FR3029780A1 - COMPOSITION COMPRISING HESPERETIN - Google Patents

Abstract

The invention relates to a composition comprising, in a physiologically acceptable aqueous medium, hesperetin, and at least one compound having solubility parameters according to the HANSEN solubility space such that 10.5 <Sa <20 and 13.5 <δd <25.5. Application to the care, makeup and / or cleaning of keratin materials, especially the skin.

Description

The subject of the present invention is a composition, preferably a cosmetic composition, comprising hesperetin and at least one compound having solubility parameters according to the particular Hansen solubility space.

Hesperetin is an organic compound of the flavanone family, a subgroup of flavonoids. It is found in nature mainly in the form of its heteroside, hesperidin which is present in fruits of the genus Citrus. Hesperetin is an interesting substance as an antioxidant, and for the treatment of cutaneous signs of aging.

However, this compound, which is in solid form at room temperature and has a high melting point (220 ° C.), is difficult to solubilize. It is notably poorly soluble in water and glycerol.

However, it is necessary for this compound to be formulated in a solubilized form in order to make the best use of its activity and it is also preferable that its solubilization be maintained over time in order to avoid any recrystallization phenomenon during storage of compositions comprising such a compound. compound.

The object of the present invention is precisely to propose a novel galenic formulation of hesperetin which makes it possible to overcome the abovementioned drawbacks, and thus to incorporate this compound in a solubilized and durable form over time, and this new formulation. The pharmaceutical use of hesperetin makes it possible in particular to improve the efficacy of the active ingredient for the treatment of keratinous substances such as the skin.

The inventors have in fact unexpectedly discovered that the combination of hesperetin with at least one compound having solubility parameters according to the particular Hansen solubility space makes it possible to solubilize hesperetin while avoiding its recrystallization. especially after storage for 2 months at room temperature (25 ° C). More specifically, the subject of the invention is a composition, in particular a cosmetic composition, comprising, in a physiologically acceptable aqueous medium, a) hesperetin, and b) at least one compound having solubility parameters according to the solubility space HANSEN such as 10.5 <8, <20 and 13.5 <8d <25.5 as defined below.

Hesperetin is a compound of chemical structure: HO H O 5 Hesperetin is also named - 3 ', 5,7-Trihydroxy-4'-methoxyflavanone, or (S) -2,3-dihydro-5, 7-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) -4H-1-benzopyran-4-one (CAS no .: 520-33-2). Hesperetin is especially available under the trade name HESPERETIN PURIFIED® from Ferrer Grupo-Exquim (Ferrer), or under the name FMLT HespeSphere 1.0® from Biospectrum, Inc., or under the name GFX. ® of the company Industrial Research Limited, or under the name Jeju Citrus Aglyconoid Liposome® of the company.

The hesperetin may be present in the composition according to the invention, in a content ranging from 0.001% to 10% by weight, relative to the total weight of the composition, particularly ranging from 0.05% to 10% by weight. preferably ranging from 0.1% to 5% by weight, preferably ranging from 0.1% to 2.5% by weight, and more preferably ranging from 0.1% to 1% by weight.

The composition according to the invention comprises at least one compound (b) having solubility parameters according to the HANSEN solubility space such that: 10.5 <8, <20 and 13.5 <8d <25.5.

Said compound (b) is present in the composition according to the invention in an effective amount, that is to say in an amount sufficient to solubilize hesperetin. Preferably said compound (b) is a solvent for hesperetin.

More particularly, the composition according to the invention comprises at least one compound (b) which is a solvent, preferably an organic solvent, having solubility parameters according to the HANSEN solubility space, such as: 10.5 <8, <20 and 13.5 <8d <25.5.

