FR3070109B1 - ANTIMICROBIAL MIXTURE CONTAINING 4- (3-ETHOXY-4-HYDROXYPHENYL) BUTAN-2-ONE AND A SALT OF ALKYLDIMETHYLBENZYLAMMONIUM, AND COSMETIC COMPOSITION CONTAINING SAME - Google Patents

Abstract

An antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and an alkyl dimethyl benzyl ammonium salt 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 an alkyldimethylbenzylammonium salt, 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 WO 2011/039445 . 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 preservatives with good antimicrobial efficacy.

The inventors have unexpectedly discovered that the combination of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one with an alkyldimethylbenzylammonium salt as defined below, in particular alkyldimethylbenzylammonium, provides an antimicrobial mixture with a synergistic antimicrobial activity, particularly on molds, especially Aspergillus niger. 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 an alkyldimethylbenzylammonium salt. of formula (I): C6H5-CH2-N + (CH3) 2R X '(I) wherein R denotes an alkyl radical having 8 to 18 carbon atoms, X- denotes a halide anion such as chloride, bromide. The subject of the invention is also a composition, in particular a cosmetic 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 formula

For the alkyldimethylbenzylammonium salt of formula (I) described above, preferably R is an alkyl group comprising from 10 to 16 carbon atoms, and preferably from 12 to 14 carbon atoms.

Preferably, X- is a chloride anion.

Preferably, alkyldimethylbenzylammonium chloride (INCI name: benzal-konium chloride) is used.

Advantageously, the alkyldimethylbenzylammonium salt is a mixture of lauryldimethylbenzyl ammonium chloride (compound la; R = C12 alkyl) and myristyldimethylbenzylammonium chloride (compound Ib, R = C14 alkyl).

A mixture chosen from: a) a mixture comprising from 60 to 80% of compound Ia and from 20 to 40% of compound Ib b) A mixture comprising from 65 to 75% of compound Ia and from 25 to 35% of compound is preferably used Ib c) A mixture comprising 68 to 72% of compound Ia and 28 to 32% of compound Ib. D) A mixture comprising 70% of compound Ia and 30% of compound Ib.

The percentages indicated are molar percentages with respect to all the moles of said mixture.

Advantageously, the 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the alkyldimethyl-benzylammonium salt (I) are present in said mixture in contents such that the weight ratio 4- (3-ethoxy- 4-hydroxyphenyl) butan-2-one / salt (I) (preferably alkyldimethylbenzylammonium chloride) is from 5 to 120, preferably from 5 to 100, and preferably from 5 to 85, and more preferably from 30 to at 85, in particular, is from 35 to 85.

The antimicrobial mixture according to the invention has a synergy of antimicrobial activity, in particular on molds, in particular on Aspergillus niger.

Preferably, the antimicrobial mixture according to the invention contains alkyldimethylbenzylammonium chloride.

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 alkyldimethylbenzylammonium salt (I) described above.

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 glycerine, 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 may be in the form of oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: Ε / Η / Ε or Η / Ε / emulsion) emulsions. Η), 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 the alkyl dimethyl benzyl ammonium salt described. previously, and one or more additional ingredients, especially cosmetic or dermatological, such as those described above. The invention is further illustrated 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 (termed substance A) and alkyl chloride (C-2-C- 4) dimethylbenzylammonium (called substance B) is achieved by calculating the synergistic index (or FIC index).

Formula__________________________________________________ | FIC Index = (CMIa with B / CMIa) + (CMIb with A / CMb)

With: CMIa with B: minimum concentration of product A in the association A + B to obtain an inhibitory effect CMIb with A: minimum concentration of product B in the association A + B to obtain the inhibitory effect. CMIa: minimal inhibitory concentration of product A alone. MICb: minimal 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%.

Regarding the associations tested, CMIa with b and CMIb with a are the respective concentrations of A and B in the combinations allowing to obtain a percentage of microbial growth 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 Aspergillus niger strain.

The microbial strain Aspergillus niger ATCC 6275 was used, and Sabouraud broth liquid culture medium supplemented with polyoxyethylenesorbitan (20 EO) monopalmitate (Tween 40 from Croda) and Phytagel® BioReagent, at double concentration.

