EP4719332A1 - Anhydrous cosmetic composition comprising an endolysin derived from staphylococcus aureus phage and mannitol - Google Patents

Abstract

An anhydrous composition comprising an endolysin derived from a Staphylococcus aureus phage and mannitol. The present invention relates to an anhydrous composition comprising (i) at least one endolysin derived from a Staphylococcus aureus phage; and (ii) mannitol, the endolysin comprising a protein sequence comprising at least 80% sequence identity with an amino acid sequence chosen from the group constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2. The invention also relates to a composition comprising, in a physiologically acceptable medium, at least one anhydrous composition of the invention. The invention 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, and to a non-therapeutic cosmetic method for caring for keratin materials comprising at least one step of topical application to said keratin materials of such a composition. The invention lastly relates to a method for stabilizing an endolysin derived from a Staphylococcus aureus phage.

Description

Description

Title: Anhydrous cosmetic composition comprising an endolysin derived from Staphylococcus aureus phage and mannitol.

Technical field

The present invention relates to an anhydrous composition (hereinafter referred to as composition A) comprising at least (i) an endolysin derived from a Staphylococcus aureus phage comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2 and (ii) mannitol.

The invention also relates to a composition (hereinafter referred to as composition B), in particular a cosmetic composition, comprising, in a physiologically acceptable medium, at least one such anhydrous composition (composition A), in particular in a solubilized form. The invention also relates in particular to the use of a composition of the invention (composition A or B) for preventing and/or treating a skin disorder associated with 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.

The invention moreover relates to a non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition A or B according to the invention.

The invention additionally relates to a method for stabilizing, in particular a method for drying, an endolysin derived from a Staphylococcus aureus phage comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, comprising bringing the endolysin into contact with mannitol and using mannitol to stabilize, in particular to dry, an endolysin derived from a Staphylococcus aureus phage.

Prior art

Human skin is permanently populated by a multitude of different microorganisms (bacteria, yeasts and fungi). The resident microbial flora, which is essential to the good health of the skin, is constituted mainly of propionibacteria (Cutibacterium acnes). staphylococci (Staphylococcus epidermidis and Staphylococcus ho minis), corynebacteria and streptococci, and also of a fungal flora composed mainly of Malassezia.

Certain dermatological disorders are usually due to the disruption of the ecological balance of the resident flora following a preponderant colonization by opportunistic microorganisms that are not beneficial to the skin, such as Staphylococcus aureus, which is known to be associated with atopic dermatitis (eczema), greasy or hyperseborrhoeic skin, and acne.

To counteract this excess colonization by these opportunistic microorganisms that are not beneficial to the skin, it is common practice to use broad- spectrum antimicrobials or bacterio stats. However, the use of these compounds poses the problem of non- specificity of action targeting both 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, and also of problems of skin tolerance (irritation, allergies, etc.).

There thus remains a need to find novel compounds with good antimicrobial efficacy which do not have the abovementioned drawbacks, and which have 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 5. aureus and lyse, and thus destroy, specifically this bacterium while preserving the resident skin flora (WO 2012/150858 Al). However, it is well known that one of the main obstacles to the application of endolysins targeting Staphylococcus species is a problem of the stability of these proteins and/or of their enzymatic activity, notably the maintenance of this activity over time.

Indeed, it has notably been observed that the lytic action of these enzymes is significantly impaired by interactions with raw materials, in particular when the endolysin is introduced into formulations, notably cosmetic formulations.

There is therefore a need for a formulation that makes it possible to increase the stability of endolysins over time and/or at temperature, in particular over time and at temperature. Indeed, such an improvement in the stability of endolysins makes it possible to have less restrictive supply, distribution, storage and usage conditions than at present, since endolysins require storage at -80°C.

It is known in particular that endolysins lose their activity in aqueous solutions. During the freeze-drying or spray-drying thereof, the inventors have found that by using mannitol as a drying support, the stability of the endolysin increases surprisingly, in particular compared to equivalent aqueous compositions.

There is also a need for an additive, the purpose of which is to promote preservation of the antimicrobial activity of the endolysins in anhydrous form over time, these endolysins retaining in particular their activity once rehydrated in a composition, in particular a cosmetic composition, with a view to use on a keratin material, in particular on the skin.

There is also a need for an additive, the purpose of which is (i) to promote preservation of the antimicrobial activity of the endolysins in anhydrous formulations over time, (ii) while retaining the specificity of these endolysins for the targeted bacteria, in particular Staphylococcus aureus in the present invention.

Disclosure of the invention

The aim of the present invention is to solve at least one abovementioned technical problem. Specifically, the inventors have now discovered that mannitol proves capable of maintaining good Staphylococcus aureus killing performance by the associated endolysin many weeks after the preparation of an anhydrous composition comprising same.

Summary of the invention

As mentioned above, the present invention thus relates to an anhydrous composition (also referred to as composition A), particularly a cosmetic composition, comprising, in a physiologically acceptable medium:

(i) at least an endolysin derived from a Staphylococcus aureus phage; and

(ii) mannitol, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2.

As illustrated in the examples below, the applicant has discovered, surprisingly, that an anhydrous composition (composition A) according to the invention, comprising an endolysin derived from a Staphylococcus aureus phage, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, and mannitol, advantageously makes it possible to maintain the .S'. aureus killing performance of the endolysin, even after a long period of storage at room temperature in anhydrous form (for example 13 weeks) after resolubilization in an aqueous medium (composition B). Moreover, this combination makes it possible to maintain the .S'. aureus killing performance of the endolysin, even at very high temperatures (2 months 45°C, 3 months 40°C and 1 h at 110°C). The present invention also relates to a composition (referred to as composition B), in particular a cosmetic composition, comprising, in a physiologically acceptable medium, at least one anhydrous composition (composition A) according to the invention, in particular in a solubilized form.

Thus, the present invention also relates in particular to the use of a composition of the invention (composition A or B) for preventing and/or treating a skin disorder associated with colonization by Staphylococcus aureus in an individual in need thereof, and in particular for preventing and/or treating acne and/or eczema in the individual.

Furthermore, the present invention also relates to a method for stabilizing an endolysin derived from a Staphylococcus aureus phage, in particular a method for drying an endolysin derived from a Staphylococcus aureus phage, comprising bringing the endolysin into contact with mannitol, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, the endolysin comprising a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

The invention moreover relates to a non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition (composition A or B) according to the invention.

The present invention additionally relates to the use of mannitol for stabilizing, in particular drying, an endolysin derived from a Staphylococcus aureus phage.

The present invention also relates to a kit for formulating a cosmetic product, comprising at least:

(i) an anhydrous composition (composition A) according to the invention; and

(ii) a cosmetic composition containing an aqueous gel or an emulsion; the anhydrous composition (i) and the cosmetic composition (ii) each being in a compartment, the two compartments being spatially separated.

The present invention additionally relates to a cosmetic composition comprising at least one anhydrous composition (composition A) according to the invention dispersed in an oil.

Detailed description

“Cosmetic” means a composition that is compatible with keratin materials, in particular the skin, mucous membranes and skin appendages, more particularly the skin. The composition according to the invention is non-therapeutic.

“Anhydrous composition'” means a composition characterized by an absence of water or the presence of water in an amount such that a qualified person can determine that it is free or substantially free of water. For example, an “anhydrous” composition according to the present invention may comprise less than 10%, notably less than 5%, in particular less than 2%, preferably less than 0.5% by weight of water, relative to the total weight of the composition. Preferably, an “anhydrous” composition according to the present invention does not comprise a detectable amount of water, the “detectable amount” signifying an amount that can be detected by a device conventionally used in the art to measure the water content.

In particular, an anhydrous composition according to the invention may be in the form of a lyophilizate or in a spray-dried form, in particular in the form of a lyophilizate.

“Keratin materials” in particular means the skin, mucous membranes, fibres, eyelashes and skin appendages.

“The skin” means all the skin of the body, and preferably the skin of the face, the scalp, the neckline, the neck, the arms and forearms, the eyelids, around the mouth or behind the ears, the hollow of the elbow, the back of the knees, the hands, the wrists and the ankles, or even more preferably the skin of the face (in particular the forehead, the nose, the cheeks and the chin), the neckline and the neck.

Certain compositions according to the invention comprise a physiologically acceptable medium, i.e. one which has a pleasant colour, odour and feel and which does not give rise to any unacceptable discomfort, i.e. stinging, tautness or redness, that is liable to discourage the user from applying this composition. Needless to say, a person skilled in the art will take care to choose a physiologically acceptable medium such that the advantageous properties of the endolysin(s) of the invention are not, or are not substantially, adversely affected. Thus, by way of illustration, a physiologically acceptable medium may consist mainly of water and/or of one or more water- miscible organic solvents. A physiologically acceptable medium according to the invention preferentially has a pH between 4 and 8, more particularly between 4.5 and 7.5. Thus, a composition according to the invention can comprise one or more pH adjusters.

As used herein, the terms “treat” and “treatment” mean the alleviation of the symptoms associated with a specific disorder or condition and/or the elimination of said symptoms and also the complete disappearance of the disorder or condition in question.

In the context of the present invention, the terms “prevent” and “prevention” denote the reduction, to a lesser degree, of the risk or probability of occurrence of a given phenomenon.

Endolysin derived from a Staphylococcus aureus phage

A composition according to the invention (composition A or B) is firstly characterized in that it comprises at least one endolysin derived from a Staphylococcus aureus phage, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2.

In the embodiments presented herein, the endolysin is an endolysin specific to Staphylococcus aureus, that is to say that it will effectively lyse Staphylococcus aureus but will not substantially lyse bacteria other than Staphylococcus aureus. In particular, an endolysin used according to the invention will lyse Staphylococcus aureus but not Staphylococcus epidermidis.

Most native Staphylococcus bacteriophage endolysins exhibiting peptidoglycan hydrolase activity, such as the Ply2638 endolysin, are composed of a C-terminal cell wall-binding domain (CBD), of a central N-acetylmuramoyl-L-alanine amidase domain, and of an N- terminal alanyl-glycyl endopeptidase domain with cysteine, in the case of Ply2638, of an N- terminal glycylalanyl-glycine endopeptidase domain with Peptidase_M23 homology, the latter three domains each exhibiting peptidoglycan hydrolase activity with distinct target binding specificity and generally being named enzymatically active domains. The endolysin used according to the invention is a recombinant chimeric endolysin specific to Staphylococcus aureus comprising several heterologous domains.

In general, endolysins are constituted of various subunits (domains), for example a cell wallbinding domain (CBD) and one or more enzymatic domains having peptidoglycan activity, such as an amidase domain, an M23 domain, and a CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain. The chimeric endolysin specific to Staphylococcus aureus used according to the invention comprises several heterologous domains and is an endolysin comprising an amidase domain from the bacteriophage Ply2638, a lysostaphin (.S'. Simulans) M23 domain, and a cell wall-binding domain from the bacteriophage Ply2638.

This chimeric endolysin specific to Staphylococcus aureus is described in detail in document WO2012/150858, which is incorporated herein by reference in its entirety.

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 for same derived from one or more bacteriophages that are capable of lysing the wall of bacteria of the species Staphylococcus aureus.

The endolysin used in the context of the present invention is in recombinant form.

