentence, such as "A, B, C, D, or mixtures thereof" means that the component(s) can be chosen from A, B, C, D, A+B, A+B+C, A+D, A+C+D, etc. , without limitation of their variations. Thus, the components can be used individually or in any combination thereof.

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

All percentages, parts and ratios stated herein are based on the total weight of the compositions of the present disclosure unless otherwise noted.

As used herein, the term "treating" (and its grammatical variations, such as "treating") 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, under-eye wrinkles and/or nasolabial folds is diminished.

As used herein, the terms "skin regeneration", "epidermis regeneration", "skin renewal" and "epidermis renewal" are used interchangeably to refer to the process of cell regeneration of the skin, including the formation of new cells and/or the elimination of old cells.

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

As used herein, the term "substantially free" or "substantially free" means that the specific material may be present in small amounts which 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 less than 2% by weight does not materially affect the characteristics fundamental and novel compositions according to the disclosure. Likewise, 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 materials specified. In addition, any components that are positively presented in the present disclosure may be negatively excluded from the claims, for example, a claimed composition may be "free", "essentially free" (or "substantially free") from one or more components which are positively set forth in the present disclosure. The term " substantially free” or “substantially free” as used herein may also mean that the specific material is not added to the composition but may still be present in a raw material that is included in the composition.

For the purposes of this disclosure, it should be noted that to provide a more concise description, some of the quantitative expressions given herein are not qualified by the term "approximately." It is understood that, whether the term "approximately" 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 of that given value which would be reasonably inferred based on ordinary skill in the art, including approximations due to experimental and/or measurement conditions of this given value. All ranges and quantities stated herein are intended to include subranges and quantities using any point indicated as a boundary. 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% by weight”, “1% by weight to 5% by weight”, “2% by weight to 10% by weight”, etc. All numbers, quantities, ranges, etc., are intended to be modified by the term "approximately", whether or not expressly stated. Likewise, a given range of "approximately 1 wt% to 10 wt%" is intended for the term "approximately" to modify both the 1 wt% and 10 wt% limits. The term "approximately" is used here to indicate a difference of up to +/- 10 wt% from the stated number, such as +/- 9 wt%, +/- 8 wt%, +/- 7 % by weight, +/- 6% by weight, +/- 5% by weight, +/- 4% by weight, +/- 3% by weight, +/- 2% by weight or +/- 1% by weight weight. Likewise, all range limits are understood to be individually disclosed, so that, for example, a range from 1:2 to 2:1 is understood to disclose a ratio of both 1:2 and 2:1 .

Unless expressly stated otherwise, it is in no way intended that any process presented herein should be construed as requiring that its steps be performed in any specific order. Accordingly, when a process claim does not expressly state an order to be followed for its steps or it is not specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it does not In no case is it intended that a particular order be inferred.

EXAMPLES

The following examples serve to illustrate the embodiments of the disclosure without being limiting. The examples are intended to be non-restrictive and explanatory only, the scope of the invention being defined by the claims. In the examples, the quantities of the ingredients of the composition are given as weight percentages of active ingredients relative to the total weight of the composition.

Example 1 – Effect on skin regeneration

The effect of acetyl trifluoromethylphenyl valylglycine and/or retinoids on skin regeneration/desquamation, filaggrin expression, desmocollin-1 expression were evaluated in an ex vivo skin model. In this study, the effects of acetyl trifluoromethylphenyl valylglycine (0.1%), retinol (0.003%), and acetyl trifluoromethylphenyl valylglycine + retinol on skin were evaluated by H&E (assessment of overall tissue health ), filaggrin (evaluation of the level of barrier renewal) and desmocollin-1 (evaluation of the tight junction between keratinocytes).

Fresh post-abdominoplasty normal human skin samples (3 batches, age 36–59 years, Hispanic/Caucasian/African American types, female) were purchased from BioIVT Inc. (Westbury, NY). The tissues were degreased and cleared of blood residue. Explant samples were then created using a 12 mm biopsy punch. Samples were cleaned with sterile PBS. Skin biopsies that had not received treatment served as controls. Skin explants were maintained at the air-liquid interface at 37°C and 5% CO ₂ in four different treatment groups (n=3 per medium type).

1. Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum and 1% penicillin-streptomycin, and 2% ethanol serving as vehicle control;

2. Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum, 1% penicillin-streptomycin, and 0.1% ER2947 in 2% ethanol, serving as the acetyl treatment group -trifluoromethylphenyl-valylglycine;

3. Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum, 1% penicillin-streptomycin, and 0.003% retinol in 2% ethanol, serving as the retinol treatment group;

4. Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum, 1% penicillin-streptomycin, and 0.1% ER2947 + 0.003% retinol in 2% ethanol serving as the treatment group with acetyl trifluoromethylphenyl valylglycine/retinol.

The fresh media were renewed every two days, except on weekends. After a 7-day culture period, samples of all explants were collected for histological and immunohistochemical analysis.

Skin explants were processed for hematoxylin and eosin staining, and immunohistochemical staining (Reveal Biosciences, CA). H&E staining was performed according to the standard protocol (Reveal Biosciences, CA). Immunohistochemical staining was performed using a Leica Bond automatic immunostainer (Reveal Biosciences, CA). Tissue samples were embedded as formalin-fixed paraffin (FFPE) blocks. 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 anti-rabbit Poly-HRP IgG respectively and was detected using the Bond Polymer Refine detection kit (DS9800, Leica Biosystems, UK). All sections were then counterstained with hematoxylin nuclear stain and imaged with an inverted microscope (Leica DM500, Germany).

The complementary and synergistic effects of the combination of acetyl trifluoromethylphenyl valylglycine and retinol are illustrated by the immunohistochemical evaluation presented in the . There shows the images of the stained explants on the seventh day of culture after application of acetyl trifluoromethylphenyl valylglycine and/or retinol. In the figures, tissues treated with 2 wt% ethanol in the medium serve as negative controls that show what untreated 2D ex vivo histological sections would look like, with no significant changes in tissue health or biomarkers assessed. Tissue structure and integrity after retinol and/or acetyl trifluoromethylphenyl valylglycine treatment were observed in hematoxylin and eosin-stained tissues and by immunohistochemistry. An increase in filaggrin (FLG) expression and a reduction in desmocollin-1 (DSC1) expression were indicators of epidermal renewal. The effects of retinol can be observed by the change in H&E (depicting a mild level of skin irritation) and the decrease in desmocollin-1 expression (suggesting a weakening of the skin barrier). Addition of acetyl trifluoromethylphenyl valylglycine increases filaggrin expression. This suggests that acetyl trifluoromethylphenyl valylglycine may complement the effects of retinol by inducing recovery and renewal of the skin barrier.

Example 2 – Penetration into the skin

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

The cells were placed on a magnetic stirrer integrated into a water bath at a fixed temperature maintained so as to have 32°C ± 1°C at the skin surface. The receptor compartment of each cell was filled with the receptor fluid (PBS) and was continuously agitated. 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. Agitation of the receiving fluid has begun.

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

The experiment began immediately after applying the preparation to the skin surface and ended 16 hours after application. The preparation was removed from the skin samples by washing 16 hours after application.

The skin was then cut into strips of constant weight and application time. A maximum of 20 strips were performed on each skin sample and the strips were grouped by 5. The strip samples were stored with the solvent (methanol) at -20°C for a maximum of 5 days before being analyzes. 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. RS vials were stored with solvent (methanol) at -20°C for up to 7 days before analysis. Dermis and epidermis samples were stored with solvent at -20°C for up to 7 days before analysis. The receiving fluid was collected 16 hours after application and the samples were analyzed.

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

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

Thus, application of the 2% acetyl trifluoromethylphenyl valylglycine composition to the skin allowed approximately 0.8% to penetrate beyond the barrier of the stratum corneum and into the epidermis, dermis and fractions. of the receiving fluid. The penetration level of acetyl trifluoromethylphenyl valylglycine corresponds to the approximate level of acetyl trifluoromethylphenyl valylglycine assayed in the ex vivo skin experiments (Example 1) above.