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

The incubation time of the microplate is 24 to 48 hours aerobically for Aspergillus niger.

testing

For each compound: A = 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one compound B = (C₁-C₂-C₁4) alkyl dimethylbenzylammonium chloride = mixture of 70% by mole of benzyldimethyldodecylammonium chloride and 30% by mole of benzyldi-methyltetradecylammonium chloride chloride (sold under the name Benzalkonium chloride product No. 12060 by Sigma-Aldrich)

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 made with the 1% o agar solution. Tests of compounds A and B alone 50 μl of each of the daughter solutions obtained containing compound A or B is added to the wells of the microplate. 100 μl of Sabouraud liquid nutrient broth inoculated with the Aspergillus niger strain and 50 μl of aqueous 1% agar solution are also added. • Tests of compounds A and B in 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 100μΙ of liquid nutrient broth Sabouraud seeded double concentration by the strain Aspergillus niger. Microbial growth control

A positive control of microbial growth has also been realized. The positive microbial growth control corresponds to the mixture of 100 μΙ of a 1% aqueous solution of agar with 10ΟμΙ of Sabouraud liquid nutrient broth inoculated at double concentration by the Aspergillus niger strain in the absence of the compounds A and B. absorbance of compounds A and B alone

In parallel, an absorbance control of compounds A and B alone was carried out. This control corresponds to 10ΟμΙ of liquid Sabouraud liquid nutrient broth at double concentration + 10ΟμΙ 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 620 nm wavelength.

The following results were obtained:

Asoeraillus niaer

The results obtained show a synergy of the inhibitory activity for the mixtures: i) 0.05% of A and 0.005% of B, ie A / B ratio = 10 ii) 0.1% of A and 0.005% of B is ratio A / B = 20 iii) 0.1% of A and 0.0025% of B is ratio A / B = 40 iv) 0.2% of A and 0.005% of B is ratio A / B = 40 v) 0 , 2% of A and 0.0025% of B is ratio A / B = 80

Claims (3)

An antimicrobial mixture comprising 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and an alkyldimethylbenzylammonium salt of formula (I): C6H5-CH2-N + (CH3) 2R X '(I) in which R denotes an alkyl radical having from 8 to 18 carbon atoms, X "denotes a halide anion such as chloride, bromide. 2. Mixture according to the preceding claim, characterized in that for the alkyldimethylbenzylammonium salt of formula (I), R is an alkyl group comprising from 10 to 16 carbon atoms, preferably from 12 to 14 carbon atoms. 3. antimicrobial mixture according to one of the preceding claims, characterized in that the alkyldimethylbenzylammonium salt (I) is alkyldimethylbenzylammonium chloride. 4. Antimicrobial mixture according to one of the preceding claims, characterized in that the alkyldimethylbenzylammonium salt (I) is a mixture of lauryldimethylbenzyl ammonium chloride and myristyldimethylbenzylammonium chloride. 5. Mixture according to the preceding claim, characterized in that the alkyldimethylbenzylammonium salt (I) is chosen from the following mixtures: a) A mixture comprising from 60 to 80 mol% lauryldimethylbenzyl ammonium chloride and 20 to 40% by weight. mole of myristyldimethylbenzylammonium chloride b) A mixture comprising from 65 to 75 mol% lauryldimethylbenzyl ammonium chloride and 25 to 35 mol% myristyldimethylbenzylammonium chloride c) a mixture comprising from 68 to 72 mol% lauryldimethylbenzyl ammonium chloride and 28 to 32 mol% of myristyldimethylbenzylammonium chloride d) A mixture comprising 70 mol% of lauryldimethylbenzyl ammonium chloride and 30 mol% of myristyldimethylbenzylammonium chloride 6. Mixture according to one of the preceding claims, characterized in that it comprises 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the alkyldimethylbenzylammonium salt of formula (I) in amounts such that the weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / salt (I) ranges from 5 to 120, preferably ranges from 5 to 100, and preferably ranges from 5 to 85, and more preferentially goes from from 30 to 85. 7. antimicrobial mixture according to one of the preceding claims, characterized in that it has an antimicrobial activity on the mold Aspergillus niger. 8. Composition comprising, in a physiologically acceptable medium, an antimicrobial mixture according to one of claims 1 to 7. 9. 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. 10. Composition according to one of claims 8 or 9, 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, and preferably ranging from 0.01 to 2.5% by weight. 11. 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 8 to 10. 12. 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 according to one of claims 1 to 7. 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