FR2950885A1 - Use of at least one substituted 2-propyl-phenol compound as a preservative in a cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, which is useful as e.g. a makeup product for facial skin, body or lips - Google Patents

Abstract

Use of at least one substituted 2-propyl-phenol compound (I) as a preservative in a cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, is claimed. Use of at least one substituted 2-propyl-phenol compound of formula (I) as a preservative in a cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, is claimed. R : methyl or ethyl; R2 : H, methyl or ethyl; R3 : optionally saturated 1-12C alkyl; X : O or OH; and n : 0-3. Independent claims are included for: (1) preservation of the composition comprising incorporating (I) into the composition; (2) the substituted 2-propyl-phenol compound (I); and (3) the composition comprising (I). [Image] ACTIVITY : Fungicide; Antibacterial. MECHANISM OF ACTION : None given.

Description

The present invention relates to the use of vanillin derivatives in particular as a preservative in cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic compositions; the invention also relates to novel compounds which can be used in cosmetics, dermatology, pharmacy, nutraceutical or oral cosmetics, in particular as a preservative, as well as the compositions comprising them.

It is common to introduce into the cosmetic or dermatological compositions, chemical preservatives intended to fight against the development of microorganisms in these compositions, which would render them rapidly unsuitable for use. In particular, it is necessary to protect the compositions against the microorganisms that may develop inside the composition, for example during their manufacture, and also against those that the user could introduce therein by manipulating it, in particular when gripping with the fingers of potted products. Commonly used chemical preservatives include parabens, organic acids or formalin-releasing compounds. These preservatives, however, have the disadvantage of causing irritation, especially on sensitive skin, when they are present at relatively high rates. In addition, in the interest of the environment, consumers are increasingly looking for conservation agents that respect the environment, especially those that are not ecotoxic. In addition, the effectiveness of conventionally used preservatives is variable and their formulation may cause problems, including incompatibility or even destabilization, formulas, especially emulsions.

The object of the present invention is to propose novel preserving agents having in particular a broad antimicrobial spectrum, at least as large as or even greater than that of already existing compounds, and not having the disadvantages of the prior art, in particular having specific physicochemical properties to protect the cosmetic formulas of microbial contamination while being well tolerated.

An object of the invention is therefore the use, in a cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, of at least one compound of formula (I):

OH (RO) n (I) wherein: - n represents an integer between 0 and 3 (inclusive); R represents a methyl or ethyl radical; R2 represents a hydrogen atom, a methyl radical or an ethyl radical; - R3 represents a linear or branched alkyl radical, saturated C 1 -C 12 or unsaturated C 2 -C 12; - X is = 0 or OH; as a conservative agent.

By preservative is meant a substance that is commonly added to a composition to ensure its preservation against a contamminating agent. Advantageously, the compounds of formula (I) according to the invention are used as antimicrobial and / or antibacterial and / or antifungal agent.

Another subject of the invention is a method for preserving a cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, characterized in that it consists in incorporating into said composition at least one compound of formula (I).

Preferably, in formula (I), n = 0 or 1; Preferably, in the formula (I), R represents CH3. Preferably, in formula (I), R2 is H or CH3, more preferably R2 = H. Preferably, in the formula (I), R3 represents a saturated linear C1-C4 alkyl, preferably CH3 or C2H5.

It is of course possible to use a mixture of compounds of formula (I). Preferably, the composition does not comprise other preservatives than those of formula (I). In particular, the composition does not contain parabens. Certain compounds of formula (I) are new and also form an object of the present invention. These are the compounds of formula (I ') below:

OH (RO) n in which: - n represents an integer between 0 and 3 (inclusive); R represents a methyl or ethyl radical; R2 represents a hydrogen atom, a methyl radical or an ethyl radical; - R3 represents a linear or branched alkyl radical, saturated C 2 -C 12 or unsaturated C 2 -C 12; X is = 0 or OH. Cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic compositions comprising at least one compound of formula (I ') also form an object of the present invention.

