FR3149207A1 - Cosmetic composition comprising an endolysin and a compound of formula (I) - Google Patents

Abstract

Cosmetic composition comprising an endolysin and a compound of formula (I) The present invention relates to a composition, in particular a cosmetic composition, comprising, in a physiologically acceptable medium, at least one endolysin, in particular an endolysin derived from a Staphylococcus aureus phage and at least one compound of formula (I). It also relates to the use of such a composition for preventing and/or treating a skin disorder linked to colonization by Staphylococcus aureus in an individual in need thereof, in particular for preventing and/or treating acne and/or eczema in the individual, and a non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising at least one step of topical application to said keratin materials of such a composition. Figure for abstract: None

Description

Cosmetic composition comprising an endolysin and a compound of formula (I)

The present invention relates to a composition, in particular a cosmetic composition, comprising, in a physiologically acceptable medium, at least one endolysin, in particular an endolysin derived from a Staphylococcus aureus phage and at least one compound of formula (I).

It also relates in particular to the implementation of a composition of the invention for preventing and/or treating a skin disorder linked to colonization by Staphylococcus aureus in an individual in need thereof, and in particular for preventing and/or treating acne and/or eczema in an individual in need thereof.

Finally, it relates to a non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition according to the invention.

Human skin is permanently populated by a multitude of different microorganisms (bacteria, yeasts and fungi). The resident microbial flora, essential for good skin health, is mainly composed of propionibacteria ( Cutibacterium acnes ) , staphylococci ( Staphylococcus epidermis and Staphylococcus hominis ), corynebacteria, and streptococci, as well as a fungal flora mainly composed of Malassezia .

Some dermatological disorders are most often due to the disruption of the ecological balance of the resident flora following a preponderant colonization of opportunistic microorganisms not beneficial for the skin such as Staphylococcus aureus known to be associated with atopic dermatitis (eczema), oily or hyperseborrheic skin, and acne.

To rebalance this excess colonization by these opportunistic microorganisms that are not beneficial for the skin, it is common to use broad-spectrum antimicrobials or bacteriostatics. However, the use of these compounds poses the problem of non-specificity of action targeting indifferently the undesirable opportunistic flora and the resident beneficial flora, and the problem of the risk of the appearance of bacterial resistance or imbalances by selecting resistant bacteria, as well as problems of skin tolerance (irritations, allergies, etc.).

There remains a need to find new compounds with good antimicrobial efficacy without the above-described drawbacks, and good skin tolerance.

It has thus been demonstrated that endolysins from Staphylococcus aureus phages (i.e. phages infecting Staphylococcus aureus ) make it possible to specifically target S. aureus and to lyse, and therefore specifically destroy, this bacterium while preserving the resident skin flora (WO2012/150858). However, it is well known that one of the main obstacles to the application of endolysins targeting Staphylococcus species is a problem of stability of these proteins and/or their enzymatic activity, in particular the maintenance of this activity over time.

In fact, a significant alteration of the lytic action of these enzymes has been observed through interactions with raw materials, particularly when endolysin is introduced into formulations, particularly cosmetic ones.

There is therefore a need for raw materials that can be used in compositions, particularly cosmetic compositions, without degrading the antimicrobial activity of the endolysins also present in these compositions.

There is also a need for raw materials which can be used in compositions, in particular cosmetic compositions, without degrading (i) the antimicrobial activity of the endolysins also present in these compositions and (ii) the specificity of these ensolysins for the targeted bacteria, in particular in the present invention Staphylococcus aureus .

There is also a need for raw materials that can be used in compositions, particularly cosmetic ones:
- without degrading the antimicrobial activity of the endolysins used;
- while retaining the specificity of these endolysins for the targeted bacteria, in particular in the present invention Staphylococcus aureus ; and
- while also allowing for good sensoriality of the composition.

The present invention aims to solve at least one aforementioned technical problem.

Indeed, the inventors have now discovered that the compounds of formula (I) prove capable, in particular compared to other compounds outside the invention, of allowing the maintenance of good performance of destruction of Staphylococcus aureus by the associated endolysin, even six months after the preparation of the composition.

As mentioned above, the present invention thus relates to a composition, in particular a cosmetic composition, comprising, in a physiologically acceptable medium:
(i) at least one endolysin, in particular an endolysin derived from a Staphylococcus aureus phage; and
(ii) at least one compound of formula (I), one of its acid or base salts, organic or inorganic, one of its optical isomers, or one of its solvates:

[Chem 1]

R ₁ -C(O)-N(H)-CH(R ₂ )-C(O)-OR ₃ (I)
in which:
- R ₁ represents a (C ₆ -C ₂₀ )alkyl group;
- R ₂ represents a hydrogen atom or a (C ₁ -C ₆ )alkyl group optionally substituted by a guanidine group optionally substituted by one or more (C ₁ -C ₄ )alkyl groups; and
- R ₃ represents a hydrogen atom or a (C ₁ -C ₆ )alkyl group.

As illustrated in the examples below, the Applicant has surprisingly discovered that a composition according to the invention, comprising an endolysin, in particular derived from a Staphylococcus aureus phage and at least one compound of formula (I), advantageously makes it possible to maintain the S. aureus destruction performance of the endolysin, even after six months.

Thus, the present invention also relates to the implementation of a composition of the invention for preventing and/or treating a skin disorder linked to colonization by Staphylococcus aureus in an individual in need thereof, and in particular for preventing and/or treating acne and/or eczema in an individual in need thereof.

It further relates to a non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition according to the invention.

Detailed description

By " cosmetic " is meant a composition compatible with keratin materials, in particular the skin, mucous membranes and appendages. The composition according to the invention is non-therapeutic.

By " keratin materials " we mean in particular the skin, mucous membranes, fibres, eyelashes and appendages.

By " skin " is meant all of the skin of the body, and preferably the skin of the face, scalp, décolleté, neck, arms and forearms, eyelids, around the mouth or behind the ears, the crook of the elbow, the back of the knees, hands, wrists and ankles, or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, chin), décolleté and neck.

A composition according to the invention comprises a physiologically acceptable medium, i.e. which has a pleasant color, odor and feel and does not generate unacceptable discomfort, i.e. tingling, tightness, redness, likely to dissuade the user from applying this composition. Of course, a person skilled in the art will take care to choose a physiologically acceptable medium in such a way that the advantageous properties of the endolysin(s) of the invention are not, or are not substantially, altered. Thus, by way of illustration, a physiologically acceptable medium may mainly consist of water and/or one or more organic solvent(s) miscible in water. A physiologically acceptable medium according to the invention preferably has a pH of between 4 and 8, more particularly between 4.5 and 7.5. Thus, a composition according to the invention may comprise one or more pH adjuster(s), such as for example arginine. According to a preferred embodiment, a composition according to the invention comprises at least one pH adjuster, in particular a pH adjuster, and in particular arginine.

As used herein, the terms " treat " and " treatment " are intended to mean the alleviation of symptoms associated with a specific disorder or condition and/or the elimination of such symptoms and the complete disappearance of the disorder or condition in question.

In the context of the present invention, the terms " prevent " and " prevention " mean reducing to a lesser degree the risk or probability of occurrence of a given phenomenon.

Endolysin

A composition, in particular a cosmetic composition, according to the invention is firstly characterized in that it comprises at least one endolysin.

In the embodiments described herein, the endolysin may be a native bacteriophage endolysin or a recombinant endolysin and may be any endolysin known to those skilled in the art. Herein, the terms bacteriophage lysin, bacteriophage endolysin, and endolysin are used interchangeably. An endolysin may be selected from the group of endolysins defined in WO2011/023702, WO2012/146738, WO2003/082184, WO2010/011960, WO2010/149795, WO2010/149792, WO2012/094004, WO2011/023702, WO2011/065854, WO2011/076432, WO2011/134998, WO2012/059545, WO2012/085259, WO2012146738, WO2018/091707, Exebacase™ (Lysin CF-301); SAL200™ or Tonabacase; Auresine™ (Sigma-Aldrich SAE0083), and Ectolysin™ P128.

In the embodiments presented herein, the endolysin is a Staphylococcus aureus -specific endolysin, i.e., it will effectively lyse Staphylococcus aureus but will not substantially lyse bacteria other than Staphylococcus aureus . In particular, an endolysin implemented according to the invention will lyse Staphylococcus aureus , but not Staphylococcus epidermidis .

Most native Staphylococcus bacteriophage endolysins with peptidoglycan hydrolase activity, such as Ply2638, consist of a C-terminal cell wall-binding domain (CBD), a central N-acetylmuramoyl-L-Alanine amidase domain, and an N-terminal alanyl-glycyl endopeptidase domain with cysteine, in the case of Ply2638, an N-terminal alanyl-glycine endopeptidase domain with peptidase_M23 homology, the latter three domains each exhibiting peptidoglycan hydrolase activity with distinct target binding specificity and generally referred to as enzymatically active domains.

The endolysin may be a recombinant endolysin, such as a recombinant Staphylococcus aureus -specific endolysin, in particular a recombinant chimeric Staphylococcus aureus -specific endolysin comprising one or more heterologous domains.

In general, endolysins consist of different subunits (domains), for example a cell wall binding domain (CBD) and one or more enzymatic domains with peptidoglycan activity, such as an amidase domain, an M23 domain and a CHAP (cysteine, histidine-dependent amidohydrolases/peptidases) domain. An example of a Staphylococcus aureus -specific chimeric endolysin comprising one or more heterologous domains is an endolysin comprising an amidase domain of bacteriophage Ply2638, an M23 domain of lysostaphin (S. simulans) and a cell wall binding domain of bacteriophage Ply2638.

This Staphylococcus aureus -specific chimeric endolysin is a preferred endolysin and is described in detail in WO2012/150858. Other preferred endolysins are described in detail in WO2013/169104. Other preferred endolysins are described in detail in WO2016/142445. Other preferred endolysins are widely described in WO2017/046021. Other preferred endolysins are widely described in WO2012/146738, WO2003/082184, WO2010/011960, WO2010/149795, WO2011/076432, WO2011/134998, WO2012/085259, WO2012146738 or WO2018/091707.

An endolysin implemented according to the invention may comprise a domain having at least 80% sequence identity with a domain described in WO2012/150858, WO2013/169104, WO2016/142445, WO2017/046021, WO2012/146738, WO2003/082184, WO2010/011960, WO2010/149795, WO2011/076432, WO2011/134998, WO2012/085259, WO2012146738 or WO2018/091707.

An implemented endolysin may have at least 80% sequence identity with an endolysin described in WO2012/150858, WO2013/169104, WO2016/142445, WO2017/046021, WO2012/146738, WO2003/082184, WO2010/011960, WO2010/149795, WO2011/076432, WO2011/134998, WO2012/085259, WO2012146738, WO2018/091707, such as the endolysin with the reference amino acid sequence SEQ ID NO: 29 in WO2012/150858.

In a particular embodiment, the endolysin is an endolysin derived from a Staphylococcus aureus phage .

For the purposes of the present invention, the term "endolysin derived from a Staphylococcus aureus phage" means a native or recombinant protein such as an enzyme or nucleic acid molecule encoding the latter derived from one or more bacteriophage(s) capable of lysing the wall of bacteria of the species Staphylococcus aureus .

The endolysin comprises in particular one or more domain(s) for binding to the bacterial wall of Staphylococcus aureus and/or one or more domain(s) for lysis of the bacterial wall of Staphylococcus aureus , said binding domain(s) and domain(s) for lysis of the bacterial wall of Staphylococcus aureus being derived from one or more distinct or identical bacteriophage(s) capable of lysing the wall of bacteria of the species Staphylococcus aureus .

The endolysin used in the context of the present invention may be in native or recombinant form, in particular in recombinant form.

According to a particular embodiment, the endolysin comprises a first protein sequence comprising a cell wall binding domain of species of the genus Staphylococcus.

In particular, the first protein sequence is derived from the endolysin of the bacteriophage Φ2638a of S. aureus .

For each of the amino acid or nucleic acid sequences of interest, reference sequences are described herein. The present disclosure also encompasses amino acid or nucleic acid sequences (e.g., enzyme amino acid sequences), having specific percentages of amino acid or nucleotide identity with a reference sequence.

For obvious reasons, throughout the present description, a specific nucleic acid sequence or a specific amino acid sequence that respects, respectively, the nucleotide or amino acid identity considered, must further lead to obtaining a protein (or enzyme) that exhibits the desired biological activity. As used herein, the "percent identity" between two nucleic acid sequences or between two amino acid sequences is determined by comparing the two optimally aligned sequences across a comparison window.

The part of the nucleotide or amino acid sequence in the comparison window may therefore include additions or deletions (e.g. "gaps") compared to the reference sequence (which does not include these additions or deletions) in order to obtain an optimal alignment between the two sequences.

The terms "sequence homology" or "sequence identity" or "homology" or "identity" are used interchangeably herein. For the purposes of the invention, this means that in order to determine the percentage of sequence homology or sequence identity of two amino acid sequences or two nucleic acid sequences, the sequences are aligned for the purpose of optimal comparison. In order to optimize the alignment between the two sequences, gaps may be introduced into any of the two sequences being compared. This alignment may be performed over the entire length of the sequences being compared. The alignment may also be performed over a shorter length, for example over twenty, fifty, hundred or more nucleic acids/bases or amino acids. The sequence identity is the percentage of identical matches between the two sequences over the stated aligned region.

Comparison of sequences and determination of the percent sequence identity between two sequences can be performed using a mathematical algorithm. The skilled artisan knows that several different computer programs are available for aligning two sequences and determining the identity between two sequences (Kruskal, J. B. (1983) An overview of sequence comparison In D. Sankoff and J. B. Kruskal, (ed.), Time warps, string edits and macromolecules: the theory and practice of sequence comparison, pp. 1-44 Addison Wesley).

The percentage of sequence identity between two amino acid sequences or between two nucleotide sequences can be determined using the Needleman and Wunsch algorithm for the alignment of two sequences. (Needleman, S. B. and Wunsch, C. D. (1970) J. Mol. Biol. 48, 443-453). The algorithm allows for the alignment of both amino acid sequences and nucleotide sequences. The Needleman-Wunsch algorithm has been implemented in the computer program NEEDLE.

For the purposes of the invention, the NEEDLE program of the EMBOSS software package was used (version 2.8.0 or higher, EMBOSS: The European Molecular Biology Open Software Suite (2000) Rice, P. LongdenJ. and Bleasby,A. Trends in Genetics 16, (6) pp276- 277, http://emboss.bioinformatics.nl/). For protein sequences, EBLOSUM62 is used for the substitution matrix. For nucleotide sequences, EDNAFULL is used. Optional parameters used are a gap opening penalty of 10 and a gap extension penalty of 0.5. No end gap penalty is added. In the Output section, Yes was indicated in response to the question "Brief identity and similarity" and "SRS pairwise" was indicated as the output alignment format.

