Topical Compositions Useful for the Daily Care of Acne-Prone Skin - Patent application

Abstract

The present disclosure relates to topical compositions, such as cosmetic topical compositions, comprising a keratolytic combination of succinic acid and lactic acid, and their use for the daily care of oily skin, acne-prone skin, acned skin, and acne-treated skin.

Description

[Technical field]

[0001] The present invention relates to topical compositions, such as cosmetic topical compositions, comprising a keratolytic combination of succinic acid and lactic acid, and their use for the daily care of oily skin, acne-prone skin, acne-affected skin and skin that has been treated for acne. [Background technology]

[0002] Acne is the most common chronic disease of the pilosebaceous follicles of human skin, caused by multiple factors and leading to the appearance of various types of lesions. Acne is a chronic immune-inflammatory disease that affects approximately 900 million people worldwide, mostly young people (prevalence 80%-85%), both men and women, although the majority of affected individuals are adult women. Acne is a dermatological condition that, due to a multifactorial pathogenesis, results in the formation of comedones, papules, cysts, nodules and pustules that are prone to hypertrophic scarring in the skin, giving the skin an unsightly appearance and thus causing physical and emotional changes in the affected individual (LIMA, 2006; MANFRINATO, 2009). The pathogenesis of this many diseases, which also have genetic influences, involves four phenomena: inflammatory processes at all stages, abnormal keratinization of the distal part of the follicular orifice, eczema (quantitative and qualitative changes in sebum), the influence of androgenic hormones and the presence of Cutibacterium acnes, whose aggressiveness depends on the follicular environment and on its high antigenic potential for receptors present on the cell membrane, which are part of the patient's innate immunity.

[0003] The different types of acne can be classified according to the severity or clinical evolution of the condition as mild, moderate or severe non-inflammatory acne or inflammatory acne (MANFRINATO, 2009). Non-inflammatory acne is characterized by the presence of comedones that are not in an inflammatory state, while inflammatory acne is classified into four stages according to the intensity, amount and characteristics of the lesions: - Grade I acne (comedogenic acne - non-inflammatory): oily skin, open and closed comedones without inflammatory lesions; - Grade II acne (inflammatory papulopustular acne): open and closed comedones, papules and pustules; - Grade III acne (inflammatory nodular-cystic acne): oily skin, open and closed comedones, pustules, nodules and cysts; - Grade IV acne (acne fulminans): An infectious and generalized form of acne that occurs suddenly with unknown cause and mainly affects men. Although rare, it is devastating and serious. The etiology of acne fulminans is not the same as that of acne vulgaris. It does not occur through the same process of pilosebaceous follicle obstruction, hypersecretion, and hormonal factors. In some cases, affected individuals have papules, pustules, and nodules that develop into ulcers.

[0004] Daily skin care, including daily cleansing of the skin, is considered to be a key factor in the successful management of acne. Drug treatments may cause side effects such as erythema, peeling, edema, dryness, and roughness in the long term, or symptoms such as itching and burning. These reactions may occur due to direct effects caused by the active ingredients (e.g., retinoids, benzoyl peroxide, some topical antibiotics, etc.) or due to the properties of the vehicle. Therefore, it is paramount to select appropriate daily skin care products to avoid further traumatizing the already sensitive skin. Furthermore, the proper selection of skin care products can increase an individual's compliance with dermatological treatments and refrain from over-cleaning the skin, which may stimulate sebum production and ultimately increase the severity of acne.

[0005] Although many skin care products are available on the market, there remains a need for topical compositions that are gentle on the skin and help improve the condition of oily skin, acne-prone skin, acne-affected skin and / or acne-treated skin. Summary of the Invention

[0006] The present invention relates to a. a keratolytic combination comprising an alpha hydroxy acid consisting of succinic acid and one or more alpha hydroxy acids, preferably lactic acid; b. one or more physiologically acceptable carriers and / or adjuvants; A topical composition comprising: The topical composition relates to a composition in which the total amount of succinic acid and alpha hydroxy acid ranges from about 1% to about 8% by weight based on the total weight of the composition, and the mass ratio of succinic acid / total alpha hydroxy acid is 1 or greater.

[0007] The present invention also relates to topical compositions as disclosed herein for cleansing oily skin, acne-prone skin, acne-affected skin and / or skin that has been treated for acne, for controlling skin oiliness, and / or for reducing stratum corneum firmness while controlling epidermal integrity.

[0008] The present invention also provides a. applying a composition disclosed herein to pre-moistened skin b. optionally emulsifying with water; c. Washing the skin; and d. drying out the skin; The present invention relates to a cosmetic method for cleansing the skin, comprising:

[0009] Further aspects of the present invention are as disclosed herein and in the claims. [Brief description of the drawings]

[0010] [Figure 1A] FIG. 1A: Measurement and analysis of stratum corneum elasticity. Percentage inhibition of elastic modulus compared to controls (average of two donors): control - untreated -, 1 wt% salicylic acid, 0.6 wt% succinic acid, 0.36 wt% lactic acid, and 0.36 wt% lactic acid + 0.6 wt% succinic acid.