Preferably, in the formula (I '), n = 0 or 1; Preferably, in the formula (I '), R represents CH3. Preferably, in formula (I '), R2 is H or CH3, more preferably R2 = H. Preferably, in the formula (I '), R3 represents a linear C2-C4 saturated alkyl, preferably C2H5. The preferred compounds of formula (I) or (I ') are the following: OMe 4- (2-hydroxy-3-methoxyphenyl) butan-2-one OH (CAS 4221-49-2) Me O OMe 2- (4-hydroxybutyl) -6-methoxyphenol (266310-14-9) 4- (2-hydroxyphenyl) butan-2-one O (61844-32-4) 5 OH 2- (3-hydroxybutyl) -6-methoxyphenol hydroxybutyl) phenol Me (CAS 6952-32-5) OH 5- (2-Hydroxyphenyl) pentan-2-one O-OH-3-hydroxypentyl) phenol OH O-methyl-5- (2- hydroxy-3-methoxyphenyl) pentan-2-one OMe • OH OH 2- (2-methyl-3-hydroxy-pentyl) -6-methoxyphenol The compounds of formula (I) or (I ') can be prepared easily by a person skilled in the art on the basis of his general knowledge; especially from the corresponding starting aldehydes according to the following scheme: 1) NaOH / H 2 O o 2) HCl

R3 RO R2 Pd / C H2 (10-40 bar) (solvent) RO R3 The compounds of formula (I) or (I '), alone or mixed with one another, may be employed at a rate of 0.01 at 5% by weight, especially 0.1 to 2.5% by weight, relative to the weight of the composition, in cosmetic, dermatological or pharmaceutical compositions.

The cosmetic, dermatological or pharmaceutical compositions furthermore comprise a medium that is cosmetically, dermatologically or pharmaceutically acceptable, that is to say compatible with keratin materials such as the skin of the face or of the body, the lips, the hair , eyelashes, eyebrows and nails.

The compositions according to the invention may be in any of the galenical forms conventionally used, especially for topical application, and especially in the form of aqueous, hydroalcoholic, oil-in-water (O / W) or water-in-water emulsions. oil (W / O) or multiple (triple: W / O / W or H / W / H), aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, these spherules which may be polymeric nanoparticles such as nanospheres and nanocapsules, or lipid vesicles of ionic and / or nonionic type (liposomes, niosomes, oleosomes), nanoemulsions, or thin films. These compositions are prepared according to the usual methods. The compositions according to the invention can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, of a foam. They may optionally be applied to the skin in the form of an aerosol. They may also be in solid form, for example in the form of a stick.

The composition according to the invention may especially be in the form of: a makeup product for the skin of the face, body or lips; - an aftershave gel or lotion; - a depilatory cream; in the form of a personal hygiene composition such as a shower gel or a shampoo; a pharmaceutical composition; a solid composition such as a soap or a cleaning roll; an aerosol composition also comprising a propellant under pressure; a styling lotion, a cream or a styling gel, a dyeing composition, a restructuring hair lotion, a permanent composition, a lotion or a fall arrest gel; - a composition for oral use.

The physiologically acceptable medium in which the compounds may be employed, as well as its constituents, their quantity, the galenic form of the composition and its method of preparation, may be chosen by those skilled in the art on the basis of their general knowledge in function the type of composition sought.

In particular, the composition may comprise any fatty substance usually used in the intended field of application. Mention may in particular be made of silicone fatty substances such as oils, gums and silicone waxes, as well as non-silicone fatty substances such as oils, pastes and waxes of vegetable, mineral, animal and / or synthetic origin. . The oils may optionally be volatile or non-volatile.

Among the silicone oils, mention may be made of polydimethylsiloxanes (PDMS) which may or may not be volatile with a linear or cyclic silicone chain, which are liquid or pasty at ambient temperature, in particular cyclopolydimethylsiloxanes such as cyclohexasiloxane; polydimethylsiloxanes 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; Among the hydrocarbon-based oils of plant origin, mention may be made of liquid triglycerides of fatty acids containing from 4 to 10 carbon atoms, such as the triglycerides of heptanoic or octanoic acids, or else, for example, sunflower, corn or soybean oils. , squash, grape seed, sesame, hazelnut, apricot, macadamia, arara, sunflower, castor oil, avocado, triglycerides of caprylic / capric acids; jojoba oil, shea butter oil; Mention may also be made, as fatty substance that may be used: fatty acids having from 8 to 32 carbon atoms; esters and synthetic ethers, in particular of formula R'COOR2 and R'OR2 in which R 'represents the residue of a fatty acid containing from 8 to 29 carbon atoms, and R2 represents a hydrocarbon chain, branched or unbranched , containing from 3 to 30 carbon atoms, such as, for example, purcellin oil, isononyl iso-nonanoate, isopropyl myristate, 2-ethylhexyl palmitate, octyl stearate, 2-dodecyl, octyl-2-dodecyl erucate, isostearyl isostearate; hydroxylated 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, 2-undecylpentadecanol, oleic alcohol or linoleic alcohol.