Example 3 - Clinical studies

A single-center, full-face, randomized, double-blind study was conducted to evaluate the clinical effectiveness and consumer perception of three home care regimens for improving facial dyschromia and signs of aging in healthy Caucasian women. health. One hundred and twenty-six (126) healthy Caucasian women, aged 40 to 65 years (mean age 57.5 years), with mild to moderate signs of aging and Fitzpatrick skin phototype II and III were included in the study. this study. Pregnant or breastfeeding women who have used retinol or a related product and/or who have received treatment with chemical peeling, laser, photorejuvenation, dermabrasion, botulinum toxin, injectable fillers or other skin tightening treatments in the 6 months preceding the start date of the study were excluded. Once enrolled, subjects were asked to stop their usual skin care regimen. Subjects in Table 1 were trained in the self-application of all test products before the start of the study.

Demographics of enrolled subjects: N = 126 (population per protocol) GROUP 1:
Product At retinol GROUP 2:
Scrub home & product At peptide GROUP 3:
Scrub home & product At peptide + retinol N = 46
Average age (years): 58.6
17 Fitz II & 29 Fitz III
First users of retinol: 38; retinol users: 8
N = 40
Average age (years): 57.1
19 Fitz II & 21 Fitz III
First users of retinol: 33; retinol users: 7
N = 40
Average age (years): 56.7
17 Fitz II & 23 Fitz III
First users of retinol: 38; retinol users: 2

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) to use during the washing period. The cleanser and sunscreen were also used during the 12 weeks of treatment. After the washout period, subjects were randomly assigned to three home care groups, as shown in Figure 3A. The diets are described below:

Diet 1 consisted of a moisturizer, applied every morning; a product containing retinol, applied every three evenings for the first week following the washout period, then every other day for the second week, and finally applied every evening for the remainder of the study duration.

Diet 2 consisted of a composition based on 2% acetyl trifluoromethylphenyl valylglycine, applied daily morning and evening; a home chemical scrub based on 0.45% salicylic acid/11.11% lactic acid, applied three times a week in the evening.

Diet 3 consisted of a 2% composition of acetyl trifluoromethylphenyl valylglycine, applied daily in the morning and evening; a home chemical scrub based on 0.45% salicylic acid and 11.11% lactic acid, applied three times a week in the evening. Additionally, subjects were instructed to apply a product combination containing 1.7% acetyl trifluoromethylphenyl valylglycine/3% retinol twice weekly on days without chemical peel treatment for the first week after washing , then three times per week on days without chemical peel treatment for the remainder of the study duration.

Diet Group 1 used the same product routine for all 12 weeks of treatment. For diet groups 2 and 3, the 12-week treatment periods were divided into two phases, performed twice (Figure 3B): 4 weeks of use of 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 use of topical products, but not chemical peel treatment (week 5 to week 6 and week 11 to week 12).

Clinical efficacy and tolerability of subjects were assessed at the start of the study and at weeks 2, 4, 6, 10 and 12. Photoaging parameters were assessed globally using a modified Griffith scale in 10 points according to the following numerical definition (half-point grades were used where necessary for precision): 0 = none, 1 to 3 = mild, 4 to 6 = moderate, and 7 to 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 objectively assessed at each visit by the investigator by assessing signs of erythema, dryness, scaling and peeling. In addition, the subjects' self-assessment of the degree of burning, tingling, 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 points were used if necessary for precision): where 0 = none; 1 = light; 2 = moderate; and 3 = severe.

Self-assessment questionnaires were given to the subjects to assess their perception of the facial skin condition, the effectiveness of the product and its sensory effects at the start of the study, then at weeks 4, 6 and 12, according to the following system: completely agree, somewhat agree, neither agree nor disagree, somewhat disagree and completely disagree.

For the 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 effects and time effect. Effect size and p-values were used to interpret significant differences (p-values < 0.05 were considered statistically significant and classify effect size).