A solvent is a substance, liquid at its temperature of use, which has the property of dissolving, or of diluting chemically and without itself modifying itself. The term "organic solvent" refers to solvents which are organic compounds which contain carbon atoms. In particular, the composition according to the invention comprises an effective amount of at least one compound (b) having solubility parameters according to the HANSEN solubility space, such as: 10.5 <8, <20 and 13.5 < 8d <25.5. The overall solubility parameter 8 according to the HANSEN solubility space is defined in the article "Solubility parameter values" by Eric A. Grulke of "Polymer Handbook" 15 3rd edition, Chapter VII, pages 519-559 by the relation: = (82 = 8d2 8p2 + 6h2) 112 in which 20 - 8d characterizes the LONDON dispersion forces resulting from the formation of dipoles induced during molecular shocks, - 8p characterizes the DEBYE interaction forces between permanent dipoles - 8h characterizes the specific interaction forces (hydrogen bonds, acid / base, donor / acceptor, etc.). The definition of solvents in the HANSEN three-dimensional solubility space is described in the article by C. M. Hansen: "The three dimensional solubility parameters" J. Paint Technol. 39, 105 (1967). The parameter 8 is defined by the following relation: 6a2 = 8p2 8h2 = 828d2 The parameters 8d, 8p, 8h s and 8, are expressed in (J / cm3) 1/2. Preferably, the compound (b) has solubility parameters such that 10.5 <8a <19.6 and 15.5 <8d <20 The compound (b) used according to the invention can be selected from PEG- 8 (polyethylene glycol containing 8 ethylene glycol units) (8, = 14.80, 8d = 17.90); dipropylene glycol (8, = 19.48, 8d = 16.20), dimethylisosorbide (8, = 10.76, 8d = 17.42), or a mixture thereof.

Preferably, the compound (b) is chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units); dipropylene glycol, and dimethylisosorbide.

Particularly preferably, the compound (b) is selected from PEG-8 (polyethylene glycol containing 8 ethylene glycol units), and dipropylene glycol. The compound (s) (b) may be present in the composition according to the invention in a content ranging from 0.1% to 70% by weight, relative to the total weight of the composition, of Preferably ranging from 2% to 40% by weight, and preferably ranging from 5% to 30% by weight. According to one embodiment, the compound (b) according to the invention and the hesperetin described above may be present in the composition according to the invention in a mass ratio compound (b) / hesperetin at least equal to 2, in particular ranging from 2 to 50, and preferably from 5 to 20. According to a preferred embodiment, the compound (b) according to the invention is PEG-8 (polyethylene glycol containing 8 ethylene glycol units), and said compound (b) and hesperetin are present in the composition according to the invention in a mass ratio PEG-8 / hesperetin which is at least 2, for example ranging from 2 to 30, and preferably ranging from According to a preferred embodiment, the compound (b) according to the invention is dipropylene glycol, and said compound (b) and hesperetin are present in the composition according to the invention. a mass ratio dipropylene glycol / hesperetin which is at least ins is equal to 2, for example ranging from 2 to 50, and preferably ranging from 5 to 20. The subject of the present invention is also the use in a composition, preferably a cosmetic composition, of at least one compound ( b) having solubility parameters according to the HANSEN solubility space such that: 10.5 <8, <20 and 13.5 <8d <25.5 as defined above, as a solvent for hesperetin. More particularly, the invention relates to the use in a composition, preferably a cosmetic composition, of at least one compound (b) chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units); dipropylene glycol, and dimethylisosorbide and a mixture thereof as a solvent for hesperetin.

The compositions used according to the invention contain a physiologically acceptable medium, that is to say a medium which is suitable for the topical administration of a composition, that is to say compatible with keratin materials. human beings such as skin, scalp, hair, nails. According to the invention a physiologically acceptable medium is preferably a cosmetically acceptable medium, that is to say without odor, or unpleasant appearance, and which is perfectly compatible with the topical route of administration.