[0011] [Figure 1B]FIG. 1B: Measurement and analysis of cell-cell adhesion in the deeper layers of the epidermis (control for intact epidermis). Percentage inhibition of elastic modulus compared to salicylic acid (average of two donors): 1% by weight salicylic acid, 0.36% by weight lactic acid + 0.6% by weight succinic acid.

[0012] [Diagram 2] Figure 2: Overall lesion count on the trunk, error bars: 95% CI, ***p-value ≤ 0.001.

[0013] definition The term "about" means in the context of the present invention that the value in question may be 10%, particularly 5%, especially 1% lower or higher than the indicated value.

[0014] This includes the stated value and values ​​10%, particularly 5%, particularly 1% below or above the stated value. By way of example, if a range is said to vary from about X to about Y, this includes the range from X to Y, and optionally values ​​10%, particularly 5%, particularly 1% below X and values ​​10%, particularly 5%, particularly 1% above Y.

[0015] As used herein, the term "keratolytic agent" refers to an agent that softens, disrupts, dissolves, solubilizes, or loosens keratinized obstructions.

[0016] Description of the invention Surprisingly, it has been found that topical compositions comprising a combination of succinic acid and one or more alpha hydroxy acids, particularly lactic acid as disclosed herein, effectively improve the condition of acne-prone skin, acned skin and / or acne-treated skin due to the combined bactericidal and keratolytic action of succinic acid and the alpha hydroxy acids, particularly lactic acid, while preserving the integrity of the epidermis.

[0017] As used herein, "alpha hydroxy acid" means an organic carboxylic acid having one hydroxyl group attached to the alpha carbon of the carboxylic acid functional group. Examples of suitable alpha hydroxy acids include, but are not limited to, lactic acid, glycolic acid, tartaric acid, malic acid, citric acid, and mandelic acid.

[0018] In some embodiments, the topical compositions of the present invention comprise: a. a keratolytic combination comprising succinic acid and one or more alpha hydroxy acids (preferably selected from the group consisting of lactic acid, glycolic acid, tartaric acid, malic acid, citric acid, mandelic acid, and combinations thereof); b. one or more physiologically acceptable carriers and / or adjuvants; Includes; The total amount of succinic acid and total alpha hydroxy acids ranges from about 1% by weight to about 8% by weight based on the total weight of the composition, and the mass ratio of succinic acid / total alpha hydroxy acids is 1 or greater, preferably 1.5 or greater.

[0019] In some preferred embodiments, the topical compositions of the present invention comprise: a. a combination of keratolytic agents including an alpha hydroxy acid consisting of succinic acid and lactic acid; b. one or more physiologically acceptable carriers and / or adjuvants; Includes; The total amount of succinic acid and lactic acid is in the range of about 1% by weight to about 8% by weight based on the total amount of the composition, and the mass ratio of succinic acid / lactic acid is 1 or more, preferably 1.5 or more.

[0020] As used herein, "topical composition" means a composition for application to human skin. The topical composition may be a cosmetic topical composition or a pharmaceutical / dermatological topical composition.

[0021] As used herein, "cosmetic topical composition" means a skin care composition. Skin care compositions are generally used to cleanse, protect, moisturize, and / or treat the skin, ie, to provide beneficial substances in improving the condition of the skin to which they are applied.

[0022] The topical compositions of the present invention may be in any form suitable for skin care. For example, topical compositions may be in the form of a solution, micellar solution, lotion, emulsion, suspension, cream, ointment, serum, mask, foam or gel. Solutions, lotions, foams and gels may be preferred. The selection of suitable carriers and adjuvants described herein will largely depend on the selected form of the composition.

[0023] The topical composition preferably has a pH in the range of from 4.5 to 5.1, for example from 4.8 to 5.1.

[0024] The compositions of the present invention are suitable for cleansing oily or acne-prone skin, individuals who have acne and / or have undergone acne treatment. Thus, in some preferred embodiments, the present invention provides a. a keratolytic combination comprising succinic acid and one or more alpha hydroxy acids (preferably selected from the group consisting of lactic acid, glycolic acid, tartaric acid, malic acid, citric acid, mandelic acid, and combinations thereof); b. one or more physiologically acceptable carriers and / or adjuvants; A topical cleansing composition comprising: The total amount of succinic acid and alpha hydroxy acid is in the range of about 1% by weight to about 8% by weight based on the total amount of the composition; the mass ratio of succinic acid / total alpha hydroxy acid is 1 or more, preferably 1.5 or more. This invention relates to topical cleansing compositions.

[0025] In some preferred embodiments, the present invention provides a. a combination of keratolytic agents including an alpha hydroxy acid consisting of succinic acid and lactic acid; b. one or more physiologically acceptable carriers and / or adjuvants; A topical cleansing composition comprising: The topical cleansing composition relates to a composition in which the total amount of succinic acid and lactic acid is in the range of about 1% by weight to about 8% by weight based on the total amount of the composition; the mass ratio of succinic acid / lactic acid is 1 or more, preferably 1.5 or more.

[0026] It has been found that topical cleansing compositions comprising the combination of succinic acid and alpha hydroxy acid, particularly lactic acid, disclosed herein effectively and gently cleanse the skin without causing local skin reactions (e.g., dryness, irritation) and without overcompensating for sebum production. The topical cleansing compositions effectively remove dirt, contamination and excess sebum. It has been observed that the oiliness and shine of the skin is instantly reduced, and a long-lasting mattifying effect and / or anti-blemish effect is obtained. Additionally, as previously discussed and further detailed below, the topical cleansing composition helps improve the condition of oily skin, acne-prone skin, acne-affected skin and acne-treated skin.

