FORMULATION OF PUNICA GRANATUM EXTRACT WITH IMPROVED STABILITY AND ITS APPLICATIONS

Abstract

FORMULATION OF PUNICA GRANATUM EXTRACT WITH IMPROVED STABILITY AND APPLICATIONS THEREOF The present disclosure relates to a formulation in a cosmetically acceptable medium, comprising: a) an extract of Punica granatum; b) at least one stabilizer comprising sodium thiosulfate; c) water; and d) at least one organic solvent. The present disclosure also relates to a kit comprising the formulation and a method for the cosmetic treatment of keratinous materials, using the formulation. Figure for abstract: none

Description

Title of the invention: FORMULATION OF PUNICA GRANATUM EXTRACT WITH IMPROVED STABILITY AND ITS APPLICATIONS FIELD OF THE INVENTION

[0001] The present disclosure relates to the field of cosmetics. The present disclosure relates in particular to a formulation comprising an extract of Punica granatum with improved stability. The invention further relates to a method for the cosmetic treatment of keratinous materials using the formulation. CONTEXT OF THE INVENTION

[0002] Antioxidants are key active ingredients in cosmetic products targeting keratinous materials, especially the skin. There are already a large number of antioxidants, such as tocopherol (vitamin E) or its derivatives, vitamin C or its derivatives, carotenoids, ubiquinone, etc. In particular, products comprising antioxidants derived from natural sources are preferred by consumers over synthetic antioxidants. Plant extracts are important natural sources of antioxidants that are used in cosmetic products. Extracts of Punica granatum are known from the prior art as an antioxidant active agent. Document FR3031901 describes an extract of Punica granatum obtained with a mixture of 70% w / w ethanol / 30% w / w water, comprising at most 1.93% ellagic acid, with a weight ratio [ellagic acid / punicalagins A and B] equal to 0.2.Document WO2021064034A1 describes an extract of Punica granatum comprising at least 10% by weight of the total weight of the dry extract, of punicalagins and at least 10% by weight of the total weight of the dry extract, of ellagic acid in which the weight ratio [ellagic acid / punicalagins] ranges from 0.5 to 2. The antioxidant activity of such extracts must be stable over time in the formulations, in particular after storage at room temperature for 2 weeks, 1 or 2 months. In particular for the extract of Punica granatum, the stability can be measured by the stability of the punicalagin content, and a formulation is considered stable if this content is greater than 91% after storage at room temperature for 2 weeks, 1 or 2 months. In some cases, the Punica granatum extracts contained in the formulation are, moreover, supposed to be stable even under accelerated conditions, such as 45°C for 2 months or 55°C for 2 weeks.

[0003] Therefore, it is essential to develop a cosmetic formulation in which the natural sources of antioxidants remain stable throughout the shelf life of the formulation under ambient conditions without compromising the aesthetic and sensory aspects of the formulation. In particular, there is a need for a cosmetic formulation containing Punica granatum extract, which remains stable at least when stored at room temperature for 2 weeks, 1 or 2 months, in which the punicalagin content is higher than 91% after storage compared to the punicalagin content without storage. There is also a need for a cosmetic formulation containing Punica granatum extract which is, in addition, expected to be stable even under accelerated conditions, such as 45°C for 2 months or 55°C for 2 weeks.

[0004] The Applicant has unexpectedly demonstrated that a formulation containing a) Punica granatum extract and preferably comprising at least 10% by weight of the total weight of the dry extract, of punicalagins; and at least 10% by weight of the total weight of the dry extract, of ellagic acid; in which the weight ratio [ellagic acid / punicalagins] ranges from 0.5 to 2 and b) at least one stabilizer comprising sodium thiosulfate; and c) water; and d) at least one organic solvent, is stable after storage at room temperature for 2 weeks, 1 or 2 months, i.e. in such a formulation, the punicalagins content is greater than 91% after storage compared to the content without storage. Summary of the invention

[0005] In one aspect of the present disclosure, there is provided a formulation in a cosmetically acceptable medium, comprising: a) an extract of Punica granatum; b) at least one stabilizer comprising sodium thiosulfate; c) water; and d) at least one organic solvent.

[0006] In another aspect of the present disclosure, there is provided a kit comprising (a) the formulation as disclosed herein; (b) a container; and (c) optionally, an applicator.

[0007] In another aspect of the present disclosure, there is provided a method for cosmetic treatment of keratinous materials, comprising applying said formulation, as disclosed herein, to the keratinous materials, preferably to the skin.

[0008] These and other features, aspects, and advantages of the present subject matter will be better understood with reference to the following description and the appended claims. This summary is provided to present a selection of concepts in a simplified form. This summary is not intended to identify key features or essential characteristics of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. DETAILED DESCRIPTION OF THE INVENTION

[0009] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions, and compounds designated or indicated in this specification, individually or collectively, and any combination of one or more of such steps or features.

[0010] Definitions

[0011] For convenience, before describing the present disclosure in more detail, certain terms used in the specification and examples are defined herein. These definitions should be read in light of the remainder of the disclosure and understood as by a person skilled in the art. The terms used herein have the meanings recognized and known to those skilled in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

[0012] The terms “include” or “contain” and “comprising” or “containing” are used in the inclusive and open sense, meaning that additional elements may be included. They are not intended to be interpreted as “consists solely of”.

[0013] The expression "at least one" is used to mean one or more and therefore includes individual components as well as mixtures / combinations.

[0014] The term "polyol" is used to designate an organic compound which contains at least 2 hydroxy radicals such as 2 or 3 or 4 or 5 or 6 hydroxy radicals.