After alignment by the NEEDLE program described above, the percent sequence identity between a query sequence and a sequence of the invention is calculated as follows: Number of matching positions in the alignment showing an identical amino acid or nucleotide in both sequences divided by the total length of the alignment after subtracting the total number of gaps in the alignment. The identity defined herein can be obtained from NEEDLE using the NOBRIEF option and is labeled in the program output as "longest identity".

The similarity of nucleotide and amino acid sequences, i.e. the percentage of sequence identity, can be determined by sequence alignments using several other known algorithms, preferably with the mathematical algorithm of Karlin and Altschul (Karlin & Altschul (1993) Proc. Natl. Acad. Sci. USA 90: 5873-5877), with hmmalign (HMMER package, http://hmmer.wustl.edu/) or with the CLUSTAL algorithm (Thompson, J. D., Higgins, D. G. & Gibson, T. J. (1994) Nucleic Acids Res. 22, 4673-80) available for example at https://www.ebi.ac.uk/Tools/msa/clustalo/ or the GAP program (University of Iowa mathematical algorithm) or the mathematical algorithm of Myers and Miller (1989 - Cabios 4: 11-17) or Clone Manager 9. The preferred settings used are the default settings as defined at https://www.ebi.ac.uk/Tools/msa/clustalo/.

The degree of sequence identity (sequence concordance) can be calculated using, for example, BLAST, BLAT or BlastZ (or BlastX). A similar algorithm is incorporated in the BLASTN and BLASTP programs of Altschul et al (1990) J. Mol. Biol. 215, 403-410. BLAST polynucleotide searches are performed with the BLASTN program, score = 100, word length = 12, in order to obtain polynucleotide sequences homologous to the nucleic acids that encode the protein of interest.

BLAST searches on proteins are performed with the program BLASTP, score = 50, word length = 3, to obtain amino acid sequences homologous to the SHC polypeptide. To obtain gapped alignments for comparison, Gapped BLAST is used as described in Altschul et al (1997) Nucleic Acids Res. 25, 3389-3402. When using the BLAST and Gapped BLAST programs, the default settings of the respective programs are used. Sequence correspondence analysis can be complemented by established homology mapping techniques such as Shuffle-LAGAN (Brudno M., Bioinformatics 2003b, 19 Suppl 1: 154-162) or Markov random fields. Where reference is made to sequence identity percentages in this application, such percentages are calculated relative to the total length of the longest sequence, unless otherwise indicated.

In particular embodiments, the percent identity between two sequences is determined using CLUSTAL O (version 1.2.4).

Thus, according to a particular embodiment, the first protein sequence comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 1 .

By at least 80% sequence identity between two sequences, it is meant that the first sequence may comprise 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the second sequence, whether amino acid sequences or nucleic acid sequences.

In particular, the first protein sequence consists of a reference amino acid sequence SEQ ID NO: 1 .

The protein sequences described herein may be encoded by one or more allelic variants.

An allelic variant refers to any of two or more alternative forms of a gene occupying the same chromosomal locus. A preferred nucleic acid variant is a nucleotide sequence that contains one or more silent mutations. Alternatively or in combination, a nucleic acid variant may also be obtained by the introduction of nucleotide substitutions, which do not give rise to another amino acid sequence of the polypeptide encoded by the nucleotide sequence, but which correspond to the codon usage of the host organism intended for the production of the polypeptide of the invention. In a preferred embodiment, a nucleic acid variant encodes a polypeptide still exhibiting its biological function. More preferably, a nucleotide sequence variant encodes a polypeptide exhibiting binding to the cell wall of species of the genus Staphylococcus and/or lytic activity. Even more preferably, a nucleic acid variant encodes a polypeptide exhibiting enhanced Staphylococcus species cell wall binding and/or lytic activity, as defined below. Nucleic acids encoding a polypeptide exhibiting Staphylococcus species cell wall binding and/or lytic activity may be isolated from any microorganism.

All these variants can be obtained using techniques known to those skilled in the art, such as library screening by hybridization (southern blotting procedures) under low to medium to high hybridization conditions. Low to medium to high stringency conditions mean prehybridization and hybridization at 42°C in 5X SSPE, 0.3% SDS, 200 pg/ml sheared and denatured salmon sperm DNA, and either 25%, 35% or 50% formamide for low to medium to high stringencies respectively. Then, the hybridization reaction is washed three times for 30 minutes using for each wash 2XSSC, 0.2% SDS and at 55°C, 65°C or 75°C for low to medium to high stringencies.

According to a particular embodiment, the first protein sequence is encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 2 .

In particular, the first protein sequence is encoded by a nucleic acid sequence consisting of a reference nucleic acid sequenceSEQ ID NO: 2.

Binding of a domain to the peptidoglycan cell wall of Staphylococcus genera can be assessed using assays well known to those skilled in the art. In a preferred embodiment, an immunohistochemical technique and/or a gene fusion technique resulting in labeled constructs of either domain are used to assess specific binding of peptides, polypeptides or proteins to the peptidoglycan cell wall of Staphylococcus genera. Methods for quantifying signals used in the above-mentioned immunohistochemical or fusion techniques are well known in the art.

In one embodiment, binding to the Staphylococcus cell wall of peptidoglycan can be quantified using a fluorescent fusion construct comprising a polypeptide comprising a domain comprised within a first protein sequence as previously described. Such a cell wall binding assay is described in detail by Loessner et al. (Molecular Microbiology 2002, 44(2):335-349). In this assay, a solution comprising said fluorescent fusion construct or a negative control, preferably green fluorescent protein (GFP), is subjected to Staphylococcus cells, preferably S. aureus cells, more preferably S. aureus BB255, for a specified period of time, after which the cells are pelleted by centrifugation together with the bound fluorescent fusion constructs. The fluorescent signal of Staphylococcus cells exposed to a fluorescent fusion construct, subtracted from the fluorescent signal of Staphylococcus cells exposed to a negative control, preferably GPF, is a measure of cell binding for the purposes of the present invention.

Examples of the evaluation of the binding of an endolysin to the cell wall of species of the genus Staphylococcus are illustrated in particular in WO 2012/150858 Al.

Preferably, in the context of the present text, a protein sequence will be said to comprise a peptidoglycan cell wall binding domain of the Staphylococcus genera when, using this assay, an increase in the fluorescent signal of the sedimented cells is detected. The binding is preferably said to be specific. Preferably, there is described an endolysin comprising a domain which exhibits a binding capacity, as defined herein, of at least 50, 60, 70, 80, 90 or 100, 150 or 200% of the peptidoglycan cell wall binding of the S. aureus bacteriophage endolysin Φ2638a (Ply2638) encoded by the reference nucleic acid sequence SEQ ID NO: 5 .

According to a particular embodiment, the cell wall binding activity of species of the genus Staphylococcus is measured by an immunohistochemical technique and/or a gene fusion technique, in particular fluorescent fusion, more particularly fusion with a green fluorescent protein.

According to a particular embodiment, the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence chosen from the group consisting of the reference amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4 .

According to a particular embodiment, the endolysin comprises a protein sequence encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 5 .

In particular, the protein sequence may be encoded by a nucleic acid sequence consisting of a reference nucleic acid sequenceSEQ ID NO: 5.

According to a particular embodiment, the endolysin may further comprise a heterologous protein sequence.

By "heterologous protein sequence" is meant a protein sequence, i.e., an amino acid sequence or a nucleic acid sequence encoding the protein sequence, that is not naturally found operably linked as a neighboring sequence to said first protein sequence. As used herein, the term "heterologous" may mean "recombinant." "Recombinant" refers to a genetic entity distinct from that generally found in nature. As applied to a nucleotide sequence or nucleic acid molecule, it means that said nucleotide sequence or nucleic acid molecule is the product of various combinations of cloning, restriction and/or ligation steps, and other procedures that result in the production of a construct that is distinct from a sequence or molecule found in nature.

Such protein or nucleic recombination methods are well known to those skilled in the art.

According to a particular embodiment, the endolysin comprises a heterologous protein sequence comprising a lytic domain. Preferably, said lytic domain has a peptidoglycan hydrolase activity.

A "peptidoglycan hydrolase activity", also defined herein as a "lytic activity", can be assessed by methods well known to those skilled in the art. In one embodiment, the lytic activity can be assessed spectrophotometrically by measuring the decrease in turbidity of cell suspensions of the substrate. Preferably, the lytic activity can be assessed spectrophotometrically by measuring the decrease in turbidity of a suspension of S. aureus , the turbidity being quantified by measuring the OD ₅₉₅ by spectrophotometry (Libra S22, Biochrom). More preferably, 200 nM of a polypeptide encoded by a nucleic acid molecule as identified herein is incubated with a suspension of S. aureus having an initial OD ₆₀₀ of 1 ± 0.05, as assessed by spectrophotometry (Libra S22, Biochrom), in PBS buffer pH 7.4, 120 mM sodium chloride for 30 min at 37 °C. The decrease in turbidity is calculated by subtracting the OD ₅₉₅ after 30 min of incubation from the OD ₅₉₅ before 30 min of incubation. In the context of the present text, a protein sequence will be said to comprise a lytic domain when using this assay, a decrease in turbidity of at least 10, 20, 30, 40, 50 or 60% is detected. Preferably, a decrease of at least 70% is detected. Preferably, there is provided an endolysin comprising a domain which exhibits a lytic activity of at least 50, 60, 70, 80, 90, 100, 150 or 200% or more of a lytic activity of the S. aureus bacteriophage endolysin Φ2638a (Ply2638) encoded by the reference nucleic acid sequence SEQ ID NO: 5 .

According to a particular embodiment, the lytic activity of endolysin is measured by spectrophotometry by measuring the decrease in turbidity of a suspension of S. aureus .

In one embodiment, the endolysin may not be encoded by an amino acid sequence comprising or consisting of an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4 .

In particular, the endolysin may not be encoded by a nucleic acid sequence comprising or consisting of the reference nucleic acid sequence SEQ ID NO: 5 , encoding the bacteriophage endolysin Φ2638 of S. aureus .

According to a particular embodiment, the heterologous protein sequence comprises a lytic domain, said lytic domain comprising a second and a third protein sequences, said second protein sequence comprising an M23 endopeptidase domain and said third protein sequence comprising an amidase domain.

An endopeptidase domain as used herein preferentially cleaves pentaglycine cross-bridges (Trayer, HR and Buckley, CE (1970) Molecular properties of lysostaphin, a bacteriolytic agent specific for Staphylococcus aureus. J Biol. Chem. 245, 4842-4846) found in the cell wall of Staphylococcus genera, preferably in the cell wall of S. aureus , S. simulans and S. carnosus .

An amidase domain as used herein preferentially hydrolyzes gamma-glutamyl-containing substrates.

The functionality and activity of these domains in a polypeptide can be confirmed by characterizing the cleavage products upon incubation of said polypeptides containing any of these domains with a purified peptidoglycan.

According to a particular embodiment, the endopeptidase and/or amidase activity of endolysin is measured by characterization of the cleavage products.

According to a particular embodiment, the endopeptidase and/or amidase activity of the endolysin can be measured by measuring the optical density of the bacteria in the presence of the endolysin. Such methods are notably described in Park et al. (Characterization of an endolysin, LysBPS13, from a Bacillus cereus bacteriophage, FEMS Microbiol Lett. 2012 Jul;332(1):76-83) and in Grishin et al. (A Simple Protocol for the Determination of Lysostaphin Enzymatic Activity, Antibiotics (Basel). 2020 Dec 17;9(12):917).

Preferably, each of the protein sequences and nucleotide sequences encoding the second or third domain is of bacterial or bacteriophage origin.

According to a particular embodiment, said second and third protein sequences are derived, independently of one another, from an enzyme selected from the group consisting of the endolysin of the bacteriophage Φ2638a of S. aureus and the lysostaphin of S. simulans . In particular, one of the second and third protein sequences is derived from the endolysin of the bacteriophage Φ2638a of S. aureus and the other sequence of the second and third protein sequences is derived from the lysostaphin of S. simulans .

According to a particular embodiment, said second protein sequence comprises at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 6 and said third protein sequence comprises at least 80%, in particular 90%, more particularly 95% sequence identity with the reference amino acid sequence SEQ ID NO: 8 .

According to a particular embodiment, said second protein sequence is encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 7 and said third protein sequence is encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 9 .

According to a particular embodiment, said second protein sequence is encoded by a nucleic acid sequence consisting of the reference nucleic acid sequence SEQ ID NO: 7 and said third protein sequence is encoded by a nucleic acid sequence consisting of the reference nucleic acid sequence SEQ ID NO: 9 .

According to a particular embodiment, the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence chosen from the group consisting of the reference amino acid sequences SEQ ID NO: 10 , and SEQ ID NO: 11 .

In particular, the endolysin may comprise a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 10 .

According to a particular embodiment, the endolysin comprises a protein sequence encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with a reference nucleic acid sequence SEQ ID NO: 12 .

In particular, the endolysin may comprise a protein sequence encoded by a nucleic acid sequence consisting of a reference nucleic acid sequence SEQ ID NO: 12 .

An endolysin comprising a protein sequence encoded by a reference nucleic acid sequence SEQ ID NO: 12 differs from S. aureus bacteriophage endolysin Φ2638a in that the N-terminal M23 endopeptidase domain is substituted by an M23 endopeptidase domain from S. simulans lysostaphin.

Endolysins suitable according to the invention can be obtained by any method known to those skilled in the art for producing recombinant proteins. In particular, endolysins according to the invention can be obtained by introducing one or more gene(s) of interest, such as the nucleic acid sequences described above, into the genome of a host organism via a vector.

In another aspect, there is provided a nucleic acid construct comprising at least one of the nucleic acid sequences as defined above. This nucleic acid construct may comprise a first nucleic acid sequence encoding a polypeptide comprising a cell wall binding domain, possibly further comprising a second and a third nucleic acid sequences as defined above.

Also disclosed is an expression vector comprising such a nucleic acid construct. Preferably, an expression vector comprises a nucleotide sequence as mentioned above, which is operably linked to one or more control sequences, which direct the production or expression of the encoded polypeptide in a cell, subject or cell-free expression system.

An expression vector may be considered a recombinant expression vector. This vector may consist of a plasmid, a cosmid, a bacteriophage or a virus which is transformed by the introduction of a nucleic acid molecule according to the invention. Such transformation vectors depending on the host organism to be transformed are well known to those skilled in the art and widely described in the literature.

Another object described in the present text is a method for the transformation of host organisms by the integration of at least one nucleic acid sequence as described, this transformation being able to be carried out by any suitable means known and widely described in the specialized literature, more particularly by the vector described above.

In another aspect, there is provided a cell, which comprises a nucleic acid construct or an expression vector as defined above. A cell may be any microbial, prokaryotic or eukaryotic cell, which is suitable for expression of an endolysin suitable according to the invention. In a preferred embodiment, said cell is an E. Coli cell. In an even more preferred embodiment, said cell is E. Coli CL1blue MRF.

The obtained endolysin can then be purified according to purification methods known in the art such as column chromatography, high performance liquid chromatography, etc.