[0027] The topical cleansing composition is preferably an aqueous composition, i.e., the topical cleansing composition is not an oil-based composition, an emulsion-type composition, or a solvent-based composition (e.g., an alcohol-based composition). Preferred topical cleansing compositions are single phase compositions.

[0028] The topical cleansing composition is preferably a liquid. Preferably, the topical cleansing composition may have a viscosity that varies within a wide range at ambient temperature (25°C), for example in the range of 500 to 3500 cPs, preferably 1400 to 3500 cPs. The viscosity is usually measured at 25°C using a Brookfield DV1RV viscometer.

[0029] In some embodiments, the topical cleansing composition is in the form of an aqueous gel.Topical cleansing compositions are generally rinse-off compositions.By "rinse-off composition" is meant a composition that is applied to the skin for a short period of time (a few seconds or minutes) and then rinsed off with water.

[0030] The topical composition may be supplied as a liquid that can be dispensed from a package onto a device (e.g., cotton pad, cloth) or directly onto the skin. Alternatively, the topical composition may be absorbed into a wipe.

[0031] The components of the topical compositions, particularly the components of the topical cleansing compositions, are as described herein below.

[0032] keratolytic substances The topical composition comprises a combination of keratolytic agents, including succinic acid and one or more alpha hydroxy acids, particularly lactic acid. It has been found that succinic acid and one or more alpha hydroxy acids, particularly lactic acid, effectively soften and separate the keratinized epidermis of the skin (relieving the adhesion of the stratum corneum), resulting in a synergistic effect that causes skin desquamation while preserving the integrity of the epidermis. As a result, a decrease in skin firmness may be observed. The keratolytic agent helps to remove comedonal plugs (i.e., solid masses of keratinized cells that clog hair follicles), reducing the continued accumulation of keratinized cells that contribute to the enlargement of comedones. As a result, a decrease in pore size may be observed.

[0033] Additionally, the combination of succinic acid with one or more alpha hydroxy acids, especially lactic acid, provides a bactericidal effect. Succinic acid and one or more alpha hydroxy acids, especially lactic acid, have been shown to be effective in targeting Cutibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermis, which may cause acne, although Cutibacterium acnes is the primary trigger of acne.

[0034] Typically, the topical composition does not include an additional keratolytic agent.

[0035] In some embodiments, the topical composition does not include salicylic acid.

[0036] In some embodiments, the topical composition does not include a derivative of salicylic acid.

[0037] In some embodiments, the topical composition is free of resorcinol, sulfur, and benzoyl peroxide.

[0038] In a preferred embodiment, the alpha hydroxy acid comprises lactic acid.

[0039] In a preferred embodiment, the combination of keratolytic agents consists of succinic acid and lactic acid.

[0040] The total amount of succinic acid and alpha hydroxy acid in the topical composition ranges from about 1% to 8% by weight, for example from about 2% to 8% by weight, or from about 3% to 8% by weight, or from about 4% to 8% by weight, or from about 4% to 7% by weight, or from about 4% to 6% by weight, or about 5% by weight, based on the total weight of the composition.

[0041] When the alpha hydroxy acid comprises lactic acid, the total amount of succinic acid and lactic acid in the topical composition ranges from about 1% to 8% by weight, e.g., from about 2% to 8% by weight, or from about 3% to 8% by weight, or from about 4% to 8% by weight, or from about 4% to 7% by weight, or from about 4% to 6% by weight, or about 5% by weight, based on the total weight of the composition.

[0042] When the topical composition does not include an additional keratolytic agent, the topical composition comprises from about 1% to 8% by weight of the combination of keratolytic agents, for example from about 2% to 8% by weight, or from about 3% to 8% by weight, or from about 4% to 8% by weight, or from about 4% to 7% by weight, or from about 4% to 6% by weight, or about 5% by weight, based on the total weight of the composition.

[0043] The mass ratio of succinic acid / total alpha hydroxy acids is 1 or greater, preferably 1.5 or greater, more preferably 1.6 or greater. Preferably, the mass ratio of succinic acid / total alpha hydroxy acids is 4 or less, alternatively 3 or less, alternatively 2 or less, alternatively 1.7 or less.

[0044] When the alpha hydroxy acid comprises lactic acid, the succinic acid / lactic acid weight ratio is 1 or more, preferably 1.5 or more, more preferably 1.6 or more. Preferably, the succinic acid / lactic acid weight ratio is 4 or less, alternatively 3 or less, alternatively 2 or less, alternatively 1.7 or less.

[0045] In some embodiments, the topical composition comprises about 0.5% to about 6% by weight, preferably about 1% to about 6% by weight, or about 2% to about 6% by weight, or about 3% to about 6% by weight, or about 2% to about 4% by weight of succinic acid, and about 0.5% to about 5% by weight, preferably about 1% to about 5% by weight, or about 1% to about 4% by weight, or about 2% to about 5% by weight, or about 1% to about 3% by weight of an alpha hydroxy acid, based on the total weight of the composition.