[0015] Throughout this patent specification, unless the context otherwise requires, the term "comprise", and variations such as "comprises" and "comprising", shall be understood to imply the inclusion of a recited element or step or group of elements or steps, but not the exclusion of any other element or step or group of elements or steps.

[0016] The term "including" is used to mean "including, but not limited to." "including" and "including, but not limited to" are used interchangeably.

[0017] The term "INCI" is an abbreviation for the International Nomenclature of Cosmetic Ingredients, which is a system of names provided by the International Nomenclature Committee of the Personal Care Products Council to identify ingredients in cosmetic or personal care products.

[0018] The term "keratinous materials" as used herein means skin, hair, eyelashes, eyebrows and nails, preferably skin.

[0019] The term “cosmetically acceptable medium” as used herein means a medium compatible with “keratinous materials”, preferably the skin and / or its superficial bodily growths, which has a pleasant color, odor, and feel, and which does not cause unacceptable discomfort (tingling or tightness) that would discourage the consumer from using this formulation for cosmetic applications. Examples of cosmetically acceptable media include, but are not limited to, water, glycols, water-glycol simplex, water-in-oil or oil-in-water emulsions to form creams, serums, or lotions, as well as surfactant-based shampoos or facial or hair cleansers, a water-surfactant mixture for toiletry preparations, etc.

[0020] The term "treatment" as used herein means any action intended to improve the comfort or well-being of a person. Accordingly, this term covers the alleviation, relief or suppression of the symptoms of aged / damaged skin, but is limited to cosmetic treatment.

[0021] The term "room temperature," as used herein, refers to a temperature between 18°C ​​and 25°C.

[0022] All percentages, parts, and ratios are based on the total weight of the composition of the present disclosure unless otherwise indicated. Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that this range format is used solely for convenience and brevity and is to be flexibly interpreted to include not only the numerical values ​​explicitly cited as the limits of the range, but also to include all individual numerical values ​​or subranges encompassed within that range as if each numerical value and subrange were explicitly cited. For example, a percentage range of about 10% to 70% is to be interpreted to include not only the explicitly cited limits of about 10% to about 70%, but also to include subranges, such as 20% to 30%, 30% to 45%, etc., as well as individual quantities, including fractional quantities, within the specified ranges, such as 28.4%, and 64%, for example. .

[0023] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by a person skilled in the art to which this disclosure pertains. Although any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the disclosure, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference.

[0024] The present disclosure should not be limited in scope by the specific embodiments described herein, which are intended for exemplary purposes only. Functionally equivalent products, compositions and processes clearly fall within the scope of the disclosure as described herein.

[0025] Embodiments of the present document relate to a formulation in a cosmetically acceptable medium for treating skin. The disclosed embodiments include a formulation, a kit comprising the formulation, and a method of treating keratinous materials by applying said formulation. In various embodiments of the present document, the formulation is in the form of a serum whose Punica granatum extract has improved stability. Cosmetic products comprising Punica granatum extract have been found to be beneficial in treating damaged skin and treating / preventing skin aging. Polyphenols, such as punicalagins and ellagic acid, are the key active compounds present in the extract, which contribute to the treatment of skin.However, Punica granatum extract suffers from poor stability in these cosmetic products due to the sensitivity of its phenolic antioxidants in a water-based formulation, which affects the overall stability of the product. It is therefore necessary to choose the ingredients of the formulation in such a way that they promote the stability of the extract, which is the key active ingredient of the formulation. Thus, the formulation according to embodiments of the present document, comprises at least one stabilizer, namely sodium thiosulfate, which improves the stability of Punica granatum extract to more than 91% when stored at room temperature. Thus, the use of an additional stabilizer, such as N-acetylcysteine, improves the stability of Punica granatum extract to more than 91% when stored under accelerated conditions. Formulation

[0026] Embodiments of the present document provide the formulation for treating a keratinous material, preferably the skin. In one aspect of the present disclosure, there is provided a formulation in a cosmetically acceptable medium, comprising: a) an extract of Punica granatum; b) at least one stabilizer comprising sodium thiosulfate; c) water; and d) at least one organic solvent. In other embodiments, the composition further comprises additives selected from pH adjusters, surfactants, thickening agents or mixtures thereof. Punica granatum extract

[0027] The formulation according to embodiments of the present document includes an extract of Punica granatum.

[0028] Punica granatum is a deciduous shrub or small fruit tree of the Lythraceae family that reaches a height of between five and 10 m (16 to 30 feet). Its showy red, white, or variegated flowers are found at the tips of its branches, either singly or in clusters of up to five flowers. Almost spherical, but crowned at the base by a prominent calyx, the pomegranate fruit has a tough, leathery skin or rind and is usually yellow tinged with light or dark pink or intense red. The interior is divided by membranous walls and white spongy tissue into chambers containing translucent sacs filled with tangy, flavorful, fleshy, and juicy pulp (the aril). Within each sac is a white or red, angular, soft, or hard seed. Arils make up about 52% of the weight of the whole fruit.

[0029] In a preferred embodiment, the fruit of Punica granatum is harvested in the Indian state of Jammu and Kashmir in the region of Ramban district (Kanga village) during the period from September to December, more particularly at a latitude and longitude of about 32° N, 74° E.

[0030] The extract of Punica granatum is preferably an ethanolic extract or a dry extract of the fruit, in particular of the pericarp of Punica granatum. The expression "dry extract", as used herein, denotes an extract, which comprises not more than 7% by weight of solvents relative to the total weight of the dry extract, preferably not more than 5%, more preferably not more than 3% by weight of solvents relative to the total weight of the dry extract. In a preferred embodiment of the present disclosure, the dry extract comprises not more than 1% by weight of solvents relative to the total weight of the dry extract. In another preferred embodiment, the dry extract does not contain any solvent (i.e. 0%), the solvent being able to be water or C2 to C5 monoalcohols selected from ethanol, propanol, isopropanol, butanol and pentanol, and mixtures thereof.