Tolerability results :

Table 2 below shows the average ratings on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe).

Skin Tolerance Classification (Mean Score) in Home Care Regimen Groups Settings WEEK 6 WEEK 12 Group 1
(n = 32 reactions Group 2
(n = 15 reactions) Group 3
(n = 15 reactions) Group 1
(n = 16 reactions) Group 2
(n = 9 reactions Group 3
(n = 8 reactions Objective estimate (investigator) Erythema 1 (n=25) 1 (n=12) 1.1 (n=12) 1 (n=15) 1.2 1.2 Scrub 1.3 (n=4) 1 (n=1) 1.3 (n=3) 1 (n=1) 0 0 Drought 1.5 (n=2) 1 (n=1) 0 0 0 0 Edema 1.5 (n=1) 0 0 0 0 0 Subjective estimate (reported by the subject) Tingling/burning/itching 1 (n=1) 0 0 0 0 0 Tingling 0 0 0 0 0 0 Pulling 0 0 0 0 0 0

Group 1: retinol product
Group 2: Home scrub & peptide product
Group 3: At-home scrub & peptide + retinol product

More subjects in Group 1 than in Groups 2 and 3 experienced mild to moderate local intolerances at week 6, with signs of erythema as the determining factor. One subject also reported tingling, burning, and itching. At week 12, only mild erythematous reactions were clinically observed. Approximately half as many subjects in groups 2 and 3 experienced mild to moderate local intolerances at week 12 compared to group 1.

E undesirable events :

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

E evaluations of the ’ efficiency :

Clinical evaluation of anti-aging parameters demonstrated significant improvement from baseline for all three skin care regimen groups at week 2 and 4 for overall fine lines ( ) (Or ). At week 6, groups 2 and 3, which included at-home exfoliation, showed significant improvement in the appearance of under-eye lines/crow's feet and nasolabial fold lines compared to baseline. (figures 7 and 9) (or figures 12 and 14). At week 12, all treatment groups showed significant improvement in all parameters assessed compared to baseline, with the exception of group 1 which showed no relevant change in overall wrinkle appearance , as illustrated in Figures 6 to 10 (or Figures 11 to 15).

Treatment comparisons in the figures showed that group 3 (at-home scrub and acetyl trifluoromethylphenyl valylglycine + retinol-containing product), performed significantly better in improving overall fine lines and overall healthy appearance than group 1 (product containing retinol) at week 2, and that group 2 (at-home scrub and product containing acetyl trifluoromethylphenyl valylglycine) for fine lines. Group 3 significantly outperformed Group 1 at week 12 for all anti-aging parameters assessed (Figures 6 to 10) (or Figures 11 to 15).

The anti-aging routine containing acetyl trifluoromethylphenyl valylglycine + at least one retinoid + at least one additional chemical exfoliation provides superior benefits in anti-aging effect and skin quality in an accelerated kinetic manner, and also provides greater tolerance compared to the use of retinol alone.

Claims (3)

Kit including:
(i) a first container comprising a composition comprising 0.01 to 25% by weight, more preferably 0.1 to 5% by weight, even more preferably 0.5 to 4% by weight, of most preferably from 0.75 to 3% by weight of acetyl trifluoromethylphenyl valylglycine;
(ii) a second container comprising a composition comprising from 0.0001 to 10% by weight, preferably from 0.001 to 7% by weight of at least one retinoid or a derivative thereof; And
(iii) optionally a third container comprising a composition comprising at least one additional skin exfoliating agent, preferably chosen from α-hydroxy acids, β-hydroxy acids or mixtures thereof. Kit according to claim 1, wherein the α-hydroxy acid is selected from lactic acid, glycolic acid, citric acid, malic acid, tartaric acid, mandelic acid, derivatives thereof, or mixtures thereof, preferably lactic acid. A kit according to claim 1, wherein the β-hydroxy acid is selected from salicylic acid, derivatives thereof, or mixtures thereof, preferably salicylic acid.