[0046] In some embodiments, when the alpha hydroxy acid comprises lactic acid, the topical composition comprises from about 0.5% to about 6% by weight, preferably from about 1% to about 6% by weight, or from about 2% to about 6% by weight, or from about 3% to about 6% by weight, or from about 2% to about 4% by weight of succinic acid, and from about 0.5% to about 5% by weight, preferably from about 1% to about 5% by weight, or from about 1% to about 4% by weight, or from about 2% to about 5% by weight, or from about 1% to about 3% by weight of lactic acid, based on the total weight of the composition.

[0047] Physiologically acceptable carriers and / or adjuvants Since the compositions of the present invention are intended for topical application, the carrier(s) and / or excipient(s) must be physiologically acceptable.

[0048] The term "physiologically acceptable" means compatible with the skin (e.g., body, face, eyelids) and mucous membranes (e.g., lips), i.e., not eliciting undue toxicity, incompatibility, instability, irritation, allergic response, etc.

[0049] The selection of suitable carriers and adjuvants will largely depend on the chosen form of the topical composition.

[0050] Carrier Topical compositions comprise from about 10% to about 90% by weight of the composition, for example, from about 10% to about 70% or from about 15% to about 60% by weight of one or more carriers.

[0051] Although the physiologically acceptable carrier may be an organic solvent (e.g., propylene glycol, polyethylene glycol, polypropylene glycol, glycerol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, and mixtures thereof), silicone solvents, oils, lipids, and / or waxes, the physiologically acceptable carrier of the topical composition is generally water. Preferably, water is used as the only carrier. Thus, the topical composition is preferably an aqueous composition, i.e., the topical composition is not an oily composition, an emulsion-type composition, or a solvent-based composition (e.g., an alcohol-based composition). Thus, in a preferred embodiment, the topical composition does not include an oil phase and an oil-containing component.

[0052] Adjuvants The topical composition may also contain adjuvants common in the cosmetic or dermatological field, such as surfactants, thickeners, gelling agents, moisturizers, active agents (e.g., plant extracts, vitamins), preservatives, emulsifiers, fragrances, etc. The amounts of these various adjuvants are those conventionally used in the field under consideration, for example from about 0.0001% to about 30% by weight, or from about 0.0001% to about 20% by weight, or from about 0.01% to about 20% by weight, relative to the total amount of the topical composition.

[0053] The topical composition is preferably free of an oil phase or oil-containing components, and the topical composition generally does not contain emulsifiers, which may contribute to dehydration of the skin.

[0054] The topical composition may include one or more surfactants. The surfactant may be a polymeric or non-polymeric surfactant. The surfactant provides cleaning benefits, lathering properties, and rheological properties to the topical composition. The surfactant or combination of surfactants is usually mild, meaning that the surfactant provides adequate cleaning but does not overly dry the skin.

[0055] The total amount of surfactant in the topical composition may range from about 1% to about 30% by weight, for example, from about 1% to 20% by weight or from about 1% to 15% by weight, based on the total amount of the composition. The surfactant may be cationic, anionic, zwitterionic, amphoteric, nonionic, or a combination thereof. Although in principle any surfactant class can be used, when used for cleaning applications, the topical composition is usually formulated with an anionic surfactant, or a combination of one or more anionic surfactants with one or more surfactants selected from other surfactant classes. Thus, the topical composition, in particular the topical cleaning composition, comprises from about 1% to about 20% by weight, for example, from about 1% to about 18% by weight or from about 1% to about 15% by weight, of one or more anionic surfactants, and from about 1% to about 15% by weight, for example, from about 1% to about 12% by weight or from about 1% to about 10% by weight, of a surfactant selected from other surfactants, for example, a nonionic surfactant.

[0056] A wide variety of anionic surfactants are useful in the present invention. Anionic surfactants may include counterions such as sodium, potassium, ammonium, triethanolamine, etc. Non-limiting examples of anionic surfactants include those selected from the group consisting of carboxylates, sarcosinates, sulfates, sulfonates, isethionates, taurates, phosphates, lactates, citrates, glutamates, and mixtures thereof. Anionic surfactants selected from the group consisting of carboxylates, sarcosinates, isethionates, taurates, phosphates, lactates, citrates, glutamates, and mixtures thereof, or anionic surfactants selected from the group consisting of carboxylates, taurates, lactates, citrates, glutamates, or anionic surfactants selected from the group consisting of lactates, citrates, glutamates, and mixtures thereof, especially glutamates, are preferred. Suitable anionic surfactants include, but are not limited to, amino acid-based anionic surfactants, such as disodium cocoyl glutamate. Preferably, the surfactant is disodium cocoyl glutamate, disodium coco glucoside citrate, or a combination thereof.

[0057] Nonionic surfactants useful herein include, but are not limited to, those selected from the group consisting of alkyl glucosides, alkyl polyglucosides, polyhydroxy fatty acid amides, alkoxylated fatty acid esters, alkoxylated fatty alcohol ethers, sucrose esters, and mixtures thereof. A preferred nonionic surfactant is decyl glucoside.

