FR3070107B1 - ANTIMICROBIAL MIXTURE CONTAINING 4- (3-ETHOXY-4-HYDROXYPHENYL) BUTAN-2-ONE AND PHENOXYALCOOL, AND COSMETIC COMPOSITION CONTAINING SAME - Google Patents

Abstract

The invention relates to an antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a phenoxyalcohol of the formula C6H6-OR-OH, wherein R denotes a divalent hydrocarbon radical having 2 or 3 carbon atoms, as well as a cosmetic composition containing such a mixture. Application to the care, makeup and cleansing of keratin materials.

Description

The present invention relates to an antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a phenoxyalcohol, and a cosmetic composition containing such a mixture.

4- (3-Ethoxy-4-hydroxyphenyl) butan-2-one (ketone compound) is a substance of interest as a preservative of cosmetic compositions for protecting the compositions from microbial contamination, as described in WO2011 / 039445.

However, it is desirable to incorporate said ketone compound in reduced concentration in compositions, especially cosmetic or dermatological, while maintaining a good antimicrobial preservation performance. It is therefore sought for this purpose combinations of the ketone compound with other compounds having antimicrobial efficacy.

The inventors have discovered, unexpectedly, that the combination of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one with a phenoxy alcohol such as 2-phenoxyethanol makes it possible to obtain an antimicrobial mixture having a synergistic effect. antimicrobial activity, in particular on molds, in particular on Aspergillus niger, on Gram + bacteria, in particular on Enterococcus faecalis and Staphylococcus aureus, on Gram - bacteria, in particular on Pseudomonas aeruginosa, and on yeasts, in particular on Candida albicans . The results of Example 1 described hereinafter show the synergistic antimicrobial activity obtained with the minimum inhibitory concentration (MIC) measurements made with several mixtures. The antimicrobial activity is considered to be synergistic when the antimicrobial mixture makes it possible to obtain a percentage of growth of the strain of less than or equal to 20%.

Application FR-A-2962333 describes a cosmetic composition for the treatment of oily skin comprising a 2-alkoxy-4-alkylketonephenol compound and an essential oil. The composition may comprise an additional asset for the care of oily skin, such as antimicrobial agents among which phenoxyethanol is mentioned. This document does not specifically describe an antimicrobial mixture consisting of the combination of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one with phenoxyethanol, nor does it suggest that such a mixture exhibits antimicrobial activity. synergistic on molds, particularly on Aspergillus niger, on Gram + bacteria, in particular on Enterococcus faecalis and Staphylococcus aureus, on Gram - bacteria, especially on Pseudomonas aeruginosa, and on yeasts, in particular on Candida albicans.

More specifically, the subject of the invention is an antimicrobial mixture comprising, or consisting of (or consisting of), 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a phenoxyalcohol of formula CqHq-OR -OH, R denoting a divalent hydrocarbon radical having 2 or 3 carbon atoms. The subject of the invention is also a composition, in particular a cosmetic or dermatological composition, comprising in a physiologically acceptable medium the said mixture described above. The subject of the invention is also a non-therapeutic cosmetic treatment process for keratinous materials comprising the application to the keratin materials of a composition as described above. The process may be a cosmetic process for caring for or making up or cleaning keratin materials. The invention also relates to a method for preserving a composition comprising a physiologically acceptable medium, in particular a cosmetic or dermatological composition, characterized in that it consists in incorporating into said composition an antimicrobial mixture as described above.

4- (3-Ethoxy-4-hydroxyphenyl) butan-2-one is a compound of the formula:

The phenoxyalcohol described above may be chosen from 2-phenoxyethanol or 1-phenoxy-2-propanol. Preferably, 2-phenoxyethanol is used.

2-Phenoxyethanol corresponds to the compound of formula C6H5-O-CH2-CH2-OH (CAS No. 122-99-6).

Advantageously, the 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the phenoxyalcohol described above are present in said mixture in a content such that the weight ratio 4- (3-ethoxy-4-hydroxyphenyl) butane 2-one / phenoxyalcohol ranges from 0.15 to 3.5, preferably ranges from 0.15 to 3.2, and more preferably ranges from 0.2 to 3.2.

The antimicrobial mixture may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.6 to 1.6, preferably ranging from 0.7 to 1.4, preferably ranging from from 0.8 to 1.2 and more preferably from 0.9 to 1.1. Such a mixture has good antimicrobial activity on molds, especially Aspergillus niger.