The composition may also comprise an aqueous medium which comprises water, a hydroalcoholic medium containing a C2-C6 alcohol such as ethanol or isopropanol, or an organic medium comprising usual organic solvents such as C2 alcohols. -C6, especially ethanol and isopropanol, glycols such as propylene glycol, ketones.

The composition according to the invention may also comprise the usual adjuvants in the cosmetic and dermatological fields, such as thickeners, emulsifiers, surfactants, gelling agents, cosmetic active ingredients, perfumes, fillers, dyestuffs, moisturizers, vitamins, polymers. The amounts of these various adjuvants are those conventionally used in the fields under consideration, for example from 0.001 to 20% of the total weight of the composition. These adjuvants, as well as their concentrations, must be such that they do not adversely affect the advantageous properties of the compounds according to the invention.

The pH of the compositions according to the invention, when they comprise at least one aqueous phase (aqueous solutions, emulsions for example), is preferably between 4 and 9, preferably between 4 and 7, advantageously between 5 and 6.

The invention is illustrated in more detail in the following exemplary embodiments.

Example 1: Determination of the antimicrobial activity of compounds according to the invention

The antimicrobial efficacy of compounds of formula (I) was evaluated by the method of the Challenge Test or artificial contamination.

Compounds tested OMe Compose 1: OH 4- (2-hydroxy-3-methoxyphenyl) butan-2-one (CAS 4221-49-2) Me O OMe OH Compound 2: O Me 2- (3-hydroxybutyl) -6 -methoxyphenol OH (266310-14-9) 10 Protocol The challenge-test method consists of an artificial contamination of the sample by microbial strains of collection (bacteria, yeasts and molds) and an evaluation of the number of microorganisms revive seven days after inoculation. In order to demonstrate the effect of compounds of formula (I), the antimicrobial activity of a cosmetic formula containing respectively 2% of compound according to the invention was compared with the same formula alone (control), after inoculation about 106 CFU (colony-forming units) / gram of cosmeetic formula.

Cosmetic formula (% by weight) - Sorbitan tristearate (Croda Span 65 V®) 0.9% - Polyethylene glycol stearate (40 0E) (Croda's Myrj 52 P®) 2.0% 25 - Mono-distearate blend (36 / 64) glycerol / potassium stearate 3.0% - Vegetable fatty acids (stearic acid / palmitic acid / myristic acid 53/44/3) 1.0% - Cetyl alcohol - Myristyl myristate - Cyclopentasiloxane - Fillers - Glycerine - Hydrogenated isoparaffin - White Vaseline - Water3.8% 2.0% 5.0% 0.8% 3.0% 7.2% 4.0% qs 100% Micro-organism cultures 5 pure cultures of microorganisms are used. GERMS Transplanting medium T ° ATCC Escherichia coli (Ec) Trypto-casein soy 35 ° C 8739 Enterococcus faecalis (Ef) Trypto-casein soy 35 ° C 33186 Pseudomonas aeruginosa (Pa) Trypto-casein soy 35 ° C 19429 Candida albicans (Ca ) Sabouraud 35 ° C 10231 Aspergillus piger (An) Malt 35 ° C 6275 ATCC = American Type Culture Collection Strains of Gram - bacteria (Escherichia coli and Pseudomonas aeruginosa), gram + bacteria (Enterococcus faecalis), yeast (Candida albicans), and mildew (Aspergillus piger) are seeded in transplanting medium, respectively the day before inoculation for bacteria and yeast, and 5 days before inoculation for mold.

On the day of inoculation: a suspension in Tryptone salt diluent is prepared for the bacteria and the yeast, respectively, so as to obtain, on the spectrophotometer, an optical density suspension of between 35% and 45% of light transmitted at 544 nm. ; for mildew, the spores are removed by washing the agar with 6 to 7 ml of harvest solution and the suspension is recovered in a sterile flask or tube.

