FR3070110B1 - ANTIMICROBIAL MIXTURE CONTAINING 4- (3-ETHOXY-4-HYDROXYPHENYL) BUTAN-2-ONE AND A CRESOL COMPOUND, AND COSMETIC COMPOSITION CONTAINING THE SAME - Google Patents

Abstract

The invention relates to an antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a cresol compound, such as 4-isopropyl-3-methylphenol, and a cosmetic composition containing such a mixture. Application to the care, makeup and cleansing of keratin materials.

Description

The subject of the present invention is an antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a cresol compound, as well as 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 cresol compound, in particular 4-isopropyl-3-methylphenol, makes it possible to obtain an antimicrobial mixture having a synergy of antimicrobial activity, in particular on Gram + bacteria, in particular on Enterococcus faecalis, 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%.

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 particular cresol compound such as as defined below. 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. I a 4-t3-Âthn ¥ v-4-hvrirn ¥ vnhânvnhi itan-2-nna a mnnnsé dp fnrmiilp

The cresol compound used according to the invention is a compound of formula (I):

wherein R1 denotes H or an isopropyl radical.

The compound of formula (I) may be chosen from 3-methylphenol (CAS No. 108-39-4), 2-methylphenol (CAS No. 95-48-7), 4-methylphenol (CAS No. 106-44-5), 4-isopropyl-3-methylphenol (CAS No. 3228-02-2). Preferably the compound of formula (I) is 4-isopropyl-3-methylphenol.

Advantageously, 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the cresol compound of formula (I) are present in said mixture in a content such that the weight ratio 4- (3-ethoxy-4- hydroxyphenyl) butan-2-one / compound (I) is from 0.5 to 15, preferably from 1 to 15, and more preferably from 1 to 12.

Preferably, the antimicrobial mixture according to the invention contains 4-isopropyl-3-methylphenol.

The antimicrobial mixture may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / cresol compound (I) (in particular 4-isopropyl-3-methylphenol) ranging from 2 to 15, preferably ranging from from 2.2 to 15, and more preferably from 2.2 to 12. Such a mixture has a good antimicrobial activity on the bacterium Gram + Enterococcus faecalis

The antimicrobial mixture may have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / cresol compound (I) (in particular 4-isopropyl-3-methylphenol), ranging from 0.5 to 15, preferably ranging from 1 to 15, preferably from 1 to 12, and more preferably from 2 to 8. 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 the cresol compound of formula (I).

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 preparing a composition, in particular a cosmetic or dermatological composition, comprising a step of mixing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the cresol compound (I). and 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 4-isopropyl-3-methylphenol (referred to as Substance B ) is performed by calculating 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 Enterococcus faecalis and Candida albicans.

The microbial strain Enteroccoccus faecalis ATCC 33186 was used and a double concentration broth BHI (Brain Heart Infusion) 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 for the above-mentioned strains is 18 to 24 hours aerobically for Candida albicans. from 24 to 48 hours aerobically for Enteroccoccus faecalis.

testing

For each compound: A = 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one compound B = 4-isopropyl-3-methylphenol 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 Candida albicans strain and 50 μl of 1% aqueous agar solution are also added thereto.

Trials 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. 100 μl of Sabouraud liquid nutrient broth inoculated at double concentration with the Candida albicans strain are also added. 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 solution of agar with 100 μl of Sabouraud liquid nutritional broth inoculated at a double concentration with the Candida albicans 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 Candida albicans strain present in the final volume of the wells (200 μL) and is between 2 and 6.105 CFU / mL in Candida albicans.

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 strain Enteroccoccus faecalis.

The following results were obtained:

Candida Albicans

The results obtained show a synergy of the inhibitory activity for the mixtures: i) 0.125% of A and 0.05% of B, ie ratio A / B = 1.25 ii) 0.25% of A and 0.05% of B or ratio A / B = 2.5 iii) 0.5% of A and 0.05% of B, ie ratio A / B = 5

Claims (3)

An antimicrobial mixture comprising 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a cresol compound of formula (I): (I) wherein R1 denotes H or an isopropyl radical. 2. Mixture according to the preceding claim wherein the cresol compound of formula (I) is chosen from 2-methylphenol, 3-methylphenol, 4-methylphenol, 4-isopropyl-3-methylphenol. 3. Mixture according to one of the preceding claims wherein the cresol compound of formula (I) is 4-isopropyl-3-methylphenol. 4. Mixture according to one of the preceding claims, characterized in that it comprises 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the cresol compound (I) in amounts such that the weight ratio 4 - (3-ethoxy-4-hydroxyphenyl) butan-2-one / cresol compound (I) is from 0.5 to 15, preferably from 1 to 15, and more preferably from 1 to 12. 5. Antimicrobial mixture according to the invention one of the preceding claims, characterized in that it has an antimicrobial activity on yeasts, in particular on Candida albicans, and on Gram + bacteria, in particular on Enteroccoccus faecalis. 6. antimicrobial mixture according to claims 1 to 4, characterized in that it has an antimicrobial activity on yeast Candida Albicans. 7. The antimicrobial mixture according to claims 1 to 3, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / cresol compound (I) ranging from 2 to 15, preferably ranging from 2.2 to 15, and more preferably ranging from 2.2 to 12. 8. Antimicrobial mixture according to the preceding claim, characterized in that it has an antimicrobial activity on the bacterium Gram + Enteroccoccus faecalis. 9. Composition comprising, in a physiologically acceptable medium, an antimicrobial mixture according to one of claims 1 to 8. 10. 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. 11. Composition according to one of Claims 9 or 10, characterized in that 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. 12. 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 9 to 11. 13. 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 8. The 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, ΓΙ.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 No: FR1757743 Publication No .: FR3070110 ΪΓ SELECTED TELECENT ELEMENTS BEFORE INJURY IN | ________ CONSIDERATION IN APPRAISING THE PATENTABILITY OF THE INVENTION _______ | US 2004/059005 A1 (WHITE MICHAEL JOHN ROBERT [NL ] AND AL) March 25, 2004 (2004-03-25) | WO 2011/039445 A1 (OREAL [EN]; DALKO MARI A [FR]) April 7, 2011 (2011 -04-07) 2. ELEMENTS OF THE STATE OF THE ART ILLUSTRATING THE GENERAL TECHNICAL BACKGROUND Ineant 3. ELEMENTS OF THE STATE OF THE TECHNIQUE WHERE THE RELEVANCE DEPENDS __________________________ ON THE VALIDITY OF PRIORITIES ___________________ Ineant 2/2