The antimicrobial blend may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.4 to 0.8, preferably from 0.45 to 0.7, and more preferably ranging from 0.45 to 0.6. Such a mixture has good antimicrobial activity on the Gram + Enterococcus faecalis bacterium.

The antimicrobial mixture may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.3 to 3.2, preferably from 0.3 to 2.4, preferably ranging from 0.3 to 1.4, and more preferably ranging from 0.3 to 1.2. Such a mixture has good antimicrobial activity on the Gram + Staphylococcus aureus bacterium.

The antimicrobial mixture may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.2 to 3.2, preferably from 0.4 to 3.2, preferably ranging from 0.8 to 3.2, preferably from 1.6 to 3.2; preferably ranging from 0.2 to 2.4, preferably ranging from 0.4 to 2.4, preferentially ranging from 0.8 to 2.4 and more preferably ranging from 1.6 to 2.4. Such a mixture has a good antimicrobial activity on the Gram - bacterium, especially on Pseudomonas aeruginosa.

The antimicrobial blend may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.15 to 1.3, preferably from 0.15 to 0.7, and more preferably ranging from 0.25 to 0.5. Such a mixture has a good antimicrobial activity on yeasts, in particular on Candida Albicans. The invention also relates to a composition comprising, in a physiologically acceptable medium, the antimicrobial mixture described above.

Physiologically acceptable medium means a medium compatible with keratin materials of human beings such as the skin, the scalp, the hair, the nails. The said medium may comprise one or more additional ingredients, distinct from the ketone compound and 2-phenoxyethanol.

The compound 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one may be present in the composition according to the invention, in a content ranging from 0.01% to 5% by weight, relative to the total weight of the composition, preferably ranging from 0.01% to 3% by weight, preferably ranging from 0.01 to 2.5% by weight, and more preferably ranging from 0.01 to 2% by weight.

The composition may comprise at least one additional ingredient selected from water, oils, polyols having 2 to 10 carbon atoms, gelling agents, surfactants, film-forming polymers, dyestuffs, fragrances, fillers, UV filters, plant extracts, cosmetic and dermatological active ingredients, and salts.

The composition according to the invention may comprise an aqueous phase.

The composition may comprise water which may be present in a content ranging from 5% to 90% by weight, based on the total weight of the composition, and preferably ranging from 35% to 75% by weight.

The composition may also comprise a water-miscible polyol at ambient temperature (25 ° C.), chosen in particular from polyols having in particular from 2 to 10 carbon atoms, preferably having from 2 to 6 carbon atoms, such as glycerin, propylene glycol, 1,3-propanediol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol, diglycerine. Advantageously, the composition according to the invention comprises 1,3-propanediol, especially in a content ranging from 0.1 to 20% by weight, relative to the total weight of the composition, and preferably ranging from 0.1 to 10. % by weight, preferably ranging from 0.5 to 5% by weight.

The compositions according to the invention can be in the form of oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O / W or W / O / H) emulsions. ), oily solutions, oily gels, aqueous solutions, aqueous gels, solid compositions. 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 or a compact powder.

The composition according to the invention may especially be in the form of: a makeup product, in particular the skin of the face, of the body or of the lips or eyelashes; - an aftershave gel or lotion; shaving product; - a deodorant (stick, roll-on, aerosol) - 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 styling cream or gel, a dyeing composition, a permanent composition, a lotion or a fall-prevention gel, an after-treatment shampoo; - a care composition or cleansing of the skin. The subject of the invention is also a process for the preparation of a composition, in particular a cosmetic or dermatological composition, comprising a step of mixing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one, of phenoxyalcohol, and of one or more additional ingredients, especially cosmetic or dermatological, such as those described above. The invention is illustrated in more detail in the following example. The contents of the ingredients are expressed in percentage by weight.

Example 1: Determination of the synergistic antimicrobial activity in MIC

Demonstration of a synergistic effect of antimicrobial activity with a mixture of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one (referred to as Substance A) and 2-phenylethanol (referred to as Substance B) is accomplished by the calculation of the synergy index (or FIC index), according to the following formula: FIC Index = (CMI of A with B / CMI of A) + (CMI of B with A / CMI of B) with: - MIC of A with B: minimum concentration of product A in the association A + B to obtain an inhibitory effect; - MIC of B with A: minimum concentration of product B in the association A + B to obtain the inhibitory effect; - MIC of A: minimal inhibitory concentration of product A alone; - MIC of B: minimum inhibitory concentration of product B alone.