[0058] Amphoteric surfactants useful herein include, but are not limited to, surfactants broadly described as derivatives of aliphatic secondary and tertiary amines, where the aliphatic radical can be straight or branched chain, one of the aliphatic substituents contains from about 8 to about 18 carbon atoms, and one contains an anionic water-solubilizing group such as carboxy, sulfonate, sulfate, phosphate, or phosphonate.

[0059] Useful amphoteric surfactants include the group consisting of cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate, lauroamphodiacetate and mixtures thereof. In some embodiments, the topical composition is free of amphoteric surfactants.

[0060] Zwitterionic surfactants useful herein include, but are not limited to, surfactants broadly described as derivatives of aliphatic quaternary ammonium, phosphonium and sulfonium compounds, in which the aliphatic radical can be straight or branched chain, one of the aliphatic substituents contains from about 8 to about 18 carbon atoms, and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate or phosphonate.

[0061] Useful zwitterionic surfactants include betaines, amphoacetates and sulfobetaines, such as cocamidopropyl betaine, sodium lauryl amphoacetate and cocamidopropyl hydroxysultaine.

[0062] In some embodiments, the topical composition does not include a zwitterionic surfactant.

[0063] In some embodiments, the topical composition comprises at least one amino acid surfactant as a surfactant, preferably at least disodium cocoyl glutamate. The amount of amino acid surfactant can range from about 0.1% to about 12% by weight or from about 2% to about 10% by weight, preferably from about 5% to about 10% by weight, based on the total weight of the composition.

[0064] In some embodiments, the topical composition comprises at least one amino acid based surfactant, preferably at least disodium cocoyl glutamate, which may be in the ratios disclosed herein, and at least one surfactant different from the amino acid based surfactant, e.g., at least disodium coco glucoside citrate or at least decyl glucoside.

[0065] Preferably, the topical composition comprises a mixture of an anionic surfactant and a nonionic surfactant.

[0066] Therefore, it should be understood that the topical composition does not include amphoteric and zwitterionic surfactants. More specifically, in some embodiments, the topical composition includes a mixture of disodium cocoyl glutamate, disodium coco glucoside citrate, and decyl glucoside.

[0067] Generally, the mixture contains from about 0.1% to about 12% by weight of disodium cocoyl glutamate, from about 0.5% to about 6% by weight of disodium cocoglucoside citrate, and from about 1% to about 15% by weight of decyl glucoside, based on the total weight of the composition.

[0068] In some embodiments, the weight ratio of one or more anionic surfactants to another class of surfactant, such as a nonionic surfactant, is about 50 / 50.

[0069] The topical composition may include thickening agents, such as cellulose derivatives (e.g., hydroxymethylcellulose and hydroxypropylcellulose), starch and starch derivatives, acrylic acid and acrylate polymers and copolymers, polyethylene glycol derivatives, natural gums (e.g., xanthan gum, scleroglucan gum and / or carrageenan gum) and salts (e.g., sodium chloride).In some embodiments, the thickening agent is ceteareth 60 myristyl glycol.

[0070] Topical compositions may contain preservatives, such as benzoic acid or a salt thereof, benzyl alcohol, sorbic acid or a salt thereof, urea (e.g., imidazolidinyl urea, diazolidinyl urea), parabens, dehydroacetic acid, sodium dehydroacetate, PHMB (polyhexamethylene biguanide), phenoxyethanol, ethylhexylglycerol, salicylic acid or a salt thereof, and sodium benzoate.

[0071] The topical composition may also include additional active agents. Active agents are substances that further improve the condition of the skin to which they are applied.

[0072] Suitable active agents may be antiseborrheic agents and / or pore refiners. Examples of antiseborrheic agents include, but are not limited to, 2,3-dihydroxypropyl dodecanoate, sabal extract, pumpkin seed oil, urtica dioic extract, and combinations thereof, preferably 2,3-dihydroxypropyl dodecanoate. Examples of pore refiners include, but are not limited to, Lens esculenta seed extract.

[0073] However, topical compositions generally do not include anti-acne agents, particularly ichtyol, retinoic acid and / or zinc gluconate.

[0074] In some embodiments, the topical composition comprises the following ingredients: [Table 1]

[0075] Further embodiments of the present invention

[0076] In some further aspects, the present invention provides a method for the preparation of a a. a keratolytic combination comprising succinic acid and one or more alpha hydroxy acids; b. one or more physiologically acceptable carriers and / or adjuvants; A topical composition comprising: The total amount of succinic acid and alpha hydroxy acid in the topical composition ranges from about 1% to about 8% by weight based on the total weight of the composition.

[0077] In some embodiments, the alpha hydroxy acid is selected from the group consisting of lactic acid, glycolic acid, tartaric acid, malic acid, citric acid, mandelic acid, and combinations thereof, more preferably, the alpha hydroxy acid is lactic acid.

[0078] The total amount of succinic acid and alpha hydroxy acid in the topical composition can range from about 2% to 8% by weight, or from about 3% to 8% by weight, or from about 4% to 8% by weight, or from about 4% to 7% by weight, or from about 4% to 6% by weight, or is about 5% by weight, based on the total weight of the composition.

[0079] In some preferred embodiments, the succinic acid / total alpha hydroxy acids weight ratio of the topical composition is 1 or more, preferably 1.5 or more, more preferably 1.6 or more. Preferably, the succinic acid / total alpha hydroxy acids weight ratio is 4 or less, alternatively 3 or less, alternatively 2 or less, alternatively 1.7 or less.

