Cosmetic composition comprising an endolysin derived from Staphylococcus aureus phage and 4-hydroxyacetophenone
Patent Information
- Authority / Receiving Office
- FR · FR
- Patent Type
- Patents
- Current Assignee / Owner
- LOREAL SA
- Filing Date
- 2023-08-28
- Publication Date
- 2026-06-26
Abstract
Description
Title of the invention: Cosmetic composition comprising an en-dolysine derived from Staphylococcus aureus phage and 4-hydroxyacetophenone technical field
[0001] The present invention relates to a composition, in particular a cosmetic one, comprising, in a physiologically acceptable medium, at least one endolysin derived from a Staphylococcus aureus phage and 4-hydroxyacetophenone.
[0002] It also relates in particular to the implementation of a composition of the invention to prevent and / or treat a skin disorder related to colonization by Staphylococcus aureus in an individual in need, and in particular to prevent and / or treat acne and / or eczema in an individual in need.
[0003] It also relates to a non-therapeutic cosmetic process for the care of keratinous materials, in particular of the skin, comprising the topical application on these keratinous materials of a composition according to the invention.
[0004] It also relates to the use of 4-hydroxyacetophenone to increase the stability of the enzymatic activity of an endolysin derived from a Staphylococcus aureus phage. Previous technique
[0005] Human skin is permanently populated by a multitude of different microorganisms (bacteria, yeasts and fungi). The resident microbial flora, essential for good skin health, consists mainly of propionibacterium (Cutibacterium acnes), staphylococci (Staphylococcus epidermidis and Staphylococcus hominis), corynebacteria, and streptococci, as well as a fungal flora mainly composed of Malassezia.
[0006] Some dermatological disorders are most often due to the disruption of the ecological balance of the resident flora following a predominant colonization of opportunistic microorganisms not beneficial to the skin such as Staphylococcus aureus known to be associated with atopic dermatitis (eczema), oily or hyperseborrheic skin, and acne.
[0007] To rebalance this excessive colonization by these unbeneficial opportunistic microorganisms on the skin, it is common to use broad-spectrum antimicrobials or bacteriostatics. However, the use of these compounds raises the problem of their non-specificity of action, targeting indiscriminately both undesirable opportunistic flora and resident beneficial flora, and the risk of the emergence of bacterial resistance or imbalances by selecting for resistant bacteria, as well as... skin tolerance problems (irritations, allergies,...).
[0008] There therefore remains a need to find new compounds with good antimicrobial efficacy without presenting the aforementioned disadvantages, and good skin tolerance.
[0009] It has thus been demonstrated that endolysins from Staphylococcus aureus phages (i.e., phages infecting Staphylococcus aureus) can specifically target S. aureus and lyse, and therefore destroy, this bacterium while preserving the resident skin flora (WO2012 / 150858). However, it is well known that one of the main obstacles to the application of endolysins targeting Staphylococcus species is a problem of the stability of these proteins and / or their enzymatic activity, particularly the maintenance of this activity over time.
[0010] Indeed, a significant alteration of the lytic action of these enzymes has been observed through interactions with raw materials, particularly when endolysin is introduced into formulations, especially cosmetics.
[0011] There is therefore a need for raw materials, in particular preservatives, which can be used in compositions, especially cosmetics, without degrading the antimicrobial activity of the endolysins also present in these compositions.
[0012] There is also a need for raw materials, in particular preservatives, which can be used in compositions, especially cosmetics, without degrading (i) the antimicrobial activity of the endolysins also present in these compositions and (ii) the specificity of these endolysins for the targeted bacteria, in particular in the present invention Staphylococcus aureus.
[0013] There is also a need for raw materials, in particular preservatives, that can be used in compositions, especially cosmetic ones: - without degrading the antimicrobial activity of the endolysins used; - while maintaining the specificity of these endolysins for the targeted bacteria, particularly in the present invention Staphylococcus aureus; and - while also allowing for good sensory appeal of the composition.
[0014] There is also a need to increase the stability, in particular the stability over time, of the enzymatic activity of endolysins in formulations, particularly cosmetics, in particular the enzymatic activity of an endolysin derived from a Staphylococcus aureus phage. Statement of the invention
[0015] The present invention aims to solve at least one technical problem aforementioned.
