FORMULATION OF IMPROVED STABILITY PUNICA GRANATUM EXTRACT AND ITS APPLICATIONS

Abstract

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

Description

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

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

[0002] Antioxidants are key active ingredients in cosmetic products targeting keratinous materials, particularly the skin. A large number of antioxidants already exist, such as tocopherol (vitamin E) or its derivatives, vitamin C or its derivatives, carotenoids, ubiquinone, etc. In particular, products containing antioxidants derived from natural sources are preferred by consumers over synthetic antioxidants. Plant extracts are important natural sources of antioxidants 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 dry extract weight of punicalagins and at least 10% by weight of the total dry extract weight of ellagic acid, in which the [ellagic acid / punicalagins] weight ratio ranges from 0.5 to 2. The antioxidant activity of such extracts must be stable over time in formulations, particularly after storage at room temperature for 2 weeks, 1, or 2 months. Specifically for the Punica granatum extract, 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 also said 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 that remains stable at least during storage at room temperature for 2 weeks, 1, or 2 months, in which the punicalagin content is greater than 91% after storage compared to the punicalagin content without storage. There is also a need for a cosmetic formulation containing Punica granatum extract that is further expected to be stable even under accelerated conditions, such as 45°C for 2 months or 55°C for 2 weeks.

[0004] The Applicant unexpectedly demonstrated that a formulation containing a) Punica granatum extract and preferably comprising at least 10% by weight of the total dry extract weight of punicalagins; and at least 10% by weight of the total dry extract weight 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. that in such a formulation, the punicalagin content is greater than 91% after storage compared to the content without storage. Summary of the invention

[0005] In one aspect of this disclosure, a formulation in a cosmetically acceptable medium is proposed, 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 this disclosure, a kit is proposed comprising (a) the formulation as disclosed herein; (b) a container; and (c) optionally, an applicator.

[0007] In another aspect of this disclosure, a cosmetic treatment process for keratinous materials is proposed, comprising the application of said formulation, as disclosed herein, to the keratinous materials, preferably on the skin.

[0008] These features, aspects, and advantages, as well as others, of the present subject matter will be better understood by reference to the following description and the attached 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 features 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 this disclosure is subject to variations and modifications other than those specifically described. It should be understood that this 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 these steps or features.

[0010] Definitions

[0011] For convenience, before describing this disclosure in more detail, certain terms used in the descriptive document and examples are defined here. These definitions should be read in light of the rest of the disclosure and understood as by a person skilled in the art. The terms used here have meanings recognized and known to persons skilled in the art; however, for convenience and completeness, specific terms and their meanings are set out below.

[0012] The terms “include” or “contain” and “comprising” or “containing” are used in an 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 memorandum, unless the context otherwise requires, the term "include", and variations such as "includes" and "comprising", shall be understood to imply the inclusion of any element or step or group of elements or steps stated, 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, not limited to". "Including" and "including, without being limited to" are used interchangeably.

[0017] The term “INCI” is an abbreviation for 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 of cosmetic or personal care products.

[0018] The expression "keratinous materials" as used herein refers to skin, hair, eyelashes, eyebrows and nails, preferably skin.

[0019] The expression "cosmetically acceptable medium" as used here means a medium compatible with "keratinous materials", preferably the skin and / or its Superficial body growths that have a pleasant color, odor, and feel, and that do not cause unacceptable discomfort (tingling or pulling) likely to discourage the consumer from using the 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 for use in creams, serums, or lotions, as well as surfactant-based shampoos or facial or hair cleansers, water-surfactant mixtures for toiletries, etc.

[0020] The term “treatment” as used herein refers to any action aimed at improving a person’s comfort or well-being. Accordingly, this term covers the alleviation, relief, or elimination of the symptoms of aging / damaged skin, but is limited to cosmetic treatments.

[0021] The expression "room temperature", as used here, 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 this disclosure, unless otherwise stated. Ratios, concentrations, quantities, and other numerical data may be presented herein in a range format. It should be understood that this range format is used solely for convenience and conciseness and should be interpreted flexibly as including not only the numerical values ​​explicitly stated as the range limits, but also as including all individual numerical values ​​or subranges encompassed within that range as if each numerical value and subrange were explicitly stated. For example, a percentage range of approximately 10% to 70% should be interpreted as including not only the explicitly stated limits of approximately 10% to approximately 70%, but also as including subranges, such as 20% to 30%, 30% to 45%, etc., as well as individual quantities, including fractional quantities, within 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 of this disclosure. Although all processes and materials similar or equivalent to those described herein may be used in the practice or testing of the disclosure, preferred processes and materials are now described. All publications referred to herein are incorporated herein by reference.