For each of the amino acid or nucleic acid sequences of interest, reference sequences are described herein. The present description also encompasses amino acid or nucleic acid sequences (for example 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 which respects, respectively, the nucleotide or amino acid identity under consideration must also lead to the production of a protein (or enzyme) which displays the desired biological activity. As used herein, the “percentage identity” between two nucleic acid sequences or between two amino acid sequences is determined by comparing the two optimally aligned sequences through a comparison window.

The portion of the nucleotide or amino acid sequence in the comparison window may thus comprise additions or deletions (e.g. “gaps”) relative to the reference sequence (which does not comprise these additions or deletions) so as to achieve 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 optimal comparison. In order to optimize the alignment between the two sequences, gaps may be introduced in either 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 about twenty, fifty, one hundred or more nucleic acids/bases or amino acids. Sequence identity is the percentage of identical matches between the two sequences over the reported aligned region.

The comparison of sequences and the determination of the percentage of sequence identity between two sequences may be performed using a mathematical algorithm. A person skilled in the art 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, pages 1-44 Addison Wesley).

The percentage of sequence identity between two amino acid sequences or between two nucleotide sequences may be determined using the Needleman-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 the alignment of both amino acid sequences and nucleotide sequences. The Needleman-Wunsch algorithm was implemented in the NEEDLE computer program.

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. Longden, J. and Bleasby, A. Trends in Genetics 16, (6) pages 276-277, http://emboss.bioinformatics.nl/). For protein sequences, EBLOSUM62 is used for the substitution matrix. For nucleotide sequences, EDNAFULL is used. The optional parameters used are a space opening penalty of 10 and a space extension penalty of 0.5. No end gap penalty is added. In the Output section, Yes has been indicated in response to the question “Brief identity and similarity” and “SRS pairwise” has been indicated as the output alignment format. After alignment by the NEEDLE program described above, the percentage of 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 the two sequences divided by the total length of the alignment after subtracting the total number of gaps in the alignment. The identity defined here may be obtained from NEEDLE using the NOBRIEF option and is labelled in the output of the program as “longest identity”.

The similarity of nucleotide and amino acid sequences, i.e. the percentage identity of the sequences, may be determined by sequence alignments using several other known algorithms, preferably 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 (mathematical algorithm of the University of Iowa) or the mathematical algorithm of Myers and Miller (1989 - Cabios 4: 11-17) or Clone Manager 9. The preferred parameters used are the default parameters as defined at https://www.ebi.ac.uk/Tools/msa/clustalo/.

The degree of sequence identity (sequence matching) may 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, so as to obtain polynucleotide sequences homologous to the nucleic acids which encode the protein of interest.

BLAST protein searches are performed with the BLASTP program, 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 matching analysis may 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 percentages of sequence identity in the present patent application, these percentages are calculated relative to the total length of the longest sequence, unless otherwise indicated.

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

Thus, as indicated above, the endolysin used according to the invention 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2.

In particular, the endolysin may comprise a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

The term “at least 80% sequence identity between two sequences” means 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 they are amino acid sequences or nucleic acid sequences.

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

An allelic variant denotes any one 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 introducing nucleotide substitutions, which do not result in another amino acid sequence of the polypeptide encoded by the nucleotide sequence, but which correspond to the use of codons of the host organism intended for the production of the polypeptide of the invention. According to a preferred embodiment, a nucleic acid variant encodes a polypeptide still having its biological function. More preferably, a nucleotide sequence variant encodes a polypeptide displaying 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 displaying increased binding to the cell wall of species of the genus Staphylococcus and/or lytic activity, as defined hereinbelow. Nucleic acids encoding a polypeptide displaying binding to the cell wall of species of the genus Staphylococcus and/or lytic activity may be isolated from any microorganism. All these variants may be obtained using techniques known to those skilled in the art, such as library screening by hybridization (Southern blot procedures) under low to medium to high hybridization conditions. Low to medium to high stringency conditions means 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. Next, 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.

The binding of a domain to the peptidoglycan cell wall of Staphylococcus genera may be evaluated using assays that are well known to those skilled in the art. In a preferred embodiment, an immunohistochemical technique and/or a gene fusion technique resulting in labelled constructs of either domain are used to evaluate the specific binding of peptides, polypeptides or proteins to the peptidoglycan cell wall of Staphylococcus genera. The signal quantification processes used in the abovementioned immunohistochemical or fusion techniques are well known in the art.

In one embodiment, the binding to the peptidoglycan cell wall of Staphylococcus may be quantified using a fluorescent fusion construct comprising a polypeptide comprising a domain included in a first protein sequence as described previously. Such a cell wall binding assay is described in detail by Loessner et al. (Molecular Microbiology 2002, 44(2): 335- 349). In said 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 cells, for a specified period of time, after which the cells are sedimented 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 evaluation of the binding of an endolysin to the cell wall of species of the genus Staphylococcus which are suitable according to the invention are particularly illustrated in WO 2012/150858 Al. Preferably, in the context of the present text, a protein sequence will be said to comprise a domain for binding to the peptidoglycan cell wall of 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.

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

“Heterologous protein sequence” means a protein sequence, i.e. an amino acid sequence or a nucleic acid sequence encoding the protein sequence, which is not naturally functionally linked as a neighbouring sequence to said first protein sequence. As used herein, the term “heterologous” may mean “recombinant”. The term “recombinant” refers to a genetic entity different from that generally found in nature. When applied to a nucleotide sequence or nucleic acid molecule, this 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 different from a sequence or molecule found in nature.

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

As indicated above, an endolysin used according to the invention comprises a heterologous protein sequence comprising a lytic domain, said lytic domain exhibiting peptidoglycan hydrolase activity.

“Peptidoglycan hydrolase activity”, also defined herein as “lytic activity”, may be evaluated via processes that are well known to those skilled in the art. In one embodiment, the lytic activity may be evaluated spectrophotometric ally by measuring the decrease in turbidity of substrate cell suspensions. Preferably, the lytic activity may be evaluated spectrophotometrically by measuring the decrease in turbidity of a suspension of .S'. aureus, the turbidity being quantified by measuring the OD595 spectrophotometrically (Libra S22, Biochrom). More preferably, 200 nM of a polypeptide encoded by a nucleic acid molecule as identified herein are incubated with a suspension of .S'. aureus having an initial ODeoo of 1 ± 0.05, as evaluated spectrophotometrically (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 OD595 after 30 min of incubation from the OD595 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.

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

An endopeptidase domain as used herein preferably cleaves pentaglycine cross-bridges (Trayer, H.R. and Buckley, C.E. (1970) Molecular properties of lysostaphin, a specific bacteriolytic agent for Staphylococcus aureus. J. Biol. Chem. 245, 4842-4846) which are 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 preferably hydrolyzes substrates containing gammaglutamyl.

The functionality and activity of such domains in a polypeptide may 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 the endolysin is measured by characterizing the cleavage products.

According to a particular embodiment, the endopeptidase and/or amidase activity of the endolysin may be measured by measuring the optical density of 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 (Basle). 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 each other, from an enzyme chosen from the group constituted by the endolysin from <I>2638a bacteriophage 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 <I»2638a bacteriophage of S. aureus and the other sequence of the second and third protein sequences is derived from the lysostaphin of S. simulans.

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: 3. 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: 3.

An endolysin comprising a protein sequence encoded by a reference nucleic acid sequence SEQ ID NO: 3 differs from the endolysin of the <I>2638a bacteriophage of S. aureus in that the N-terminal M23 endopeptidase domain is substituted with an M23 endopeptidase domain from the lysostaphin of S. simulans.

Endolysins that are suitable for use in the invention may be obtained via any method known to those skilled in the art for producing recombinant proteins. In particular, endolysins according to the invention may be obtained by introducing one or more genes of interest, such as the nucleic acid sequences described previously, into the genome of a host organism via a vector.

In another aspect, a nucleic acid construct comprising at least one of the nucleic acid sequences as defined previously is described.

Also described is an expression vector comprising such a nucleic acid construct. Preferably, an expression vector comprises a nucleotide sequence as mentioned previously, which is operatively linked to one or more control sequences, which direct the production or expression of the encoded polypeptide in a cell, a subject or a cell-free expression system. An expression vector may be considered a recombinant expression vector. This vector may be constituted of a plasmid, cosmid, bacteriophage or virus which is transformed by the introduction of a nucleic acid molecule according to the invention. Such transformation vectors according to the host organism to be transformed are well known to those skilled in the art and widely described in the literature.

Another subject described herein is a process for transforming host organisms by integration of at least one nucleic acid sequence as described, which transformation may be performed via any suitable means known and widely described in the specialized literature, more particularly via the vector described above.

In another aspect, a cell is described, which comprises a nucleic acid construct or an expression vector as defined previously. A cell may be any microbial, prokaryotic or eukaryotic cell, which is suitable for expressing an endolysin that is suitable for use in the invention. In a preferred embodiment, said cell is an E. coli cell. In an even more preferred embodiment, said cell is E. coli CLlblue MRF.

The endolysin obtained may 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 the purification of the resulting endolysin. Preferably, said tag is chosen from, but is not limited to, a group constituted of a FLAG tag, a poly(His) tag, an HA tag and an 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: 4.

An anhydrous composition (composition A) according to the invention may comprise a content of endolysin derived from a Staphylococcus aureus phage as described above ranging from 0.01% to 0.6% by weight relative to the total weight of the anhydrous composition, in particular from 0.05% to 0.5% by weight relative to the total weight of the anhydrous composition, more particularly from 0.1% to 0.3% by weight relative to the total weight of the anhydrous composition.

A composition according to the invention (composition B) may comprise a content of endolysin derived from a Staphylococcus aureus phage as described above 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.

Mannitol

Mannitol, or hexane-l,2,3,4,5,6-hexol, is a polyol structurally derived from mannose.

It can play several roles in a cosmetic composition such as the roles of humectant, fixing agent, masking agent, moisturizer, skin care agent. In particular, in the compositions according to the invention, mannitol acts as an endolysin stabilizer.

Mannitol corresponds to the following chemical formula (I).

[Chem 1]

An anhydrous composition according to the invention (composition A) may comprise mannitol in a content ranging from 30% to 90% by weight relative to the total weight of the anhydrous composition, in particular from 40% to 80% by weight relative to the total weight of the anhydrous composition, more particularly from 45% to 75% by weight relative to the total weight of the anhydrous composition.

A composition according to the invention (composition B) may comprise a content of mannitol ranging from 0.01% to 21% by weight relative to the total weight of the composition, in particular from 0.05% to 9% by weight relative to the total weight of the composition, more particularly from 0.1% to 3% by weight relative to the total weight of the composition.

A composition according to the invention (composition A or B) may comprise one or more endolysins according to the invention and mannitol in an endolysin(s)/mannitol weight ratio of between 0.001 and 0.003 and in particular between 0.002 and 0.003.

An example of mannitol suitable according to the invention is the mannitol sold under the name “Beaute by Roquette® PO 260” by the company ROQUETTE®. Anhydrous composition according to the invention (also referred to as composition A) As indicated above, an anhydrous composition according to the invention comprises at least one endolysin derived from a Staphylococcus aureus phage comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, the endolysin comprising a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1. It also comprises mannitol.

As indicated above, an anhydrous composition according to the invention may comprise a content of endolysin derived from a Staphylococcus aureus phage as described above ranging from 0.01% to 0.6% by weight relative to the total weight of the anhydrous composition, in particular from 0.05% to 0.5% by weight relative to the total weight of the anhydrous composition, more particularly from 0.1% to 0.3% by weight relative to the total weight of the anhydrous composition.