[0016] Indeed, the inventors have now discovered that 4-hydroxyacetophenone is suitable, particularly compared to other cosmetic preservatives such as sodium benzoate, for maintaining good Staphylococcus aureus destruction performance by the associated endolysin. The inventors have also discovered that 4-hydroxyacetophenone increases the stability, in particular the long-term stability, of the enzymatic activity of an endolysin derived from a Staphylococcus aureus phage. Summary of the invention
[0017] As mentioned above, the present invention thus relates to a composition, in particular a cosmetic one, comprising, in particular in a physiologically acceptable environment: (i) at least one endolysin derived from a Staphylococcus aureus phage; And (ii) 4-hydroxyacetophenone, one of its salts, in particular its basic salts, organic or mineral, one of its optical isomers, one of its geometric isomers, or one of its solvates such as hydrates.
[0018] As illustrated in the examples below, the Applicant has surprisingly discovered that a composition according to the invention, comprising an endolysin derived from a Staphylococcus aureus phage and 4-hydroxyacetophenone, advantageously maintains the S. aureus destructive performance of the endolysin.
[0019] Thus, the present invention also relates to the implementation of a composition of the invention for a skin disorder linked to colonization by Staphylococcus aureus in an individual in need, and in particular for preventing and / or treating a skin disorder linked to colonization by Staphylococcus aureus in an individual in need, in particular for preventing and / or treating acne and / or eczema in an individual in need.
[0020] It also relates to a cosmetic process, particularly non-therapeutic, for the care of keratinous materials, in particular of the skin, comprising the topical application on these keratinous materials of a composition according to the invention.
[0021] It further relates to the use of 4-hydroxyacetophenone, one of its salts, in particular its basic salts, organic or mineral, one of its optical isomers, one of its geometric isomers, or one of its solvates such as hydrates, to increase the stability of the enzymatic activity of an endolysin derived from a Staphylococcus aureus phage. Detailed description
[0022] For the purposes of this invention, "preservative agent" means any ingredient whose principal role is to inhibit the growth of microorganisms such as defined in Annex V of the European cosmetic regulation (EC) No 1223 / 2009 of 30 November 2009 relating to cosmetic products, as well as any multifunctional ingredient with, among other things, antimicrobial properties contributing to the preservation of formulas.
[0023] By "cosmetic," we mean a composition compatible with keratinous materials, in particular skin, mucous membranes, and hair. The composition according to the invention is non-therapeutic.
[0024] By "keratinous materials", we mean in particular the skin, mucous membranes, fibers, eyelashes and hair appendages.
[0025] By "skin" we mean the entire skin of the body, and preferably the skin of the face, scalp, décolletage, neck, arms and forearms, eyelids, around the mouth or behind the ears, the hollow of the elbow, the back of the knees, hands, wrists and ankles, or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, chin), décolletage and neck.
[0026] A composition according to the invention comprises a physiologically acceptable medium, that is, one that has a pleasant color, odor, and feel and does not generate unacceptable discomfort, such as tingling, tightness, or redness, likely to deter the user from applying the composition. Naturally, a person skilled in the art will ensure that a physiologically acceptable medium is chosen in such a way that the advantageous properties of the endolysin(s) of the invention are not, or are not substantially, altered. Thus, by way of illustration, a physiologically acceptable medium may primarily consist of water and / or one or more water-miscible solvent(s). A physiologically acceptable medium according to the invention more particularly has a pH between 4 and 8, more particularly between 4.5 and 7.5. Therefore, a composition according to the invention may comprise one or more pH adjuster(s).
[0027] As used herein, the terms "treat" and "treatment" are intended to refer to the alleviation of symptoms associated with a specific disorder or condition and / or the elimination of said symptoms as well as the complete disappearance of the disorder or condition in question.
[0028] In the context of the present invention, the terms "prevent" and "prevention" refer to the reduction to a lesser degree of the risk or probability of occurrence of a given phenomenon.
[0029] By "improving" or "increasing" the stability, in particular increasing the stability over time, of the enzymatic activity of an endolysin, the present invention means strengthening the ability to maintain the enzymatic activity of the endolysin over a prolonged period in the presence of 4-hydroxyacetophenone, of a of its salts, particularly its basic salts, organic or mineral, of one of its optical isomers, one of its geometric isomers, or one of its solvates such as hydrates, compared to the absence of that compound. The improvement is observed compared to a situation where that compound is absent. In this context, the terms "increase" and "improve" are used interchangeably.
[0030] Endolvsin derived from a Staphylococcus aureus phage
[0031] A composition, in particular a cosmetic one, according to the invention is first of all characterized in that it comprises at least one endolysin derived from a Sta-phylococcus aureus phage.