Keratinic material according to the invention means the skin, the body, the face and / or the contour of the eyes, the lips, the nails, the mucous membranes, the eyelashes, the eyebrows, the hairs, the scalp and / or the hair. , or any other skin area of the body. More particularly, the keratin materials according to the invention are the scalp, the hair, and / or the skin.

The keratin materials according to the invention are preferably the scalp and / or the hair. Preferably the keratin materials according to the invention is the skin. By "the skin" is meant all of the skin of the body, and preferably the skin of the face, décolleté, neck, arms and forearms, or more preferably still, facial skin, including forehead, nose, cheeks, chin, eye area. As specified below, hesperetin is advantageously present in the compositions in accordance with the invention in a solubilized form. By way of example, the composition according to the invention may be intended to be administered topically, that is to say by surface application of the keratin material in question, such as the skin in question. The composition of the invention may be a cosmetic composition (either intended for cosmetic use) or dermatological. Preferably, according to the invention, the composition is a cosmetic composition and even more preferentially a cosmetic composition for topical application. The term "cosmetic composition" is understood to mean a substance or a preparation intended to be brought into contact with the various superficial parts of the human body, in particular the epidermis, the hair and hair systems, the nails, the lips and the mucous membranes. Orally, in view, exclusively or principally, to cleanse, moisturize, perfume, modify, protect, maintain or repair body odors.

The compositions according to the invention can be in the form of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: E / W) emulsions. H / E or H / E / H), aqueous gels. These compositions are prepared according to the usual methods.

The composition may comprise at least one oil. Suitable oils that may be used include, for example: hydrocarbon-based oils of vegetable origin, such as liquid triglycerides of fatty acids containing from 4 to 10 carbon atoms, for instance triglycerides of heptanoic or octanoic acids or, for example, sunflower, corn, soy, squash, grape seed, sesame, hazelnut, apricot, macadamia, arara, castor oil, avocado, caprylic / capric acid triglycerides such as those sold by Stearineries Dubois or those sold under the names "Miglyol 810", "812" and "818" by Dynamit Nobel, jojoba oil, 15 shea butter oil; esters and synthetic ethers, in particular of fatty acids, such as the oils of formulas R 1 COOR 2 and R 1 OR 2 in which R 1 represents the residue of a fatty acid comprising from 8 to 29 carbon atoms, and R 2 represents a hydrocarbon-based chain, branched or unbranched, containing from 3 to 30 carbon atoms, such as for example purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, stearate octyl-2-dodecyl, octyl-2-dodecyl erucate, isostearyl isostearate; hydroxyl esters such as isostearyl lactate, octyl hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate; heptanoates, octanoates, decanoates of fatty alcohols; polyol esters, such as propylene glycol dioctanoate, neopentyl glycol diheptanoate and diethylene glycol diisononanoate; and pentaerythritol esters such as pentaerythrityl tetraisostearate; linear or branched hydrocarbons of mineral or synthetic origin, such as paraffin oils, volatile or not, and their derivatives, petroleum jelly, polydecenes, hydrogenated polyisobutene such as parleam oil; Fatty alcohols having from 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetylstearyl alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol and 2-undecylpentadecanol; , oleic alcohol or linoleic alcohol; silicone oils such as volatile or non-volatile polymethylsiloxanes (PDMS) with a linear or cyclic silicone chain, which are liquid or pasty at room temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; poly-dimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenyl silicones such as phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes, 2-phenylethyltrimethylsiloxysilicates, and polymethylphenylsiloxanes; - their mixtures.

The term "hydrocarbon-based oil" in the list of oils mentioned above, any oil predominantly comprising carbon and hydrogen atoms, and optionally ester, ether, fluoro, carboxylic acid and / or alcohol groups. The composition according to the invention may comprise solid bodies at room temperature (25 ° C.), for example fatty acids containing from 8 to 30 carbon atoms, such as stearic acid, lauric acid, sodium hydroxide and the like. palmitic acid and oleic acid; waxes such as lanolin, beeswax, carnauba or candelilla wax, paraffin waxes, microcrystalline waxes, ceresin or ozokerite, synthetic waxes such as polyethylene waxes, Fischer waxes, Tropsch.