[0031] In a preferred embodiment, the process for preparing the extract of Punica granatum comprises at least the following steps: i. providing a pericarp of Punica granatum; ii. extracting from said pericarp, at least the punicalagins and the ellagic acid, with ethanol titrated at least to 99.5% at a temperature ranging from 37°C to 45°C for 2 to 5 hours; iii. filtering and repeating step (ii) at least two more times; iv. optionally drying the filtrate obtained at the end of step (iii) at a temperature ranging from 35°C to 40°C under vacuum. m

[0032] Advantageously, the ethanol in step (ii) has a humidity level of less than 0.5%, more preferably less than 0.2%.

[0033] Preferably, the extract of Punica granatum comprises punicalagins and ellagic acid.

[0034] The term "punicalagins", as used herein, designates a mixture of two diastereoisomers, punicalagins A and B. They belong to the family of polyphenols, and are in particular complex ellagitannins formed from a glucose linked to ellagic acid and gallagic acid, with a molar mass of approximately 1084 gmol-1 formed by the isomers of 2,3-(S)-hexahydroxydiphenoyl-4,6-(S,S)-gallagyl-D-glucose of chemical formula (I).

[0035] The term "ellagic acid", as used herein, refers to a polyphenol of formula (II).

[0036] In a preferred embodiment, the weight ratio [pericarp / absolute ethanol] is 1:5.

[0037] Advantageously, the temperature of the extraction step (ii) ranges from 40°C to 43°C; more preferably, it is 42°C.

[0038] Filtration step (iii) is carried out according to a conventional filtration method well known to those skilled in the art, for example using a Buchner funnel.

[0039] Preferably, the temperature of the drying step (iv) ranges from 37°C to 39°C, more preferably, it is 38°C. 0 0- / (H)

[0040] Preferably, the process for preparing the extract of Punica granatum comprises: i. providing a pericarp of Punica granatum; ii. extracting from said pericarp, at least the punicalagins and the ellagic acid, with ethanol titrated at least to 99.5% at a temperature ranging from 37°C to 45°C for 2 to 5 hours; iii. filtering and repeating step (ii) at least two more times; iv. optionally drying the filtrate obtained at the end of step (iii) at a temperature ranging from 35°C to 40°C under vacuum.

[0041] According to embodiments of the present document, the extract of Punica granatum comprises i) at least 10% by weight of the total weight of the dry extract, of punicalagins; and ii) at least 10% by weight of the total weight of the dry extract, of ellagic acid; wherein the weight ratio [ellagic acid / punicalagins] is in a range from 0.5 to 2.

[0042] The extract according to the invention may further comprise 1% to 5% by weight of the total weight of the dry extract, of punicalins, preferably 2% to 4.5%, even more preferably 3% to 4%.

[0043] Advantageously, the weight ratio [ellagic acid / punicalagins] ranges from 0.6 to 1.6, more preferably from 0.7 to 1.3, even more preferably from 0.7 to 1.

[0044] In a preferred embodiment, the extract according to the invention comprises: i) from 11.7% to 14.6% by weight of the total weight of the dry extract, of punicalagins, and ii) from 11.2% to 14.5% by weight of the total weight of the dry extract of ellagic acid, and in which the weight ratio [ellagic acid / punicalagins] ranges from 0.6 to 1.6, more preferably from 0.7 to 1.3, even more preferably from 0.7 to 1.

[0045] In another preferred embodiment, the extract according to the invention comprises: i) from 11.7% to 14.6% by weight of the total weight of the dry extract, of punicalagins, and ii) from 11.2% to 14.5% by weight of the total weight of the dry extract of ellagic acid, and iii) from 3% to 4% by weight of the total weight of the dry extract, of punicalins, and in which the weight ratio [ellagic acid / punicalagins] ranges from 0.6 to 1.6, more preferably from 0.7 to 1.3, even more preferably from 0.7 to 1.

[0046] The amount of Punica granatum extract present in the formulation, according to embodiments of the present document, may vary. The Punica granatum extract, according to embodiments of the present document, may be present in the formulation in a weight range of 0.01% to 10%, preferably in a weight range of 0.02% to 5% relative to the total weight of the formulation, more preferably in a weight range of 0.05% to 3% relative to the total weight of the formulation.

[0047] In other embodiments of the present document, the formulation comprises the extract of Punica granatum comprising i) at least 0.001% by weight of the total weight of the formulation, of punicalagins, preferably in a weight range of 0.001% to 1% relative to the total weight of the formulation; ii) at least 0.001% by weight of the total weight of the formulation, of ellagic acid preferably in a weight range of 0.001% to 1% relative to the total weight of the formulation; and wherein the weight ratio [ellagic acid / punicalagins] is from 0.5 to 2. Stabilizer

[0048] The formulation, according to embodiments of the present document, includes at least one stabilizer.

[0049] The term "stabilizer," as used herein, refers to substances that are used to maintain the function and activity of active ingredients, such as plant extracts in cosmetic formulations. In addition, stabilizers are also essential to maintain the functionality and aesthetics of formulations when stored under appropriate conditions.

[0050] According to embodiments of the present document, the formulation comprises at least one stabilizer comprising sodium thiosulfate.

[0051] Examples of optional additional stabilizers that may be used in the formulation of the present disclosure include, but are not limited to, N-acetylcysteine.

[0052] The amount of sodium thiosulfate present in the formulation, according to the invention, may vary. Sodium thiosulfate may be present in the formulation in a weight range of 0.01% to 2%, preferably in a weight range of 0.03% to 1%, more preferably in a weight range of 0.05% to 0.8% relative to the total weight of the formulation, such as 0.2%.