[0032] In the embodiments described herein, the endolysin may be a native bacteriophage endolysin or a recombinant endolysin and may be any endolysin known to qualified persons in art. In this document, the terms bacteriophage lysin, bacteriophage endolysin and endolysin are used interchangeably. An endolysin may be chosen from the group of endolysins defined in documents WO2011 / 023702, WO2012 / 146738, WO2003 / 082184, WO2010 / 011960, WO2010 / 149795, WO2010 / 149792, WO2012 / 094004, WO2011 / 023702, WO2011 / 065854, WO2011 / 076432, WO2011 / 134998, WO2012 / 059545, WO2012 / 085259, WO2012146738, WO2018 / 091707, Exebacase™ (Lysin CF-301); SAL200™ or Tonabacase; Auresine™ (Sigma-Aldrich SAE0083), and Ectolysin™ P128.
[0033] In the embodiments presented here, the endolysin is a Staphylococcus aureus-specific endolysin, meaning that it will efficiently lyse Staphylococcus aureus but will not substantially lyse any bacteria other than Staphylococcus aureus. In particular, an endolysin implemented according to the invention will lyse Staphylococcus aureus, but not Staphylococcus epidermidis.
[0034] Most native Staphylococcus bacteriophage endolysins exhibiting peptidoglycan hydrolase activity, such as endolysin Ply2638, consist of a C-terminal cell wall binding (CBD) domain, a central N-acetylmuramoyl-L-Alanine amidase domain and an N-terminal Alanyl-glycyl endopeptidase domain with cysteine, in the case of Ply2638, an N-terminal lalanyl-glycine endopeptidase domain with peptidase_M23 homology, these last three domains each exhibiting peptidoglycan hydrolase activity with a distinct target binding specificity and generally referred to as enzymatically active domains.
[0035] The endolysin may be a recombinant endolysin, such as a recombinant endolysin specific to Staphylococcus aureus, in particular a chimeric recombinant endolysin specific to Staphylococcus aureus comprising one or more heterologous domains.
[0036] In general, endolysins are made up of different subunits (domains), For example, a cell wall-binding domain (CBD) and one or more enzymatic domains with peptidoglycan activity, such as an amidase domain, an M23 domain, and a CHAP domain (cysteine, amidohydrolases / histidine-dependent peptidases). An example of a Staphylococcus aureus-specific chimeric endolysin comprising one or more heterologous domains is an endolysin comprising an amidase domain from bacteriophage Ply2638, an M23 domain from lysostaphin (S. simulans), and a cell wall-binding domain from bacteriophage Ply2638.
[0037] This chimeric endolysin specific for Staphylococcus aureus is a preferred endolysin and is described in detail in document WO2012 / 150858. Other preferred endolysins are described in detail in document WO2013 / 169104. Other preferred endolysins are described in detail in document WO2016 / 142445. Other preferred endolysins are extensively described in WO2017 / 046021. Other preferred endolysins are extensively described in WO2012 / 146738, WO2003 / 082184, WO2010 / 011960, WO2010 / 149795, WO2011 / 076432, WO2011 / 134998, WO2012 / 085259, WO2012 / 146738 or WO2018 / 091707.
[0038] An implemented endolysin may comprise a domain having at least 80% sequence identity with a domain described in WO2012 / 150858, WO2013 / 169104, WO2016 / 142445, WO2017 / 046021, WO2012 / 146738, WO2003 / 082184, WO2010 / 011960, WO2010 / 149795, WO2011 / 076432, WO2011 / 134998, WO2012 / 085259, WO2012 / 146738 or WO2018 / 091707.
[0039] An implemented endolysin may have at least 80% sequence identity with an endolysin described in WO2012 / 150858, WO2013 / 169104, WO2016 / 142445, WO2017 / 046021, WO2012 / 146738, WO2003 / 082184, WO2010 / 011960, WO2010 / 149795, WO2011 / 076432, WO2011 / 134998, WO2012 / 085259, WO2012 / 146738, WO2018 / 091707, such as the endolysin with the reference amino acid sequence SEQ ID NO: 29 in WO2012 / 150858.
[0040] For the purposes of the present invention, "endolysin derived from a Staphylococcus aureus phage" means a native or recombinant protein such as an enzyme or nucleic acid molecule encoding it, derived from one or more bacteriophages capable of lysing the cell wall of bacteria of the species Staphylococcus aureus.
[0041] The endolysin includes in particular one or more Staphylococcus aureus bacterial cell wall binding domain(s) and / or one or more Staphylococcus aureus bacterial cell wall lysis domain(s), said Staphylococcus aureus bacterial cell wall binding domain(s) and Staphylococcus aureus bacterial cell wall lysis domain(s) being derived from one or more distinct or identical bacteriophage(s) capable of lysing the cell wall of Staphylococcus aureus bacteria.