These fatty substances may be chosen in a varied manner by those skilled in the art in order to prepare a composition having the desired properties, for example of consistency or texture. According to a particular embodiment of the invention, the composition according to the invention is a water-in-oil (W / O) or oil-in-water (O / W) emulsion. The proportion of the oily phase of the emulsion may range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The emulsions generally contain at least one emulsifier, especially chosen from amphoteric, anionic, cationic or nonionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are suitably selected according to the emulsion to be obtained (W / O or O / W). The emulsifier and the co-emulsifier are generally present in the composition, in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition. . For the W / O emulsions, examples of emulsifiers that may be mentioned include dimethicone copolyols, such as the mixture of cyclomethicone and dimethicone copolyol, sold under the name "DC 5225 C" by the company Dow Corning, and the alkyl dimethicone copolymers. Polyols such as Laurylmethicone copolyol sold under the name Dow Corning 5200 Formulation Aid by the company Dow Corning and Cetyl dimethicone copolyol sold under the name Abil EM 90® by the company Goldschmidt. It is also possible to use, as surfactant of W / O emulsions, a crosslinked elastomeric solid organopolysiloxane comprising at least one oxyalkylene group, such as those obtained according to the procedure of Examples 3, 4 and 8 of US Pat. No. 5,412,004 and examples of US-A-5,811,487, including the product of Example 3 (synthetic example) of US-A-5,412,004. and such as that marketed under the reference KSG 21 by the company Shin Etsu. For O / W emulsions, mention may be made, for example, as emulsifiers, of nonionic emulsifiers such as oxyalkylenated (more particularly polyoxyethylenated) fatty acid esters of glycerol; oxyalkylenated fatty acid and sorbitan esters; oxyalkylenated fatty acid esters (oxyethylenated and / or oxypropylenated); oxyalkylenated fatty alcohol ethers (oxyethylenated and / or oxypropylenated); sugar esters such as sucrose stearate; and mixtures thereof such as the mixture of glyceryl stearate and PEG-40 stearate.

The composition may be an aqueous gel, and especially include conventional aqueous gelling agents. In a known manner, the composition according to the invention may also contain adjuvants which are customary in the cosmetic or dermatological field, such as gelling agents, film-forming polymers, preservatives, perfumes, fillers, UV filters, bacteriological agents and the like. acids, odor absorbers, dyestuffs, plant extracts, cosmetic and dermatological active agents, and salts. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition.

The subject of the invention is also a process for the cosmetic treatment of keratin materials, comprising the application to the keratin materials, in particular the skin, or the oral administration to an individual of a composition as described above. Said cosmetic treatment method is non-therapeutic. More particularly, the subject of the invention is also a process for the cosmetic treatment of skincare, make-up and / or cleaning of keratinous substances, in particular the skin, comprising the application on said keratin materials, in particular the skin, of a composition according to the invention as described above. Said method of cosmetic treatment of care, makeup, and / or cleansing of the skin is non-therapeutic.

More particularly, the subject of the invention is also a cosmetic process for preventing and / or treating cutaneous signs of aging, comprising at least one step of topical application to keratinous substances, such as the skin, of a skin. Position according to the invention as described above. The cutaneous signs of the aging to be prevented and / or treated in the cosmetic process according to the invention may be chosen from the lines and wrinkles, and / or to fight against the skin withered, soft and / or thinned.

The invention also relates to the cosmetic use of a composition according to the invention as defined above, for the care, makeup and / or cleaning of keratin materials. More particularly, the subject of the invention is the cosmetic use of a composition as defined above, for the care of the skin, preferably for preventing and / or treating the cutaneous signs of aging. The invention relates to a method for the cosmetic treatment of skincare, makeup, and / or cleaning of keratinous substances, in particular the skin, comprising the administration, orally, to an individual of a composition as defined above. In another embodiment, the invention also relates to the cosmetic use as defined above, in which the combination of hesperetin and at least one organic solvent as defined above, or the composition comprising it, is implementation within a food supplement.