This formula has been described for the first time in the article by F. C. Kull, P. C. Eisman, H. D. Sylwestrowka, and R. L. Mayer, Applied Microbiology 9: 538-541, 1961.

For each compound tested alone, the MIC is considered the first concentration to obtain a percentage of microbial growth of less than or equal to 20%.

With regard to the associations tested, CMI of A with B and CMI of B with A are the respective concentrations of A and B in the combinations making it possible to obtain a percentage of microbial growth of less than or equal to 20%.

Interpretation of the FIC Index:

When the value of the index FIC is less than or equal to 1, it is considered that the combination of the tested compounds has a synergistic effect.

The summary of the results obtained is presented in the following tables. The combination of compounds A and B was tested on the following strains: Aspergillus niger, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans.

The microbial strain Aspergillus niger ATCC 6275 was used, and Sabouraud broth liquid culture medium supplemented with polyoxyethylenesorbitan monopalmitate (20 EO) (Tween 40 from Croda) and Phytagel © BioReagent, at double concentration (a mixture of 5 g Phytagel +0.6 g tween 40 + 60g Sabouraud broth).

The microbial strain Enteroccoccus faecalis ATCC 33186 was used and a double concentration broth BHI (Brain Heart Infusion) liquid culture medium.

The microbial strain Staphylococcus aureus ATCC 6538 was used and a double concentration nutrient broth liquid culture medium.

The microbial strain Pseudomonas aeruginosa ATCC 9027 was used and a double concentration nutrient broth liquid culture medium.

The microbial strain Candida albicans ATCC 10231 was used and Sabouraud broth liquid culture medium, double concentration.

A 96-well microplate is used at an incubation temperature of 32.5 ° C.

The incubation time of the microplate is: - from 18 to 24 hours aerobically for Candida albicans ATCC 10231, Pseudomonas aeruginosa ATCC 9027 and Staphylococcus aureus ATCC 6538. - 24 to 30 hours aerobically for microbial Aspergillus niger ATCC 6275; - from 24 to 48 hours in aerobiosis for Enteroccoccus faecalis ATCC 33186.

testing

For each compound: A = 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one compound B = 2-phenoxyethanol compound

A 10% (w / v) stock solution was prepared by mixing 1 g of compound in 9 ml of 1% aqueous agar solution. Successive dilutions were performed with the 1% o agar solution.

Tests of Compounds A and B alone 50 μl of each of the obtained daughter solutions containing Compound A or B is added to the wells of the microplate. 100 μl of Sabouraud liquid nutrient broth inoculated at double concentration with the Aspergillus niger strain and 50 μl of aqueous 1% agar solution are also added.

Tests of compounds A and B in a mixture 50 μl of each of the daughter solutions obtained containing compound A and 50 μl of each of the daughter solutions obtained containing compound B are added to the wells of the microplate. It also adds 100 μΙ of Sabouraud liquid nutrient broth inoculated at double concentration by the Aspergillus niger strain. Microbial growth control

A positive control of microbial growth has also been realized. The positive microbial growth control corresponds to the mixture of 100 μl of a 1% aqueous agar solution with 100 μl of Sabouraud liquid nutritional broth inoculated at a double concentration with the Aspergillus niger strain in the absence of the compounds A and B. Absorbance control of compounds A and B alone

In parallel, an absorbance control of compounds A and B alone was carried out. This control corresponds to 100 μl of sterile double-strength Sabouraud liquid nutrient broth + 100 μl of compound A or B at double concentration.

In all three cases (absorbance control, growth control and test), the final volume present in each well of the microplate is 200 μL.

In both cases (test and control), the inoculum represents the concentration of the Aspergillus niger strain present in the final volume of the wells (200 μl) and is between 2 and 6 × 10 5 CFU / ml in Aspergillus niger.

The minimum inhibitory concentration (MIC) of each compound A and B alone and in combination was determined in a known manner using optical density measurements at the wavelength of 620 nm.

The test as described above (tests, absorbance controls and growth control) was again performed to test the A + B association on the following strains Enteroccoccus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans.

The following results were obtained:

Aspergillus niger

The results obtained show a synergy of the inhibitory activity for the mixture: 0.125% of A and 0.125% of B, ie ratio A / B = 1.