In a particular embodiment, one or more of the protein sequences as defined in the text may comprise a sequence encoding a tag to facilitate purification of the resulting endolysin. Preferably, said tag is selected from, but is not limited to, a group consisting of a FLAG tag, a poly(His) tag, an HA tag and a Myc tag. More preferably, said tag is a 6xHis tag. Even more preferably, said tag is an N-terminal 6xHis tag identical to SEQ ID NO: 13 .

Endolysins and methods for obtaining them are described in particular in application WO 2012/150858 A1.

An endolysin, in particular an endolysin derived from a Staphylococcus aureus phage , suitable according to the invention may be present in the composition in freshly prepared form or in lyophilized form.

In this text, “freshly prepared” is preferably defined as storage for no more than 2 days after production at 1.63 mg/mL in lyophilization buffer (50 mM Tris, 500 mM sucrose, 200 mM mannitol, 0.05% polysorbate 20 + 50% glycerol) at -20°C followed by thawing immediately prior to evaluating lytic activity in an assay as identified herein.

By "lyophilized" we mean an endolysin that has been dehydrated by freeze-drying, which involves freezing the protein and then dehydrating it to remove the water.

After lyophilization, a lyophilized endolysin may undergo a subsequent reconstitution step by the addition of water. In one embodiment, lyophilization and reconstitution may be performed by dialysis against 3 changes of 300 ml lyophilization buffer (50 mM phosphate or Tris, 500 mM sucrose, 200 mM mannitol, pH 7.4) aliquot and freezing in the gas phase of liquid nitrogen. Lyophilization may be performed under standard conditions, preferably at -40 °C and under vacuum at 75 mTorr for 60 minutes, before increasing the temperature for 5 hours at -10 °C and further increasing for 60 minutes at -10 °C at the same vacuum levels. As a final step, the temperature is preferably increased to 25 °C for 10 hours. The samples are reconstituted by the addition of water.

A composition according to the invention may comprise a content of endolysin(s), in particular endolysin(s) derived from a Staphylococcus aureus phage , ranging from 0.0001% to 0.1% by weight relative to the total weight of the composition, in particular from 0.0005% to 0.01% by weight relative to the total weight of the composition, more particularly from 0.001% to 0.005% by weight relative to the total weight of the composition.

Compounds of formula (I)

A composition according to the invention comprises at least one compound of formula (I), one of its acid or base salts, organic or mineral, one of its optical isomers, or one of its solvates such as hydrates:

[Chem 2]

R ₁ -C(O)-N(H)-CH(R ₂ )-C(O)-OR ₃ (I)
Formula (I) in which:
- R ₁ represents a (C ₆ -C ₂₀ )alkyl group;
- R ₂ represents a hydrogen atom or a (C ₁ -C ₆ )alkyl group optionally substituted by a guanidine group optionally substituted by one or more (C ₁ -C ₄ )alkyl groups; and
- R ₃ represents a hydrogen atom or a (C ₁ -C ₆ )alkyl group.

By "organic or mineral acid salt" is meant more particularly the salts chosen from a salt derived from i) hydrochloric acid HCl, ii) hydrobromic acid HBr, iii) sulfuric acid H ₂ SO ₄ , iv) alkylsulfonic acids: Alk-S(O) ₂ OH such as methylsulfonic acid and ethylsulfonic acid; v) arylsulfonic acids: Ar-S(O) ₂ OH such as benzenesulfonic acid and toluenesulfonic acid; vi) citric acid; vii) succinic acid; viii) tartaric acid; ix) lactic acid, x) alkoxysulfinic acids: Alk-OS(O)OH such as methoxysulfinic acid and ethoxysulfinic acid; xi) aryloxysulfinic acids such as tolueneoxysulfinic acid and phenoxysulfinic acid; xii) phosphoric acid H ₃ PO ₄ ; xiii) acetic acid CH ₃ C(O)OH ; and xiv) triflic acid CF ₃ SO ₃ H and xv) tetrafluoroboric acid HBF ₄ .

By "organic or mineral base salt" is meant the salts of bases or alkaline agents as defined below as alkali metal hydroxides such as soda, potash, ammonia, amines or alkanolamines.

By “alkyl group” is meant a saturated, linear or branched hydrocarbon group. A “(C ₆ -C ₂₀ )alkyl group” is a saturated, linear or branched C ₁ -C ₂₀ hydrocarbon radical, preferably C ₁ -C ₆ ((C ₁ -C ₆ )alkyl group), more preferably C ₁ -C ₄ ((C ₁ -C ₄ )alkyl group) such as methyl or ethyl.

Preferably, in formula (I), R ₁ represents a (C ₆ -C ₂₀ )alkyl group, linear or branched, preferably linear, more particularly R ₁ represents a (C ₆ -C ₁₂ )alkyl group, linear or branched, preferably linear.

Preferably, in formula (I), R ₂ represents a hydrogen atom.

Alternatively, in formula (I), R ₂ represents in particular a (C ₁ -C ₆ )alkyl group, preferably substituted by a guanidine group optionally substituted by one or more (C ₁ -C ₄ )alkyl groups. According to this embodiment, R ₂ is substituted by a guanidine group –NH-C(=NH)-NH ₂ .

Preferably, in formula (I), R ₃ represents a hydrogen atom.

Alternatively, in formula (I), R ₃ represents in particular a (C ₁ -C ₆ )alkyl group.

Preferably, the compound of formula (I) is chosen from laurylethyl arginate and capryloyl glycine (also called N-octanoyl glycine).

More preferably, in a compound of formula (I) according to the invention:
R ₁ represents a linear or branched (C ₆ -C ₁₂ )alkyl group, preferably linear, in particular a linear -C ₇ H ₁₅ group; and
_R2 and _R3 represent hydrogen atoms.

Preferably, the compound of formula (I) is capryloyl glycine.

Capryloyl glycine is a compound of formula (II):

(II)

Laurylethyl arginate is a compound of formula (III):

(III)

The composition according to the invention preferably comprises a total content of compound(s) of formula (I), preferably capryloyl glycine, ranging from 0.01% to 3% by weight relative to the total weight of the composition, preferably from 0.02% to 1.0% by weight, and more preferably from 0.05% to 0.5% by weight, relative to the total weight of the composition.

By total content of compound(s) of formula (I) is meant the sum of the contents of each of the compound(s) of formula (I) present in the composition, or, when only one compound of formula (I) is present in the composition, is meant the content of this compound of formula (I).

A composition according to the invention may comprise one or more endolysin(s) according to the invention and one or more compound(s) of formula (I) according to the invention in a mass ratio of endolysin(s)/compound(s) of formula (I) of between 0.0001 and 0.01 and in particular of between 0.002 and 0.004.

A composition according to the invention may comprise water and optionally an organic solvent miscible in water.

In particular, a composition according to the invention may comprise a quantity of water of at least 10% by weight relative to the total weight of the composition, in particular a quantity of water ranging from 10% to 98% by weight, more particularly from 20% to 95% by weight, in particular from 30% to 90% by weight and more particularly from 35% to 85% by weight relative to the total weight of the composition.

The water can be sterile demineralized water and/or floral water and/or natural thermal or mineral water.

By " water-miscible organic solvent " according to the present invention is meant an organic compound which is liquid at room temperature and whose miscibility in water is greater than 50% by weight at 25°C and at atmospheric pressure.

The water-miscible organic solvents that can be used in the composition of the invention may in particular be volatile.

Among the water-miscible organic solvents which can be used in a composition of the invention, there may be mentioned, for example, lower monoalcohols having from 2 to 5 carbon atoms such as ethanol and isopropanol, and polyols such as propylene glycol, glycerol.

According to one embodiment, a composition according to the invention may be free of lower monoalcohols having from 2 to 5 carbon atoms.

The water-miscible organic solvents may be present in the composition according to the invention in a content ranging from 5% to 20% by weight relative to the total weight of the composition, preferably from 10% to 15% by weight relative to the total weight of the composition.

According to a particular embodiment, a composition according to the invention may comprise less than 2% by weight of ethanol, preferably less than 1% by weight, more particularly less than 0.5% by weight, relative to the total weight of the composition, in particular less than 0.1% by weight of ethanol, and preferably may be free of ethanol.

Additional ingredients

In addition to the above-mentioned compounds, a composition according to the invention may of course comprise one or more additional ingredient(s).

Of course, the person skilled in the art will take care to choose one or more additional ingredient(s) such that the advantageous properties of the endolysin(s) of the invention are not, or not substantially, altered.

The additional ingredients are present in the compositions in a usual content for each of them in a cosmetic composition, in particular in a usual content for each of them allowing them to retain their cosmetic properties, more particularly in a usual content for each of them allowing them, when they are each the only ingredient of a composition according to the invention having this property, to retain their cosmetic property.

Thus, a composition according to the invention may comprise one or more of the following additional ingredient(s) chosen from surfactants; fatty substances; colorants; preservatives; perfumes; pH adjusters such as organic acids such as citric acid; antioxidants; hydrophilic gelling agents such as hydroxypropylmethylcellulose; amino acids such as arginine; carbohydrates; chelating agents; sugar alcohols; cosmetic active ingredients; and mixtures thereof.

Of course, the person skilled in the art will take care to choose this or these possible additional ingredient(s) and/or their quantity in such a way that the advantageous properties of a composition according to the invention are not, or not substantially, altered by the envisaged addition.

The additional ingredient(s) other than those listed below may be present in the composition according to the invention in a concentration of between 0.001% and 20% by weight, in particular from 0.01% to 10% by weight, more particularly between 0.1% and 5% by weight relative to the total weight of the composition.

According to a particular embodiment, a composition according to the invention may comprise at least one additional ingredient chosen from an oil, an aromatic alcohol of formula (I), an organic filler, a nonionic surfactant, and their mixtures.

Oil

A composition according to the invention may comprise at least one oil.

For the purposes of the present invention, “oil” means a liquid compound at 25°C and atmospheric pressure (1.013.10 ⁵ Pa), immiscible with water.

By "immiscible" is meant that the mixture of the same quantity of water and oil, after stirring, does not result in a stable solution comprising only one phase, under the aforementioned temperature and pressure conditions. The observation is made visually or using a phase contrast microscope if necessary, on 100 g of mixture obtained after sufficient Rayneri stirring to cause a vortex to appear within the mixture (as an indication 200 to 1000 rpm); the resulting mixture is left to stand, in a closed bottle, for 24 hours at room temperature before observation.

The term “hydrocarbon oil” means an oil containing mainly hydrogen and carbon atoms and possibly one or more functions chosen from hydroxyl, ester, ether and carboxylic functions. A hydrocarbon oil therefore does not contain any silicon or fluorine atoms.

By “silicone oil” is meant an oil comprising at least one silicon atom, and in particular at least one Si-O group, and more particularly an organopolysiloxane.

The term “fluorinated oil” means an oil comprising at least one fluorine atom.

By “non-polar hydrocarbon oil” we mean a hydrocarbon oil comprising only carbon and hydrogen atoms, in particular non-aromatic (also called hydrocarbon).

By “polar hydrocarbon oil” we mean hydrocarbon oils mainly comprising hydrogen and carbon atoms and one or more functions chosen from hydroxyl, ester, ether and carboxylic functions.

In particular, the composition according to the invention may comprise at least one oil chosen from volatile oils and non-volatile oils, in particular with the exception of paraffin oils.

Volatile oils

"Volatile oil" means an oil (or non-aqueous medium) capable of evaporating on contact with the skin in less than one hour, at room temperature and atmospheric pressure. Volatile oil is a volatile cosmetic oil, liquid at room temperature, having in particular a non-zero vapor pressure, at room temperature and atmospheric pressure, in particular, having a vapor pressure ranging from 0.13 Pa to 40,000 Pa (10 ^-3 to 300 mm Hg), and in particular, ranging from 1.3 Pa to 13,000 Pa (0.01 to 100 mm Hg), and more particularly ranging from 1.3 Pa to 1300 Pa (0.01 to 10 mm Hg).

According to a particular embodiment of the invention, the volatile oils are such that the flash points are less than 120°C and the vapor pressure is less than 5 Pa, more particularly whose flash point is less than 90°C and the vapor pressure is greater than 1 Pa, even more particularly whose flash point is less than or equal to 60°C and the vapor pressure is greater than 5 Pa and even more particularly whose flash point is less than 60°C and the vapor pressure is greater than 100 Pa.

The volatile oil(s) may be chosen from volatile hydrocarbon oils such as:
- hydrocarbon oils having 8 to 16 carbon atoms, and in particular:
(a) branched C8-C16 alkanes such as isoalkanes such as isoalkanes (also called isoparaffins) such as C8-C9 Isoparaffin, C13-C16 Isoparaffin, isododecane, isodecane, isohexadecane, and for example oils sold under the trade names Isopars or Permetyls, alone or in mixtures, in particular isododecane (also called 2,2,4,4,6-pentamethylheptane), for example marketed by INEOS, more particularly isododecane;
(b) linear C6-C16 alkanes, alone or in mixtures, for example such as hexane, decane, undecane, tridecane, isoparaffins such as, or n-dodecane (C12) and n-tetradecane (C14) sold by Sasol respectively under the references PARAFOL 12-97 and PARAFOL 14-97, the undecane-tridecane mixture, the mixtures of n-undecane (C11) and n-tridecane (C13) obtained in examples 1 and 2 of application WO 2008/155059 of the Cognis Company, and their mixtures as well as the mixtures of n-undecane (C11) and n-tridecane (C13) Cetiol Ultimate® of the BASF company;
(c) volatile, non-aromatic, C5-C12 cyclic alkanes;
- short-chain esters having 3 to 8 carbon atoms in total, such as methyl acetate, ethyl acetate, propyl acetate, n-butyl acetate or isobutyl acetate, for example sold by SOLVAY, DOW or OXEA;
- volatile carbonate hydrocarbon oils of structure R'1-OC(O)-O-R'2 in which R'1 and R'2, identical or different, independently denote a linear, branched or cyclic C4-C8 alkyl group, in particular a linear C4-C8 alkyl group. It may be preferable for R1 and R2 to be identical. In particular R'1 and R'2 denote a linear butyl alkyl radical, a pentyl group. Advantageously, the ether oil is chosen from dibutylcarbonate or dipentylcarbonate;
- volatile ether oils of formula R1-O-R2 in which R1 and R2, which are identical or different, independently denote a linear, branched or cyclic C4-C8 alkyl group, in particular a linear or branched C4-C8 alkyl group. It is preferable for R1 and R2 to be identical. As a linear alkyl group, mention may be made of a butyl group, a pentyl group. As a branched alkyl group, mention may be made of a 1-methylpropyl group, a 2-methylpropyl group, a t-butyl group, a 1,1-dimethylpropyl group.

In particular, the volatile hydrocarbon oil(s) are chosen from C8-C16 alkanes, in particular linear ones, and more particularly are chosen from C9-C12 alkanes, even more particularly are chosen from a mixture of C9-C12 alkanes such as VEGELIGHT SILK® marketed by BioSynthIs.