As also indicated above, an anhydrous composition according to the invention may comprise mannitol in a content ranging from 30% to 90% by weight relative to the total weight of the anhydrous composition, in particular from 40% to 80% by weight relative to the total weight of the anhydrous composition, more particularly from 45% to 75% by weight relative to the total weight of the anhydrous composition.

An anhydrous composition according to the invention (composition A) may in particular comprise no sucrose (i.e. comprise 0% by weight of sucrose relative to the total weight of the composition).

An anhydrous composition according to the invention can be obtained by freeze drying or by spray drying. In particular, an anhydrous composition according to the invention is obtained by freeze drying.

Thus, an anhydrous composition according to the invention may be in the form of a lyophilizate or in a spray-dried form. In particular, an anhydrous composition according to the invention is in the form of a lyophilizate.

Obtaining a lyophilizate or a spray-dried form involves performing freeze drying or spray drying respectively. Freeze drying or spray drying can be carried out according to conventional methods known to those skilled in the art (Fakhrossadat Emami et al., Pharmaceutics. 2018 Sep; 10(3): 131).

Preferably, an anhydrous composition according to the invention is in the form of a powder, a cake, a tablet, a gel capsule, or a sheet, in particular a powder.

It can be advantageous for the anhydrous composition to further comprise a freeze-drying additive, in particular to facilitate the freeze drying via the texturing of the composition, but also the rehydration of the freeze-dried form. Needless to say, a person skilled in the art will take care to choose a physiologically acceptable medium such that the advantageous properties of the endolysin(s) of the invention are not, or are not substantially, adversely affected. By way of example of freeze-drying additives, mention may be made of cellulose derivatives such as HPMC.

An anhydrous composition according to the invention (composition A) can be adapted so that dispersing the whole of this composition in a fixed amount of physiologically acceptable medium provides a dilute composition intended for a single use.

The contacting operation of an anhydrous composition according to the invention (composition A) can be carried out extemporaneously by direct immersion in the water of a bath, for example. It is also possible to envisage carrying out this contacting operation more gradually. Thus, there exist shower head devices constructed to enable the insertion into the head of anhydrous compositions intended for example for care purposes. The solubilization of the anhydrous composition is then assured gradually on contact with the water diffusing through the head.

Such a composition may be used directly in its anhydrous form on a keratin material in accordance with the uses described herein, or may be solubilized in a physiologically acceptable medium, in particular in an aqueous medium, in order to form a composition according to the invention (composition B) comprising in particular, in addition to a physiologically acceptable medium, an anhydrous composition according to the invention (composition A).

In the case where an anhydrous composition according to the invention (composition A) is not used directly but must first be solubilized, the use thereof is then combined with that of a physiologically acceptable medium which is in a fluid form suitable for the solubilization of the anhydrous composition, as detailed below. The present invention additionally relates to a method for stabilizing an endolysin derived from a Staphylococcus aureus phage, in particular a method for drying an endolysin derived from Staphylococcus aureus, comprising bringing the endolysin into contact with mannitol, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, the endolysin comprising a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

The endolysin “stabilization method" means a method that makes it possible to both maintain the physical integrity of the endolysin and also maintain its enzymatic activity, in particular its killing activity with respect to S. aureus.

This contacting operation can for example be carried out according to methods known in the art (Fakhrossadat Emami et al., Pharmaceutics. 2018 Sep; 10(3): 131).

This stabilization method, in particular drying method, comprises a step during which (i) the endolysin and (ii) the mannitol are mixed in an aqueous liquid, in particular water, which is then freeze dried.

Advantageously, this contacting operation is carried out with an (endolysin)/(mannitol) weight ratio of between 0.001 and 0.003 and in particular between 0.002 and 0.003.

The present invention also relates to the use of mannitol for stabilizing, in particular drying, an endolysin derived from a Staphylococcus aureus phage. In particular, 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, comprises a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1. This use comprises in particular mixing, in an aqueous liquid, in particular water, (i) the endolysin and (ii) mannitol, this mixture then being freeze dried.

As indicated above, this contacting operation is advantageously carried out with an (endolysin)/(mannitol) weight ratio of between 0.001 and 0.003 and in particular between 0.002 and 0.003. A) to the invention

Such a composition according to the invention (composition B) comprises in particular, in addition to a physiologically acceptable medium, and in particular water, an anhydrous composition (composition A) according to the invention.

Thus, such a composition (composition B) also comprises:

(i) at least one endolysin derived from a Staphylococcus aureus phage; and

(ii) mannitol, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, the endolysin comprising a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

A physiologically acceptable medium, as defined above, may comprise water and/or one or more water- miscible organic solvents.

In particular, a composition (composition B) according to the invention may comprise an amount of water of at least 40% by weight relative to the total weight of the composition, in particular an amount of water ranging from 40% to 95% by weight, more particularly from 50% to 90% by weight, notably from 75% to 95% by weight and more particularly from 80% to 95% by weight relative to the total weight of the composition.

The water may be sterile demineralized water and/or floral water and/or natural spring or mineral water.

In the present invention, “water-miscible organic solvent” means an organic compound which is liquid at room temperature and the miscibility of which in water is greater than 50% by weight at 25°C and atmospheric pressure.

The water-miscible organic solvents that may be used in a composition (composition B) of the invention may also be volatile.

Among the water-miscible organic solvents that may be used in a composition (composition B) of the invention, mention may be made, for example, of lower monoalcohols having from 2 to 5 carbon atoms, such as ethanol and isopropanol, polyols such as propylene glycol and 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 composition B 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.

A composition according to the invention comprises mannitol in a total content ranging from 0.01% to 21% by weight relative to the total weight of the composition, in particular from 0.05% to 9% by weight relative to the total weight of the composition, more particularly from 0.1% to 3% by weight relative to the total weight of the composition.

Such a composition (composition B) according to the invention, which comprises, in addition to a physiologically acceptable medium, an anhydrous composition (composition A) according to the invention, can be obtained in particular by means of a method comprising at least the steps consisting in (a) providing a physiologically acceptable aqueous medium, (b) providing an anhydrous composition according to the invention (composition A), in particular in the form of a lyophilizate or in spray-dried form, in particular in the form of a lyophilizate, (c) bringing said anhydrous composition (composition A) (b) into contact extemporaneously with said aqueous medium (a) under conditions suitable for the solubilization of the components of said anhydrous composition (composition A) in said medium.

According to a particular embodiment, such a composition (composition B) according to the invention, which comprises, in addition to a physiologically acceptable medium, an anhydrous composition according to the invention (composition A), may be obtained by a method comprising a step consisting in solubilizing the anhydrous composition (composition A) of the invention in the water of a bath or a shower or a thermal water and therefore intended to be brought into contact with a keratin material and in particular the skin.

Additional ingredients

In addition to the abovementioned compounds, a composition (composition A or B, in particular B) according to the invention may of course comprise one or more additional ingredients, other than the mannitol defined above. Needless to say, a person skilled in the art will take care to select one or more additional ingredients such that the advantageous properties of the endolysin(s) of the invention are not, or are not substantially, adversely affected.

The additional ingredients are present in the compositions in a content which is usual for each of them in a cosmetic composition, in particular in a content which is usual for each of them and which enables them to retain their cosmetic properties, more particularly in a content which is usual for each of them and which enables 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 ingredients, chosen from: surfactants; fatty substances; colorants; preserving agents; fragrances; pH adjusters such as organic acids, for instance citric acid; antioxidants; hydrophilic gelling agents such as hydroxypropyl methylcellulose; amino acids such as arginine; carbohydrates; chelating agents; sugar alcohols; cosmetic active agents; and mixtures thereof.

Needless to say, a person skilled in the art will take care to select this or these optional additional ingredient(s), and/or the amount thereof, such that the advantageous properties of a composition according to the invention are not, or are not substantially, adversely affected by the envisioned addition.

The additional ingredient(s) different from 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 (II), an organic filler, a nonionic surfactant, and mixtures thereof.

Oil

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

For the purposes of the present invention, “oil” means a water-immiscible compound which is liquid at 25°C and atmospheric pressure (1.013xl0⁵ Pa). “Immiscible” means that the mixing of the same amount of water and oil, after stirring, does not result in a stable solution comprising only a single phase, under the abovementioned temperature and pressure conditions. Observation is performed by eye or using a phasecontrast microscope, if necessary, on 100 g of mixture obtained after sufficient stirring with a Rayneri blender to produce a vortex within the mixture (as a guide, 200 to 1000 rpm), the resulting mixture being left to stand, in a closed flask, for 24 hours at room temperature before observation.

“Hydrocarbon oil” means an oil mainly containing hydrogen and carbon atoms and optionally one or more functions selected from hydroxyl, ester, ether and carboxylic functions. A hydrocarbon oil thus consequently does not comprise any silicon or fluorine atoms.

The term “silicone oil” refers to an oil comprising at least one silicon atom, and notably at least one Si-0 group, and more particularly an organopolysiloxane.

The term “fluoro oil” denotes an oil comprising at least one fluorine atom.

The term “non-polar hydrocarbon oil” means a hydrocarbon oil comprising only carbon and hydrogen atoms, which is in particular non-aromatic (also called a hydrocarbon).

The term “polar hydrocarbon oil” denotes hydrocarbon oils mainly comprising hydrogen and carbon atoms and one or more functions selected from hydroxyl, ester, ether and carboxylic functions.

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

Volatile oils

“Volatile oil” means an oil (or non-aqueous medium) that can evaporate on contact with the skin in less than one hour, at room temperature and at atmospheric pressure. The volatile oil is a volatile cosmetic oil, which is liquid at room temperature, particularly having a non-zero vapour pressure at room temperature and at atmospheric pressure, in particular having a vapour pressure ranging from 0.13 Pa to 40 000 Pa (10‘³ to 300 mmHg), in particular ranging from 1.3 Pa to 13 000 Pa (0.01 to 100 mmHg) and more particularly ranging from 1.3 Pa to 1300 Pa (0.01 to 10 mmHg). According to a particular embodiment of the invention, the volatile oils are such that the flash points are below 120°C and the vapour pressure is less than 5 Pa, more particularly for which the flash point is below 90°C and the vapour pressure is greater than 1 Pa, even more particularly for which the flash point is below or equal to 60°C and the vapour pressure is greater than 5 Pa, and more particularly still for which the flash point is below 60°C and the vapour pressure is greater than 100 Pa.

The volatile oil(s) may be chosen from volatile hydrocarbon oils such as:

- hydrocarbon oils containing from 8 to 16 carbon atoms, and notably: a) branched C8-C16 alkanes for instance isoalkanes (also known as isoparaffins) such as C8-C9 Isoparaffin, C13-C16 Isoparaffin, isododecane, isodecane, isohexadecane, and for example oils sold under the trade names Isopar or Permethyl, alone or as mixtures, in particular isododecane (also known as 2,2,4,4,6-pentamethylheptane), for example sold by Ineos, more particularly isododecane; b) linear C6-C16 alkanes, alone or as mixtures, for example such as hexane, decane, undecane, tridecane, isoparaffins for instance 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 (Cl l) and n-tridecane (Cl 3) obtained in Examples 1 and 2 of patent application WO 2008/155059 by the company Cognis, and mixtures thereof, and also mixtures of n-undecane (Cl l) and n-tridecane (C13) Cetiol Ultimate® from the company BASF; c) volatile C5-C12 cyclic, non-aromatic alkanes;

- short-chain esters containing 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-O-C(O)-O-R'2 in which R'l and R'2, which may be 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'l and R'2 denote a linear butyl alkyl radical or a pentyl group. Advantageously, the ether oil is chosen from dibutyl carbonate or dipentyl carbonate; - volatile ether oils of formula R1-0-R2 in which R1 and R2, which may be 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. Linear alkyl groups that may be mentioned include a butyl group and a pentyl group. Branched alkyl groups that may be mentioned include a 1 -methylpropyl group, a 2- methylpropyl group, a t-butyl group and a 1,1 -dimethylpropyl group.