Enterococcus faecalis

0.0625 B 87 83 87 97 8234 0.125 B 86 90 80 95 7330 0.25 B 84 95 75 83 7430 0.5 B 80 79 68 5 ~ 372 (FIC 0.75) TB 6 6 2 3 | 2-23

CMI of Ascle CMI of B only CMI of each FIC Ratio A / B in% in% compound in Index mixture A% B% ï ï ^ ^ 0 0 0 0 Ô?

The results obtained show a synergy of the inhibitory activity for the mixture: 0.25% of A and 0.25% of B is ratio A / B = 0.5

Staphylococcus aureus

Concentrations 0A 0.0625A 0.125A 0.25A0.5A tested (in% wt.) B 7I 57 52i 0.0625 B 66 68 62 38 0, 0.125 B 73 65 55 17 ((FIC 2) 0.25 B 58 43 15 1 (FIC 0.5) (FIC 1) 0.5 B ï ï Ô ïÔ

CMI of Ascle CMI of B only CMI of each FIC Ratio A / B in% in% compound in mixture Index A% B% ~ 0J5 0J5 0 ^ 25 0 ^ 25 ïCL5

The results obtained show a synergy of the inhibitory activity for the mixtures: i) 0.25% of A and 0.125% of B, ie A / B ratio = 2 ii) 0.125% of A and 0.25% of B is ratio A / B = 0.5 iii) 0.25% of A and 0.25% of B is ratio A / B = 1

Pseudomonas aeruginosa

Concentrations 0A 0.0625 A 0.125 A 0.25 A 0.5 A1A tested (in% wt.) "ΔB 49 82 Ï6 67 ^ 4 0.0625 B 45 86 Ï8 92 8727 0.125 B 39 89 82 95 7816 0.25 B 39 16 14 10 02Ô (FIC 0.25) (FIC 0.5) (FIC 1) (FIC 2) 0.5 B Ô 0 0 0 065 H Ô Ô Ô Ô Ô Ô4 CMI of A single CMI of B only CMI of each compound FIC Ratio A / B in % by% by mixtureIndex A% B% 1 C / 5 C / 5 C / 25 ï 25

The results obtained show a synergy of the inhibitory activity for the mixtures: i) 0.0625% of A and 0.25% of B, ie A / B ratio = 0.25 ii) 0.125% of A and 0.25% of B A / B ratio = 0.5 iii) 0.25% of A and 0.25% of B is ratio A / B = 1 iv) 0.5% of A and 0.25% of B is ratio A / B = 2

Candida Albicans

OA concentrations 0.025 A 0.05 A0.1 A tested (in% wt.) "ΔB 2916 0.0625 B 44 26 178 (FIC 0.75) 0.125 B 22" 10 5i (FIC 0.75) (FIC 1) 0.25 B 2

MIC of A single MIC of B only MIC of each FIC Ratio A / B in% in% compound in mixture Index A% B% Ô 0 0 25 0 ^ 05 0.125 ÔJ5C ^ 2

The results obtained show a synergy of the inhibitory activity for the mixtures: i) 0.05% of A and 0.0625% of B, ie A / B ratio = 0.8 ii) 0.05% of A and 0.125% of B the ratio A / B = 0.4 iii) 0.025% of A and 0.125% of B, ie ratio A / B = 0.2

Example 2: Determination of the antimicrobial activity of the antimicrobial mixture The antimicrobial efficacy of the 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one + 2-phenoxyethanol antimicrobial mixture (respective weight ratio of 0.1) was evaluated by the Challenge Test method.

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 revivable microorganisms seven days after inoculation.

In order to demonstrate the effect of the antimicrobial mixture, the antimicrobial activity of a cosmetic formulation containing 0.05% 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and 0.5% of 2- phenoxyethanol was compared with the same formula alone (control), after inoculation of about 106 CFU (Colony forming units) / gram of cosmetic formula.

Cosmetic formula

An oil-in-water facial care emulsion having the following composition (percentages by weight) was prepared:

Sorbitan tristearate (Croda SPAN 65 V) 0.9% Mono / distearate (36/64) mixture of glyceryl / potassium stearate (Tegin Pellets from Goldschmidt) 3%

Polyethylene glycol stearate (40 ethylene oxide units) 2% 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one 0.05% 2-Phenoxyethanol 0.5%

Propane-1,3-diol 2% Blend of mineral oil, microcrystalline wax and paraffin (VASELINE WHITE CODEX 236 from Aiglon) 4%

Shea butter liquid fraction (Shea Olein from Olvea) 1%

Cyclopentadimethylsiloxane 5%

Cetyl alcohol 4%

Apricot kernel oil 0.3%

Hydrogenated Polyisobutene (PARLEAM from NOF Corporation) 7.2%

Myristyl myristyl 2%

Stearic acid 1.2%

Caffeine 0.1%

Citric acid 0.2%

Glycerin 3%

Sodium hydroxide 0.05%

Water qs 100%

Control Formula A: Formula similar to the previous one containing 0.05% 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and without 2-phenoxyethanol (0.5% compensated by water).