The volatile oil(s) may be chosen from volatile silicone oils such as:
- silicone oils comprising in particular from 2 to 7 silicon atoms, these silicone oils optionally comprising alkyl or alkoxy groups having from 1 to 10 carbon atoms. As volatile silicone oil that can be used in the invention, mention may be made in particular of dimethicones with a viscosity of 5 and 6 cSt, cyclopentadimethylsiloxane, dodecamethylpentasiloxane, cyclohexadimethylsiloxane, octamethyl cyclotetrasiloxane, decamethyl cyclopentasiloxane, dodecamethyl cyclohexasiloxane, heptamethyl hexyltrisiloxane, heptamethyloctyl trisiloxane, hexamethyl disiloxane, octamethyl trisiloxane, decamethyl tetrasiloxane, dodecamethyl pentasiloxane, and mixtures thereof. Examples include dodecamethylpentasiloxane such as the DM-FLUID-2cs reference marketed by SHIN-ETSU or cyclohexadimethylsiloxane such as the XIAMETER PMX-0246 CYCLOHEXASILOXANE reference marketed by DOW CHEMICAL.

Non-volatile oils

By "non-volatile oil" is meant an oil whose vapour pressure at 25°C and atmospheric pressure is non-zero and less than 2.66 Pa, more particularly less than 0.13 Pa. For example, the vapour pressure can be measured using the static method or by the isothermal thermogravimetry effusion method, depending on the vapour pressure of the oil (OECD standard 104).

The non-volatile oil(s) may be of natural or synthetic origin, particularly natural.

Non-volatile oils include:
- non-volatile fluorinated oils which may in particular be chosen from fluorinated polyethers, as well as from fluorosilicone oils, fluorinated silicones as described in document EP-A-847752;
- non-volatile silicone oils may in particular be chosen from non-volatile silicones with the following INCI names: dimethicone, dimethiconol, trimethyl pentaphenyl trisiloxane, tetramethyl tetraphenyl trisiloxane, diphenyl dimethicone, trimethylsiloxyphenyl dimethicone, phenyltrimethicone, diphenylsiloxy phenyl trimethicone; as well as mixtures thereof.
These products are notably marketed under the names PH-1555 HRI Cosmetic Fluid (Trimethyl Pentaphenyl Trisiloxane), Dow Corning 556 Cosmetic Grade Fluid (Phenyltrimethicone) by Dow Corning; Diphenyl Dimethicone such as the products KF-54, KF54HV, KF-50-300CS, KF-53 d, KF-50-100CS or Diphenylsiloxy Phenyl Trimethicone KF56 A marketed by Shin Etsu, marketed by Shin Etsu; the products Belsil PDM 1000, Belsil PDM 20 marketed by Wacker Chemie (Trimethylsiloxy Phenyl Dimethicone), alone or in mixtures;
- non-volatile apolar hydrocarbon oils which may in particular be chosen from linear or branched compounds, of mineral or synthetic origin such as for example: i) squalane such as the reference NEOSSANCE SQUALANE marketed by AMYRIS, isoeicosane, ii) mixtures of linear, saturated hydrocarbons, particularly in C14-C30, more particularly in C15-C28, such as mixtures whose INCI names are for example the following: (C15-C19)alkane, (C18-C21)Alkane, (C21-C28)alkane, such as for example the products Gemseal 40, Gemseal 60, Gemseal 120 marketed by Total, Emogreen L19 marketed by SEPPIC, Emogreen L15 marketed by SEPPIC, iii) polybutenes, hydrogenated or not, such as for example products of the Indopol range marketed by the company INEOS Oligomers, products with the INCI name HYDROGENATED POLYISOBUTENE; iv) polyisobutenes, hydrogenated or not, in particular hydrogenated such as for example the non-volatile compounds of the Parléam® range marketed by the company NIPPON OIL FATS, v) polydecenes, hydrogenated or not, such as for example non-volatile compounds of the PURESYN® range marketed by the company Exxonmobil), vi) decene/butene copolymers, butene/isobutene copolymers and vii) their mixtures;
- polar non-volatile hydrocarbon oils which may be chosen from:
(i) fatty alcohols, saturated, unsaturated, linear or branched, C10-C26, liquid at room temperature (25°C), in particular monoalcohols. In particular, C10-C26 alcohols are fatty alcohols, in particular branched when they comprise at least 16 carbon atoms; in particular, the fatty alcohol comprises from 10 to 24 carbon atoms, and more particularly from 12 to 22 carbon atoms, such as in particular lauryl alcohol, isostearyl alcohol, oleyl alcohol, 2-butyloctanol, 2-undecyl pentadecanol, 2-hexyldecyl alcohol, isocetyl alcohol, octyldodecanol and mixtures thereof;
(ii) triglycerides consisting of fatty acid esters of glycerol, in particular the fatty acids of which may have chain lengths varying from C4 to C36, and in particular from C18 to C36, these oils being able to be linear or branched, saturated or unsaturated; examples which may include in particular heptanoic or octanoic triglycerides, caprylic/capric acid triglycerides; vegetable oils such as wheat germ, sunflower, grape seed, sesame, corn, apricot kernel, castor, shea, avocado, olive, soybean, sweet almond, palm, rapeseed, cottonseed, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, squash, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, candlenut, passionflower, musk rose, peanut, coconut, argan, passionflower, kaya; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; as well as mixtures thereof;
(iii) linear aliphatic hydrocarbon esters of formula RC(O)-OR' in which RC(O)-O- represents the carboxylic acid residue containing from 2 to 40 carbon atoms, and R' represents a hydrocarbon chain containing from 1 to 40 carbon atoms, aliphatic hydrocarbon esters of alkylene glycol, in particular ethylene glycol or propylene glycol; the total number of carbon atoms being advantageously at least 10. As examples of such esters, mention may be made, for example, of isoamyl laurate, cetostearyl octanoate, isopropyl stearate or isostearate, ethyl palmitate, 2-ethylhexyl palmitate, isostearyl isostearate, octyl stearate, isostearyl heptanoate, octanoates, decanoates or ricinoleates of alcohols or polyalcohols such as propylene glycol dioctanoate, cetyl octanoate, coco caprylate caprate, tridecyl octanoate, 2-ethylhexyl palmitate, alkyl benzoate, polyethylene diheptanoate glycol, propylene glycol diethyl 2-hexanoate and mixtures thereof, hexyl laurate, neopentanoic acid esters such as isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyl-2-docecyl neopentanoate, isononanoic acid esters such as isononyl isononanoate, isotridecyl isononanoate, octyl isononanoate, oleyl erucate; lauroyl isopropyl sarcosinate, diisopropyl sebacate, isocetyl stearate, isodecyl neopentanoate, isostearyl behenate, myristyl myristate; and mixtures thereof;
iv) hydroxylated esters such as polyglycerol-2 triisostearate;
(v) aromatic esters such as tridecyl trimellitate, C12-C15 alcohol benzoate, 2-phenyl ethyl ester of benzoic acid, butyl octyl salicylate;
(vi) esters of linear fatty acids having a total carbon number ranging from 35 to 70 such as pentaerythrityl tetrapelargonate;
(vii) esters of fatty alcohols or branched C24-C28 fatty acids such as triisoarachidyl citrate, pentaerythrityl tetraisononanoate, glyceryl triisostearate, glyceryl tridecyl-2 tetradecanoate, pentaerythrityl tetraisostearate, polyglyceryl-2 tetraisostearate or pentaerythrityl tetradecyl-2 tetradecanoate;
(viii) polyesters obtained by condensation of dimer and/or trimer of unsaturated fatty acid and diol such as those with the INCI name dilinoleic acid / butanediol copolymer, dilinoleic acid / propanediol copolymer; polyesters obtained by condensation of dimer of fatty acid and dimer diol such as dimer dilinoleyl dimer dilinoleate;
ix) synthetic ether of formula R1-O-R2 in which R1 and R2, identical or different, independently denote a linear, branched or cyclic C6-C24 alkyl group, in particular a C6-C18 alkyl group, and more particularly a C8-C12 alkyl group. It may be preferable for R1 and R2 to be identical. As a linear alkyl group, mention may be made of a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undodyl group, a dodecyl group, a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group, an eicosyl group, a behenyl group, a docosyl group, a tricosyl group and a tetracosyl group. As the branched alkyl group, there may be mentioned a 1,1-dimethylpropyl group, a 3-methylhexyl group, a 5-methylhexyl group, an ethylhexyl group, a 2-ethylhexyl group, a 5-methyloctyl group, a 1-ethylhexyl group, a 1-butylpentyl group, a 2-butyloctyl group, an isotridecyl group, a 2-pentylnonyl group, a 2-hexyldecyl group, an isostearyl group, a 2-heptylundecyl group, a 2-octyldodecyl group, a 1,3-dimethylbutyl group, a 1-(1-methylethyl)-2-methylpropyl group, a 1,1,3,3-tetramethylbutyl group, a 3,5,5-trimethylhexyl group, a 1-(2-methylpropyl)-3-methylbutyl group, a 3,7-dimethyloctyl group, and a 2-(1,3,3-trimethylbutyl)-5,7,7-trimethyloctyl group. As a cyclic alkyl group, mention may be made of a cyclohexyl group, a 3-methylcyclohexyl group and a 3,3,5-trimethylcyclohexyl group., dilauryl ether, diisostearyl ether, dioctyl ether, nonylphenyl ether, dodecyl dimethylbutyl ether, cetyl dimethylbutyl ether, cetyl isobutyl ether and mixtures thereof. Among the non-volatile ether oils, mention may be made of dicaprylyl ether, such as the reference CETIOL OE marketed by BASF;
x) carbonates of formula R8-OC(O)-O-R9, with R8 and R9, identical or different, represent a C4 to C12, and in particular C6 to C10, linear or branched alkyl chain; the carbonate oils may be dicaprylyl carbonate (or dioctyl carbonate), marketed under the name Cetiol CC® by the company BASF, di(ethyl–2-hexyl) carbonate, marketed under the name TEGOSOFT DEC® by the company Evonik, dipropylheptyl carbonate (Cetiol 4 AII from BASF), dibutyl carbonate; di-neopentyl carbonate; dipentyl carbonate; di neoheptyl carbonate; di-heptyl carbonate; di-isononyl carbonate; or di-nonyl carbonate; and more particularly dioctyl carbonate;
(xi) vinylpyrrolidone copolymers such as vinylpyrrolidone/1-hexadecene copolymer (INCI name);
(xii) higher C6-C26 fatty acids liquid at room temperature (25°C) such as oleic acid, linoleic acid, linolenic acid, or isostearic acid; and
xiii) their mixtures.

According to a particular embodiment, the composition comprises at least one oil chosen from volatile C8-C16 alkane hydrocarbon oils, non-volatile silicone oils, non-volatile apolar hydrocarbon oils with the exception of paraffin oils, non-volatile polar hydrocarbon oils as defined above, and mixtures thereof, more particularly chosen from non-volatile polar hydrocarbon oils and mixtures thereof.

According to a particular embodiment, the composition comprises at least one oil chosen from polar hydrocarbon non-volatile oils, more particularly, the composition according to the invention comprises at least one oil chosen from polar hydrocarbon non-volatile oils and does not comprise non-polar hydrocarbon non-volatile oils, even more particularly the composition according to the invention comprises at least one oil chosen from polar hydrocarbon non-volatile oils and does not comprise non-polar hydrocarbon non-volatile oils, fluorinated non-volatile oils, silicone non-volatile oils or volatile oils.

According to a particular embodiment, the polar hydrocarbon non-volatile oils are chosen from:
(i) fatty alcohols, saturated, unsaturated, linear or branched, C10-C26, liquid at room temperature (25°C), in particular monoalcohols. In particular, C10-C26 alcohols are fatty alcohols, in particular branched when they comprise at least 16 carbon atoms; more particularly, the fatty alcohol comprises from 10 to 24 carbon atoms, and even more particularly from 12 to 22 carbon atoms, such as in particular lauryl alcohol, isostearyl alcohol, oleyl alcohol, 2-butyloctanol, 2-undecyl pentadecanol, 2-hexyldecyl alcohol, isocetyl alcohol, octyldodecanol and mixtures thereof;
(ii) triglycerides consisting of fatty acid esters of glycerol, in particular the fatty acids of which may have chain lengths varying from C4 to C36, and in particular from C18 to C36, these oils being able to be linear or branched, saturated or unsaturated; examples which may include in particular heptanoic or octanoic triglycerides, caprylic/capric acid triglycerides; vegetable oils such as wheat germ, sunflower, grape seed, sesame, corn, apricot kernel, castor, shea, avocado, olive, soybean, sweet almond, palm, rapeseed, cottonseed, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, squash, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, candlenut, passionflower, musk rose, peanut, coconut, argan, passionflower, kaya; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; as well as mixtures thereof;
(iii) linear aliphatic hydrocarbon esters of formula RC(O)-OR' in which RC(O)-O- represents the carboxylic acid residue containing from 2 to 40 carbon atoms, and R' represents a hydrocarbon chain containing from 1 to 40 carbon atoms, aliphatic hydrocarbon esters of alkylene glycol, in particular ethylene glycol or propylene glycol; the total number of carbon atoms being advantageously at least 10. As examples of such esters, mention may be made, for example, of isoamyl laurate, cetostearyl octanoate, isopropyl stearate or isostearate, ethyl palmitate, 2-ethylhexyl palmitate, isostearyl isostearate, octyl stearate, isostearyl heptanoate, octanoates, decanoates or ricinoleates of alcohols or polyalcohols such as propylene glycol dioctanoate, cetyl octanoate, coco caprylate caprate, tridecyl octanoate, 2-ethylhexyl palmitate, alkyl benzoate, polyethylene diheptanoate glycol, propylene glycol diethyl 2-hexanoate and mixtures thereof, hexyl laurate, neopentanoic acid esters such as isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyl-2-docecyl neopentanoate, isononanoic acid esters such as isononyl isononanoate, isotridecyl isononanoate, octyl isononanoate, oleyl erucate; lauroyl isopropyl sarcosinate, diisopropyl sebacate, isocetyl stearate, isodecyl neopentanoate, isostearyl behenate, myristyl myristate; and mixtures thereof;
ix) synthetic ether of formula R1-O-R2 in which R1 and R2, identical or different, independently denote a linear, branched or cyclic C6-C24 alkyl group, in particular a C6-C18 alkyl group, and more particularly a C8-C12 alkyl group. It may be preferable for R1 and R2 to be identical. As a linear alkyl group, mention may be made of a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undodyl group, a dodecyl group, a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group, an eicosyl group, a behenyl group, a docosyl group, a tricosyl group and a tetracosyl group. As the branched alkyl group, there may be mentioned a 1,1-dimethylpropyl group, a 3-methylhexyl group, a 5-methylhexyl group, an ethylhexyl group, a 2-ethylhexyl group, a 5-methyloctyl group, a 1-ethylhexyl group, a 1-butylpentyl group, a 2-butyloctyl group, an isotridecyl group, a 2-pentylnonyl group, a 2-hexyldecyl group, an isostearyl group, a 2-heptylundecyl group, a 2-octyldodecyl group, a 1,3-dimethylbutyl group, a 1-(1-methylethyl)-2-methylpropyl group, a 1,1,3,3-tetramethylbutyl group, a 3,5,5-trimethylhexyl group, a 1-(2-methylpropyl)-3-methylbutyl group, a 3,7-dimethyloctyl group, and a 2-(1,3,3-trimethylbutyl)-5,7,7-trimethyloctyl group. As a cyclic alkyl group, mention may be made of a cyclohexyl group, a 3-methylcyclohexyl group and a 3,3,5-trimethylcyclohexyl group., dilauryl ether, diisostearyl ether, dioctyl ether, nonylphenyl ether, dodecyl dimethylbutyl ether, cetyl dimethylbutyl ether, cetyl isobutyl ether and mixtures thereof. Among the non-volatile ether oils, mention may be made of dicaprylyl ether, such as the reference CETIOL OE marketed by BASF;
x) carbonates of formula R8-OC(O)-O-R9, with R8 and R9, identical or different, represent a C4 to C12, and in particular C6 to C10, linear or branched alkyl chain; the carbonate oils may be dicaprylyl carbonate (or dioctyl carbonate), marketed under the name Cetiol CC® by the company BASF, di(ethyl–2-hexyl) carbonate, marketed under the name TEGOSOFT DEC® by the company Evonik, dipropylheptyl carbonate (Cetiol 4 AII from BASF), dibutyl carbonate; di-neopentyl carbonate; dipentyl carbonate; di neoheptyl carbonate; di-heptyl carbonate; di-isononyl carbonate; or di-nonyl carbonate; and more particularly dioctyl carbonate;
More particularly, the polar hydrocarbon non-volatile oils are chosen from:
(ii) triglycerides consisting of fatty acid esters of glycerol, in particular the fatty acids of which may have chain lengths varying from C4 to C36, and in particular from C18 to C36, these oils being able to be linear or branched, saturated or unsaturated; examples which may include in particular heptanoic or octanoic triglycerides, caprylic/capric acid triglycerides; vegetable oils such as wheat germ, sunflower, grape seed, sesame, corn, apricot kernel, castor, shea, avocado, olive, soybean, sweet almond, palm, rapeseed, cottonseed, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, squash, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, candlenut, passionflower, musk rose, peanut, coconut, argan, passionflower, kaya; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; as well as mixtures thereof.