In particular, the volatile hydrocarbon oil(s) is/are selected from C8-C16 alkanes, in particular linear C8-C16 alkanes, and more particularly are selected from C9-C12 alkanes, even more particularly are selected from a mixture of C9-C12 alkanes such as Vegelight Silk® sold by BioSynthls.

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 including alkyl or alkoxy groups containing from 1 to 10 carbon atoms. As volatile silicone oils that may be used in the invention, mention may notably be made of dimethicones with viscosities of 5 and 6 cSt, cyclopentadimethylsiloxane, dodecamethylpentasiloxane, cyclohexadimethylsiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, heptamethylhexyltrisiloxane, heptamethyloctyltrisiloxane, hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane and dodecamethylpentasiloxane, and mixtures thereof. Mention may notably be made of dodecamethylpentasiloxane, such as the reference DM-Fluid-2cs sold by Shin-Etsu, or cyclohexadimethylsiloxane, such as the reference Xiameter PMX-0246 Cyclohexasiloxane sold by Dow Chemical.

Non-volatile oils

The term “non-volatile oil” means an oil having a vapour pressure at 25°C and atmospheric pressure which is non-zero and is less than 2.66 Pa and more particularly less than 0.13 Pa. By way of example, the vapour pressure may be measured according to the static method or via the effusion method by isothermal thermogravimetry, depending on the vapour pressure of the oil (OECD standard 104).

The non-volatile oil(s) may be of natural or synthetic origin, in particular natural. Among the non-volatile oils, mention may be made of:

- non-volatile fluoro oils, which may notably be chosen from among fluorinated polyethers, and also from the fluorosilicone oils and the fluoro silicones as described in EP-A-847752;

- non-volatile silicone oils, which may notably be chosen from the non-volatile silicones having the following INCI names: dimethicone, dimethiconol, trimethyl pentaphenyl trisiloxane, tetramethyl tetraphenyl trisiloxane, diphenyl dimethicone, trimethylsiloxyphenyl dimethicone, phenyl trimethicone, diphenylsiloxyphenyl trimethicone; and also mixtures thereof.

These products are notably sold under the names PH-1555 HRI Cosmetic Fluid (trimethyl pentaphenyl trisiloxane) and Dow Coming 556 Cosmetic Grade Fluid (phenyl trimethicone) by Dow Coming; diphenyl dimethicones such as the products KF-54, KF54HV, KF-50-300CS, KF-53 d and KF-50-100CS or Diphenylsiloxy Phenyl Trimethicone KF56 A sold by Shin-Etsu; the products Belsil PDM 1000 and Belsil PDM 20 sold by Wacker Chemie (trimethylsiloxy phenyl dimethicone), alone or as mixtures;

- non-polar non-volatile hydrocarbon oils, which may notably be chosen from linear or branched compounds of mineral or synthetic origin, for instance: i) squalane such as the reference Neossance Squalane sold by Amyris, or isoeicosane, ii) mixtures of linear, saturated hydrocarbons, particularly C14-C30 and more particularly C15-C28 hydrocarbons, such as mixtures for which the INCI names are, for example, the following: (C15-C 19) Alkane, (C18-C21) Alkane, (C21-C28) Alkane, for instance the products Gemseal 40, Gemseal 60 and Gemseal 120 sold by Total, Emogreen L19 sold by SEPPIC, Emogreen LI 5 sold by SEPPIC, iii) hydrogenated or non-hydrogenated polybutenes, for instance the products of the Indopol range sold by Ineos Oligomers, products having the INCI name Hydrogenated Polyisobutene; iv) hydrogenated or non-hydrogenated polyisobutenes, in particular hydrogenated, for instance the non-volatile compounds of the Parleam® range sold by the company Nippon Oil Fats, v) hydrogenated or non- hydrogenated poly decenes, for instance the non-volatile compounds of the Puresyn® range sold by the company ExxonMobil, vi) decene/butene copolymers, butene/isobutene copolymers, and vii) mixtures thereof;

- polar non-volatile hydrocarbon oils, which may be chosen from: i) saturated, unsaturated, linear or branched C10-C26 fatty alcohols, which are liquid at room temperature (25 °C), in particular monoalcohols. In particular, the C10-C26 alcohols are fatty alcohols, which are 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, notably such as lauryl alcohol, isostearyl alcohol, oleyl alcohol, 2-butyloctanol, 2-undecylpentadecanol, 2-hexyldecyl alcohol, isocetyl alcohol, octyldodec anol and mixtures thereof; ii) triglycerides consisting of fatty acid esters of glycerol, in particular the fatty acids of which may have chain lengths ranging from C4 to C36, and notably from C18 to C36, it being possible for these oils to be linear or branched, and saturated or unsaturated; by way of example, mention may notably be made of heptanoic or octanoic triglycerides, caprylic/capric acid triglycerides, plant oils such as wheat germ oil, sunflower oil, grapeseed oil, sesame seed oil, com oil, apricot kernel oil, castor oil, shea oil, avocado oil, olive oil, soybean oil, sweet almond oil, palm oil, rapeseed oil, cottonseed oil, hazelnut oil, macadamia oil, jojoba oil, alfalfa oil, poppy oil, pumpkin oil, marrow oil, blackcurrant oil, evening primrose oil, millet oil, barley oil, quinoa oil, rye oil, safflower oil, candlenut oil, passionflower oil, musk rose oil, groundnut oil, coconut oil, argan oil, passionflower oil, kaya oil; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; and also mixtures thereof; iii) linear aliphatic hydrocarbon esters of formula R-C(O)-OR’ in which R-C(O)-O- represents a carboxylic acid residue including 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 advantageously being at least 10. As examples of such esters, mention may be made 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 of polyalcohols, such as propylene glycol dioctanoate, cetyl octanoate, cocoyl caprylate/caprate, tridecyl octanoate, 2-ethylhexyl palmitate, alkyl benzoate, polyethylene glycol diheptanoate, propylene glycol bis(2-ethylhexanoate) and mixtures thereof, hexyl laurate, neopentanoic acid esters, such as isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate or 2- octyldodecyl neopentanoate, isononanoic acid esters, such as isononyl isononanoate, isotridecyl isononanoate or octyl isononanoate, oleyl erucate, isopropyl lauroyl sarcosinate, diisopropyl sebacate, isocetyl stearate, isodecyl neopentanoate, isostearyl behenate or myristyl myristate; and mixtures thereof; iv) hydroxylated esters such as polyglyceryl-2 triiso stearate; v) aromatic esters such as tridecyl trimellitate, C12-C15 alcohol benzoate, the 2- phenylethyl ester of benzoic acid, and butyloctyl salicylate; vi) linear fatty acid esters with a total carbon number ranging from 35 to 70, for instance pentaerythrityl tetrapelargonate; vii) esters of C24-C28 branched fatty acids or fatty alcohols such as triisoarachidyl citrate, pentaerythrityl tetraisononanoate, glyceryl triisostearate, glyceryl tris(2- decyltetradecanoate), pentaerythrityl tetraisostearate, polyglyceryl-2 tetraisostearate or pentaerythrityl tetrakis(2-decyltetradecanoate) ; viii) the polyesters obtained by condensation of dimer and/or trimer of unsaturated fatty acid and of diol, such as those with the INCI name Dilinoleic Acid/Butanediol Copolymer or Dilinoleic Acid/Propanediol Copolymer; the polyesters obtained by condensation of fatty acid dimer and of diol dimer, such as dimer dilinoleyl dimer dilinoleate; ix) synthetic ethers of formula R1-O-R2 in which R1 and R2, which may be 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. Linear alkyl groups that may be mentioned include a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl 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. Branched alkyl groups that may be mentioned include 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 l-(l-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-(l,3,3- trimethylbutyl)-5,7,7-trimethyloctyl group. As cyclic alkyl groups, 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 nonvolatile ether oils, mention may be made of dicaprylyl ether, such as the reference Cetiol OE sold by BASF; x) carbonates of formula R8-O-C(O)-O-R9, with R8 and R9, which may be identical or different, representing a linear or branched C4 to C12 and in particular C6 to CIO alkyl chain; the carbonate oils may be dicaprylyl carbonate (or dioctyl carbonate), sold under the name Cetiol CC® by the company BASF, bis(2-ethylhexyl) carbonate, sold under the name Tegosoft DEC® by the company Evonik, dipropylheptyl carbonate (Cetiol 4 All from BASF), dibutyl carbonate, dineopentyl carbonate, dipentyl carbonate, dineoheptyl carbonate, diheptyl carbonate, diisononyl carbonate or dinonyl carbonate, and more particularly dioctyl carbonate; xi) vinylpyrrolidone copolymers such as vinylpyrrolidone/ 1 -hexadecene copolymer (INCI name); xii) higher C6-C26 fatty acids which are liquid at room temperature (25 °C), such as oleic acid, linoleic acid, linolenic acid or isostearic acid; and xiii) mixtures thereof.

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-polar nonvolatile hydrocarbon oils with the exception of liquid paraffins, polar non-volatile hydrocarbon oils as defined previously, and mixtures thereof more particularly chosen from polar non-volatile hydrocarbon oils and mixtures thereof.