[0080] In some embodiments, the topical composition comprises from about 0.5% to about 6% by weight, preferably from about 1% to about 6% by weight, or from about 2% to about 6% by weight, or from about 3% to about 6% by weight, or from about 2% to about 4% by weight of succinic acid, and from about 0.5% to about 5% by weight, preferably from about 1% to about 5% by weight, or from about 1% to about 4% by weight, or from about 2% to about 5% by weight, or from about 1% to about 3% by weight of total alpha hydroxy acid, based on the total weight of the composition.

[0081] In some preferred embodiments, the alpha hydroxy acid comprises lactic acid.

[0082] In some further aspects, the present invention provides a method for the preparation of a a. a keratolytic combination comprising succinic acid and one or more alpha hydroxy acids; b. one or more physiologically acceptable carriers and / or adjuvants; A topical cleansing composition comprising: The topical cleansing composition comprises a total amount of succinic acid and alpha hydroxy acid ranging from about 1% to about 8% by weight based on the total weight of the composition.

[0083] In some embodiments, the alpha hydroxy acid is selected from the group consisting of lactic acid, glycolic acid, tartaric acid, malic acid, citric acid, mandelic acid, and combinations thereof, more preferably, the alpha hydroxy acid is lactic acid.

[0084] The total amount of succinic acid and alpha hydroxy acid in the topical cleansing composition can range from about 2% to 8% by weight, or from about 3% to 8% by weight, or from about 4% to 8% by weight, or from about 4% to 7% by weight, or from about 4% to 6% by weight, or is about 5% by weight based on the total weight of the composition.

[0085] In some preferred embodiments, the succinic acid / total alpha hydroxy acids weight ratio of the topical cleansing composition is 1 or greater, preferably 1.5 or greater, more preferably 1.6 or greater.Preferably, the succinic acid / total alpha hydroxy acids weight ratio is 4 or less, alternatively 3 or less, alternatively 2 or less, alternatively 1.7 or less.

[0086] In some embodiments, the topical cleansing composition comprises from about 0.5% to about 6% by weight, preferably from about 1% to about 6% by weight, or from about 2% to about 6% by weight, or from about 3% to about 6% by weight, or from about 2% to about 4% by weight of succinic acid, and from about 0.5% to about 5% by weight, preferably from about 1% to about 5% by weight, or from about 1% to about 4% by weight, or from about 2% to about 5% by weight, or from about 1% to about 3% by weight of an alpha hydroxy acid, based on the total weight of the composition.

[0087] In some preferred embodiments, the alpha hydroxy acid comprises lactic acid.

[0088] Further aspects of these topical compositions include those described herein above, e.g., as "keratolytic agents" and " Physiologically acceptable carriers and / or adjuvants" The composition may be as disclosed in the above paragraph.

[0089] Methods and Uses The topical composition may be used to protect, cleanse, moisturize and treat oily skin, acne-prone skin, acne-affected skin and / or acne-treated skin. More specifically, the topical cleansing composition may be used to cleanse oily skin, acne-prone skin, acne-affected skin and / or acne-treated skin.

[0090] Thus, the present invention relates to the cosmetic use of the topical compositions disclosed herein for protecting, cleansing or moisturizing oily skin, acne-prone skin, acne-affected skin and / or skin that has been treated for acne.

[0091] The present invention also relates to the cosmetic use of the topical compositions disclosed herein to control skin oiliness, or to provide a sustained antibacterial effect, or to beneficially affect the skin's bacterial flora, or to reduce the hardness of the stratum corneum while controlling the integrity of the epidermis.

[0092] Cosmetic use includes applying an effective amount of the topical composition described herein to the skin of an individual in need thereof, particularly the face or trunk.Application may be performed daily, for example twice a day, for example once in the morning and once at night.Application may be performed over a period ranging from one week to several weeks or even several months, preferably at least 3 weeks.

[0093] The present invention also relates to a cosmetic (non-therapeutic) method for improving the condition of oily skin, acne-prone skin, acned skin and / or acne-treated skin, comprising applying an effective amount of the topical composition described herein to an individual in need thereof.

[0094] The present invention also provides a cosmetic method for cleansing the skin, comprising the steps of: a. applying a composition described herein to pre-moistened skin, preferably twice daily (e.g., morning and night); b. optionally emulsifying with water; c. Generally, thorough rinsing; and d. drying out the skin; The present invention relates to a method comprising the steps of:

[0095] For sustained effect, application may be repeated for at least 3 weeks, preferably at least 4 weeks.

[0096] The present invention also relates to therapeutic uses of the topical compositions disclosed herein.

[0097] The present invention also relates to the use of the topical compositions disclosed herein in the treatment of acne.

[0098] The present invention also relates to the use of the topical compositions disclosed herein in the preparation of a medicament for the treatment of acne.

[0099] The present invention also relates to a method of treating acne, comprising applying an effective amount of the topical composition described herein to an individual in need thereof.

[0100] The present invention also relates to the topical compositions disclosed herein for use in the treatment of acne.