[0042] The endolysin used in the present invention can be under native or recombinant form, particularly in recombinant form.
[0043] According to a particular embodiment, the endolysin comprises a first protein sequence including a cell wall binding domain of species of the genus Staphylococcus.
[0044] In particular, the first protein sequence is derived from the endolysin of the bacteriophage <e>2638a of S. aureus.
[0045] For each of the amino acid or nucleic acid sequences of interest, reference sequences are described herein. This description also includes amino acid or nucleic acid sequences (e.g., amino acid sequences of enzymes) having specific percentages of amino acid or nucleotide identity with a reference sequence.
[0046] For obvious reasons, throughout this description, a specific nucleic acid sequence or a specific amino acid sequence that respects, respectively, the nucleotide or amino acid identity under consideration, must also lead to the production of a protein (or enzyme) that exhibits the desired biological activity. As used here, the "percentage of identity" between two nucleic acid sequences or between two amino acid sequences is determined by comparing the two optimally aligned sequences across a comparison window.
[0047] The portion of the nucleotide or amino acid sequence in the comparison window may therefore include additions or deletions (for example, "holes") compared to the reference sequence (which does not include these additions or deletions) in order to obtain optimal alignment between the two sequences.
[0048] The terms "sequence homology," "sequence identity," "homology," or "identity" are used interchangeably in this document. For the purposes of the invention, this means that 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. 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 twenty, fifty, one hundred, or more nucleic acids / bases or amino acids. Sequence identity is the percentage of identical matches between the two sequences in the declared aligned region.
[0049] The comparison of sequences and the determination of the percentage of sequence identity between two sequences can be carried out using a mathematical algorithm. Those skilled in the art know that several computer programs different methods are available to align two sequences and determine the identity between two sequences (Kruskal, JB (1983) An overview of sequence comparison In D. Sankoff and JB Kruskal, (ed.), Time warps, string edits and macromolecules: the theory and practice of sequence comparison, pp. 1-44 Addison Wesley).
[0050] The percentage of sequence identity between two amino acid sequences or between two nucleotide sequences can be determined using the Needleman-Wunsch algorithm for aligning two sequences. (Needleman, SB and Wunsch, CD (1970) J. Mol. Biol. 48, 443-453). The algorithm allows for the alignment of both amino acid sequences and nucleotide sequences. The Needleman-Wunsch algorithm has been implemented in the NEEDLE computer program.
[0051] 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) pp276-277, http: / / emboss.bioinformatics.nl / ). For protein sequences, EBLOSUM62 was used for the substitution template. For nucleotide sequences, EDNAFULL was used. The optional parameters used were a gap opening penalty of 10 and a gap extension penalty of 0.5. No end gap penalty was added. In the Output section, Yes was indicated in response to the question "Brief identity and similarity" and "SRS pairwise" was indicated as the output alignment format.
[0052] After alignment using 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 corresponding positions in the alignment showing an identical amino acid or nucleotide in both sequences divided by the total length of the alignment after subtracting the total number of gaps in the alignment. The identity defined here can be obtained from NEEDLE using the NOBRIEF option and is labeled in the program output as "longest identity".
[0053] The similarity of nucleotide and amino acid sequences, i.e., the percentage of sequence identity, can be determined by sequence alignments using several other known algorithms, in particular the Karlin and Altschul mathematical algorithm (Karlin & Altschul (1993) Proc. Natl. Acad. Sci. USA 90: 5873-5877), hmmalign (HMMER package, http: / / hmmer.wustl.edu / ), or the CLUSTAL algorithm (Thompson, JD, Higgins, DG & Gibson, TJ (1994) Nucleic Acids Res. 22, 4673-80), available for example at https: / / www.ebi.ac.uk / Tools / msa / clustalo / , or the GAP program (University of Iowa mathematical algorithm), or the Myers and Miller mathematical algorithm. (1989 - Cabios 4: 11-17) or Clone Manager 9. The preferred settings used are the default settings as defined on https: / / www.ebi.ac.uk / Tools / msa / clustalo / .
[0054] The degree of sequence identity (sequence concordance) can be calculated using, for example, BLAST, BLAT, or BlastZ (or BlastX). A similar algorithm is incorporated in the BLASTN and BLASTP programs of Altschul et al. (1990) J. Mol. Biol. 215, 403-410. BLAST polynucleotide searches are performed with the BLASTN program, score = 100, word length = 12, in order to obtain polynucleotide sequences homologous to the nucleic acids that encode the protein of interest.