According to a particular embodiment, the composition comprises at least one oil selected from polar non-volatile hydrocarbon oils; more particularly, the composition according to the invention comprises at least one oil selected from polar non-volatile hydrocarbon oils and does not comprise any non-polar non-volatile hydrocarbon oils; even more particularly, the composition according to the invention comprises at least one oil selected from polar non-volatile hydrocarbon oils and does not comprise any non-polar non-volatile hydrocarbon oils, non-volatile fluoro oils, non-volatile silicone oils or volatile oils. According to a particular embodiment, the polar non-volatile hydrocarbon oils are chosen from: i) saturated, unsaturated, linear or branched C10-C26 fatty alcohols, which are liquid at room temperature (25 °C), in particular monoalcohols. In particular, the C10-C26 alcohols are fatty alcohols, which are 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, notably such as lauryl alcohol, isostearyl alcohol, oleyl alcohol, 2-butyloctanol, 2-undecylpentadecanol, 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 ranging from C4 to C36, and notably from C18 to C36, it being possible for these oils to be linear or branched, and saturated or unsaturated; by way of example, mention may notably be made of heptanoic or octanoic triglycerides, caprylic/capric acid triglycerides, plant oils such as wheat germ oil, sunflower oil, grapeseed oil, sesame seed oil, com oil, apricot kernel oil, castor oil, shea oil, avocado oil, olive oil, soybean oil, sweet almond oil, palm oil, rapeseed oil, cottonseed oil, hazelnut oil, macadamia oil, jojoba oil, alfalfa oil, poppy oil, pumpkin oil, marrow oil, blackcurrant oil, evening primrose oil, millet oil, barley oil, quinoa oil, rye oil, safflower oil, candlenut oil, passionflower oil, musk rose oil, groundnut oil, coconut oil, argan oil, passionflower oil, kaya oil; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; and also mixtures thereof; iii) linear aliphatic hydrocarbon esters of formula R-C(O)-OR’ in which R-C(O)-O- represents a carboxylic acid residue including 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 advantageously being at least 10. As examples of such esters, mention may be made 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 of polyalcohols, such as propylene glycol dioctanoate, cetyl octanoate, cocoyl caprylate/caprate, tridecyl octanoate, 2-ethylhexyl palmitate, alkyl benzoate, polyethylene glycol diheptanoate, propylene glycol bis(2-ethylhexanoate) and mixtures thereof, hexyl laurate, neopentanoic acid esters, such as isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate or 2- octyldodecyl neopentanoate, isononanoic acid esters, such as isononyl isononanoate, isotridecyl isononanoate or octyl isononanoate, oleyl erucate, isopropyl lauroyl sarcosinate, diisopropyl sebacate, isocetyl stearate, isodecyl neopentanoate, isostearyl behenate or myristyl myristate; and mixtures thereof; ix) synthetic ethers of formula R1-0-R2 in which R1 and R2, which may be 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. Linear alkyl groups that may be mentioned include a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl 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. Branched alkyl groups that may be mentioned include 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 l-(l-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-(l,3,3- trimethylbutyl)-5,7,7-trimethyloctyl group. As cyclic alkyl groups, 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 nonvolatile ether oils, mention may be made of dicaprylyl ether, such as the reference Cetiol OE sold by BASF; x) carbonates of formula R8-O-C(O)-O-R9, with R8 and R9, which may be identical or different, representing a linear or branched C4 to C12 and in particular C6 to CIO alkyl chain; the carbonate oils may be dicaprylyl carbonate (or dioctyl carbonate), sold under the name Cetiol CC® by the company BASF, bis(2-ethylhexyl) carbonate, sold under the name Tegosoft DEC® by the company Evonik, dipropylheptyl carbonate (Cetiol 4 All from BASF), dibutyl carbonate, dineopentyl carbonate, dipentyl carbonate, dineoheptyl carbonate, diheptyl carbonate, diisononyl carbonate or dinonyl carbonate, and more particularly dioctyl carbonate;

More particularly, the polar non-volatile hydrocarbon oils are chosen from: ii) triglycerides consisting of fatty acid esters of glycerol, in particular the fatty acids of which may have chain lengths ranging from C4 to C36, and notably from C18 to C36, it being possible for these oils to be linear or branched, and saturated or unsaturated; by way of example, mention may notably be made of heptanoic or octanoic triglycerides, caprylic/capric acid triglycerides, plant oils such as wheat germ oil, sunflower oil, grapeseed oil, sesame seed oil, com oil, apricot kernel oil, castor oil, shea oil, avocado oil, olive oil, soybean oil, sweet almond oil, palm oil, rapeseed oil, cottonseed oil, hazelnut oil, macadamia oil, jojoba oil, alfalfa oil, poppy oil, pumpkin oil, marrow oil, blackcurrant oil, evening primrose oil, millet oil, barley oil, quinoa oil, rye oil, safflower oil, candlenut oil, passionflower oil, musk rose oil, groundnut oil, coconut oil, argan oil, passionflower oil, kaya oil; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; and also mixtures thereof.

According to a particular embodiment, the composition comprises at least one oil chosen from the group consisting of:

- polar non-volatile hydrocarbon oils of the triglyceride type constituted by esters of fatty acids and of glycerol, in particular the fatty acids of which may have chain lengths ranging from C4 to C36, and notably from C18 to C36, it being possible for these oils to be linear or branched, and saturated or unsaturated, chosen from soybean oil, jojoba seed oil, shea butter olein, capric and caprylic acid triglycerides, and mixtures thereof,

- volatile C8-C16 alkane oils, such as C9-C12 alkanes and isoparaffin,

- non-polar non-volatile oils such as squalane,

- polar non-volatile hydrocarbon oils of the synthetic ether type of formula R1-0-R2, in which R1 and R2, which may be 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, - polar non-volatile hydrocarbon oils of the saturated, unsaturated, linear or branched C10- C26 fatty alcohol type, which are liquid at room temperature (25 °C), such as octyldodecanol,

- polar non-volatile hydrocarbon oils such as the carbonates of formula R8-O-C(O)-O-R9, in which R8 and R9, which may be identical or different, represent a linear or branched C4 to C12, in particular C6 to CIO, alkyl chain, such as dicaprylyl carbonate, and

- mixtures thereof.

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 liquid paraffins, i.e. the composition comprises 0% liquid paraffins.

The oils according to the invention may advantageously be present in a composition according to the invention in a content customary for a cosmetic composition, in particular in a customary 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 customary 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.

The oil may play various cosmetic roles, such as that of a consistency factor, sustaining an emulsion under cold conditions, or obtaining the smooth appearance of the composition, particularly in the case of an emulsion. It may also contribute towards facilitating the spreading and gliding of the composition over the skin, and also its penetration. Finally, the oil may act on the skin through its occlusive effect, its lubricating effect (to the touch) or its emollient/hydrating 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.

“Total oil content” means the sum of the contents of each of the abovementioned oils present in the composition, or, when only one of these oils is present in the composition, it means the content of this oil.

Aromatic alcohols

A composition according to the invention may also comprise at least one aromatic alcohol of formula (II), a salt thereof, notably a salt of an organic or mineral base, an optical isomer thereof, a geometrical isomer thereof or a solvate thereof, such as hydrate: [Chem 2] in which:

- R¹ represents a group chosen from the group consisting of: a) a linear or branched hydroxy(Ci-C4)alkyl, in particular a hydroxy(Ci-C2)alkyl group, b) a group chosen from -OR⁵, -C(O)R⁶, -C(O)OR⁷ and -(CH₂)_n-C(H)(R⁸)-C(O)R⁹, with:

R⁵ representing a linear or branched (C3-C4)alkyl group optionally substituted with one or more hydroxyl (OH) groups,

R⁶ representing a hydrogen atom or a linear or branched (Ci-C4)alkyl, phenyl or benzyl group, optionally substituted with one or more hydroxyl groups,

R⁷ representing a linear or branched (Ci-C4)alkyl, phenyl or benzyl group, optionally substituted with one or more hydroxyl groups, R⁸ representing a hydrogen atom or a linear or branched (Ci-C4)alkyl group such as methyl or ethyl, in particular R⁸ representing a hydrogen atom;

R⁹ representing a hydrogen atom, or a linear or branched, in particular linear, (Ci-Ci2)alkyl group optionally substituted with one or more hydroxyl groups, or a linear or branched, in particular linear, (C2-Ci2)alkenyl group optionally substituted with one or more hydroxyl groups, n is 0, 1 or 2, in particular n is 1,

- R² represents a hydrogen atom; a halogen atom, in particular a chlorine atom; or a hydroxyl group; and

- R³ represents a hydrogen atom or a group chosen from hydroxyl and linear or branched (Ci-C6)alkoxy, in particular (Ci-C4)alkoxy such as methoxy -OCH3 or ethoxy -OC2H5; in particular, R³ represents a hydrogen atom or an ethoxy group; and

- R⁴ is a hydrogen atom or a hydroxyl group; it being understood that at least one of the groups R¹, R², R³ or R⁴ bears or represents a hydroxyl group.

More particularly, the aromatic alcohol(s) of formula (II) of the invention is/are such that:

- when R¹ represents a -C(O)OR⁷ group, then R² is an -OH group;

- when R¹ represents a -C(O)R⁶ group, then at least one from among R², R³ and R⁴ is an -OH group;

- when R¹ represents a -(CH2)_n-C(H)(R⁸)-C(O)R⁹ group, then R² is an -OH group.

In particular, the aromatic alcohol may have the formula (II) below: [Chem 3] in which:

R¹ is chosen from the group consisting of: i) a linear or branched hydroxy(Ci-C4)alkyl, in particular a hydroxy(Ci-C2)alkyl group such as hydroxymethyl or hydroxyethyl, ii) an -OR⁵ group with R⁵ representing a (C3-C4)hydroxy alkyl group, notably -OR⁵ representing -O-CH2-CH(OH)-CH2OH, iii) a -C(O)R⁶ group with R⁶ representing a linear or branched (Ci-C4)alkyl group, notably -C(O)R⁶ representing -C(0)-CH3, iv) a -C(O)OR⁷ group with R⁷ representing a linear or branched (Ci-C4)alkyl group, notably R⁷ representing a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or benzyl group, and v) a -CH2-CH2-C(O)R⁹ group with R⁹ representing a linear or branched (Ci-C6)alkyl group, in particular -CH2-CH2-C(O)R⁹ representing a -CH2-CH2-C(O)CH3 group;

R² is chosen from the group consisting of a hydrogen atom; a halogen atom, in particular a chlorine atom; and a hydroxyl group;

R³ is a hydrogen atom or a methoxy or ethoxy group; and

R⁴ is a hydrogen atom or a hydroxyl group; it being understood that at least one of the groups R¹, R² or R⁴ bears or represents a hydroxyl group.

Such compounds notably act as preserving agents, in particular in cosmetic compositions. Some also act as fragrances, notably in cosmetic compositions.

The term “organic or mineral base salt” means salts of bases or alkaline agents as defined below. As examples of base salts, mention may be made of 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; aqueous ammonia and organic amines such as unsubstituted or hydroxysubstituted mono-, di- or trialkylamines; dicyclohexylamines; tributylamines; pyridine; N- methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris-(2- hydroxyalkylamines) such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert- butylamine, tris(hydroxymethyl)methylamine; N,N-dialkyl-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” or "alkyl radical” means a saturated, linear or branched, substituted or unsubstituted monovalent hydrocarbon radical, in particular methyl, ethyl, propyl, isopropyl, butyl or tert-butyl radicals.

The term "hydroxyalkyl group” means a saturated, linear or branched hydrocarbon group comprising at least one -OH group. A hydroxy(Ci-C4)alkyl group is a saturated, linear or branched C1-C4 hydrocarbon radical comprising at least one -OH group, in particular comprising a single -OH group. A hydroxy(Ci-C2)alkyl group is a saturated, linear or branched C1-C2 hydrocarbon radical comprising at least one -OH group, in particular comprising a single -OH group.

According to a particular embodiment, the hydroxy(Ci-C4)alkyl group is chosen 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, l-(hydroxymethyl)-2-hydroxyethyl, 2,3-dihydroxybutyl, 3,4- dihydroxybutyl and 2-(hydroxymethyl)-3-hydroxypropyl. In particular, the hydroxy(Ci- C4)alkyl group is hydroxymethyl or 2-hydroxyethyl.

“Halogen atom” means one of the chemical elements of Group 17 of the Periodic Table of the Elements, namely fluorine, chlorine, bromine or iodine. In particular, the halogen atom is a chlorine atom.