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

[0025] The embodiments of this document relate to a formulation in a cosmetically acceptable medium for skin treatment. The disclosed embodiments include a formulation, a kit comprising the formulation, and a method for treating keratinous materials by applying said formulation. In various embodiments of this document, the formulation is in the form of a serum in which the Punica granatum extract has improved stability. Cosmetic products comprising Punica granatum extract have been shown to be beneficial for 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 skin treatment.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 select formulation ingredients that promote the stability of the extract, which is the key active ingredient in the formulation. Thus, the formulation according to embodiments of this document includes at least one stabilizer, namely sodium thiosulfate, which improves the stability of Punica granatum extract to over 91% when stored at room temperature. Furthermore, the use of an additional stabilizer, such as N-acetylcysteine, improves the stability of Punica granatum extract to over 91% when stored under accelerated conditions. Formulation

[0026] The embodiments of this document propose a formulation for treating keratinous material, preferably skin. In one aspect of this disclosure, a formulation in a cosmetically acceptable medium is proposed, comprising: a) an extract of Punica granatum; b) at least one stabilizer including 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. Extract of Punica granatum

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

[0028] Punica granatum is a deciduous fruit-bearing shrub or small 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 hard, leathery skin or rind and is generally yellow tinged with light or dark pink or deep red. The interior is divided by membranous walls and a white, spongy tissue into compartments 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. The arils make up about 52% of the weight of the entire fruit.

[0029] In a preferred embodiment, the fruit of Punica granatum is harvested in the Indian state of Jammu and Kashmir in the Ramban district region (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 the pericarp of Punica granatum. The term "dry extract," as used herein, refers to an extract that does not include more than 7% by weight of solvents relative to the total weight of the dry extract, preferably not more than 5%, and more preferably not more than 3% by weight of solvents relative to the total weight of the dry extract. In a preferred embodiment of this disclosure, the dry extract does not include more than 1% by weight of solvents relative to the total weight of the dry extract. In another preferred embodiment, the dry extract contains no solvent (i.e., 0%), the solvent being 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. supplying a pericarp of Punica granatum; ii. extracting from said pericarp, at least punicalagins and ellagic acid, with ethanol standardized to at least 99.5% at a temperature of 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 of 35 °C to 40 °C under vacuum. m

[0032] Advantageously, the ethanol in step (ii) has a moisture content 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 here, refers to a mixture of two diastereomers, punicalagins A and B. They belong to the family of polyphenols, and are in particular complex ellagitannins formed of a glucose linked to ellagic acid and gallagic acid, with a molar mass of about 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] The filtration step (iii) is carried out according to a conventional filtration process well known to those skilled in the art, for example by 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. supplying a pericarp of Punica granatum; ii. extracting from said pericarp, at least the punicalagins and ellagic acid, with ethanol standardized to at least 99.5% at a temperature of 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 of 35 °C to 40 °C under vacuum.

[0041] According to embodiments of this 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 of 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 wherein 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) 11.7% to 14.6% by weight of the total weight of the dry extract, of punicalagins, and ii) 11.2% to 14.5% by weight of the total weight of the dry extract of ellagic acid, and iii) 3% to 4% by weight of the total weight of the dry extract, of punicalins, and wherein 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 this document, may vary. The Punica granatum extract, according to embodiments of this 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 this document, the formulation comprises the Punica granatum extract comprising i) at least 0.001% by weight of the total weight of the formulation, punicalagins, preferably in a weight range of 0.001% to 1% by weight of the total weight of the formulation; ii) at least 0.001% by weight of the total weight of the formulation, ellagic acid, preferably in a weight range of 0.001% to 1% by weight of 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 this document, includes at least one stabilizer.

[0049] The term “stabilizer,” as used here, refers to substances used to maintain the function and activity of active ingredients, such as plant extracts in cosmetic formulations. Furthermore, stabilizers are also essential for maintaining the functionality and aesthetic appeal of formulations when stored under appropriate conditions.

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

[0051] Examples of optional additional stabilizers that may be used in the formulation of this 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. The 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 quantity of one or more optional additional stabilizers present in the formulation, according to the invention, may vary. The total quantity 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 of this document, may vary. The stabilizer, according to embodiments of this document, 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%, relative to 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 0% 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 this document, includes at least one organic solvent.

[0061] According to embodiments of this document, the organic solvent is 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.

[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 selected from pentylene glycol, glycerin, butylene glycol, hexylene glycol, dipropylene glycol, propylene glycol or mixtures thereof, more preferably selected from glycerin, pentylene glycol, butylene glycol or mixtures thereof.