[0053] N-acetylcysteine ​​may be present in the formulation according to the invention, in a weight range of 0.01% to 2%, preferably in a weight range of 0.03% to 1% relative to the total weight of the formulation.

[0054] The amount of one or more optional additional stabilizers present in the formulation, according to the invention, may vary. The total amount of optional additional stabilizer that may be present in the formulation is in a weight range of 0% to 2%, preferably in a weight range of 0% to 1%, more preferably in a weight range of 0% to 0.8% relative to the total weight of the formulation, such as 0.1%.

[0055] The amount of stabilizer (i.e., sodium thiosulfate and optionally an additional stabilizer, preferably N-acetylcysteine) present in the formulation, according to embodiments herein, may vary. The stabilizer, according to embodiments herein, may be present in the formulation in a weight range of 0.01 to 4%, preferably in a weight range of 0.03% to 1%, based on the total weight of the formulation, such as 0.3%.

[0056] Water

[0057] According to the invention, the formulation comprises water. In a preferred embodiment, the formulation comprises more than 10% and less than 70% by weight of water relative to the total weight of the formulation.

[0058] In a more preferred embodiment, the formulation comprises water in a weight range, preferably in a weight range of 10% to 70%, more preferably in a weight range of 40% to 60%, relative to the total weight of the formulation.

[0059] Organic solvent

[0060] The formulation, according to embodiments of the present document, includes at least one organic solvent.

[0061] According to embodiments of the present document, the organic solvent is chosen from C1-C4 monoalcohols (ethanol or isopropanol or 2-ethoxy ethanol), or polyols such as C2-C8 polyols (triol, such as glycerol; hexols, such as sorbitol; diols, such as caprylyl glycol, 1,2-pentanediol, propanediol, butanediol, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, 1,2-propylene glycol, 1,3-butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol monomethyl ether or triethylene glycol monomethyl ether), or mixtures thereof.

[0062] In one embodiment, the formulation comprises a mixture of at least one C1-C4 monoalcohol, preferably ethanol, and at least one polyol, preferably in a total weight ratio of polyols / total weight of C1-C4 monoalcohol > 1, more preferably > 5.

[0063] In one embodiment, the formulation comprises at least one polyol chosen from pentylene glycol, glycerin, butylene glycol, hexylene glycol, dipropylene glycol, propylene glycol or mixtures thereof, more preferably chosen from glycerin, pentylene glycol, butylene glycol or mixtures thereof.

[0064] The amount of organic solvent present in the formulation, according to embodiments of the present document, may vary. According to embodiments of the present document, the formulation comprises more than 30% and less than 90% by weight of organic solvent relative to the total weight of the formulation.

[0065] In a preferred embodiment, the formulation comprises an organic solvent in a weight range of 34% to 80%, preferably in a weight range of 35% to 60%, more preferably in a weight range of 37% to 50% relative to the total weight of the formula. Cosmetic formulations

[0066] The present disclosure also relates to a cosmetic formulation comprising, in a cosmetically acceptable medium, a formulation as defined above.

[0067] The cosmetically acceptable medium is generally adapted to the nature of the support on which the formulation is to be applied, as well as to the appearance of the packaging of the formulation. According to one embodiment of the present document, the cosmetically acceptable medium is a medium compatible with keratinous materials, preferably with the skin. The cosmetically acceptable medium of the formulation may more particularly comprise water and optionally a cosmetically acceptable water-soluble organic solvent as described herein. Additives

[0068] The formulations according to the present disclosure may, in addition, comprise additives commonly used in cosmetic products such as ascorbic acid, Tinogard Q, or active ingredients other than Punica granatum extract, pH regulators, surfactants, thickening agents, and mixtures thereof.

[0069] In one embodiment of the present disclosure, the formulation comprises one or more actives different from the Punica granatum extract. In one embodiment, the formulation comprises ascorbic acid as an additional active different from the Punica granatum extract. In another embodiment, the formulation comprises Tinogard Q as an additional active different from the Punica granatum extract. In a further embodiment, the formulation comprises ascorbic acid and Tinogard Q as additional actives different from the Punica granatum extract. pH correctors

[0070] The formulation, according to embodiments of the present document, includes at least one pH corrector.

[0071] The term "pH adjuster," as used herein, refers to substances that establish and maintain the pH of formulations within a desired range.

[0072] The pH adjusters may be an “acidifying agent”, which may be inorganic acids, such as hydrochloric acid, orthophosphoric acid or sulfuric acid; or organic acids, preferably carboxylic acids, such than acetic acid, tartaric acid, citric acid or lactic acid, or sulfonic acids, and mixtures thereof.

[0073] The pH correctors may be a "basifying agent", which may be organic, such as arginine, lysine, amines such as mono-, di- and triethanolamines, or inorganic, such as ammonia, alkali metal carbonates, sodium hydroxide, potassium hydroxide or mixtures thereof.

[0074] In one embodiment of the present disclosure, the pH corrector is one or more basifying agents selected from arginine, triethanolamine, sodium hydroxide, or mixtures thereof.

[0075] The amount of pH adjusters present in the formulation may vary and is determined based on the desired pH to be maintained for the formulation. Surfactants

[0076] The formulation, according to embodiments of the present document, includes one or more surfactants, selected from amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, or mixtures thereof.

[0077] According to preferred embodiments, the surfactant is an anionic surfactant chosen from polyglyceryl-2-laurate, sodium cocoyl sarcosinate, isopropyl lauroyl sarcosinate, or mixtures thereof.