According to a particular embodiment, R¹ is chosen from the group constituted by (Ci- C2)hydroxyalkyl, 2-hydroxyethyl, hydroxymethyl, an -O-CH2-CH(OH)-CH2OH group, a -CH2-CH2-C(O)-CH3 group and a -C(0)-0CH3 group,

R² is chosen from the group constituted by a hydrogen atom, a halogen atom, in particular a chlorine atom, and a hydroxyl group,

R³ is chosen from the group constituted by a hydrogen atom and an -O-C2-H5 group, and R⁴ is a hydrogen atom.

According to one embodiment, R¹ represents a hydroxy(Ci-C4)alkyl group, more particularly a hydroxy(Ci-C2)alkyl group, R² represents a hydrogen atom, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom. According to a particular embodiment, R¹ represents 2-hydroxyethyl, R² represents a hydrogen atom, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom. According to a particular embodiment, R¹ represents a hydroxymethyl, R² represents a hydrogen atom, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom.

According to a particular embodiment, R¹ represents an -OR⁵ group with R⁵ representing a linear or branched (C3-C4)alkyl group substituted with one or more hydroxyl groups, R² represents a halogen atom, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom. More particularly, R¹ represents an -OR⁵ group with R⁵ representing a linear (C3- C4)alkyl group substituted with two hydroxyl groups, R² represents a halogen atom, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom.

According to a particular embodiment, R¹ represents an -O-CH2-CH(OH)-CH2OH group, R² represents a chlorine atom, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom.

According to a particular embodiment, R¹ represents a -(CH2)_n-C(H)(R)⁸-C(O)R⁹ group, with R⁸ representing a hydrogen atom or a methyl or ethyl group, and R⁹ representing a linear (Ci-Ci2)alkyl group optionally substituted with a hydroxyl group or a (C2- Ci2)alkenyl group optionally substituted with a hydroxyl group, and n is as defined previously; in particular, n is 1, R² represents a hydroxyl group, R³ represents an -OCH3 or -OC2H5 group and R⁴ represents a hydrogen atom. More particularly, R¹ represents a -CH2- CH2-C(O)R⁹ group, R⁹ representing a linear (Ci-Ci2)alkyl group, in particular a linear (Ci- Cejalkyl such as methyl, R² represents a hydroxyl group, R³ represents an -OC2H5 group and R⁴ represents a hydrogen atom.

According to a particular embodiment, R¹ represents a -C(O)OR⁷ group, with R⁷ representing a linear or branched (Ci-C4)alkyl group, a phenyl or a benzyl, optionally substituted with one or more hydroxyl groups, R² represents a hydroxyl group, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom.

According to a particular embodiment, R¹ represents a -C(0)-0CH3 group, R² represents a hydroxyl group, R³ represents a hydrogen atom and R⁴ represents a hydrogen atom. According to a particular embodiment, the aromatic alcohol of formula (II) is chosen from the group consisting of phenylethyl alcohol; benzyl alcohol; chlorphenesin (also known as 3-(4-chlorophenoxy)-l,2-propanediol); zingerone; ethylzingerone (also known as 4-(3- ethoxy-4-hydroxyphenyl)butan-2-one); vanillin; parabens, in particular (Ci- C6)alkylparabens or arylparabens, in particular methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben or benzylparaben; salts thereof and mixtures thereof.

According to a particular embodiment, the aromatic alcohol of formula (II) is chosen from the group consisting of phenylethyl alcohol; benzyl alcohol; chlorphenesin (also known as 3-(4-chlorophenoxy)-l,2-propanediol); zingerone; ethylzingerone (also known as 4-(3- ethoxy-4-hydroxyphenyl)butan-2-one); parabens, in particular methylparaben; salts thereof and mixtures thereof.

The composition according to the invention comprises in particular a total content of aromatic alcohol(s) of formula (II) 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. The term “total content of aromatic alcohol(s) of formula (II)” means the sum of the contents of each of the aromatic alcohol(s) of formula (II) present in the composition, or, when only one aromatic alcohol of formula (II) is present in the composition, means the content of this aromatic alcohol of formula (II).

Organic fillers

A composition according to the invention may also comprise one or more organic fillers. For the purposes of the present invention, the term “organic filler” is intended to denote colourless or white organic, natural or synthetic solid particles of any form, which are in a form that is insoluble and dispersed in the medium of the composition.

The composition according to the invention may also comprise at least one organic filler selected from an unmodified starch, an N-acylamino acid, salts thereof and mixtures thereof. Unmodified starches

The composition according to the present invention may comprise one or more unmodified starches.

For the purposes of the present invention, “unmodified starch” means native starch, or else starch which has not been chemically or physically modified, notably by one or more of the following reactions: pregelatinization, oxidation, crosslinking, esterification, etherification, amidation, heat treatment.

The unmodified starch molecules that can be used in the present invention may originate from any plant source of starch, particularly cereal crops and tuber crops; more particularly, they may be starches from corn, rice, cassava, barley, potato, wheat, sorghum, pea or oat. According to a particular embodiment, the unmodified starch is selected from com starches, rice starches, potato starches and mixtures thereof; in particular, the unmodified starch is selected from corn or potato starches.

According to a particular embodiment, the composition according to the invention is totally free of tapioca starch; in particular, the composition according to the invention is totally 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 sold under the name Beauty-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-Acylamino acids and salts thereof

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

“Salt” of an N-acylamino acid according to the invention means a salt formed by an inorganic or organic acid or an inorganic or organic base.

As examples of acid salts, mention may be made of the 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.

As examples of base salts, mention may be made of hydroxides of alkali metals such as sodium, potassium and lithium; hydroxides of alkaline-earth metals such as calcium and magnesium; hydroxides of other metals such as aluminium and zinc; aqueous ammonia and organic amines such as unsubstituted or hydroxy-substituted mono-, di- or trialkylamines; dicyclohexylamines; tributylamines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris(2-hydroxyalkylamines) such as mono-, bis- or tris(2- hydroxyethyl)amine, 2-hydroxy-tert-butylamine or 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.

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

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

The amino acid may be of D or L configuration, in particular L.

According to a particular embodiment of the invention, the C8-C22 N-acylamino acids are selected from lauroyl lysine, salts thereof and mixtures thereof, in particular N-lauroyl-L- lysine, salts thereof and mixtures thereof.

N-Lauroyl-L-lysine is notably sold under the name Amihope LL® by the company Ajinomoto.

The N-acylamino acid(s) and the salts thereof 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 endolysins according to the invention and one or more organic fillers in an endolysin(s)/organic filler(s) weight ratio of between 0.0001 and 0.04, in particular between 0.0002 and 0.004 and more particularly between 0.0006 and 0.002.

Non-ionic surfactants

The composition according to the invention may also comprise at least one nonionic surfactant, in particular chosen from nonionic surfactants comprising one or more carbohydrate residues, nonionic surfactants of the C6-C30 fatty acid alkanolamide type.

For the purposes of the present invention, the term “surfactant” means any compound which modifies the surface tension between two surfaces. Surfactant compounds are amphiphilic molecules, i.e. they have two parts of different polarity, one lipophilic (fat-retaining) and non-polar, the other hydrophilic (water-miscible) and polar. They thus allow two immiscible phases to be dissolved, by interacting with the non-polar (i.e. lipophilic and thus hydrophobic) phase, via its hydrophobic part; whereas with the other phase, which is polar, it will interact via its hydrophilic part.

The term “nonionic surfactant” means a surfactant which has no net charge (i.e. it does not become ionized in water).

Nonionic surfactant comprising one or more carbohydrate residues

The composition according to the invention may also comprise at least one nonionic surfactant comprising one or more carbohydrate residues.

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

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

According to a particular embodiment, the nonionic surfactant(s) comprising one or more carbohydrate residues is/are chosen from:

(i) fatty acid esters of sugar(s) such as fatty acid (poly)glyceryl esters of glucose or alkylglucose with a linear or branched, saturated or unsaturated, C6-C22, in particular Cl 6- 20, hydrocarbon chain;

(ii) fatty alcohol ethers of sugar(s) such as alkyl (poly)glycosides; and (iii) mixtures thereof.

According to a particular embodiment, the nonionic surfactant(s) comprising one or more carbohydrate residues is/are chosen from alkyl(poly)glycosides and fatty acid (poly)glyceryl esters of glucose or alkylglucose having a linear or branched, saturated or unsaturated, C6- C22, in particular Cl 6-20, hydrocarbon chain, and mixtures thereof.

The nonionic surfactants of alkyl(poly)glycoside type are notably represented by the general formula (III) below:

[Chem 4]

R¹O-(R²O)t-(G)_v (HI) in which:

- R¹ represents a linear or branched alkyl or alkenyl radical including 6 to 24 carbon atoms and notably 8 to 20 carbon atoms, or an alkylphenyl radical of which the linear or branched alkyl radical includes 6 to 24 carbon atoms and notably 8 to 20 carbon atoms;

- R² represents an alkylene radical including 2 to 4 carbon atoms,

- G represents a sugar unit including 5 to 6 carbon atoms;

- 1 denotes a value ranging from 0 to 10 and in particular from 0 to 4;

- v denotes a value ranging from 1 to 15 and 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:

- R¹ denotes a linear or branched, saturated or unsaturated alkyl radical including from 8 to 20 carbon atoms,

- R² represents an alkylene radical including 2 to 4 carbon atoms,

- 1 denotes a value ranging from 0 to 3 and in particular equal to 0,

- G denotes glucose, fructose or galactose, in particular glucose,

- it being possible for the degree of polymerization, i.e. the value of v, to range from 1 to

15 and in particular from 1 to 4; the mean degree of polymerization more particularly being between 1 and 2. The glucoside bonds between the sugar units are generally of 1-6 or 1-4 type and in particular of 1-4 type.

As examples of alkyl(poly)glycosides, mention may be made of caprylyl/capryl glucoside, such as the product sold under the name Oramix CG 110L® by the company SEPPIC; decyl glucoside sold under the name Sorbithix L-100® by the company Applechem; arachidyl glucoside glucoside, optionally as a mixture with arachidyl alcohol and behenyl alcohol, sold, for example, under the name Montanov 202® by the company SEPPIC; cetylstearyl glucoside, optionally as a mixture with cetylstearyl alcohol, sold, 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 name Tego Care CG 90 MB® by the company Evonik Goldschmidt; cocoyl glucoside, such as the product sold under the name Lamesoft PO65® by the company BASF; octyldodecyl xyloside, sold, for example, under the name Fluidanov 20X by the company SEPPIC.

The alkyl(poly)glycoside may be used as a mixture with at least one fatty alcohol, notably a fatty alcohol containing from 6 to 24 carbon atoms and more particularly from 8 to 20 carbon atoms.

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

The fatty alcohol/alkyl polyglycoside emulsifying mixtures as defined above are known per se. They are described especially in applications WO92/06778, WO95/13863 and WO98/47610 and prepared according to the preparation processes indicated in these documents.

Among the fatty alcohol/alkyl(poly)glycoside mixtures, mention may be made of the products sold by the company SEPPIC under the name Montanov®, such as the following mixtures:

- arachidyl alcohol and behenyl alcohol/arachidyl glucoside - Montanov 202®

- cetylstearyl alcohol/cetylstearyl glucoside - Montanov 68MB®.

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

In a particular embodiment, the composition according to the invention does not comprise any decyl glucoside. - Fatty acid (poly)glyceryl esters of glucose or alkylglucose

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

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

Among the commercial products, mention may be made of the product sold by the company Evonik Goldschmidt under the name Tego Care 450.