Control Formula B: Similar Formula Containing 0.5% 2-Phenoxyethanol and Without 4- (3-Ethoxy-4-hydroxyphenyl) butan-2-one (0.05% Offset with Water)

Cultures of microorganisms 5 pure cultures of microorganisms were used.

GERMS Transplantation medium T ° ATCC

Escherichia coli (Ec) Trypto-casein soy 35 ° C8739

Enterococcus faecalis (Ef) Soy Trypto-casein 35 ° C33186

Pseudomonas aeruginosa (Pa) Trypto-casein soy 35 ° C19429

Candida albicans (Ca) Sabouraud 35 ° C10231

Aspergillus niger (Year) Malt 35 ° C6275 ATCC = American Type Culture Collection

Strains of bacteria Gram - (Escherichia coli and Pseudomonas aeruginosa), Gram + bacterium (Enterococcus faecalis), yeast (Candida albicans), and mold (Aspergillus niger) are inoculated in transplanting medium, respectively the day before the 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 at the spectrophotometer a suspension of optical density of between 35% and 45% of light transmitted at 544 nm. ; for mildew, the spores are removed by washing the agar with 6-7 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 1x108 and 3 × 10 8 CFU per ml) are introduced into each pillbox and the microbial suspension is perfectly homogenized by means of a spatula. 20 g of product (= cosmetic formula).

The level of microorganisms present in the product corresponds, after homogenization, to a concentration of 106 seeds per gram of product, ie inoculation at 1% of an inoculum with 108 seeds 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.

Claims (3)