[0078] The amount of surfactant present in the formulation, according to embodiments of this document, may vary. Surfactants, according to embodiments of this document, may be present in the formulation in a weight range of 0.1% to 20%, preferably in a weight range of 0.5% to 15%, more preferably in a weight range of 1% to 10% relative to the total weight of the formulation. Thickening agent

[0079] The formulation, according to the embodiments of the present document, includes one or more thickening agents, which impart the desired viscosity to the formulation.

[0080] Examples of thickening agents include, but are not limited to, carboxy polymers, crosslinked polymers of acrylates / C10-C30 alkylacrylate, polyacrylamides and derivatives, polysaccharides, water-soluble or dispersible silicone derivatives, or mixtures thereof.

[0081] Examples of carboxy vinyl polymers suitable for use in the present disclosure are Carbopols (Carbomers) and Pemulens, such as Pemulen TRI and Pemulen TR2 (crosslinked polymer of acrylates / C10-C30 alkylacrylate).

[0082] Examples of polyacrylamides and derivatives that may be used appropriately in the present disclosure are the crosslinked copolymers sold under the names Sepigel 305 (CTFA name: Polyacrylamide / C13-14 isoparaffin / laureth-7) or Simulgel 600 (CTFA name: acrylamide / sodium acryloyl dimethyl taurate copolymer / isohexadecane / polysorbate 80) from the company SEPPIC; polymers and copolymers of 2-acrylamido-2-methylpropanesulfonic acid, optionally crosslinked and / or neutralized, such as poly(2-acrylamido-2-methylpropanesulfonic acid) sold by Hoechst under the trade name Hostacerin AMPS (CTFA name: ammonium polyacryloyldimethyl taurate) or Simulgel 800 sold by SEPPIC (CTFA name: sodium polyacryloyldimethyl taurate / polysorbate 80 / sorbitan oleate); copolymers of 2-acrylamido-2-methylpropanesulfonic acid and hydroxyethyl acrylate such as Simulgel NS and Sepinov EMT 10 sold by SEPPIC.

[0083] Examples of polysaccharides that may be suitably used in the present disclosure are gums, such as xanthan gum, chitosan; linear polysaccharides, such as chitosan and beta-glucan; and cellulose derivatives, such as hydroxyethylcellulose; water-soluble or water-dispersible silicone derivatives, such as acrylic silicones, polyether silicones and cationic silicones, and mixtures thereof.

[0084] In one embodiment of the present disclosure, the thickening agent is preferably chosen from polysaccharides, more preferably chosen from cellulose derivatives, gums, linear polysaccharides, or mixtures thereof.

[0085] The amount of thickening agent present in the formulation, according to the embodiments of the present document, may vary. The thickening agent, according to embodiments of the present document, may be present in the formulation in a weight range of 0.1% to 10%, preferably in a weight range of 0.2% to 8%, more preferably in a weight range of 0.5% to 5% relative to the total weight of the formulation. Other additives

[0086] The formulation may further comprise other additives which are conventionally used in the cosmetic and / or dermatological field, such as perfumes, preservatives, fillers, oils and colorants. It is understood that the person skilled in the art will take care to choose the optional additives and / or their quantity such that the advantageous properties of the formulation used according to the disclosure are not, or substantially not, compromised by the envisaged addition. All these embodiments, including the optional additives, are understood to be included within the scope of the present disclosure.

[0087] In one embodiment of the present disclosure, the formulation comprises no or less than 0.2% trisodium ethylenediamine disuccinate. In Another embodiment of the present disclosure, the formulation comprises less than 0.2%, less than 0.1%, less than 0.05% by weight of its trisodium ethylenediamine disuccinate, based on the total weight of the formulation.

[0088] Preparation of the formulations according to the disclosure

[0089] The formulations according to the disclosure may be prepared using known methods, generally used in the cosmetic or dermatological field. Generally, the method includes mixing water, a pH adjuster, at least one surfactant and at least one stabilizer to obtain a first mixture. Mixing Punica granatum and at least one organic solvent to obtain a clear transparent solution, which is added with one or more additives to the first mixture and then mixed to obtain a homogeneous transparent or translucent formulation (cosmetic formulation). Applications

[0090] A formulation, according to embodiments of the present document, may more particularly be a formulation intended for the treatment of keratinous materials, such as the skin. Preferably, the formulation, according to embodiments of the present document, is a formulation intended for the treatment of the skin. Accordingly, the formulation, in various embodiments of the present document, may be in the form of a serum.

[0091] In one embodiment of the present disclosure, the pH of the formulation is in a range of from 2 to 8, preferably from 3 to 7.

[0092] In one embodiment of the present disclosure, the formulation has a punicalagin marker stability of greater than 91% when stored at room temperature for at least 2 months. In another embodiment of the present disclosure, the formulation has a punicalagin marker stability of greater than 91% when stored at room temperature for 4 months, for 6 months, for 8 months, for 10 months or for 12 months.

[0093] In one embodiment of the present disclosure, the formulation has a punicalagin marker stability of greater than 91% when stored at room temperature for 2 weeks, 1 month or 2 months, for example 2 weeks.

[0094] In one embodiment of the present disclosure, the formulation, when comprising N-acetylcysteine ​​as an additional stabilizer, exhibits a punicalagin marker stability of greater than 91% when stored under accelerated conditions for 2 weeks, 1 month or 2 months, e.g., 2 weeks.

[0095] The formulation, according to embodiments of the present document, may be optionally applied with an applicator to the skin, followed by working the formulation into the skin.