The nonionic surfactant(s) comprising one or more carbohydrate residues 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, even more particularly 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 endolysins according to the invention and one or more nonionic surfactants comprising one or more carbohydrate residues according to the invention in a mass ratio of endolysin(s)/nonionic surfactant(s) comprising one or more carbohydrate residues of between 0.0001 to 0.5, in particular between 0.0002 and 0.1, more particularly between 0.0004 and 0.05, even better still between 0.0006 and 0.02.

C6-C30 fatty acid alkanolamides

The composition according to the invention may also contain at least one nonionic surfactant chosen from C6-C30 fatty acid alkanolamides.

Such surfactants may be chosen from mono- and di-alkanolamides of formula (IV):

[Chem 5]

R^XCONR²R³ (IV) in which: R¹ is a linear or branched, saturated or unsaturated hydrocarbon group containing from 6 to 30 carbon atoms,

R² and R³, independently, are hydrogen or a linear or branched, saturated or unsaturated alkanol group containing from 1 to 10 carbon atoms, on condition that only one from among R² and R³ is hydrogen.

As examples of surfactants of this type, mention may be made of 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 plant oil fatty acid monoethanolamide, and mixtures thereof.

According to a particular embodiment in formula (IV), R¹ is a linear or branched, saturated or unsaturated hydrocarbon group containing from 8 to 18 carbon atoms,

R² and R³, independently, are hydrogen or a linear or branched, saturated or unsaturated alkanol group containing from 2 to 5 carbon atoms, on condition that only one from among R² and R³ is hydrogen.

According to a particular embodiment, in formula (IV), R² is hydrogen, and R³ is a saturated linear or branched alkanol group containing 2 to 5 carbon atoms.

According to a particular embodiment, the appropriate C6-C30 fatty acid alkanolamide of formula (IV) is chosen from coconut oil fatty acid monoethanolamide (INCI: cocamide MEA or cocamide monoethanolamine), coconut oil fatty acid monoisopropanolamide (INCI: cocamide MIPA or cocamide monoisopropanolamine), and mixtures thereof.

Such products are available: for example, coconut oil fatty acid monoethanolamide (cocamide MEA) sold under the name Comperlan® 100 by the company Cognis (BASF), coconut oil fatty acid monoisopropanolamide (cocamide MIPA) sold 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 monoisopropanolamine. 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 (composition A or B) according to the invention comprises an amount of less than 2% by weight, relative to the total weight of the composition, of fatty acid(s) that are solid 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 fatty acid(s) that are solid at room temperature (25 °C), or even is free of (0% by weight relative to the total weight of the composition) fatty acid(s) that are solid at room temperature (25°C), and in particular does not comprise any stearic acid.

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

According to a particular embodiment, a composition according to the invention (composition A or B) 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 soybean lecithin, sodium alginate, polyacrylamidomethylpropanesulfonic acid, carbomer, cellulose, sodium polyacrylate, konjac gum, agar, and Caesalpinia spinosa gum; more particularly, according to one embodiment of the invention, the composition is free of (0% by weight relative to the total weight of the composition) carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soybean lecithin, sodium alginate, polyacrylamidomethylpropanesulfonic acid, carbomer, cellulose, sodium polyacrylate, konjac gum, agar and Caesalpinia spinosa gum. According to a particular embodiment, a composition according to the invention (composition A or B) comprises an amount of less than 0.5% in total amount by weight, relative to the total weight of the composition, of 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 (composition A or B) comprises an amount of less than or equal to 0.5% in total amount by weight, relative to the total weight of the composition, of 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 (composition A or B) comprises an amount of 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 (composition A or B) comprises an amount of less than or equal to 0.5% in total amount by weight, relative to the total weight of the composition, of zwitterionic surfactant, and more particularly is free of zwitterionic surfactant (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention (composition A or B) 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 surfactants, 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 surfactants; better still, according to a particular embodiment, the composition is free of anionic, cationic, amphoteric and zwitterionic surfactants (0% by weight relative to the total weight of the composition).

According to a particular embodiment, a composition according to the invention (composition A or B) 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, alkyl sulfate such as sodium lauryl sulfate, alkyl ether sulfate such as sodium laureth sulfate, disodium cocoamphodiacetate, fatty acid polyglyceryl esters such as polyglyceryl-4 isostearate and polyglyceryl-4 diisostearate polyhydroxystearate sebacate, and sodium stearate, glyceryl stearate citrate, alkyl sulfate such as sodium lauryl sulfate, alkyl ether sulfate such as sodium laureth sulfate, disodium cocoamphodiacetate, fatty acid polyglyceryl esters 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 (composition A or B) 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, and 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 even is free of (0% by weight relative to the total weight of the composition) kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica.

According to a particular embodiment, a composition according to the invention (composition A or B) comprises an amount of less than 0.1% by weight, relative to the total weight of the composition, of fatty acid that is solid at room temperature (25°C), and notably does not comprise any stearic acid; of benzoic acid, and/or salts thereof, notably alkali metal or alkaline-earth metal benzoates such as sodium benzoate, of sorbic acid and/or salts thereof, notably alkali metal or alkaline-earth metal sorbate, including potassium sorbate; of carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soybean lecithin, sodium alginate, polyacrylamidomethylpropanesulfonic acid, carbomer, sodium poly acrylate, konjac gum, agar and Caesalpinia spinosa gum; of glyceryl stearate citrate, alkyl sulfate such as sodium lauryl sulfate, alkyl ether sulfate such as sodium laureth sulfate, disodium cocoamphodiacetate, fatty acid polyglyceryl esters such as polyglyceryl-4 isostearate and polyglyceryl-4 diisostearate polyhydroxystearate sebacate, and sodium stearate; of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica. A composition according to the invention (composition A or B) may in particular comprise no sucrose (i.e. comprise 0% by weight of sucrose relative to the total weight of the composition).

A composition according to the invention (composition B) comprising an anhydrous composition (composition A) may also comprise water, in particular may comprise a water content of greater than 35% by weight, in particular greater than 40% by weight relative to the total weight of the composition. In particular, a composition (composition B) according to the invention may comprise a water content of between 45% and 99% by weight of water relative to the total weight of the composition.

A composition (composition B) according to the invention, notably comprising an anhydrous composition (composition A) according to the invention, may be in any presentation form normally used in the cosmetics field, for instance in the form of an aqueous gel, a lotion, a foam, micellar water, a cream, a paste or a serum.

A composition according to the invention (composition A or B) is preferentially suitable for topical administration.

Thus, a composition (composition B) according to the invention notably comprising an anhydrous composition (composition A) according to the invention may comprise all the constituents usually employed in the envisaged topical administration and application.

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

More particularly, a composition (composition B) according to the invention notably comprising an anhydrous composition (composition A) 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 off after application. A composition (composition A or B) according to the invention is preferentially intended to be applied to skin.

A composition (composition B) according to the invention notably comprising, in addition to a physiologically acceptable medium, an anhydrous composition (composition A) according to the invention, and in particular a mixture of an anhydrous composition (composition A) according to the invention and of the physiologically acceptable medium, can be applied by any means that enables a uniform distribution and in particular using a cotton wool swab, a rod, a brush, a gauze, a spatula or a pad, or also by spraying, and may or may not be removed by rinsing with water or using a mild detergent.

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

A composition (composition B) according to the invention notably comprising an anhydrous composition (composition A) according to the invention may alternatively be in the form of a face and/or body care or makeup product, and may be packaged, for example, in the form of a cream in a jar or a fluid in a tube or a pump bottle or a dropper bottle.

In particular, the compositions according to the invention (composition B) notably comprising an anhydrous composition (composition A) according to the invention may be used on all keratin materials, such as the skin, the scalp, head hair, the eyelashes, the eyebrows, the nails or the mucous membranes, in particular in the form of a hygiene product, for example in the form of a product for cleansing the skin, mucous membranes and/or head hair or the beard, in particular in the form of a product for cleansing and/or removing makeup from the skin (of the face and/or of the body), in the form of a shower product, in the form of a shampoo and conditioner, in the form of a shaving product, in the form of a rinse- off mask, in the form of an exfoliating product (also called desquamating or deep cleansing agent), both for the face and for the body or for the hands, after addition of exfoliating particles.

A composition (composition B) according to the invention notably comprising an anhydrous composition (composition A) according to the invention may be manufactured by any known process generally used in the cosmetic field.

The ingredients are mixed before forming, in the order and under conditions readily determined by a person skilled in the art. According to a particular mode 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 (composition A or B).

Uses and methods of implementation

According to one of its aspects, the present invention relates to the cosmetic use, notably the topical use, of an anhydrous composition according to the invention (composition A) or of a composition according to the invention (composition B) comprising this anhydrous composition, 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.

In particular, such a composition is suitable for topical administration.

A non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, notably acneic skin, according to the invention may in particular comprise at least the topical application to these keratin materials of an anhydrous composition (composition A) according to the invention or of a composition according to the invention (composition B) comprising this anhydrous composition, in particular comprising this anhydrous composition in a solubilized form.

A skin may in particular be a skin with acne or at risk of having acne and/or a skin with eczema or at risk of having eczema.

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

The cosmetic uses and methods of the invention are preferentially performed by topically administering an anhydrous composition (composition A) according to the invention or a composition according to the invention (composition B) comprising this anhydrous composition according to the invention.

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

By way of illustration, the cosmetic use or method according to the invention may be performed by topical, for example daily, application of at least one anhydrous composition (composition A) according to the invention or one composition according to the invention (composition B) comprising this anhydrous composition, which may be formulated, for example, in the form of a cream, gel, serum, lotion, emulsion or makeup-removing milk. The application may be repeated for example once or twice daily over a day or more, and generally over an extended period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage.

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

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

Throughout the description, including the claims, the terms “between ... and ...”, and “ranging from ... to ...” should be understood as meaning limits included, unless otherwise specified.

The examples that follow illustrate the present invention without limiting the scope thereof. In the examples, unless otherwise specified, the temperature is room temperature (20°C) and is expressed in degrees Celsius, and the pressure is atmospheric pressure.

Example:

Protocol (experimental conditions)

Preparation of the working suspension of Staphylococcus aureus (S. aureus from a lyophilizate ATCC 6538 (according to the recommendations of the standard NF EN 12353). The lyophilizate is rehydrated in Trypticase soy broth, plated on Trypticase soy agar (TSA plates) and incubated for 24 hours at 32.5°C. The cells are then recovered and resuspended in a commercial cryoprotectant solution with cryobeads for storage at -80°C for a maximum of 14 months (long-term storage stock).

From a cryobead of this -80°C stock, subculturing is performed on a TSA agar slant 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 subculturing the stock culture onto Trypticase soy agar and incubating it for 24 hours at 35°C. The working suspension is prepared by suspending the cells of this working culture in a tryptone salt diluent. This suspension is calibrated between 1 and 3xl0⁸ CFU (colony forming units )/mL by measuring the absorbance at 620 nm.

Evaluation of the antimicrobial activity of the samples against .S'. aureus

The compositions of Table 1 above were tested.

At T = 2, 7 and 11 weeks of the manufacture of the formulations, 20-gram aliquots of each formulation are inoculated with 0.2 ml of a calibrated suspension of .S'. aureus. After homogenization, the microorganism content in the product represents a concentration of .S'. aureus of 10⁶ CFU per gram of product, i.e. a 1% inoculation of a suspension of 10⁸ CFU per ml (the inoculum content 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 9.0 ml of Eugon FT 100 supp broth are then added, followed by mixing until fully homogenized. This mixture is then serially diluted in Eugon ET100 supp broth to 1/100 dilution.