25 The expressions "between ... and ..." and "from ... to ...", or "at least ..", or "at least .." must be understood as inclusive, except if the opposite is specified.

The following examples of compositions according to the invention are given by way of illustration and without limitation. The compounds are indicated in chemical name or INCI name. The contents of the ingredients are expressed in percentage by weight.

Example 1: Solubility Test In a beaker, the test compound (solvent) was poured, hesperetin was added with magnetic stirring for 10 minutes. Then the mixture was heated at 60 ° C for 10 minutes with magnetic stirring, then allowed to stand for 1 hour to 24 hours at room temperature. The mixture was then heated to 60 ° C and allowed to cool to room temperature (25 ° C) for 24 hours. It was then observed whether the amount of hesperetin introduced recrystallizes or remains solubilized.

The amount of hesperetin which can be solubilized in the test compound was determined in this way. The maximum value corresponds to that of the amount from which the hesperetin begins not to solubilize in the solvent evaluated. The following results were obtained in several compounds (solvents) evaluated: Test compound Solubilization rate (% by weight) ethanol 1% water <1% PEG-8 (POLYETHYLENE GLYCOL 400 DUB PEG 8® from STEARINERIE DUBOIS) 20% glycerin <1% 1,3-PROPANEDIOL (ZEMEA PROPANEDIOLO from DUPONT TATE AND LYLE BIO PRODUCTS) 1% propylene glycol (1,2-PROPYLENEGLYCOL CAREO from BASF) 1% dipropylene glycol (DIPROPYLENE GLYCOL LO + ® from DOW CHEMICAL) 10% butylene glycol (1,3 BUTYLENE GLYCOL® from ALZO) 1% isododecane (isododecane from INEOS) <1% Isopropyl Myristate ester or isopropyl myristate (PALMESTER 1510® from KLK OLEO) <1% N-LAUROYL ISOPROPYL SARCOSINATE (ELDEW SL -205® from AJINOMOTO) 1% 3029780 11 isononyl isononate (ISONONYL ISONONANOATE (DUB ININ) 0 from STEARINERIE DUBOIS) <1% DIMETHYL ISOSORBIDE (ARLASOLVE DMI-LQ- (AP) ® from CRODA) 20% POLYISOBUTEN HYDROGEN (parleam® NOF CORPORATION) <1% PHENETHYL BENZOATE (and) BENZOIC ACID (2- PHENETHYLBENZOATE X-TEND 226® from ISP) <1% Octy l-2 dodecanol (ISOFOL 20 N / RD from SASOL) <1% CAPRYLIC ACID / CAPRIC ACID TRIGLYCERIDES (TRIGLYCERIDES C8C10 70/30 (DUB MCT 7030) 0 from STEARINERIE DUBOIS) <1% C12-15 ALKYL BENZOATE (Finsolv TN ® of INNOSPEC ACTIVE CHEMICALS) <1% It has thus been found that hesperetin is very well solubilized with PEG-8, dipropylene glycol, and dimethylisosorbide and is not very solubilized with ethanol, 1,3-propanediol propylene glycol, butylene glycol, and isopropyl N-lauroyl sarcosinate.