According to a particular embodiment, the composition comprises at least one oil chosen from the group consisting of:
- polar hydrocarbon non-volatile oils of the triglyceride type consisting of fatty acid esters and glycerol, in particular the fatty acids of which may have chain lengths varying from C4 to C36, and in particular from C18 to C36, these oils being able to be linear or branched, saturated or unsaturated, chosen from soybean oil, jojoba seed oil, shea butter olein, capric acid and caprylic acid triglycerides, and mixtures thereof,
- volatile C8-C16 alkane oils, such as C9-C12 alkanes and isoparaffin,
- non-volatile apolar oils such as squalane,
- non-volatile polar hydrocarbon oils of the synthetic ether type of formula R1-O-R2 in which R1 and R2, identical or different, independently denote a linear, branched or cyclic C6-C24 alkyl group, in particular a C6-C18 alkyl group, and more particularly a C8-C12 alkyl group, such as dicaprylyl ether,
- non-volatile silicone oils such as dimethicone,
- non-volatile polar hydrocarbon oils such as fatty alcohols, saturated, unsaturated, linear or branched, C10-C26, liquid at room temperature (25°C) such as octyldodecanol,
- non-volatile polar hydrocarbon oils of the carbonate type of formula R8-OC(O)-O-R9, with R8 and R9, identical or different, representing a C4 to C12, in particular C6 to C10, linear or branched alkyl chain such as dicaprylyl carbonate and
- their mixtures.

According to a particular embodiment, the oil is selected from the group consisting of octyldodecanol, soybean oil, shea butter olein, dicaprylyl carbonate, dimethicone, jojoba oil, isoparaffin, isononyl isonanoate, caprylic/capric acid triglycerides, C9-C12 alkanes, squalane, dicaprylyl ether, and mixtures thereof.

According to a particular embodiment, the oil is selected from the group consisting of soybean oil, shea butter olein, jojoba oil, isononyl isonanoate, caprylic/capric acid triglycerides, and mixtures thereof.

According to a particular embodiment, the composition is free of paraffin oils, that is to say that the composition comprises 0% paraffin oils.

The oils according to the invention may advantageously be present in a composition according to the invention in a usual content for a cosmetic composition, in particular in a usual content allowing them to play their cosmetic role in a composition of the invention, in particular in a cosmetic composition according to the invention, more particularly in a usual content allowing them to play their cosmetic role when they are the only ones to play this role in a composition according to the invention.

Oil can play different cosmetic roles such as that of a consistency factor, of holding an emulsion in the cold, or of providing the smooth appearance of the composition, in particular in the case of an emulsion. It can also help to facilitate the spreading and sliding of the composition on the skin, as well as its penetration. Finally, oil can act on the skin by its occlusive effect, its lubricating effect (to the touch) or its emollient/moisturizing effect.

A composition according to the invention may comprise a total oil content ranging from 1% to 80% by weight relative to the total weight of the composition, in particular from 2% to 60% by weight relative to the total weight of the composition, more particularly from 5% to 40% by weight, even more particularly from 10% to 30% by weight relative to the total weight of the composition.

By total oil content(s), we mean the sum of the contents of each of the previously mentioned oils present in the composition, or, when only one of these oils is present in the composition, we mean the content of this oil.

Aromatic alcohols

A composition according to the invention may, in addition, comprise at least one aromatic alcohol of formula (IV), one of its salts, in particular its base salts, organic or mineral, one of its optical isomers, one of its geometric isomers or one of its solvates such as hydrates:

in which
- R¹represents a group selected from the group consisting of:
a) hydroxy(C₁-C₄) linear or branched alkyl, in particular a hydroxy group (C₁-C₂)alkyl,
b) a group chosen from -OR⁵, -C(O)R⁶, -C(O)OR⁷, and -(CH₂)_n-C(H)(R⁸ ₎-HORN⁹,
with :
R⁵representing a group (C₃-C₄) linear or branched alkyl, optionally substituted by one or more hydroxyl group(s) (OH),
R⁶representing a hydrogen atom or a group (C₁-C₄) linear or branched alkyl, phenyl or benzyl, optionally substituted by one or more hydroxyl group(s),
R⁷representing a group (C₁-C₄) linear or branched alkyl, phenyl or benzyl, optionally substituted by one or more hydroxyl group(s),
R⁸representing a hydrogen atom or a group (C₁-C₄) linear or branched alkyl such as methyl or ethyl, in particular R⁸representing a hydrogen atom;
R⁹representing a hydrogen atom, or a group (C₁-C₁₂)alkyl, linear or branched, in particular linear, optionally substituted by one or more hydroxyl group(s) or a group (C₂-C₁₂)alkenyl, linear or branched, in particular linear, optionally substituted by one or more hydroxyl group(s),
n is 0, 1 or 2, in particular n is 1
- R²represents a hydrogen atom; a halogen atom, in particular a chlorine atom; or a hydroxyl group; and
- R³represents a hydrogen atom or a group selected from hydroxyl and (C₁-C₆) linear or branched alkoxy, in particular (C₁-C₄)alkoxy such as methoxy -OCH_3,ethoxy -OC₂H_5,in particular R³represents a hydrogen atom or an ethoxy group; and
- R⁴is a hydrogen atom or a hydroxyl group;
it being understood that at least one of the R groups¹, R², R³or R⁴carries or represents a hydroxyl group.

More particularly, the aromatic alcohol(s) of formula (IV) of the invention are such that:
- when R¹represents a group -C(O)OR⁷ _,then R²is an -OH group;
- when R¹represents a group -C(O)R⁶ _,then at least one of the R², R³and R⁴is an -OH group;
- when R¹represents a group –(CH₂)_n-C(H)(R⁸)-HORN⁹ _, then R²is an -OH group.

In particular, the aromatic alcohol may have the following formula (IV):

in which
R¹is selected from the group consisting of a group:
i) hydroxy(C₁-C₄) linear or branched alkyl, in particular a hydroxy group (C₁-C₂)alkyl such as hydroxymethyl or hydroxyethyl,
ii) a -OR group⁵with R⁵representing a group (C₃-C₄)hydroxyalkyl, especially -OR⁵representative -O-CH₂-CH(OH)-CH₂OH,
iii) a -C(O)R group⁶with R⁶representing a group (C₁-C₄) linear or branched alkyl, in particular -C(O)R⁶representative -C(O)-CH₃,
iv) a -C(O)OR group⁷with R⁷representing a group (C₁-C₄) linear or branched alkyl, in particular R⁷representing a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or benzyl group, and
v) a -CH group₂-CH₂-HORN⁹with R⁹representative a group (C₁-C₆)alkyl, linear or branched, in particular -CH₂-CH₂-HORN⁹representing a group -CH₂-CH₂-C(O)CH₃;
R²is selected from the group consisting of a hydrogen atom; a halogen atom, in particular a chlorine atom; and a hydroxyl group;
R³is a hydrogen atom, a methoxy or ethoxy group; and
R⁴is a hydrogen atom or a hydroxyl group;
it being understood that at least one of the R groups¹, R²or R⁴carries or represents a hydroxyl group.

Such compounds play the role of preservatives, especially in cosmetic compositions. Some also play the role of fragrances, especially in cosmetic compositions.

The term “organic or mineral base salt” means the salts of bases or alkaline agents as defined below. Examples of base salts include alkali metal hydroxides such as sodium, potassium and lithium hydroxides; alkaline earth metal hydroxides such as calcium and magnesium hydroxides; hydroxides of other metals, such as aluminium and zinc hydroxides; ammonia and organic amines such as unsubstituted or hydroxy-substituted mono-, di- or tri-alkylamines; dicyclohexylamines; tributylamines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris-(2-hydroxy-alkylamines) such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris-(hydroxymethyl)methylamine; N,N-di-alkyl-N-(hydroxyalkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine and lysine.

For the purposes of the present invention, the term “ alkyl group ”, “ alkyl group ” or “ alkyl radical ” means a saturated, linear or branched monovalent hydrocarbon radical, in particular the methyl, ethyl, propyl, isopropyl, butyl, tert-butyl radicals, substituted or unsubstituted.

By " hydroxyalkyl group " is meant a saturated, linear or branched hydrocarbon group comprising at least one -OH group. A hydroxy(C ₁ -C ₄ )alkyl group is a saturated, linear or branched C ₁ -C ₄ hydrocarbon radical comprising at least one -OH group, in particular comprising a single -OH group. A hydroxy(C ₁ -C ₂ )alkyl group is a saturated, linear or branched C ₁ -C ₂ hydrocarbon radical comprising at least one -OH group, in particular comprising a single -OH group.

According to a particular embodiment, the hydroxy(C ₁ -C ₄ )alkyl group is selected from the group consisting of hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 1-(hydroxymethyl)-2-methylpropyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl, 2,3-dihydroxypropyl, 1-(hydroxymethyl)-2-hydroxyethyl, 2,3-dihydroxybutyl, 3,4-dihydroxybutyl and 2-(hydroxymethyl)-3-hydroxypropyl. In particular, the hydroxy(C ₁ -C ₄ )alkyl group is hydroxymethyl or 2-hydroxyethyl.

By "halogen atom" is meant one of the chemical elements of the 17th group of the periodic table of elements, namely fluorine, chlorine, bromine, iodine. In particular, the halogen atom is the chlorine atom.

According to a particular embodiment, R ¹ is selected from the group consisting of (C ₁ -C ₂ )hydroxyalkyl, 2-hydroxyethyl, hydroxymethyl, a -O-CH ₂ -CH(OH)-CH ₂ OH group, a -CH ₂ -CH ₂ -C(O)-CH ₃ group, and a -C(O)-OCH _{3 group,}
R ² is selected from the group consisting of a hydrogen atom, a halogen atom, in particular a chlorine atom, and a hydroxyl group,
R ³ is selected from the group consisting of a hydrogen atom and a -OC ₂ -H ₅ group, and
R ⁴ is a hydrogen atom.

According to one embodiment, R ¹ represents a hydroxy(C ₁ -C ₄ )alkyl group, more particularly a hydroxy(C ₁ -C ₂ )alkyl group, R ² represents a hydrogen atom, R ³ represents a hydrogen atom and R ⁴ represents a hydrogen atom.

According to a particular embodiment, R ¹ represents a 2-hydroxyethyl, R ² represents a hydrogen atom, R ³ represents a hydrogen atom and R ⁴ represents a hydrogen atom.

According to a particular embodiment, R ¹ represents a hydroxymethyl, R ² represents a hydrogen atom, R ³ represents a hydrogen atom, and R ⁴ represents a hydrogen atom.

According to a particular embodiment, R ¹ represents a group -OR ⁵ with R ⁵ representing a linear or branched (C ₃ -C ₄ ) alkyl group, substituted by one or more hydroxyl group(s), R ² represents a halogen atom, R ³ represents a hydrogen atom, and R ⁴ represents a hydrogen atom. More particularly, R ¹ represents a group -OR ⁵ with R ⁵ representing a linear (C ₃ -C ₄ ) alkyl group substituted by 2 hydroxyl groups, R ² represents a halogen atom, R ³ represents a hydrogen atom, and R ⁴ represents a hydrogen atom.

According to a particular embodiment, R ¹ represents a group -O-CH ₂ -CH(OH)-CH ₂ OH, R ² represents a chlorine atom, R ³ represents a hydrogen atom and R ⁴ represents a hydrogen atom.

According to a particular embodiment, R¹represents a group -(CH₂)_n-C(H)(R)⁸-HORN⁹, with R⁸representing a hydrogen atom or a methyl or ethyl group, and R⁹representing a group (C₁-C₁₂) linear alkyl optionally substituted by a hydroxyl group or a group (C₂-C₁₂)alkenyl optionally substituted by a hydroxyl group, and n is as defined above, in particular n is 1, R²represents a hydroxyl group, R³represents a group -OCH₃or -OC₂H₅and R⁴represents a hydrogen atom. More specifically, R¹represents a -CH group₂-CH₂-HORN⁹, R⁹representing a group (C₁-C12) linear alkyl, in particular a (C₁-C₆) linear alkyl such as methyl, R²represents a hydroxyl group, R³represents a -OC group₂H₅, and R⁴represents a hydrogen atom.

According to a particular embodiment, R ¹ represents a -C(O)OR ⁷ group, with R ⁷ representing a linear or branched (C ₁ -C ₄ )alkyl group, a phenyl or a benzyl, optionally substituted by one or more hydroxyl group(s), R ² represents a hydroxyl group, R ³ represents a hydrogen atom and R ⁴ represents a hydrogen atom.

According to a particular embodiment, R ¹ represents a -C(O)-OCH ₃ group, R ² represents a hydroxyl group, R ³ represents a hydrogen atom and R ⁴ represents a hydrogen atom.