[0096] Although the present disclosure has been described in considerable detail with reference to certain embodiments and their implementations, other embodiments are possible to cover modifications and variations of the present disclosure. EXAMPLES

[0097] The disclosure will now be illustrated by practical examples, which are intended to illustrate the operation of the disclosure and are not intended to restrictively impose limitations on the scope of this disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by a person skilled in the art to which this disclosure pertains. Although methods and materials similar or equivalent to those described herein may be used in practicing the disclosed methods and compositions, the exemplary methods, devices, and materials are described herein. It is to be understood that this disclosure is not limited to the particular methods and experimental conditions described, as such methods and conditions may apply.

[0098] The quantities of ingredients are indicated in the following examples as percentages of weight of active ingredient. Example#l Preparation of an extract of Punica granatum

[0099] The dried pericarp of Punica granatum (1 kg) was extracted at 42 °C with 5 liters of ethanol (purity 99.5%) under stirring at 800 rpm for a brief period of 4 h. The obtained ethanolic extract was filtered through a Buchner funnel containing a cotton filter (mesh size: 20 microns). The filtered extract was evaporated under vacuum at 38 °C to obtain a brown amorphous powder. The extraction was repeated successively two consecutive times under the conditions explained above. The combined dried extract consists of the main phenolic compounds, namely: ellagic acid and punicalagins.

[0100] The specifications of the extract are shown in Table 1 and Table 2:

[0101] [Table 1] Table 1 Parameters Values ​​in % w / w Punicalagins 14.44% Punicalins 3.28% Total polyphenols (punicalins, punicalagins and ellagic acid, gallic acid, epicatechin gallate, gallagic acid, ellagic acid hexoside / glycoside) 42% Total Fat 2.6% Total Protein 0.73% Total Sugars 19.1% Moisture 6.5%

[0102] [Table 2] Table 2 Extract Specifications Ellagic acid % w / w Punicalagins % w / w Weight ratio [Ellagic acid / Punicalagins] 11.35% 14.44% 0.79 Example#!#: Preparation of formulations

[0103] The formulations listed in Table 3 and Table 4 were prepared as described below.

[0104] The ingredients of phase A (a pH adjuster, at least one surfactant and at least one stabilizer) were weighed and added with water to a first container and mixed at 400 rpm. The ingredients of phase B (Punica granatum extract according to Example 1 and at least one organic solvent) were weighed and added to a second container and mixed in a magnetic stirrer at 300 rpm at 45 to 50 °C to obtain a clear transparent solution, which was then added to the first container with stirring at 400 rpm. The ingredients of phase C (at least one thickening agent) were added to the first container and dispersed by stirring at 600 rpm for 10 minutes. Phase D ingredients (additional surfactants) and Phase E ingredients (an additional organic solvent) were added to the first container and mixed for 10 minutes to obtain a homogeneous transparent or translucent gel.

[0105] [Table 3] Table 3 Phase Ingredients Content (% by weight relative to the total weight of the formulation) INCI Name PK0 1 PK0 2 PK0 3 PK0 4 PK0 5 PK0 6 PK07 A Water 46.1 46.9 46.1 46 46 45.9 47.5 A Trisodium Ethylene Diamin e Disuccinate (chelating agent) 0 0.2 0.2 0.2 0.2 0.2 0 A Ascorbic acid (antioxidant) 0.1 0.1 0.1 0.1 0 0.1 0 A TRIS (Tinogard Q) (antioxidant) 1 0 1 1 1 1 0 A Sodium thiosulfate (stabilizer) 0.2 0.2 0 0.2 0.2 0.2 0 A N-acetylcysteine ​​(stabilizer) 0.1 0.1 0.1 0 0.1 0.1 0 B Dipropylene glycol (organic solvent) 9.5 9.5 9.5 9.5 9.5 9.5 9.5 B Hexylene glycol (organic solvent) 5 5 5 5 5 5 5 B Punica extract 0.5 0.5 0.5 0.5 0.5 0.5 0.5 B Propylene glycol (organic solvent) 2.2 2.2 2.2 2.2 2.2 2.2 2.2 B Pentylene glycol (organic solvent) 20 20 20 20 20 20 20 B Glycerin (organic solvent) 5 5 5 5 5 5 5 C Hydroxy ethyl cellulose (thickening agent) 0.5 0.5 0.5 0.5 0.5 0.5 0.5 C Chitosan+Betaglucan (thickening agent) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 D Isopropyl lauroyl Sarcosinat e (surfactant) 4 4 4 4 4 4 4 E Alcohol denatured (organic solvent) 5 5 5 5 5 5 5 E Phenoxyethanol (preservative) 0.7 0.7 0.7 0.7 0.7 0.7 0,7 Total 100 100 100 100 100 100 100 ,

[0106] [Table 4] Table 4 Phase Ingredients Content (% by weight relative to the total weight of the formulation) INCI Name PP1 PP2 PP3 PP4 A Water 56.38 56.28 56.18 56.08 A Sodium thiosulfate (stabilizer) 0 0 0.2 0.2 A N-acetylcysteine ​​(stabilizer) 0 0.1 0 0.1 A Arginine (pH regulator) 0.12 0.12 0.12 0.12 A Polyglyceryl-2 Laurate (surfactant) 2 2 2 2 B Pentylene glycol (organic solvent) 15 15 15 15 B Glycerin (organic solvent) 7 7 7 7 B Butylene glycol (organic solvent) 12 12 12 12 B Punica granatum extract 0.5 0.5 0.5 0.5 C Cellulose gum (thickening agent) 0.15 0.15 0.15 0.15 C Xanthan gum (thickening agent) 0.15 0.15 0.15 0.15 C Polyacrylate cross polymer (thickening agent) 0.5 0.5 0.5 0.5 D Sodium cocoyl sarcosinate (surfactant) 0.8 0.8 0.8 0.8 D Isopropyl lauroyl sarcosinate (surfactant) 2.4 2.4 2.4 2.4 E Alcohol denaturated (organic solvent) 3 3 3 3 Total 100 100 100 100 Example #3 Evaluation of the stability of formulations

[0107] Formulations PK01 to PK07 (Table 3) and formulations PP1 to PP4 (Table 4) as prepared in Example 2 above were evaluated for stability at room temperature and under accelerated conditions.