EXAMPLE 2 Composition According to the Invention A facial care cream (oil-in-water emulsion) was prepared according to the formula made having the following composition: Ingredient phase over 100 g A Mixture of glyceryl stearate and 2 g. PEG-100 stearate (ARLACELO 165 FL from Uniqema) POLYETHYLENE GLYCOL STEARATE (40%) (MYRJ S40-FL- (TH) 0 from Croda) 2,5 cetyl alcohol (NACOL 16-98® from Sasol) 1 stearyl alcohol (Sasol NACOL 18 98®) 1 hydrogenated polyisobutene (PARLEAM 0 from NOF Corporation) 5 B water 27.4 preservatives 1 C isohexadecane 15 Carboxyvinyl polymer (Carbopol 981 polymer® from Lubrizol) 0.3 D triethanolamine 0, 3 El dipropylene glycol 20 (DL PROPYLENE GLYCOL LO + ® from DOW CHEMICAL) butylene glycol (1.3 BUTYLENE GLYCOL® 8.8 from ALZO) hesperetin (HESPERETIN PURIFI EDO from 02 the company Ferrer Grupo-Exquim (Ferrer)) water 10 Mode procedure: Phase A was heated between 80 ° C and 85 ° C until complete melting of fat rps (about 85 ° C). Phase B was heated to 85 ° C. Phase A was added rapidly to phase B with vigorous stirring for ten minutes. Add A to B. The emulsion was cooled with slow stirring. Phases C to D were added after returning to room temperature.

The E1 phase was prepared with stirring at the magnetic bar and will be added at the end of the preparation.

The composition is stable and homogeneous after storage for 2 months at 45 ° C., and can be applied regularly to reduce the signs of skin aging.

Claims (13)

REVENDICATIONS1. A composition comprising, in a physiologically acceptable aqueous medium, a) hesperetin, and b) at least one compound having solubility parameters according to the HANSEN solubility space such as 10.5 <6, <20 and 13, <8d <25.5. 2. Composition according to the preceding claim, characterized in that said compound (b) has solubility parameters according to the HANSEN solubility space such that 10.5 <6a <19.6 and 15.5 <8d <20, preferably is a solvent for hesperetin. 3. Composition according to any one of the preceding claims, characterized in that said compound (b) is chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units), dipropylene glycol, dimethylisosorbide, and one of them. 4. Composition according to any one of the preceding claims, characterized in that said compound (b) is present in a content ranging from 0.1% to 70% by weight, relative to the total weight of the composition, preferably ranging from 2% to 40% by weight, and preferably ranging from 5% to 30% by weight. 5. Composition according to any one of the preceding claims, characterized in that the hesperetin is present in a content ranging from 0.05% to 10% by weight, relative to the total weight of the composition, preferably from 0 From 10% to 5% by weight, and preferably from 0.10% to 2.5% by weight. 6. Composition according to any one of the preceding claims, characterized in that the compound (b) and hesperetin are present in a compound mass ratio (b) / hesperetin at least equal to 2, in particular ranging from 2 to 50 and preferably from 5 to 20. 7. Composition according to any one of the preceding claims, wherein said solvent is PEG-8 (polyethylene glycol containing 8 ethylene glycol units) and the weight ratio PEG-8 / hesperetin is at least 2, for example ranging from 2 to 35, and preferably from 3 to 10. 8. Composition according to any one of the preceding claims, in which the said compound (b) is dipropylene glycol, and the dipropylene glycol / hes-perretin mass ratio is at least 2, for example ranging from 2 to 50, and preferably from 5 to 20. 9. Composition according to any one of the preceding claims, characterized in that it is in the form of a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. 10. Composition according to any one of the preceding claims, characterized in that it is a cosmetic composition. 10 11. A process for the cosmetic treatment of keratin materials comprising the application to keratin materials, such as the skin, of a composition according to any one of the preceding claims. 15 12. Process for the cosmetic treatment of skincare and / or make-up and / or cleaning of keratin materials, in particular the skin, comprising the application to said keratin materials, in particular the skin, of a composition as defined according to one of the following: any of claims 1 to 10. 13. A cosmetic process for preventing and / or treating cutaneous signs of aging, comprising at least one step of topical application to keratinous substances, such as the skin, of a composition as defined according to any one of the preceding claims. Claims 1 to 10.