An antimicrobial mixture comprising 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a phenoxy alcohol of the formula C q H q -O-R-OH wherein R denotes a divalent hydrocarbon radical having 2 or 3 carbon atoms. 2. Mixture according to the preceding claim, characterized in that said phenoxyalcohol is chosen from 2-phenoxyethanol or 1-phenoxy-2-propanol. 3. antimicrobial mixture according to one of the preceding claims, characterized in that said phenoxyalcohol is 2-phenoxyethanol. 4. Mixture according to one of the preceding claims, characterized in that it comprises 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and phenoxyalcohol in amounts such that the weight ratio 4- (3- ethoxy-4-hydroxyphenyl) butan-2-one / 2-phenoxyalcohol ranges from 0.15 to 3.5, preferably ranges from 0.15 to 3.2, and more preferably ranges from 0.2 to 3.2. 5. antimicrobial mixture according to one of the preceding claims, characterized in that it has an antimicrobial activity on molds, including Aspergillus niger, on yeasts, in particular on Candida albicans, on Gram + bacteria, including Enterococcus faecalis, Staphylococcus aureus, and Gram - bacteria, including Pseudomonas aeruginosa. 6. antimicrobial mixture according to one of claims 1 to 3, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.3 to 3, 2, preferably ranging from 0.3 to 2.4, preferably ranging from 0.3 to 1.4 and more preferably ranging from 0.3 to 1.2. 7. antimicrobial mixture according to the preceding claim, characterized in that it has an antimicrobial activity on the bacterium Gram + Staphylococcus aureus. 8. antimicrobial mixture according to one of claims 1 to 3, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.4 to 0, 8, preferably ranging from 0.45 to 0.7, and more preferably ranging from 0.45 to 0.6. 9. An antimicrobial mixture according to the preceding claim, characterized in that it has an antimicrobial activity on the bacterium Gram + Enterococcus faecalis. 10. antimicrobial mixture according to one of claims 1 to 3, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.15 to 1, 3, preferably ranging from 0.15 to 0.7, and more preferably ranging from 0.25 to 0.5. 11. Antimicrobial mixture according to the preceding claim, characterized in that it has an antimicrobial activity on yeast Candida Albicans. 12. antimicrobial mixture according to one of claims 1 to 3, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.6 to 1, 6, preferably ranging from 0.7 to 1.4, preferably ranging from 0.8 to 1.2 and more preferably ranging from 0.9 to 1.1. 13. Antimicrobial mixture according to the preceding claim, characterized in that it has an antimicrobial activity on the mold Aspergillus niger. 14. antimicrobial mixture according to one of claims 1 to 3, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / phenoxyalcohol ranging from 0.2 to 3, 2, preferably from 0.4 to 3.2, preferably from 0.8 to 3.2, preferably from 1.6 to 3.2, preferably from 0.2 to 2.4, preferably ranging from 0.4 to 2.4, preferably ranging from 0.8 to 2.4 and more preferably ranging from 1.6 to 2.4. 15. An antimicrobial mixture according to the preceding claim, characterized in that it has an antimicrobial activity on the bacterium Gram - Pseudomonas aeruginosa. 16. Composition comprising, in a physiologically acceptable medium, an antimicrobial mixture according to one of claims 1 to 15. 17. Composition according to the preceding claim, characterized in that it comprises at least one additional ingredient selected from water, oils, polyols having 2 to 10 carbon atoms, gelling agents, surfactants, film-forming polymers, dyestuffs, perfumes, fillers, UV filters, plant extracts, cosmetic and dermatological active agents, and salts. 18. Composition according to one of claims 16 or 17, characterized in that the 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one is present in a content ranging from 0.01% to 5% by weight , relative to the total weight of the composition, preferably ranging from 0.01% to 3% by weight, preferably ranging from 0.01 to 2.5% by weight, and more preferably ranging from 0.01 to 2% by weight. weight. 19. A method of non-therapeutic cosmetic treatment of care and / or makeup and / or cleaning of keratin materials comprising the application on said keratin materials of a composition according to any one of claims 16 to 18. 20. Process of conservation of a composition comprising a physiologically acceptable medium, in particular a cosmetic or dermatological composition, characterized in that it consists in incorporating into said composition an antimicrobial mixture as defined in one of claims 1 to 18. SEARCH REPORT Articles L.612-14, L.612-53 to 69 of the Intellectual Property Code OBJECT OF THE RESEARCH REPORT INPI appendix to each patent a "RESEARCH REPORT" citing the elements of the state of the art that may be taken into account to assess the patentability of the invention, within the meaning of Articles L. 611-11 (novelty) and L. 611-14 (inventive step) of the intellectual property code. This report deals with the claims of the patent which define the object of the invention and delimit the scope of protection. After delivery, ΙΊ.Ν.Ρ.Ι. may, at the request of any interested person, make a "DOCUMENTARY ADVICE" on the basis of the documents cited in this search report and any other document that the applicant wishes to be taken into consideration. CONDITIONS FOR ESTABLISHING THIS RESEARCH REPORT [x] The applicant submitted comments in response to the preliminary search report. [x] The plaintiff maintained the claims. □ The applicant amended the claims. □ The applicant amended the description to remove items that were no longer consistent with the new claims. □ Third parties submitted comments after publication of the preliminary search report. □ A complementary preliminary research report has been prepared. DOCUMENTS CITED IN THIS RESEARCH REPORT The distribution of documents between headings 1, 2 and 3 takes into account, where appropriate, the claims filed last and / or the observations submitted. [x] The documents listed in section 1 below may be taken into consideration in assessing the patentability of the invention. □ The documents listed in Section 2 below illustrate the general background technology. □ The documents listed in section 3 below were cited during the procedure, but their relevance depends on the validity of the claimed priorities. □ No documents were cited during the procedure. 1/2 National registration number: FR1757741 Publication no .: FR3070107 ΪΓ SELECTED TECHNICAL INFORMATION CONSIDERATIONS IN ORDER TO CONSIDER THE PATENTABILITY OF INVENTION _______ | US 2016/143825 A1 (PESARO MANUAL [DE] AND AL) May 26, 2016 (2016-05-26) | US 2009/004120 A1 (NATSCH ANDREAS [CH]) January 1, 2009 (2009-01-01) | WO 2011/039445 A1 (OREAL [EN]; DALKO MARIA [Search this site] FR]) April 7, 2011 (2011-04-07) GENERAL TECHNOLOGY Ineant 3. ELEMENTS OF THE STATE OF THE TECHNIQUE WHERE THE RELEVANCE DEPENDS ON THE VALIDITY OF PRIORITIES Ineant 2/2