After having homogenized the microbial suspension, 0.2 ml of inoculum (the suspensions are used pure: between 1x10 $ and 3x10 $ CFU per ml) are introduced into each pill box and the mixture is perfectly homogenized using a spatula. microbial tension in the 20 g of product (= cosmetic formula).

The level of microorganisms present in the product corresponds, after homo-geneization, to a concentration of 106 seeds per gram of product, ie the inoculation at 1% of an inoculum at 10 $ germs per ml. After 7 days of contact time between the seeds and the product at 22 ° C. ± 2 ° C. and in the dark, decimal dilutions are carried out and the number of revivifiable microorganisms remaining in the product is counted. Results Nb of CFU / gram of product at T7 days (inoculation rate at 106 seeds / g) pH value E.coli P. aerium E. fae- C. albino A. piger ginosa catis cans Compound 1 2% 7 <200 <200 <200 <200 <200 Compound 2 2% 7.2 <200 <200 <200 <200 <200 <200 PDU: sensitivity threshold of the method

This study shows that the compounds of formula (I) according to the invention have a very broad antimicrobial spectrum because of their antibacterial and fungal activity. These are effective preservatives, especially in the cosmetic formula tested. EXAMPLE 2 An emulsion comprising (% by weight): 0.9% - Sorbitan tristearate (Span 65 V® from Croda) - Polyethylene glycol stearate (40%) (Myrj 52 P® from Croda) 2% - Blend of glyceryl mono-distearate (36/64) / stearate 3% of potassium - Vegetable fatty acids (stearic acid / palmitic acid 1 / myristic acid 53/44/3) - Cetyl alcohol 3.8% - Myristyl myristate 2% - Cyclopentasiloxane 5% - Charges 0.8% - Glycerin 3% - Hydrogenated Isoparaffin 7.2% - White Vaseline 4% - Compound 1 (Example 1) 2% - Water qs 100% A similar emulsion is prepared replacing compound 1 with compound 2. EXAMPLE 3 An O / W emulsion comprising (wt%): 5 - sodium hydroxide 0.03% - vaseline oil 10% - 2-ethyl hexyl palmitate 10 % - acrylic acid / stearyl methacrylate copolymer polymerized in a mixture of ethyl acetate / cyclohexane 0.1% - glycerol 5% - cetylstearyl glucoside and alcohols mixture cetyl, stearyl (12/46/42) 2.45% - compound 1 (of example 1) 2% - microbiologically clean deionized water qs 100%

A similar emulsion is prepared by replacing compound 1 with compound 2.

EXAMPLE 4 A lotion comprising (% by weight) is prepared: - allantoin 0.05% - sodium chloride 0.09% - citric acid qsp pH 7 ± 0.2 - blueberry water 1% - hexylene glycol (2 methyl- 2,4 pentanediol) Io / o - glycerol 5% - N-cocoylamidoethyl, sodium N-ethoxycarboxymethyl glycinate 1,1% - sodium lauryl ether / sodium sulfate / magnesium (80/20) 4OE (52% DM) 0.45% compound 1 (of example 1) 1.5% - microbiologically clean deionized water qs 100%

A similar lotion is prepared by replacing compound 1 with compound 2.

Claims (15)