[0101] Embodiments of the present invention are illustrated by the following examples, which are intended for illustrative purposes only and are not intended to limit the scope of the invention. EXAMPLES

[0102] Example 1A: [Table 2]

[0103] Example 1B: [Table 3]

[0104] Example 2 : Synergistic keratolytic effect of the combination of succinic acid and lactic acid (succinic acid / lactic acid mass ratio is 1.67)

[0105] The keratolytic effect was evaluated by observing the modulation of the skin biomechanical properties (modulation of skin firmness) induced by the tested agents using atomic force microscopy (AFM) on skin explants.

[0106] One donor explant and processing Three different regions were measured by explant At least 12 measurements in one area

[0107] Protocol : skin explant Skin punches of 1.2 cm were prepared from chest skin of women aged 35-43 years. Three topical treatments using lactic acid and succinic acid alone or mixed together (succinic acid / lactic acid ratio 1.67) were applied. The first and second applications were performed within 1 h, and the third application within 3 h. After treatment, the skin explants were frozen in liquid nitrogen and stored at -80 °C. 20 μm cryosections were prepared from the treated skin explants. The mechanical properties of the cryosections of the skin explants are evaluated by AFM measurements in the stratum corneum and epidermis regions.

[0108] Atomic Force Microscope (AFM) AFM indentation experiments were performed using a Resolve Bioscope (Bruker Nano Surface, Santa Barbara, CA) mounted on an inverted optics DMI8 (Leica) and a top view Bruker. All skin stiffness measurements were performed using a cantilever with a conical tip. The cantilever was moved to conform to the irregularities of the skin surface. This deformation was quantified by the deflection of the laser beam, which correlates with the biomechanical parameters of the skin surface sample. Quantitative measurements of elastic modulus were used to evaluate the stiffness of the stratum corneum or epidermis intercellular junctions after treatment. Inhibition of stiffness was calculated between treated and untreated control explants.

[0109] result The results are shown in Figures 1A and 1B (control - untreated -, 1 wt% salicylic acid, 0.6 wt% succinic acid, 0.36 wt% lactic acid, and 0.36 wt% lactic acid + 0.6 wt% succinic acid).

[0110] The combination of succinic acid and lactic acid induces a strong inhibition of the elastic modulus of the stratum corneum (strong decrease in the stiffness of the stratum corneum), whereas succinic acid and lactic acid alone show no significant effect (Figure 1A), this inhibition is stronger than that of the reference keratolytic agent (salicylic acid).

[0111] Measurement and analysis of intercellular adhesion in the deeper layers of the epidermis showed that the combination of succinic acid and lactic acid significantly protected intercellular adhesion in the deeper layers of the epidermis compared to the reference keratolytic agent (salicylic acid) (Figure 1B).

[0112] Example 3 In vitro antibacterial effect of the composition according to the present invention

[0113] In acne skin, Cutibacterium acnes is the main trigger of acne, although other commensals such as Staphylococcus epidermidis may also play an important role. It is known that gut dysbiosis in acne patients is associated with a reduced number of S. epidermidis and hypercolonization of the pilosebaceous unit with selected phylotypes of C. acnes. This change leads to different levels of innate immune activation and, consequently, different levels of severity of inflammatory acne vulgaris.Recent studies have confirmed that the beneficial role of S. epidermidis in acne physiopathology occurs by limiting the hypercolonization of the pilosebaceous unit by C. acnes and reducing the degree of inflammation in acne vulgaris.

[0114] Time kill methodology (CEN, IS EN-1040;2006: Quantitative suspension test of chemical disinfectants and preservatives for the evaluation of the basic bactericidal activity of chemical disinfectants and preservatives - Test methods and requirements Phase 1) was applied to quantify the microorganisms C. acnes, S. epidermidis and S. aureus after exposure to the product according to Example 1B.

[0115] result At 30 seconds, a reduction of more than 99.9999% (6 log) of the initial population of C. acnes was observed, at 5 minutes a reduction of 99.9% (3 log) of the initial microbial population of S. aureus was observed, and at 5 minutes a reduction of up to 94.44% (1.26 log) of the initial population of S. epidermidis was observed.

[0116] This product has a beneficial effect on the overall skin flora, including: - Reduced proven pathogens (C. acnes, S. aureus) -And no effect on the symbiont (S. epidermidis).

[0117] Examples 4 to 7 The product used in the following in-use tests is the composition according to Example 1B.

[0118] Example 4 : An in-use test to evaluate the oil-repellent effect by Sebumeter® measurements immediately after use and after 28 days of use

[0119] participants : Prone to acne, i.e. prone to acne (acne lesions on face and trunk: subjects with at least 10-40 acne lesions in total on face and trunk), oily skin (sebum level > 100μg / cm 2 (casual level) 30 healthy subjects aged between 16 and 40 years (each subject was their own control).

[0120] Protocol For 28 days (period of application of the investigational product), subjects had to apply the composition twice a day (morning and evening) to pre-moistened skin, emulsify with water, rinse and dry.

[0121] The first application of the product (D1) was performed on a randomized half of the face by subject under the supervision of a trained technician. All other applications during the study were performed at home under normal conditions of use.

[0122] The plan for the visit was as follows: -Visit 1:D1 -Visit 2:D8 -Visit 3: Final visit (D29)

[0123] The oiliness of the subjects' skin was assessed by instrumental measurement on the forehead using a Sebumeter®.