According to a particular embodiment, the aromatic alcohol of formula (IV) is selected from the group consisting of phenylethyl alcohol; benzyl alcohol; chlorphenesin (also called 3-(4-Chlorophenoxy)-1,2-propanediol); zingerone; ethylzingerone (also called 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one); vanillin; parabens in particular (C ₁ -C ₆ )alkylparabens or arylparabens in particular methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben or benzylparaben; their salts and their mixtures.

According to a particular embodiment, the aromatic alcohol of formula (IV) is chosen from the group consisting of phenylethyl alcohol; benzyl alcohol; chlorphenesin (also called 3-(4-Chlorophenoxy)-1,2-propanediol); zingerone; ethylzingerone (also called 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one); parabens, in particular methylparaben; their salts, and their mixtures.

The composition according to the invention comprises in particular a total content of aromatic alcohol(s) of formula (IV) ranging from 0.01% to 3% by weight relative to the total weight of the composition, in particular from 0.05% to 1.5% by weight, and more particularly from 0.1% to 1.0% by weight, relative to the total weight of the composition.

By total content of aromatic alcohol(s) of formula (IV), we mean the sum of the contents of each of the aromatic alcohol(s) of formula (IV) present in the composition, or, when only one aromatic alcohol of formula (IV) is present in the composition, we mean the content of this aromatic alcohol of formula (IV).

Organic bulking agents

A composition according to the invention may further comprise one or more organic filler(s).

For the purposes of the present invention, the term “organic filler” means colorless or white, solid particles of any form, of organic, natural or synthetic nature, which are in an insoluble form and dispersed in the medium of the composition.

The composition according to the invention may further comprise at least one organic filler chosen from an unmodified starch, an N-acylated amino acid, their salts, and their mixtures.

Unmodified starches

The composition according to the present invention may comprise one or more unmodified starch(es).

For the purposes of the present invention, the term "unmodified starch" means a native starch or a starch which has not undergone any chemical or physical modification, in particular by one or more of the following reactions: pregelatinization, oxidation, crosslinking, esterification, etherification, amidation, heat treatments.

The unmodified starch molecules that can be used in the present invention can originate from any plant source of starch, in particular cereals and tubers; more particularly, they can be corn, rice, cassava, barley, potato, wheat, sorghum, pea or oat starches.

According to a particular embodiment, the unmodified starch is chosen from corn starches, rice starches, potato starches, and mixtures thereof, in particular the unmodified starch is chosen from corn or potato starches.

According to a particular embodiment, the composition according to the invention is completely free of tapioca starch, in particular, the composition according to the invention is completely free of unmodified tapioca starch.

According to a particular embodiment, the unmodified starch used in the composition of the present invention is a corn starch such as that marketed under the name BEAUTE-BY-ROQUETTE ST005 by the company ROQUETTE.

The starch(es) may be present in the composition according to the invention in a content ranging from 0.1% to 10% by weight, in particular from 0.5% to 5% by weight, more particularly from 1% to 2.5% by weight, such as 1%, 1.5% or 2% by weight, relative to the total weight of the composition.

N-acylated amino acids and their salts

A composition according to the present invention may comprise one or more N-acylated amino acids, their salts, and their mixtures.

The term “ salt ” of an N-acylated amino acid according to the invention means a salt formed by an inorganic or organic acid or an inorganic or organic base.

Examples of acid salts include sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, isonicotinate, lactate, salicylate, tartrate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, glutamate and aspartate salts.

Examples of basic salts include alkali metal hydroxides such as sodium, potassium and lithium; alkaline earth metal hydroxides such as calcium and magnesium; other metal hydroxides such as aluminium and zinc; ammonia and organic amines such as unsubstituted or hydroxy-substituted mono-, di- or tri-alkylamines; dicyclohexylamines; tributyl amines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris-(2-hydroxy-alkylamines) such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris-(hydroxymethyl)methylamine, N,N-di-alkyl-N-(hydroxyalkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine and lysine.

The N-acylated amino acids suitable as organic fillers according to the invention comprise at least one acyl group having 8 to 22 carbon atoms, in particular a 2-ethylhexanoyl, caproyl, lauroyl, myristoyl, palmitoyl, stearoyl or cocoyl group, in particular lauroyl.

The amino acid can be for example lysine, glutamic acid or alanine, preferably lysine.

The amino acid can be of D or L configuration, especially L.

According to a particular embodiment of the invention, the C8-C22 N-acylated amino acids are chosen from lauroyl lysine, its salts and their mixtures, in particular N-lauroyl-L-lysine, its salts and their mixtures.

N-lauroyl-L-lysine is notably marketed under the name AMIHOPE LL® by the AJINOMOTO Company.

The N-acylated amino acid(s) and their salts may be present in the composition according to the invention in a content ranging from 0.1% to 15% by weight, in particular from 1% to 10% by weight, more particularly from 2% to 4% by weight, such as 3% by weight, relative to the total weight of the composition.

The organic filler(s) may be present in the composition according to the invention in a total content ranging from 0.1% to 15% by weight, in particular from 0.5% to 10% by weight, more particularly from 1% to 4% by weight relative to the total weight of the composition.

A composition according to the invention may comprise one or more endolysin(s) according to the invention and one or more organic filler(s) in an endolysin(s)/organic filler(s) mass ratio of between 0.0001 and 0.04 and in particular of between 0.0002 and 0.004, more particularly of between 0.0006 and 0.002.

Nonionic surfactants

The composition according to the invention may further comprise at least one nonionic surfactant, in particular chosen from nonionic surfactants comprising one or more carbohydrate residue(s), nonionic surfactants of the _C6 - _C30 fatty acid alkanolamide type.

For the purposes of the present invention, the term "surfactant" means any compound that modifies the surface tension between two surfaces. Surfactant compounds are amphiphilic molecules, i.e. they have two parts of different polarity, one lipophilic (which retains fats) is apolar, the other hydrophilic (miscible in water) is polar. They thus make it possible to solubilize two immiscible phases, by interacting with one apolar (i.e. lipophilic and therefore hydrophobic), by its hydrophobic part; while with the other phase which is polar, it will interact by its hydrophilic part.

By "nonionic surfactant" is meant a surfactant that does not have a net charge (does not ionize in water).

Nonionic surfactant comprising one or more carbohydrate residue(s)

The composition according to the invention may further comprise at least one non-ionic surfactant comprising one or more carbohydrate residue(s).

For the purposes of the present invention, the term “carbohydrate” means a compound of the sugar or carbohydrate type, corresponding to a molecule essentially composed of carbon, hydrogen and oxygen atoms.

According to a particular embodiment, the carbohydrate residue(s) is (are) monosaccharides comprising 5 to 6 carbon atoms, more particularly chosen from glucose, fructose, xylose or galactose, even more particularly glucose.

According to a particular embodiment, the non-ionic surfactant(s) comprising one or more carbohydrate residue(s) is (are) chosen from:
(i) esters of sugar(s) and fatty acid(s) such as (poly)esters of glycerol, glucose or alkylglucose and fatty acid having a linear or branched, saturated or unsaturated hydrocarbon chain, in C6-C22, in particular in C16-20;
(ii) ethers of sugar(s) and fatty alcohol(s) such as alkyl(poly)glycosides; and
(iii) their mixtures.

According to a particular embodiment, the nonionic surfactant(s) comprising one or more carbohydrate residue(s) is (are) chosen from alkyl(poly)glycosides and (poly)esters of glycerol, glucose or alkylglucose and fatty acid having a linear or branched, saturated or unsaturated hydrocarbon chain, in C6-C22, in particular in C16-20, and mixtures thereof.

- Alkyl(poly)glycoside

Nonionic surfactants of the alkyl(poly)glycoside type are notably represented by the following general formula (V):

[Chem 7]

R ¹ O-(R ² O) _t -(G) _v (V)
in which:
- R ¹ represents a linear or branched alkyl or alkenyl radical containing 6 to 24 carbon atoms, in particular 8 to 20 carbon atoms, or an alkylphenyl radical whose linear or branched alkyl radical contains 6 to 24 carbon atoms, in particular 8 to 20 carbon atoms;
- R ² represents an alkylene radical containing 2 to 4 carbon atoms,
- G represents a sugar unit containing 5 to 6 carbon atoms,
- t denotes a value ranging from 0 to 10, in particular from 0 to 4,
- v denotes a value from 1 to 15, in particular from 1 to 4.

According to a particular embodiment, the alkyl(poly)glycoside surfactants are compounds of the formula described above in which:
- R ¹ denotes a saturated or unsaturated, linear or branched alkyl radical containing from 8 to 20 carbon atoms,
- R ² represents an alkylene radical containing 2 to 4 carbon atoms,
- t denotes a value ranging from 0 to 3, in particular equal to 0,
- G denotes glucose, fructose or galactose, in particular glucose;
- the degree of polymerization, i.e. the value of v, which can range from 1 to 15, in particular from 1 to 4; the average degree of polymerization being more particularly between 1 and 2.

The glucosidic bonds between sugar units are generally of the 1-6 or 1-4 type, particularly of the 1-4 type.

Examples of alkyl(poly)glycosides include caprylyl/capryl glucoside such as the product marketed under the name ORAMIX CG 110L® by the company SEPPIC; decyl glucoside marketed under the name SORBITHIX L-100® by the company APPLECHEM; arachidylglucoside glucoside optionally mixed with arachidyl alcohol and behenyl alcohol, marketed for example under the name MONTANOV 202® by the company SEPPIC; cetylstearyl glucoside optionally mixed with cetylstearyl alcohol, marketed for example under the name MONTANOV 68MB® by the company SEPPIC, under the name EMULGADE PL 68/50® by the company BASF and under the names TEGO CARE CG 90 MB® by the company EVONIK GOLDSCHMIDT; cocoglucoside such as the product marketed under the name LAMESOFT PO65® by the company BASF; octyldodecyl xyloside marketed for example under the name FLUIDANOV 20X by the company SEPPIC.

The alkyl(poly)glycoside can be used in a mixture with at least one fatty alcohol, in particular a fatty alcohol having from 6 to 24 carbon atoms, and more particularly from 8 to 20 carbon atoms.

For example, it is possible to jointly use a fatty alcohol and an alkyl(poly)glycoside whose alkyl part is identical to that of the fatty alcohol selected.

The fatty alcohol/alkyl polyglycoside emulsifying mixtures as defined above are known as such. They are described in particular in applications WO 92/06778, WO 95/13863 and WO 98/47610 and prepared according to the preparation processes indicated in these documents.

Among the fatty alcohol/alkyl(poly)glycoside mixtures, we can cite the products sold by the company SEPPIC under the names MONTANOV® such as the following mixtures:
- Arachidyl alcohol and behenyl alcohol/arachidylglucoside- MONTANOV 202®
- Cetearyl alcohol/Cetylstearylglucoside – MONTANOV 68MB®.

In a particular embodiment, the composition according to the invention comprises an alkyl(poly)glycoside type surfactant chosen from caprylyl/capryl glucoside, arachidyl glucoside, and mixtures thereof.

In a particular embodiment, the composition according to the invention does not comprise decyl glucoside.

- (poly)Esters of glycerol of glucose or alkylglucose and fatty acid

Glycerol (poly)esters of glucose or alkylglucose and fatty acid having a linear or branched, saturated or unsaturated, C6-C22 hydrocarbon chain are in particular glycerol (poly)esters of alkylglucose and fatty acid having a linear and saturated C6-C22 hydrocarbon chain, in particular C16-20, more particularly C18.

Among the (poly)esters of glycerol of glucose or alkylglucose and fatty acid having a linear or branched, saturated or unsaturated hydrocarbon chain, in C6-C22, polyglyceryl-3 methylglucose distearate is particularly preferred.

Commercial products include the product sold by the company, EVONIK GOLDSCHMIDT under the name TEGO CARE 450.

The nonionic surfactant(s) comprising one or more carbohydrate residue(s) may be present in the composition according to the invention in a content ranging from 0.01 to 10% by weight, in particular in a content ranging from 0.05 to 8% by weight, more particularly in a content ranging from 0.1 to 5% by weight relative to the total weight of the composition, more particularly still in a content ranging from 0.2 to 3% by weight relative to the total weight of the composition.

A composition according to the invention may comprise one or more endolysin(s) according to the invention and one or more non-ionic surfactant(s) comprising one or more carbohydrate residue(s) according to the invention in a mass ratio of endolysin(s)/non-ionic surfactant(s) comprising one or more carbohydrate residue(s) of between 0.0001 to 0.5 and in particular of between 0.0002 and 0.1, more particularly of between 0.0004 and 0.05, even better of between 0.0006 to 0.02.

Alkanolamides C6-C30 fatty acids

The composition according to the invention may further contain at least one nonionic surfactant chosen from _C6 - _C30 fatty acid alkanolamides.

Such surfactants may be chosen from mono-alkanolamides and di-alkanolamides of formula (VI),

[Chem 8]

R ¹ CONR ² R ³ (VI)
in which:
R ¹ is a linear or branched, saturated or unsaturated hydrocarbon group having from 6 to 30 carbon atoms,
R ² and R ³ , independently, are hydrogen or a linear or branched, saturated or unsaturated alkanol group having 1 to 10 carbon atoms, provided that only one of R ² or R ³ is hydrogen.

Examples of such surfactants include lauric acid monoethanolamide, lauric acid diethanolamide, lauric acid monopropanolamide, lauric acid monoisopropanolamide, myristic acid monoethanolamide, myristic acid diethanolamide, palmitic acid monoethanolamide, stearic acid monoethanolamide (stearamide MEA), acid monoethanolamide, oleic acid diethanolamide, oleic acid monoisopropanolamide, coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid monopropanolamide, coconut oil fatty acid monoisopropanolamide (cocamide MIPA), erucic acid diethanolamide, palm vegetable oil fatty acid monoethanolamide, and mixtures thereof.

According to a particular embodiment in formula (VI), R ¹ is a linear or branched, saturated or unsaturated hydrocarbon group having from 8 to 18 carbon atoms,

R ² and R ³ , independently, are hydrogen or a linear or branched, saturated or unsaturated alkanol group having 2 to 5 carbon atoms, provided that only one of R ² or R ³ is hydrogen.

According to a particular embodiment, in formula (VI), R ² is hydrogen, and R ³ is a linear or branched saturated alkanol group having 2 to 5 carbon atoms.

According to a particular embodiment, the appropriate _C6 - _C30 fatty acid alkanolamide of formula (VI) is selected from coconut oil fatty acid monoethanolamide (INCI: cocamide MEA or cocamide monoethanolamine), coconut oil fatty acid monoisopropanolamide (INCI: cocamide MIPA or cocamide mono-isopropanolamine), and mixtures thereof.

Such products are available, for example, coconut oil fatty acid monoethanolamide (cocamide MEA) marketed under the name COMPERLAN® 100 by the company COGNIS (BASF), coconut oil fatty acid monoisopropanolamide (cocamide MIPA) marketed under the trade name EMPILAN® CIS by the company Innospec active chemicals.

According to a particular embodiment, said _C6 - _C30 fatty acid alkanolamide is cocamide mono-isopropanolamine.