The dilutions are spread on Trypticase soy agar plates and incubated at 35 °C for 48 hours until the surviving colonies of .S'. aureus are counted.

The antimicrobial activity on .S'. aureus is expressed in logarithmic abatement relative to the initial content and associated with the activity of the active compound, which is the endolysin of sequence SEQ ID NO: 1 by comparing the counts of surviving .S'. aureus in formulations with and without the endolysin of sequence SEQ ID NO: 1.

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 producf .

Preparation of the compositions

The following composition was prepared according to the information given in Tables 1 to 3 below. The samples were prepared in a beaker with magnetic stirring at room temperature. All the ingredients were poured into the beaker and were stirred until the mannitol was completely solubilized, between 15 min and 30 min. This composition, once freeze-dried, is presented hereafter under the name “rehydrated lyophilizate”. [Table 1]

[Table 2]

[Table 3] Example of the protocol to be followed for freezing and freeze drying:

The systems to be dried were sampled in stainless steel cups (30 ml/cup) and then frozen in a GX821 freezer supplied by Labo Plus at -20°C overnight. The frozen samples were then transferred to a Christ Alpha 1-2 freeze dryer, supplied by FISHER SCIENTIFIC SAS. The temperature of the cryo-condenser is set to -55°C. An E2M8 vacuum pump supplied by VWR INTERNATIONAL was used to place the freeze dryer chamber under vacuum. This pump stabilizes at 0.1 mbar when the temperature of the cryo-condenser stabilizes at -55°C. The samples are recovered 48 hours later, placed in glass jars and stored at 25°C, 40°C and 45°C.

Sample preparation before sending to test:

The dry forms are resolubilized by manual stirring or magnetic stirring less than 24 h before the measurement of the activity of the endolysin of sequence SEQ ID NO: 1 in microbiology terms. 0.66 g of dry form are weighed and 29.34 g of osmosed water are added. This solution has a concentration of endolysin of SEQ ID NO: 1 of approximately 35 ppm.

Results and conclusions

The results are given by log reduction in Staphylococcus aureus population. For values close to 0, no Staphylococcus aureus was killed. For values of -5.4, 99.9996% of the Staphylococcus aureus population was killed. The formulation tested is thus particularly active when the values are close to -5.4.

A first series of measurements was taken after storage of the samples for up to 13 weeks at temperatures of 25 °C, 40°C and 45 °C.

The results are given in Table 4 below.

[Table 4]

Surprisingly, the dry form composed of mannitol and endolysin of sequence SEQ ID NO: 1 made it possible to maintain the activity of the endolysin of sequence SEQ ID NO: 1 over time and at temperature, particularly at temperature at a maximum level (identical to the starting value, after freeze drying, at 25°C and of the raw material alone after defrosting). The significant temperature control times are 2 months at 45 °C and 3 months at 40°C. For a contact time of 1 h and at the various dwell times listed above, the dry forms gave an .S'. aureus killing performance of more than 99.999% (log reduction lower than -5).

To carry out the stability tests for the endolysin of sequence SEQ ID NO: 1, freeze-dried on a mannitol support, at high temperature, the samples were also exposed to 110°C for 1 hour in a Heat Block dry bath from Benchmark. The samples were then cooled to room temperature and resolubilized to obtain a solution having a concentration of 35 ppm of endolysin of sequence SEQ ID NO: 1. The solutions were then sent to the killing test. Three replicates were produced. The results are given in Table 5 below.

[Table 5]

After 1 hour at 110°C, the inventors observed that the three replicates lost activity compared with the results presented previously but still exhibit an activity almost equal to an .S'. aureus killing performance of 99%. Under these conditions, the endolysin of sequence SEQ ID NO: 1 on mannitol support is not inactivated.

Examples of extemporaneous cosmetic products comprising an anhydrous composition according to the invention (composition A) or a composition (composition B) comprising such an anhydrous composition according to the invention

Two examples of cosmetic products are provided above:

The first is an extemporaneous cosmetic product comprising a packaging, or kit, with two spatially-separated compartments, in which the first compartment contains an anhydrous composition according to the invention (composition A) and the second compartment contains a cosmetic composition containing an aqueous gel or an emulsion.

The packaging, or kit, having 2 compartments, may be, for example, an Ariane Push-It Pack supplied by Seriplast®, which enables the restitution within the context of mixing a powder in a liquid.

The second is a cosmetic composition composed of an anhydrous composition according to the invention (composition A), dispersed in an oil.

Sequence listing

SEQ ID NO: 1 M23-LST AMI2638 CBD2638 (PROTEIN)

AATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVDFFMNIGTPVKAISSGKIV EAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVKAGQIIGWSGSTG YSTAPHLHFQRMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPTPNTGELLRPKDA KKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKITAPKP SIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVYANRNEVLWYHPTD

YVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLP

VNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHYYDGG

KLEVSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWYKAEHASFTVTAP

EGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVWVSWETFEGETVYMPV

RTWDAKTGKVGKLWGEIK

MRGSHHHHHHGSAATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVDFFMNI

GTPVKAISSGKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVK

AGQIIGWSGSTGYSTAPHLHFQRMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPT

PNTGELLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSN

HIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVYAN

RNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKV

AADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDY

FIKRIKHYYDGGKLEVSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWY

KAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVWVSW

ETFEGETVYMPVRTWDAKTGKVGKLWGEIK

GCTGCAACACATGAACATTCAGCACAATGGTTGAATAATTACAAAAAAGGATA

TGGTTACGGTCCTTATCCATTAGGTATAAATGGCGGTATGCACTACGGAGTTGA

TTTTTTTATGAATATTGGAACACCAGTAAAAGCTATTTCAAGCGGAAAAATAG

TTGAAGCTGGTTGGAGTAATTACGGAGGAGGTAATCAAATAGGTCTTATTGAA

AATGATGGAGTGCATAGACAATGGTATATGCATCTAAGTAAATATAATGTTAA

AGTAGGAGATTATGTCAAAGCTGGTCAAATAATCGGTTGGTCTGGAAGCACTG

GTTATTCTACAGCACCACATTTACACTTCCAAAGAATGGTTAATTCATTTTCAA

ATTCAACTGCCCAAGATCCAATGCCTTTCTTAAAGAGCGCAGGATATGGAAAA

GCAGGTGGTACAGTAACTCCAACGCCGAATACAGGTGAGCTCTTACGCCCTAA

AGACGCAAAGAAAGATGAAAAATCACAAGTATGTAGTGGTTTGGCTATGGAA

AAATATGACATTACAAATTTAAATGCTAAACAAGATAAATCAAAGAATGGGA

GCGTGAAAGAGTTGAAACATATCTATTCAAACCATATTAAAGGTAACAAGATT ACAGCACCAAAACCTAGTATTCAAGGTGTGGTCATCCACAATGATTATGGTAG

TATGACACCTAGTCAATACTTACCATGGTTATATGCACGTGAGAATAACGGTA

CACACGTTAACGGTTGGGCTAGTGTTTATGCAAATAGAAACGAAGTGCTTTGG

TATCATCCGACAGACTACGTAGAGTGGCATTGTGGTAATCAATGGGCAAATGC

TAACTTAATCGGATTTGAAGTGTGTGAGTCGTATCCTGGTAGAATCTCGGACA

AATTATTCTTAGAAAATGAAGAAGCGACATTGAAAGTAGCTGCGGATGTGATG

AAGTCGTACGGATTACCAGTTAATCGCAACACTGTACGTCTGCATAACGAATT

CTTCGGAACTTCTTGTCCACATCGTTCGTGGGACTTGCATGTTGGCAAAGGTGA

GCCTTACACAACTACTAATATTAATAAAATGAAAGACTACTTCATCAAACGCA

TCAAACATTATTATGACGGTGGAAAGCTAGAAGTAAGCAAAGCAGCAACTATC

AAACAATCTGACGTTAAGCAAGAAGTTAAAAAGCAAGAAGCAAAACAAATTG

TGAAAGCAACAGATTGGAAACAGAATAAAGATGGCATTTGGTATAAAGCTGA

ACATGCTTCGTTCACAGTGACAGCACCAGAGGGAATTATCACAAGATACAAAG

GTCCTTGGACTGGTCACCCACAAGCTGGTGTATTACAAAAAGGTCAAACGATT

AAATATGATGAGGTTCAAAAATTTGACGGTCATGTTTGGGTATCGTGGGAAAC

GTTTGAGGGCGAAACTGTATACATGCCGGTACGCACATGGGACGCTAAAACTG

GTAAAGTTGGTAAGTTGTGGGGCGAAATTAAATAA

MRGSHHHHHHGS

Claims

Claims

1. Anhydrous composition, especially a cosmetic composition, comprising:

(i) at least an endolysin derived from a Staphylococcus aureus phage; and

(ii) mannitol, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2.

2. Composition according to Claim 1, wherein the endolysin comprises a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

3. Composition according to either of Claims 1 and 2, wherein the endolysin derived from a Staphylococcus aureus phage is present in a content ranging from 0.01% to 0.6% by weight relative to the total weight of the composition, in particular from 0.05% to 0.5% by weight relative to the total weight of the composition, more particularly from 0.1% to 0.3% by weight relative to the total weight of the composition.

4. Composition according to any one of Claims 1 to 3, wherein the mannitol is present in a content ranging from 30% to 90% by weight relative to the total weight of the composition, in particular from 40% to 80% by weight relative to the total weight of the composition, more particularly from 45% to 75% by weight relative to the total weight of the composition.

5. Composition according to any one of Claims 1 to 4, wherein said composition is in the form of a lyophilizate.

6. Composition, especially a cosmetic composition, comprising, in a physiologically acceptable medium, at least one anhydrous composition as defined according to any one of Claims 1 to 5.

7. Cosmetic use, especially topical use, of an anhydrous composition according to any one of Claims 1 to 5, or of a composition according to Claim 6, for preventing and/or treating a skin disorder associated with 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.

8. Cosmetic use according to Claim 7, wherein the composition is suitable for topical administration.

9. Non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, notably acneic skin, comprising the topical application to these keratin materials of an anhydrous composition according to any one of Claims 1 to 5 or of a composition according to Claim 6.

10. Method for stabilizing an endolysin derived from a Staphylococcus aureus phage, in particular a method of drying an endolysin derived from a Staphylococcus aureus phage, comprising bringing the endolysin into contact with mannitol, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, the endolysin comprising a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

11. Method according to Claim 10, wherein (i) the endolysin and (ii) the mannitol are mixed in an aqueous liquid, which is then freeze-dried.

12. Use of mannitol for stabilizing, in particular drying, an endolysin derived from a Staphylococcus aureus phage, the endolysin comprising 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 constituted of the reference amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 2, in particular, the endolysin comprising a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 1.

13. Kit for formulating a cosmetic product, comprising at least:

(i) an anhydrous composition as defined in any one of Claims 1 to 5; and

(ii) a cosmetic composition containing an aqueous gel or an emulsion; the anhydrous composition (i) and the cosmetic composition (ii) each being in a compartment, the two compartments being spatially separated.

14. Cosmetic composition comprising at least one anhydrous composition as defined in any one of Claims 1 to 5 dispersed in an oil.