[0064] The amount of organic solvent present in the formulation, according to embodiments of this document, may vary. According to embodiments of this 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] This 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 substrate onto which the formulation is to be applied, as well as to the appearance of the formulation's packaging. According to one embodiment of this document, the cosmetically acceptable medium is a medium compatible with keratinous materials, preferably with 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 this disclosure may, in addition, include additives commonly used in cosmetic products such as ascorbic acid, Tinogard Q, or active ingredients other than Punica granatum extract, pH correctors, surfactants, thickening agents, and mixtures thereof.

[0069] In one embodiment of this disclosure, the formulation includes one or more active ingredients other than Punica granatum extract. In one embodiment, the formulation includes ascorbic acid as an additional active ingredient other than Punica granatum extract. In another embodiment, the formulation includes Tinogard Q as an additional active ingredient other than Punica granatum extract. In yet another embodiment, the formulation includes both ascorbic acid and Tinogard Q as additional active ingredients other than Punica granatum extract. pH adjusters

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

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

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

[0073] pH adjusters can be a "basifying agent", which can 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 this disclosure, the pH adjuster is one or more alkalizing 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 according to the desired pH to be maintained for the formulation. Surfactants

[0076] The formulation, according to embodiments of this document, includes one or more surfactants, selected from amphoteric surfactants, anionic surfactants, cationic surfactants, non-ionic surfactants, or mixtures thereof.

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

[0078] The quantity 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 this document, includes one or more thickening agents, which give the desired viscosity to the formulation.

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

[0081] Examples of carboxy vinyl polymers that may be appropriately used in this disclosure are Carbopols (Carbomers) and Pemulens, such as Pemulen TRI and Pemulen TR2 (crosslinked acrylate / C10-C30 alkyl acrylate polymer).

[0082] Examples of polyacrylamides and derivatives that may be appropriately used in this 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) by the company SEPPIC; 2-acrylamido-2-methylpropanesulfonic acid polymers and copolymers, 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); 2-acrylamido-2-methylpropanesulfonic acid and hydroxyethyl acrylate copolymers such as Simulgel NS and Sepinov EMT 10 sold by SEPPIC.

[0083] Examples of polysaccharides that may be appropriately used in this 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 this disclosure, the thickening agent is preferably chosen from polysaccharides, more preferably from cellulose derivatives, gums, linear polysaccharides, or mixtures thereof.

[0085] The amount of thickening agent present in the formulation, according to embodiments of this document, may vary. The thickening agent, according to embodiments of this 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 also include other additives that are commonly used in the cosmetic and / or dermatological fields, such as perfumes, preservatives, fillers, oils, and colorants. It is understood that those skilled in the art will take care to select the optional additives and / or their quantity in such a way that the advantageous properties of the formulation used according to the disclosure are not, or are not substantially, compromised by the intended addition. All such embodiments, including optional additives, are understood to be included within the scope of this disclosure.

[0087] In one embodiment of this disclosure, the formulation does not include trisodium ethylenediamine disuccinate or less than 0.2% thereof. In in another embodiment of this disclosure, the formulation comprises less than 0.2%, less than 0.1%, less than 0.05% by weight of its trisodium ethylenediamine disuccinate, relative to the total weight of the formulation.

[0088] Preparation of formulations according to disclosure

[0089] The formulations according to the disclosure can be prepared using known processes, generally used in the cosmetic or dermatological fields. Typically, the process includes mixing water, a pH adjuster, at least one surfactant, and at least one stabilizer to obtain a first mixture. This is followed by mixing Punica granatum with at least one organic solvent to obtain a clear, transparent solution, which is then added, along with one or more additives, to the first mixture and subsequently blended to obtain a homogeneous, transparent or translucent formulation (cosmetic formulation). Applications

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

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

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

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

[0094] In one embodiment of this disclosure, the formulation, when it includes N-acetylcysteine ​​as an additional stabilizer, exhibits punicalagin marker stability of over 91% when stored under accelerated conditions for 2 weeks, 1 month or 2 months, for example 2 weeks.

[0095] The formulation, according to embodiments of this document, can optionally be applied with an applicator to the skin, and then by working the formulation into the skin.

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

[0097] The disclosure will now be illustrated by practical examples, which are intended to demonstrate how the disclosure works and are not intended to impose restrictive limitations on the scope of this disclosure. Unless otherwise defined, all technical and scientific terms used in this document have the same meanings as those commonly understood by a person skilled in the art of this disclosure. Although processes and materials similar or equivalent to those described in this document may be used in practice for the disclosed processes and compositions, examples of processes, devices, and materials are described here. It should be understood that this disclosure is not limited to the particular processes and experimental conditions described, as these processes and conditions may be applicable.