The _C6 - _C30 fatty acid alkanolamide according to the present invention may be present in an amount ranging from 0.5% to 10% by weight, more particularly from 0.1% to 5% by weight, relative to the total weight of the composition.

According to a particular embodiment, a composition according to the invention comprises an amount of less than 2% by weight relative to the total weight of the composition of solid fatty acid(s) at room temperature (25°C), more particularly a composition according to the invention comprises an amount of less than 1% by weight relative to the total weight of the composition of solid fatty acid(s) at room temperature (25°C), i.e. or is free (0% by weight relative to the total weight of the composition) of solid fatty acid at room temperature (25°C), and in particular does not comprise stearic acid.

According to a particular embodiment, a composition according to the invention comprises an amount of less than 0.5% by weight relative to the total weight of the composition of benzoic acid, and/or its salts, in particular benzoates of alkali or alkaline earth metals such as sodium benzoate, of sorbic acid and/or its salts, in particular sorbate of alkali or alkaline earth salt including potassium sorbate, more particularly less than 0.1% by weight or even free (0% by weight relative to the total weight of the composition) of benzoic acid and/or its salts including sodium benzoate, and of sorbic acid and/or its salts including potassium sorbate.

According to a particular embodiment, a composition according to the invention comprises an amount of less than 0.1% in total amount by weight relative to the total weight of the composition of carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soy lecithin, sodium alginate, polyacrylamidomethyl propane sulfonic acid, carbomer, cellulose, sodium polyacrylate, konjac gum, agar, and caesalpinia spinosa gum, more particularly according to an embodiment of the invention the composition is free (0% by weight relative to the total weight of the composition) of carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soy lecithin, sodium alginate, polyacrylamidomethyl propanesulfonic acid, carbomer, cellulose, sodium polyacrylate, konjac gum, agar, and C aesalpinia spinosa gum.

According to a particular embodiment, a composition according to the invention comprises an amount of less than 0.5% in total amount by weight relative to the total weight of the composition in anionic surfactant, more particularly the composition is free of anionic surfactant (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention comprises an amount less than or equal to 0.5% in total amount by weight relative to the total weight of the composition in cationic surfactant, more particularly the composition is free of cationic surfactant (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention comprises an amount less than or equal to 0.5% in total amount by weight relative to the total weight of the composition of amphoteric surfactant, more particularly the composition is free of amphoteric surfactant (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention comprises an amount less than or equal to 0.5% in total amount by weight relative to the total weight of the composition in zwitteronic surfactant, more particularly is free of zwitteronic surfactant (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention comprises an amount of less than 0.5% in total amount by weight relative to the total weight of the composition of anionic, cationic, amphoteric and zwitterionic surfactant, more particularly an amount of less than 0.1% in total amount by weight relative to the total weight of the composition of anionic, cationic, amphoteric and zwitterionic surfactant, even more particularly an amount of less than 0.01% in total amount by weight relative to the total weight of the composition of anionic, cationic, amphoteric and zwitterionic surfactant, better still according to a particular embodiment the composition is free of anionic, cationic, amphoteric and zwitterionic surfactant (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention comprises an amount of less than 0.5% in total amount by weight relative to the total weight of the composition of glyceryl stearate citrate, of alkyl sulfate such as sodium lauryl sulfate, of alkyl ether sulfate such as sodium laureth sulfate, of disodium cocoamphodiacetate, of polyglycerol esters and of fatty acid such as polyglyceryl-4-isostearate, of polyglyceryl-4-diisostearate polyhydroxystearate sebacate, and of sodium stearate, glyceryl stearate citrate, of alkyl sulfate such as sodium lauryl sulfate, of alkyl ether sulfate such as sodium laureth sulfate, of disodium cocoamphodiacetate, of polyglycerol esters and of fatty acid such as polyglyceryl-4-isostearate and polyglyceryl-4-diisostearate polyhydroxystearate sebacate, and sodium stearate.

According to a particular embodiment, a composition according to the invention comprises an amount of less than 1% by weight relative to the total weight of the composition of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica, more particularly comprises an amount of less than 0.5% by weight relative to the total weight of the composition of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica, or is even free (0% by weight relative to the total weight of the composition) of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica.

According to a particular embodiment, a composition according to the invention comprises an amount of less than 0.1% by weight relative to the total weight of the composition of solid fatty acid at room temperature (25°C), and in particular does not comprise stearic acid; of benzoic acid, and/or its salts, in particular benzoates of alkali or alkaline earth metals such as sodium benzoate, of sorbic acid and/or its salts, in particular sorbate of alkali or alkaline earth salt including potassium sorbate; carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soy lecithin, sodium alginate, polyacrylamidomethyl propane sulfonic acid, carbomer, sodium polyacrylate, konjac gum, agar, and caesalpinia spinosa gum; glyceryl stearate citrate, alkyl sulfate such as sodium lauryl sulfate, alkyl ether sulfate such as sodium laureth sulfate, disodium cocoamphodiacetate, polyglycerol fatty acid esters such as polyglyceryl-4-isostearate and polyglyceryl-4-diisostearate polyhydroxystearate sebacate, and sodium stearate; kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica.

According to a particular embodiment, a composition according to the invention comprises a pH adjuster, and in particular comprises arginine.

According to one embodiment, a composition according to the invention comprises hydroxypropylmethylcellulose.

According to a particular embodiment, a composition according to the invention comprises water.

According to a particular embodiment, a composition according to the invention comprises propylene glycol.

According to a particular embodiment, a composition according to the invention comprises arginine, water, propylene glycol and hydroxypropylmethylcellulose.

A composition according to the invention may further comprise arginine in a content making it possible to maintain a pH of between 7 and 8, in particular making it possible to maintain a pH of approximately 7.5.

The composition, in particular cosmetic, may further comprise, depending on the type of application envisaged, the constituents conventionally used in the fields considered, which are present in a quantity appropriate to the desired galenic form.

A composition according to the invention can be presented in all the galenic forms normally used in the cosmetic field.

It may be in particular in the form of an aqueous, hydroalcoholic, optionally gelled solution, a dispersion of the lotion type, optionally two-phase, an oil-in-water or water-in-oil or multiple emulsion, a gel, in particular aqueous, or even a dispersion of oils in an aqueous phase, in particular using spherules, these spherules possibly being polymeric particles or better, lipid vesicles of the ionic and/or non-ionic type. In particular, a composition according to the invention may be in the form of a gel, in particular an aqueous gel. It may also be an anhydrous composition. Anhydrous composition means a composition containing less than 10% by weight of water, in particular less than 5% by weight of water, more particularly less than 2% by weight of water, or even less than 0.5% of water, and in particular free of water, the water not being added during the preparation of the composition but corresponding to the residual water provided by the mixed ingredients. The composition may be of a more or less fluid liquid consistency.

A composition according to the invention is preferentially suitable for topical administration.

Thus, a composition according to the invention can comprise all the constituents usually used in the application and topical administration envisaged.

A composition according to the invention may advantageously be in the form of an emulsion, in particular obtained by dispersing an aqueous phase in a fatty phase (W/O) or a fatty phase in an aqueous phase (O/W), of liquid or semi-liquid consistency of the milk type, or of soft consistency, or even of multiple emulsion (W/O/W or O/W/O). These compositions are prepared according to the usual known methods.

More particularly, a composition according to the invention may be intended for topical application and may preferably be in the form of an emulsion, preferably an oil-in-water emulsion. Preferably, such an emulsion is not intended to be rinsed after application.

A composition according to the invention is preferably intended to be applied to the skin.

Preferably, the skin is the skin of the face, scalp, décolleté, neck, arms or forearms, or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, chin), décolleté and neck.

The composition may alternatively take the form of a facial and/or body care or makeup product, and be packaged, for example, in the form of a cream in a pot or a fluid in a tube or in a pump bottle or dropper bottle.

The composition according to the invention can be manufactured by any known process generally used in the cosmetic field.

The ingredients are mixed before being shaped, in the order and under conditions easily determined by those skilled in the art.

According to a particular embodiment of the invention, other agents intended to enhance the appearance and/or texture of the skin may also be added to the composition according to the invention.

Uses and methods

According to one of its aspects, the present invention relates to the cosmetic use, in particular topical, of a composition according to the invention for preventing and/or treating a skin disorder linked to colonization by Staphylococcus aureus in an individual in need thereof, and in particular for preventing and/or treating acne and/or eczema in an individual in need thereof.

According to another of its aspects, the present invention relates to a non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition according to the invention.

A skin may in particular be skin with acne or at risk of acne and/or skin with eczema or at risk of eczema. Thus, as indicated above, a skin disorder related to colonization of the skin by S. aureus in an individual is in particular chosen from eczema, acne or acne and eczema.

The cosmetic uses and processes considered according to the invention are non-therapeutic.

The cosmetic uses and methods of the invention are preferably implemented by topically administering a composition according to the invention.

Topical administration consists of the external application to the skin of cosmetic compositions according to the usual techniques of use of these compositions.

By way of illustration, the cosmetic use or process according to the invention can be implemented by topical application, for example daily, of at least one composition according to the invention, which can be for example formulated in the form of a cream, gel, serum, lotion, emulsion or make-up remover milk, in particular in the form of a gel.

The application can be repeated for example 1 to 2 times daily over a day or more and generally over a prolonged period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with one or more periods of interruption where appropriate.

According to one embodiment, the application is daily (once a day) and generally over a prolonged period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of interruption.

According to one embodiment, the cosmetic treatment method according to the invention may comprise a single application.

Throughout the description, including the claims, the expressions "between ... and ..." and "ranging from ... to ..." must be understood inclusively, unless otherwise specified.

The following examples illustrate the present invention without limiting its scope.

In the examples, unless otherwise indicated, the temperature is ambient (20°C), and expressed in degrees Celsius, and the pressure is atmospheric pressure.

Examples

Preparation of the suspension of work of Staphylococcus aureus ( S. aureus ) from of a lyophilisate ATCC 6538 (according to the recommendations of standard NF EN 12353).

The lyophilisate is rehydrated in Trypticase soy broth, inoculated on Trypticase soy agar (TSA plates) and then incubated for 24 hours at 32.5°C. The cells are then recovered and resuspended in a commercial cryoprotective solution with cryobeads for storage at -80°C for up to 14 months (stock for long-term storage).

From a cryobead of this -80°C stock, a subculture is carried out on a TSA slant agar which is then incubated for 24 hours at 32.5°C to obtain the stock culture. This stock culture is stored at 4°C for a maximum of 9 weeks. The working culture is obtained by subculture of the stock culture on Trypticase soy agar then incubation for 24 hours at 35°C. The working suspension is prepared by suspending the cells of this working culture in a trypton salt diluent. This suspension is calibrated between 1 and 3x10 ⁸ CFU (colony forming units) /mL by absorbance measurement at 620nm.

Evaluation of antimicrobial activity of samples against S . aureus

Two formulas were prepared based on the information provided in Table 1 below.

INCI NAME Composition 1 (according to the invention)
pH 7.4 Composition 2 (excluding the invention)
pH 7.5 Formula base:
-WATER
-ARGININE,
- HYDROXYPROPYLMETHYLCELLULOSE
-PROPYLENE GLYCOL (PROPYLENE GLYCOL USP/EP from DOW) Qsp 100 Qsp 100 SODIUM BENZOATE (PUROXS GRAINS PURE GRADE SODIUM BENZOATE from EMERALD PERFORMANCE MATERIALS) - 0.50% CAPRYOLYL GLYCINE (LIPACIDE C8G from SEPPIC) 0.10% - ENDOLYSIN OF SEQUENCE SEQ ID NO: 10 0.002565% 0.002565%

These two formulas were also reproduced in the absence of endolysin.

Composition 1, comprising a compound of formula (I), capryloyl glycine, is a composition according to the invention. Capryloyl glycine can, among other things, play the role of a preservative in a cosmetic composition. A comparative composition, outside the invention, devoid of compound of formula (I) was also tested. The latter comprises another preservative outside the invention used in the field of cosmetics, namely sodium benzoate.

At T=6 months from the manufacture of the formulas, 20 gram aliquots of each formula are inoculated with 0.2 ml of a calibrated suspension of S. aureus . After homogenization, the level of microorganisms present in the product represents a concentration of S. aureus of 10 ⁶ CFU per gram of product, i.e. a 1% inoculation of a suspension at 10 ⁸ CFU per mL (the inoculum level is determined by spreading the suspension on Trypticase soy agar plates and incubating for 24 hours at 35°C). After t=30 minutes and t=60 minutes of contact at room temperature (20°C ± 3°C), 1 gram of the mixture is weighed and then 9.0 mL of Eugon LT100 supp broth are added and mixed until completely homogenized. This mixture is then serially diluted in Eugon LT100 supp broth until dilution ^1/100 .

Dilutions are plated on Trypticase soy agar plates and incubated at 35°C for 48 hours until surviving S. aureus colonies are counted.

The antimicrobial activity on S. aureus is expressed as a logarithmic reduction compared to the initial rate and associated with the activity of the active compound which is the endolysin of sequence SEQ ID NO: 10 by comparison of the counts of surviving S. aureus in formula with and without endolysin, in the presence of each of the compounds tested.

This method is an adaptation of the challenge test method described in the standard “ ISO 11930 Cosmetics – Microbiology – Evaluation of the antimicrobial protection of a cosmetic product ” .

The preservatives are present in the compositions of the present example in a usual content for each of them in a cosmetic composition, in particular in a usual content for each of them allowing them to play their role as cosmetic preservative.

Results and conclusions

The results are expressed as logarithmic reduction of the Staphylococcus aureus population compared to the inoculated rate. The reductions are thus between 0 log (no antimicrobial activity observed in the tested condition, i.e. complete loss of endolysin activity) and -5.5 log (maximum decrease observable in the test conditions, i.e. maintenance of endolysin activity in the tested conditions). For values close to 0, no Staphylococcus aureus was destroyed. For values close to -5.5, 99.9996% of the Staphylococcus aureus population was destroyed. The tested formula is therefore particularly active when the values are close to -5.5.

The evaluation of the antimicrobial activity of endolysin is taken at T=1 week and T=6 months from the date of manufacture of the formulas. These two evaluations are carried out according to the protocol described above, i.e. the measurement of the activity of endolysin in formula after t=30 minutes of contact and t=1 hour of contact S.aureus / formula.

The results after one week are provided in Table 2 below.

Composition pH Endolysin of sequence SEQ ID NO: 10 (%) Destruction results at T1 week Destruction results at T=6 months Reduction log at t30mn Reduction log at t1h Reduction log at t30mn Reduction log at t1h 1 according to the invention 7.4 0% 0 0 0 0 7.5 0.002565% -5.1 -5.5 -2 -3.2 2 outside invention 7.5 0% 0 0 / / 7.5 0.002565% -1.1 -1.7 / /

The results show that the combination of a compound of formula (I) according to the invention, such as capryloyl glycine, with the endolysin of sequence SEQ ID NO: 10 makes it possible to maintain the antibacterial activity against S. aureus of the endolysin even after 6 months of storage of the composition.