[0108] The formulations were stored for 2 weeks or 2 months at room temperature and analyzed for punicalagin marker content (using the ultra-high performance liquid chromatography (UPLC) method) at the initial time point (T0) and after 2 weeks (T2W) or 2 months (T2M) at room temperature. Some of the formulations were analyzed for punicalagin marker content (using the ultra-high performance liquid chromatography (UPLC) method) performance (UPLC) at the initial Time point (TO) and under accelerated conditions, i.e. after 2 weeks at 55°C (T2W 55°C).

[0109] Standard preparation of punicalagin (mixture of punicalagin A and punicalagin B): In a 10 mL volumetric flask, standard punicalagin (5 mg, purity > 93.4%, CAS NO.: 65995-63-3, Chromadex) was dissolved in methanol (10 mL) and sonicated (10 min). For the preparation of the calibration curve, serial dilutions were prepared from the standard stock solution (minimum 6 calibration points) with methanol as diluent.

[0110] [T ableaux5 ] Time (in minutes) %B 0 10 7 10 12 30 14 80 16 80 18 50 20 10 25 10

[0111] The separation was performed by reverse-phase liquid chromatography (LC) and carried out on a Nexera high-performance liquid chromatography system equipped with a photodiode array detector (Shimadzu). The details of the process are mentioned below. i. Agilent Zorbax Eclipse XDB-C18 Column, 5 pm, 4.6 x 150 mm ii. Mobile phase A: 0.1% orthophosphoric acid in water iii. Mobile phase B: 0.1% orthophosphoric acid in acetonitrile iv. Gradient: v. Flow rate: 1 mL / min vi. Running time: 25 minutes vii. Column temperature: 30°C viii. Detector: PDA ix. Detection wavelength: Punicalagin - 258 nm x. Injection volume: 10 pL xi. Retention time: Punicalagin A - 3.5 min; Punicalagin B - 4.8 min

[0112] The percentage decrease in punicalagin content was calculated using the formula below: ,. . , , ... Punicalagàie content at point Time 2 weeks ITcmixmiurc ambient or 55 VC) T(2W) Percentage decrease in punicalagma content =------------aT&Taaaa'B------------x100

[0113] The percentage decrease of less than 9% in punicalagin marker content compared to the initial content was acceptable. RESULTS

[0114] [Table 6] Table 6 Formulation % stability of punicalagin at T0 vs. after 2 weeks at room temperature PK01 (Invention) 98.7 PK02 (Invention) 97.9 PK03 (Outside invention) 75.4 PK04 (Invention) 98.3 PK05 (Invention) 95.7 PK06 (Invention) 95.8 PK07 (Outside invention) 84

[0115] From Table 6, it is evident that the formulations (PK03 and PK07) lacking sodium thiosulfate as a stabilizer displayed low marker stability of less than 91% after being stored for 2 weeks at room temperature.

[0116] A similar observation was noted for formulations PP1 and PP2 which do not include sodium thiosulfate as can be seen in Table 7.

[0117] Furthermore, it was observed that the use of N-acetylcysteine ​​as an additional stabilizer improved the stability of the punicalagin marker to more than 91% under accelerated conditions, as can be seen in Table 8 for samples PK01 and PP4, respectively.

[0118] [Table 7] Table 7 Formulations % stability of punicalagin at T0 vs. after 2 weeks at room temperature PP1 (Without any solution) Outside the invention 84 PP2 (PP1 + 0.1% N-Acetylcysteine) Outside the invention 75.4 PP3 (PP1 + 0.2% sodium thiosulfate) Invention 98.3 PP4 (PP1 + 0.2% sodium thiosulfate + 0.1% N-acetylcysteine) Invent ion 98.7

[0119] [Table 8] Table 8 Formulations % stability of punicalagin at T0 vs. after 2 weeks at 55 c PK01 (Invention) 91.3 PP1 (Without any solution) Outside invention 70 PP4 (PP1 + 0.2% sodium thiosulfate + 0.1% N-acetylcysteine) Invention 91.3 Example #4

[0120] Effect of water and organic solvent (polyol) content on the stability of formulations

[0121] The stability of formulations containing various high amounts of organic solvent was tested. The various amounts tested are listed in Table 9. Formulations P1 and P2 as tested included water, various polyols as organic solvents as well as 0.5% by weight of extract described in Example 1, 0.2% by weight of sodium thiosulfate and 0.1% by weight of N-acetylcysteine ​​(Table 10). The ingredients of phase A (at least one stabilizer) were weighed and added with water to a first container and mixed at 400 rpm.The ingredients of phase B (Punica granatum extract according to Example 1 and at least one organic solvent) were weighed and added to a second container and mixed in a magnetic stirrer at 300 rpm at 45 to 50 °C to obtain a clear transparent solution, which was then added to the first container with stirring at 400 rpm to obtain formulations PI and P2. It was observed that the presence of an organic solvent at a level of more than 30% relative to the total weight of the formulation improved the dispersion (or solubility) of the extract in the formulation and thus improved the stability of the extract in the formulation (refer to the results described for formulations PI and P2 in Table 11).