[0124] result After 28 days of use, the composition was observed to have a control effect on oiliness (-11.13%). Thus, the tested product makes it possible to control oiliness after 28 days of use (without increasing oiliness).

[0125] Example 5 : An in-use study to evaluate anti-acne efficacy after 28 days of use

[0126] participants : 30 healthy subjects aged 16-40 years with oily skin who were acne prone, i.e. prone to acne (acne lesions on the face and trunk) (each subject was their own control).

[0127] Protocol For 28 days, subjects had to apply the composition twice a day (morning and evening) to pre-moistened skin, emulsify with water, rinse and dry.

[0128] After 28 days of use, acne lesions (open comedones, closed comedones, papules, pustules and nodules) were counted on the face and trunk by a trained dermatologist.

[0129] result After 28 days of product use, the total amount of acne lesions on the face was significantly reduced (-33%) (p<0.001), proving the anti-acne effect on facial skin.

[0130] After 28 days of product use, the total amount of acne lesions on the trunk was significantly reduced (-49%) (p<0.001), demonstrating the anti-acne effect on the trunk skin (Figure 2).

[0131] As stated above, the products tested are non-comedogenic and non-acne causing.

[0132] Example 6 : In-use test to evaluate the development of pores after 7 and 28 days of use

[0133] participants: 30 healthy subjects aged 16-40 years with acne prone (acne lesions on face and trunk) and oily skin (each subject was their own control).

[0134] Protocol For 28 days, subjects had to apply the composition twice a day (morning and evening) to pre-moistened skin, emulsify with water, rinse and dry.

[0135] Dermatologists performed clinical evaluations of pores after 7 and 28 days of use.

[0136] result : Visible pores were significantly reduced (-3.3%) after 7 days of product use and -25.8% after 28 days of product use (p<0.001). Pore size was significantly reduced (-19.1%) after 7 days of product use and -36.1% after 28 days of product use (p<0.001).

[0137] Example 7 : In-use test for subjective evaluation of compositions

[0138] participants : 30 healthy subjects aged 16-40 years with acne prone (acne lesions on face and trunk) and oily skin (each subject was their own control).

[0139] Protocol For 28 days, subjects had to apply the composition twice a day (morning and evening) to pre-moistened skin, emulsify with water, rinse and dry.

[0140] Subjects were asked to report their subjective opinions regarding their experience with the use of the test product.

[0141] result After 28 days of use, the compositions were evaluated as follows: - Gentle cleansing without drying the skin: 8.2 / 10, 90% of subjects rated the composition ≧5 and 76.67% rated ≧8. - Reduction of Oiliness and Shine: 8.37 / 10, 96.67% of subjects rated the composition ≧5 and 76.67% rated ≧8.

Claims

1. a. a keratolytic combination comprising succinic acid and one or more alpha hydroxy acids, preferably lactic acid; b. one or more physiologically acceptable carriers and / or adjuvants; A topical composition comprising: The topical composition, wherein the total amount of succinic acid and alpha hydroxy acid ranges from about 1% to about 8% by weight based on the total weight of the composition, and the mass ratio of succinic acid / total alpha hydroxy acid is 1 or greater.

2. 10. The topical composition of claim 1, which is a topical cleansing composition.

3. 3. The topical composition of claim 1 or 2, wherein the carrier is water.

4. 4. The topical composition according to any one of claims 1 to 3, wherein the one or more alpha hydroxy acids consist of lactic acid, and the succinic acid / lactic acid mass ratio is 1.5 or more and 4 or less.

5. The topical composition according to any one of claims 1 to 4, wherein the combination of keratolytic agents consists of succinic acid and lactic acid.

6. The topical composition according to any one of claims 1 to 5, which is in the form of a solution, lotion, foam or gel.

7. A topical composition according to any one of claims 1 to 6, comprising one or more surfactants as adjuvants.

8. 8. The topical composition of claim 7, comprising a mixture of disodium cocoyl glutamate, disodium coco glucoside citrate and decyl glucoside as surfactants.

9. The topical composition according to any one of claims 1 to 8, which is free of salicylic acid.

10. 10. The topical composition of any one of claims 1 to 9, wherein the adjuvant comprises an antiseborrheic agent, the antiseborrheic agent being selected from the group consisting of 2,3-dihydroxypropyl dodecanoate, Sabal extract, pumpkin seed oil, extract of Urtica dioic acid, and mixtures thereof.

11. 11. The topical composition of any one of claims 1 to 10, wherein the adjuvant comprises a pore refiner, and the pore refiner is Lens esculenta seed extract.

12. A topical composition according to any one of claims 1 to 11 for cleansing oily skin, acne-prone skin, acned skin and / or skin that has undergone acne treatment.

13. A topical composition according to any one of claims 1 to 11 for controlling skin oiliness.

14. A topical composition according to any one of claims 1 to 11 for reducing the stiffness of the stratum corneum while controlling the integrity of the epidermis.

15. A cosmetic method for cleansing the skin, comprising: a. applying a composition according to any one of claims 1 to 11 to pre-moistened skin b. optionally emulsifying with water; c. Washing the skin; and d. drying out the skin; The method comprises:

16. A topical composition according to any one of claims 1 to 11 for treating acne.

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