[0098] The quantities of ingredients are indicated in the following examples as percentages by weight of active ingredient. Example #1 Preparation of an extract of Punica granatum

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

[0100] The specifications of the extract are given 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 45–50 °C to obtain a clear, transparent solution, which was then added to the first container while 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. The ingredients of phase D (additional surfactants) and the ingredients of phase E (an additional organic solvent) were added to the first container and mixed for 10 minutes to obtain a homogeneous clear 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 Water 46.1 46.9 46.1 46 46 45.9 47.5 A Trisodium Ethylene Diamine 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 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 Hydroxyethyl 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 Sarcosinate (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 total formulation weight) 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 adjuster) 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 denatured (organic solvent) 3 3 3 3 Total 100 100 100 100 Example #3 Evaluation of formulation stability

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

[0108] The formulations were stored for 2 weeks or 2 months at room temperature and analyzed to determine the punicalagin marker content (using ultra-high-performance liquid chromatography (UPLC) at baseline (T0) and after 2 weeks (T2W) or 2 months (T2M) at room temperature. Some of the formulations were analyzed to determine the punicalagin marker content (using ultra-high-performance liquid chromatography). 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 the diluent.

[0110] [Tableaux5] Time (in minutes) %B 0 10 7 10 12 30 14 80 16 80 18 50 20 10 25 10

[0111] The separation was carried out by reversed-phase liquid chromatography (LC) 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: Orthophosphoric acid at 0.1% in water iii. Mobile phase B: 0.1% orthophosphoric acid in acetonitrile iv. Gradient: v. Flow rate: 1 mL / min vi. Duration of execution: 25 minutes vii. Column temperature: 30 °C viii. Detector: PDA ix. Detection wavelength: Punicalagine - 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: ...Punical content at point T (2 weeks) (at ambient temperature or 55 VC) T(2W) Percentage reduction in punicalagme content =------------aT&Taaaa'B------------x100

[0113] A decrease of less than 9% in the punicalagin marker content from the initial level 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 (Non-invention) 75.4; PK04 (Invention) 98.3; PK05 (Invention) 95.7; PK06 (Invention) 95.8; PK07 (Non-invention) 84

[0115] According to Table 6, it is evident that the formulations (PK03 and PK07) without sodium thiosulfate as a stabilizer exhibited low marker stability, 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] In addition, it was observed that the use of N-acetylcysteine ​​as an additional stabilizer improved the stability of the punicalagine marker to over 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) Not in invention 84 PP2 (PP1 + 0.1% N-Acetylcysteine) Not in invention 75.4 PP3 (PP1 + 0.2% sodium thiosulfate) Invention 98.3 PP4 (PP1 + 0.2% sodium thiosulfate + 0.1% N-acetylcysteine) Invention 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) Not part of the 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 different 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 wt% of the extract described in Example 1, 0.2 wt% sodium thiosulfate, and 0.1 wt% 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 under stirring at 400 rpm to obtain formulations PI and P2. It was observed that the presence of an organic solvent at a concentration of more than 30% by weight of the total 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 Part polyol (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) Name INCI 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 process as described in Example 2. For example, the use of sodium metabisulfite and sodium sulfite gave 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 part of this invention) 0 0.2 0 A Sodium sulphite (not part of this invention) 0 0 0.2 A N-acetylcysteine ​​(stabilizer) 0.1 0.1 0.1 A Arginine (pH adjuster) 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 as per 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 denatured (organic solvent) 3 3 3 Total 100 100 100

[0127] [Table 13] Table 13 Formulations % stability of punical agin 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 (non-invention) 90.84 Formulation PR3 with 0.2% sodium sulfite instead of sodium thiosulfate (non-invention) 87.3 Benefits of this disclosure

[0128] In one aspect of this disclosure, a formulation in a cosmetically acceptable medium is proposed, comprising: a) an extract of Punica granatum; b) at least one stabilizer including sodium thiosulfate; c) water; and d) at least one organic solvent. The use of sodium thiosulfate as a stabilizer provides over 91% stability to punicalagin, a marker of the Punica granatum extract 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

Demands

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 extract of Punica granatum 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 any 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% by weight of 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% by weight of the total weight of the formulation; and wherein the weight ratio [ellagic acid / punicalagins] is from 0.5 to 2.

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

6. Formulation according to claim 5, wherein 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. A formulation according to any one of the preceding claims, wherein the formulation comprises at least one organic solvent selected from C1-C4 monoalcohols (ethanol or isopropanol or 2-ethoxyethanol), or polyols such as C2-C8 polyols (triols, 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, wherein 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 any one of the preceding claims, wherein water constitutes more than 10% and less than 70% by weight relative to the total weight of the formulation.

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