REVENDICATIONS1. Use, in a cosmetic, dermatological, pharmaceutical-5, nutraceutical or oral cosmetic composition, of at least one compound of formula (I): OH (RO) n (I) in which: n represents an integer understood between 0 and 3 (inclusive); R represents a methyl or ethyl radical; R2 represents a hydrogen atom, a methyl radical or an ethyl radical; - R3 represents a linear or branched alkyl radical, saturated C 1 -C 12 or unsaturated C 2 -C 12; X is = O or OH; as a conservative agent. 2. Use according to claim 1, wherein formula (I) satisfies at least one of the following characteristics: -n = 0 or 1; - R represents CH3. - R2 represents H or CH3, - R3 represents a C1-C4 saturated linear alkyl, preferably CH3 or C2H5. 25 3. The use as claimed in one of the preceding claims, in which the compound of formula (I) is chosen from the following compounds: ## STR1 ## ## STR1 ## 4. Use according to one of the preceding claims, wherein the compound of formula (I), alone or in mixture, is present in a proportion of 0.01 to 5% by weight, especially 0.1 to 2.5% by weight. weight, relative to the weight of the composition. 5. Use according to one of the preceding claims, wherein the composition comprises a physiologically acceptable medium which comprises at least one ingredient selected from silicone fatty substances such as oils, gums and silicone waxes; non-silicone fatty substances such as oils, pastes and waxes of vegetable, mineral, animal and / or synthetic origin; fatty acids having 8 to 32 carbon atoms; esters and synthetic ethers, in particular of formula R'COOR2 and R'OR2 in which R 'represents the residue of a fatty acid containing from 8 to 29 carbon atoms, and R2 represents a hydrocarbon chain, branched or unbranched, containing from 3 to 30 carbon atoms; linear or branched hydrocarbons of mineral or synthetic origin; fatty alcohols having from 8 to 26 carbon atoms; some water; C2-C6 alcohols; glycols such as propylene glycol, ketones; thickeners, emulsifiers, surfactants, gelling agents, cosmetic active ingredients, perfumes, fillers, dyestuffs, moisturizers, vitamins, polymers. 6. Use according to one of the preceding claims, wherein the composition is in the form of a makeup product of the skin of the face, body or lips; a gel or aftershave; a depilatory cream; a personal hygiene composition such as a shower gel or a shampoo; a pharmaceutical composition; a solid composition such as a soap or a cleaning bar; an aerosol composition also comprising a propellant under pressure; a styling lotion, styling cream or gel, dyeing composition, hair resurfacing lotion, permanent composition, lotion or an anti-fall gel; of a composition for oral use. 7. A method for preserving a cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, characterized in that it consists in incorporating into said composition at least one compound of formula (I) as defined in one of the Claims 1 to 3. 8. Compound of formula (I '): OH (RO) n in which: - n represents an integer between 0 and 3 (inclusive); R represents a methyl or ethyl radical; R2 represents a hydrogen atom, a methyl radical or an ethyl radical; R 3 represents a linear or branched alkyl radical, saturated with C 2 -C 12 or unsaturated C 2 -C 12; X is = 0 or OH. The compound of claim 8, wherein the formula (I ') satisfies at least one of the following characteristics: n = 0 or 1; - R represents CH3. - R2 represents H or CH3, - R3 represents a saturated linear C2-C4 alkyl, preferably C2H5. 25 10. Compound according to one of claims 8 to 9, selected from the following compounds: 11. Cosmetic, dermatological, pharmaceutical, nutraceutical or oral cosmetic composition, comprising at least one compound of formula (I ') such that OMe OMe OHdefined in one of claims 8 to 10. 12. Composition according to claim 11, wherein the compound of formula (I), alone or as a mixture, is present in a proportion of 0.01 to 5% by weight, in particular 0.1 to 2.5% by weight, by weight. relative to the weight of the composition. 13. Composition according to one of claims 11 to 12, comprising a physiologically acceptable medium which comprises at least one ingredient selected from silicone fatty substances such as oils, gums and silicone waxes; non-silicone fatty substances such as oils, pastes and waxes of vegetable, mineral, animal and / or synthetic origin; fatty acids having 8 to 32 carbon atoms; esters and synthetic ethers, in particular of formula R'COOR2 and R'OR2 in which R 'represents the residue of a fatty acid containing from 8 to 29 carbon atoms, and R2 represents a hydrocarbon chain, branched or unbranched, containing from 3 to 30 carbon atoms; linear or branched hydrocarbons of mineral or synthetic origin; fatty alcohols having from 8 to 26 carbon atoms; some water; C2-C6 alcohols; glycols such as propylene glycol, ketones; thickeners, emulsifiers, surfactants, gelling agents, cosmetic active ingredients, perfumes, fillers, dyestuffs, moisturizers, vitamins, polymers. 14. Composition according to one of claims 11 to 13, in the form of a make-up product of the skin of the face, body or lips; a gel or aftershave; a depilatory cream; a personal hygiene composition such as a shower gel or a shampoo; a pharmaceutical composition; a solid composition such as a soap or a cleaning bar; an aerosol composition also comprising a propellant under pressure; a styling lotion, a styling cream or gel, a dyeing composition, a restructuring hair lotion, a permanent composition, a lotion or a fall arrest gel; of a composition for oral use. 15