Conversely, a composition comprising sodium benzoate instead of the compound of formula (I) does not allow the endolysin to maintain its killing activity against S. aureus .

Sequence Listing

SEQ ID NO: 1 CBD-2638 (protein)

WKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK

SEQ ID NO: 2 CBD-2638 (nucleic)

TGGAAACAGAATAAAGATGGCATTTGGTATAAAGCTGAACATGCTTCGTTCACAGTGACAGCACCAGAGGGAATTATCACAAGATACAAAGGTCCTTGGACTGGTCACCCACAAGCTGGTGTATTACAAAAAGGTCAAACGA TTAAATATGATGAGGTTCAAAAATTTGACGGTCATGTTTGGGTATCGTGGGAAACGTTTGAGGGCGAAACTGTATACATGCCGGTACGCACATGGGACGCTAAAACTGGTAAAGTTGGTAAGTTGTGGGGCGAAATTAAATAA

SEQ ID NO: 3 Ply2638 (protein)

MLTAIDYLTKKGWKISSDPRTYDGYPKNYGYRNYHENGINYDEFCGGYHRAFDVYSNETNDVPAVTSGTVIEANDYGNFGGTFVIRDANDNDWIYGHLQRGSMRFVVGDKVNQGDIIGLQG NSNYYDNPMSVHLHLQLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVYANRNE VLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHYYDGGKLEV SKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK

SEQ ID NO: 4 Ply2638 (protein)

MRGSHHHHHGSMLTAIDYLTKKGWKISSDPRTYDGYPKNYGYRNYHENGINYDEFCGGYHRAFDVYSNETNDVPAVTSGTVIEANDYGNFGGTFVIRDANDNDWIYGHLQRGSMRFVVGDKVN QGDIIGLQGNSNYYDNPMSVHLHLQLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASV YANRNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHYYDGGK LEVSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK

SEQ ID NO: 5 Ply2638 (nucleic)

ATGCTAACTGCTATTGACTATCTTACGAAAAAAGGTTGGAAAATATCATCTGACCCTCGCACTTACGATGGTTACCCTAAAAACTACGGCTACAGAAATTACCATGAAAACGGCATTAATTATGATGAGTTTTGTGGTGGTTATCATAGAGCTTTTGATGTTTACAGTAACGAAACTAACGA CGTGCCTGCTGTTACTAGCGGAACAGTTATTGAAGCAAACGATTACGGTAATTTTGGTGGTACATTCGTTATTAGAGACGCTAACGATAACGATTGGATATATGGGCATCTACAACGTGGCTCAATGCGATTTGTTGTAGGCGACAAAGTCAATCAAGGTGACATTATTGGTTTACAAGGTAA TAGCAACTATTACGACAATCCTATGAGTGTACATTTACATTTACAATTACGCCCTAAAGACGCAAAGAAAGATGAAAAAATCACAAGTATGTAGTGGTTTGGCTATGGAAAAATATGACATTACAAATTTAAATGCTAAACAAGATAAATCAAAGAATGGGAGCGTGAAAGAGTTGAAACATA TCTATTCAAACCATATTAAAGGTAACAAGATTACAGCACCAAAACCTAGTATTCAAGGTGTGGTCATCCACAATGATTATGGTAGTATGACACCTAGTCAATACTTACCATGGTTATATGCACGTGAGAATAACGGTACACACGTTAACGGTTGGGCTAGTGTTTATGCAAATAGAAACGAAG TGCTTTGGTATCATCCGACAGACTACGTAGAGTGGCATTGTGGTAATCAATGGGCAAATGCTAACTTAATCGGATTTGAAGTGTGTGAGTCGTATCCTGGTAGAATCTCGGACAAATTATTCTTAGAAAATGAAGAAGCGACATTGAAAGTAGCTGCGGATGTGATGAAGTCGTACGGATTA CCAGTTAATCGCAACACTGTACGTCTGCATAACGAATTCTTCGGAACTTCTTGTCCACATCGTTCGTGGGACTTGCATGTTGGCAAAGGTGAGCCTTACACAACTACTAATATTAATAAAATGAAAGACTACTTCATCAAACGCATCAAACATTATTATGACGGTGGAAAGCTAGAAGTAAGC AAAGCAGCAACTATCAAACAATCTGACGTTAAGCAAGAAGTTAAAAAGCAAGAAGCAAAACAAATTGTGAAAGCAACAGATTGGAAACAGAATAAAGATGGCATTTGGTATAAAGCTGAACATGCTTCGTTCACAGTGACAGCACCAGAGGGAATTATCACAAGATACAAAGGTCCTTGGACT GGTCACCCACAAGCTGGTGTATTACAAAAAGGTCAAACGATTAAATATGATGAGGTTCAAAAATTTGACGGTCATGTTTGGGTATCGTGGGAAACGTTTGAGGGCGAAACTGTATACATGCCGGTACGCACATGGGACGCTAAAACTGGTAAAGTTGGTAAGTTGTGGGGCGAAATTAAATAA

SEQ ID NO: 6 M23-LST (protein)

AATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVDFFMNIGTPVKAISSGKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVKAGQIIGWSGSTGYSTAPHLHFQRMVNSFSNSTAQDPMPFLKSAGY

SEQ ID NO: 7 M23-LST (nucleic)

GCTGCAACACATGAACATTCAGCACAATGGTTGAATAATTACAAAAAAGGATATGGTTACGGTCCTTATCCATTAGGTATAAATGGCGGTATGCACTACGGAGTTGATTTTTTTATGAATATTGGAACACCAGTAAAAGCTATTTCAAGCGGAAAAATAGTTGAAGCTGGTTGGAGTAATTACGGAGGAGGTAATCAAATAGG TCTTATTGAAAATGATGGAGTGCATAGACAATGGTATATGCATCTAAGTAAATATAATGTTAAAGTAGGAGATTATGTCAAAGCTGGTCAAATAATCGGTTGGTCTGGAAGCACTGGTTATTCTACAGCACCACATTTACACTTCCAAAGAATGGTTAATTCATTTTCAAATTCAACTGCCCAAGATCCAATGCCTTTCTTAAA GAGCGCAGGATAT

SEQ ID NO: 8 Ami-2638 (protein)

NKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVYANRNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHYYDG

SEQ ID NO: 9 Ami-2638 (nucleic)

GGTAACAAGATTACAGCACCAAAACCTAGTATTCAAGGTGTGGTCATCCACAATGATTATGGTAGTATGACACCTAGTCAATACTTACCATGGTTATATGCACGTGAGAATAACGGTACACACGTTA ACGGTTGGGCTAGTGTTTATGCAAATAGAAACGAAGTGCTTTGGTATCATCCGACAGACTACGTAGAGTGGCATTGTGGTAATCAATGGGCAAATGCTAACTTAATCGGATTTGAAGTGTGTGAGTCG TATCCTGGTAGAATCTCGGACAAATTATTCTTAGAAAATGAAGAAGCGACATTGAAAGTAGCTGCGGATGTGATGAAGTCGTACGGATTACCAGTTAATCGCAACACTGTACGTCTGCATAACGAAT TCTTCGGAACTTCTTGTCCACATCGTTCGTGGGACTTGCATGTTGGCAAAGGTGAGCCTTACACAACTACTACTAATATTAATAAAATGAAAGACTACTTCATCAAACGCATCAAACATTATTATGACGGT

SEQ ID NO: 10 M23-LST Ami2638 CBD2638 (protein)

AATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVDFFMNIGTPVKAISSGKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVKAGQIIGWSGSTGYSTAPHLHFQRMVNSFSNS TAQDPMPFLKSAGYGKAGGTVTPTPNTGELLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNG WASVYANRNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHYYDG GKLEVSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK

SEQ ID NO: 11 M23-LST Ami2638 CBD2638 (protein)

MRGSHHHHHGSAATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVDFFMNIGTPVKAISSGKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVKAGQIIGWSGSTGYSTAPHLHFQ RMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPTPNTGELLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENN GTHVNGWASVYANRNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHY YDGGKLEVSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK

SEQ ID NO: 12 M23-LST Ami2638 CBD2638 (nucleic)

GCTGCAACACATGAACATTCAGCACAATGGTTGAATAATTACAAAAAAGGATATGGTTACGGTCCTTATCCATTAGGTATAAATGGCGGTATGCACTACGGAGTTGATTTTTTTATGAATATTGGAACACCAGTAAAAGCTATTTCAAGCGGAAAAATAGTTGAAGCTGGTTGGAGTAATTACGGAGGA GGTAATCAAATAGGTCTTATTGAAAATGATGGAGTGCATAGACAATGGTATATGCATCTAAGTAAATATAATGTTAAAGTAGGAGATTATGTCAAAGCTTGTCAAATAATCGGTTGGTCTGGAAGCACTGGTTATTCTACAGCACCACATTTACACTTCCAAAGAATGGTTAATTCATTTTCAAATTCAA CTGCCCAAGATCCAATGCCTTTCTTAAAGAGCGCAGGATATGGAAAAGCAGGTGGTACAGTAACTCCAACGCCGAATACAGGTGAGCTCTTACGCCCTAAAGACGCAAAGAAAGATGAAAAAATCACAAGTATGTAGTGGTTTGGCTATGGAAAAATATGACATTACAAATTTAAATGCTAAACAAGATAA ATCAAAGAATGGGAGCGTGAAAGAGTTGAAACATATCTATTCAAACCATATTAAAGGTAACAAGATTACAGCACCAAAACCTAGTATTCAAGGTGTGGTCATCCACAATGATTATGGTAGTATGACACCTAGTCAATACTTACCATGGTTATATGCACGTGAGAATAACGGTACACACGTTAACGGTTGG GCTAGGTTTATGCAAATAGAAACGAAGTGCTTTGGTATCATCCGACAGACTACGTAGAGTGGCATTGTGGTAATCAATGGGCAAATGCTAACTTAATCGGATTTGAAGTGTGTGAGTCGTATCCTGGTAGAATCTCGGACAAATTATTCTTAGAAAATGAAGAAGCGACATTGAAAGTAGCTGCGGATG TGATGAAGTCGTACGGATTACCAGTTAATCGCAACACTGTACGTCTGCATAACGAATTCTTCGGAACTTCTTGTCCACATCGTTCGTGGGACTTGCATGTTGGCAAAGGTGAGCCTTACACAACTACTACTAATATTAATAAAATGAAAGACTACTTCATCAAACGCATCAAACATTATTATGACGGTGGAAA GCTAGAAGTAAGCAAAGCAGCAACTATCAAACAATCTGACGTTAAGCAAGAAGTTAAAAAGCAAGAAGCAAAACAAATTGTGAAAGCAACAGATTGGAAACAGAATAAAGATGGCATTTGGTATAAAGCTGAACATGCTTCGTTCACAGTGACAGCACCAGAGGGAATTATCACAAGATACAAAGGTCCT TGGACTGGTCACCCACAAGCTGGTGTATTACAAAAAGGTCAAACGATTAAATATGATGAGGTTCAAAAATTTGACGGTCATGTTTGGGTATCGTGGGAAACGTTTGAGGGCGAAACTGTATACATGCCGGTACGCACATGGGACGCTAAAACTGGTAAAGTTGGTAAGTTGTGGGGCGAAATTAAATAA.

SEQ ID NO: 13 N-terminal 6xHis tag

MRGSHHHHHHGS

Claims (19)

Composition, in particular cosmetic, comprising, in a physiologically acceptable medium:
(i) at least one endolysin; and
(ii) at least one compound of formula (I), one of its acid or base salts, organic or inorganic, one of its optical isomers, or one of its solvates:
R ₁ -C(O)-N(H)-CH(R ₂ )-C(O)-OR ₃ (I)
in which:
- R ₁ represents a (C ₆ -C ₂₀ )alkyl group;
- R ₂ represents a hydrogen atom or a (C ₁ -C ₆ )alkyl group optionally substituted by a guanidine group optionally substituted by one or more (C ₁ -C ₄ )alkyl groups; and
- R ₃ represents a hydrogen atom or a (C ₁ -C ₆ )alkyl group. The composition of claim 1, wherein the endolysin is an endolysin derived from a Staphylococcus aureus phage. A composition according to claim 1 or 2, wherein the endolysin comprises a first protein sequence comprising a cell wall binding domain of species of the genus Staphylococcus . Composition according to claim 3, in which the first protein sequence is derived from the endolysin of the bacteriophage Φ2638a of S. aureus . Composition according to claim 3 or 4, wherein the first protein sequence comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 1 . A composition according to any one of claims 1 to 4, wherein the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4 . A composition according to any one of claims 3 to 5, wherein said endolysin further comprises a heterologous protein sequence. The composition of claim 7, wherein the heterologous protein sequence comprises a lytic domain, said lytic domain comprising a second and a third protein sequence, said second protein sequence comprising an M23 endopeptidase domain and said third protein sequence comprising an amidase domain. A composition according to claim 8, wherein said second and third protein sequences are derived, independently of each other, from an enzyme selected from the group consisting of the endolysin of the bacteriophage Φ2638a of S. aureus and the lysostaphin of S. simulans , in particular one of the second and third protein sequences being derived from the endolysin of the bacteriophage Φ2638a of S. aureus and the other of the second and third protein sequences being derived from the lysostaphin of S. simulans. Composition according to claim 8 or 9, wherein said second protein sequence comprises at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 6 and said third protein sequence comprises at least 80%, in particular 90%, more particularly 95% sequence identity with the reference amino acid sequence SEQ ID NO: 8 . A composition according to any one of claims 1 to 4 and 6 to 9, wherein the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 10 , and SEQ ID NO: 11 , in particular the endolysin comprises a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 10 . Composition according to any one of claims 1 to 11, in which the endolysin is present in a content ranging from 0.0001% to 0.1% by weight relative to the total weight of the composition, in particular from 0.0005% to 0.01% by weight relative to the total weight of the composition, more particularly from 0.001% to 0.005% by weight relative to the total weight of the composition. Composition according to any one of claims 1 to 12, in which the compound of formula (I) is characterized in that:
R ₁ represents a linear or branched (C ₆ -C ₁₂ )alkyl group, preferably linear, in particular a linear -C ₇ H ₁₅ group; and
_R2 and _R3 represent hydrogen atoms Composition according to any one of claims 1 to 13, in which the compound of formula (I) is chosen from laurylethyl arginate and capryloyl glycine, in particular is capryloyl glycine. Composition according to any one of claims 1 to 14, comprising a total content of compound(s) of formula (I), preferably capryloyl glycine, of between 0.01% to 3% by weight relative to the total weight of the composition, preferably from 0.02% to 1.0% by weight, and more preferably from 0.05% to 0.5% by weight, relative to the total weight of the composition. A composition according to any one of claims 1 to 15, the composition being suitable for topical administration. Composition according to any one of claims 1 to 16 for its use in the prevention and/or treatment of a skin disorder linked to colonization by Staphylococcus aureus in an individual in need thereof, in particular for the prevention and/or treatment of acne and/or eczema in the individual. A composition for use according to claim 17, wherein the composition is suitable for topical administration. Non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition according to any one of claims 1 to 16.