[0122] [Table 9] Table 9 Description PI P2 Polyol part (Organic solvent) -40% -50% Water (qs) -60% -50%

[0123] [Table 10] Table 10 Ingredients Content (% by weight relative to the total weight of the formulation) INCI Name PI P2 Pentylene glycol (polyol, organic solvent) 17.64 22.06 Glycerin (polyol, organic solvent) 8.24 10.29 Butylene glycol (polyol, organic solvent) 14.12 17.65 Punie a G extract (polyol, organic solvent) 0.5 0.5 Sodium thiosulfate (stabilizer) 0.2 0.2 N-acetylcysteine ​​(stabilizer) 0.1 0.1 Water 59.2 49.2 Total 100 100

[0124] [Table 11] Table 11 Formulations % stability of punicalagin at T0 vs. after 2 weeks at room temperature T2W PI 98.40 P2 96.80 Example #5

[0125] Furthermore, the use of any other stabilizer other than sodium thiosulfate did not give a similar level of stability of the punicalagin marker (Table 12) after storage at room temperature for 1 month. Formulations PR1, PR2, PR3 comprising sodium thiosulfate, or sodium metabisulfite or sodium sulfite were prepared using the method as described in Example 2. For example, the use of sodium metabisulfite and sodium sulfite gave a marker stability of less than 91% compared to a formulation comprising sodium thiosulfate (PR1) (Table 13).

[0126] [Table 12] Table 12 Phase Ingredients Content (% by weight relative to the total weight of the formulation) INCI Name PR1 PR2 PR3 A Water 56.38 56.38 56.38 A Sodium thiosulfate (stabilizer) 0.2 0 0 A Sodium metabisulfite (not disclosed) 0 0.2 0 A Sodium sulfite (not disclosed) 0 0 0.2 A N-acetylcysteine ​​(stabilizer) 0.1 0.1 0.1 A Arginine (pH regulator) 0.12 0.12 0.12 A Polyglyceryl-2 Laurate (surfactant) 2 2 2 B Pentylene glycol (organic solvent) 15 15 15 B Glycerin (organic solvent) 7 7 7 B Butylene glycol (organic solvent) 12 12 12 B Punica granatum extract according to Example 1 0.5 0.5 0.5 C Cellulose gum (thickening agent) 0.15 0.15 0.15 C Xanthan gum (thickening agent) 0.15 0.15 0.15 C Polyacrylate cross polymer (thickening agent) 0.5 0.5 0.5 D Sodium cocoyl sarcosinate (surfactant) 0.8 0.8 0.8 D Isopropyl lauroyl sarcosinate (surfactant) 2.4 2.4 2.4 E Alcohol denaturated (organic solvent) 3 3 3 Total 100 100 100

[0127] [Table 13] Table 13 Formulations % stability of punical agine at T0 vs. after 1 month at room temperature Formulation PR1 with 0.2% sodium thiosulfate (invention) 98.61 Formulation PR2 with 0.2% sodium metabisulfite instead of sodium thiosulfate (not invention) 90.84 Formulation PR3 with 0.2% sodium sulfite instead of sodium thiosulfate (not invention) 87.3 Benefits of this disclosure

[0128] In one aspect of the present disclosure, there is provided a formulation in a cosmetically acceptable medium, comprising: a) an extract of Punica granatum; b) at least one stabilizer comprising sodium thiosulfate; c) water; and d) at least one organic solvent. The use of sodium thiosulfate as a stabilizer provides more than 91% stability to punicalagin, a marker of the extract of Punica granatum in the formulation. Furthermore, the use of the amino acid N-acetylcysteine ​​as an additional stabilizer provides improved stability of the formulation under accelerated conditions.

Claims

Claims

1. Formulation in a cosmetically acceptable medium, comprising: a) an extract of Punica granatum; b) at least one stabilizer comprising sodium thiosulfate; c) water and d) at least one organic solvent.

2. Formulation according to claim 1, wherein the Punica granatum extract is in a weight range of 0.01% to 10%, preferably in a weight range of 0.05% to 5%, relative to the total weight of the formulation.

3. Formulation according to one of the preceding claims comprising: i at least 0.001% by weight of the total weight of the formulation, of punicalagins preferably in a weight range of 0.001% to 1% relative to the total weight of the formulation; and ii at least 0.001% by weight of the total weight of the formulation, of ellagic acid preferably in a weight range of 0.001% to 1% relative to the total weight of the formulation; and wherein the weight ratio [ellagic acid / punicalagins] is from 0.5 to 2.

4. Formulation according to one of the preceding claims, wherein the sodium thiosulfate is in a weight range of 0.01% to 2%, preferably in a weight range of 0.03% to 1%, relative to the total weight of the formulation.

5. Formulation according to one of the preceding claims, wherein the stabilizer further comprises N-acetylcysteine.

6. Formulation according to claim 5, wherein the N-acetylcysteine ​​is in a weight range of 0.01% to 2%, preferably in a weight range of 0.03% to 1% relative to the total weight of the formulation.

7. Formulation according to one of the preceding claims, in which the formulation comprises at least one organic solvent chosen from C1-C4 monoalcohols (ethanol or isopropanol or 2-ethoxyethanol), or polyols such as C2-C8 polyols, (triol, such as glycerol; hexols, such as sorbitol; diols, such as caprylyl glycol, 1,2-pentanediol, propanediol, butanediol, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, 1,2-propylene glycol, 1,3-butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol monomethyl ether or triethylene glycol monomethyl ether), or mixtures thereof.

8. Formulation according to claim 7, in which the at least one organic solvent represents more than 30% and less than 90% by weight relative to the total weight of the formulation.

9. Formulation according to one of the preceding claims, in which the water represents more than 10% and less than 70% by weight relative to the total weight of the formulation.

10. A method for the cosmetic treatment of keratinous materials, comprising the application of said formulation according to any one of claims 1 to 9 to the keratinous materials, preferably to the skin.