[0055] BLAST searches on proteins are performed using 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 parameters of the respective programs are used. Sequence matching analysis can be supplemented by established homologous mapping techniques such as Shuffle-LAGAN (Brudno M., Bioinformatics 2003b, 19 Suppl 1: 154-162) or Markov random fields. Where reference is made to sequence identity percentages in this application, such percentages are calculated in relation to the total length of the longest sequence, unless otherwise stated.
[0056] In particular embodiments, the percentage of identity between two sequences is determined using CLUSTAL O (version 1.2.4).
[0057] Thus, according to a particular embodiment, the first protein sequence comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 1.
[0058] By at least 80% sequence identity between two sequences, it is understood 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 it be amino acid sequences or nucleic acid sequences.
[0059] In particular, the first protein sequence consists of a reference amino acid sequence SEQ ID NO: 1.
[0060] The protein sequences described in this document may be encoded by one or more allelic variants.
[0061] An allelic variant refers to any one of two or more alternative forms of a gene occupying the same chromosomal locus. A nucleic acid variant The preferred variant is a nucleotide sequence containing one or more silent mutations. Alternatively, or in combination, a nucleic acid variant can also be obtained by introducing nucleotide substitutions that do not result in a different amino acid sequence of the polypeptide encoded by the nucleotide sequence, but rather correspond to the use of codons in the host organism intended for the production of the polypeptide of the invention. In a preferred embodiment, a nucleic acid variant encodes a polypeptide that still exhibits its biological function. More preferably, a nucleotide sequence variant encodes a polypeptide exhibiting cell wall binding in species of the genus Staphylococcus and / or lytic activity.Even more preferably, a nucleic acid variant encodes a polypeptide exhibiting enhanced cell wall binding in Staphylococcus species and / or lytic activity, as defined below. Nucleic acids encoding a polypeptide exhibiting enhanced cell wall binding in Staphylococcus species and / or lytic activity can be isolated from any microorganism.
[0062] All these variants can be obtained using techniques known to those skilled in the art, such as library screening by hybridization (Southern blotting procedures) under low to medium to high stringency conditions. Low to medium to high stringency conditions mean prehybridization and hybridization at 42 °C in 5X SSPE, 0.3% SDS, 200 pg / ml of sheared and denatured salmon sperm DNA, and either 25%, 35%, or 50% formamide for low to medium to high stringency, respectively. The hybridization reaction is then washed three times for 30 minutes, using 2X SSC, 0.2% SDS, and 55 °C, 65 °C, or 75 °C for low to medium to high stringency.
[0063] According to a particular embodiment, the first protein sequence is encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 2.
[0064] In particular, the first protein sequence is encoded by a nucleic acid sequence consisting of a reference nucleic acid sequence SEQ ID NO: 2.
[0065] The binding of a domain to the peptidoglycan cell wall of Staphylococcus genera can be assessed using assays well known to those skilled in the art. In a preferred embodiment, an immunohistochemical technique and / or a gene fusion technique resulting in labeled constructs of one or the other domain are used to assess the specific binding of peptides, polypeptides, or proteins to the peptidoglycan cell wall of Staphylococcus genera. lococcus. The signal quantification methods used in the immunohistochemical or fusion techniques mentioned above are well known in art.
[0066] In one embodiment, the cell wall binding of Staphylococcus peptidoglycan can be quantified using a fluorescent fusion construct comprising a polypeptide including a domain within a first protein sequence as described above. Such a cell wall binding assay is described in detail by Loessner et al. (Molecular Microbiology 2002, 44(2): 335-349). In this assay, a solution comprising said fluorescent fusion construct or a negative control, in particular green fluorescent protein (GFP), is exposed to Staphylococcus cells, in particular S. aureus cells, more preferably S. aureus BB255, for a specified period of time, after which the cells are sedimented by centrifugation along 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, in particular GPF, is a measure of cell binding within the meaning of the present invention.
[0067] Examples of evaluation of the binding of an endolysin to the cell wall of species of the genus Staphylococcus are illustrated in particular in WO 2012 / 150858 Al.
[0068] In particular, in the context of this text, a protein sequence will be said to comprise a peptidoglycan cell wall-binding domain of Staphylococcus genera when, using this assay, an increase in the fluorescent signal of sedimented cells is detected. The binding is specifically said to be specific. In particular, an endolysin is described comprising a domain that exhibits a binding capacity, as defined herein, of at least 50, 60, 70, 80, 90, 100, 150, or 200% of the peptidoglycan cell wall binding of the endolysin. <e>2638a S. aureus bacteriophage (Ply2638) encoded by the reference nucleic acid sequence SEQ ID NO: 5.
[0069] According to a particular embodiment, the cell wall binding activity of species of the genus Staphylococcus is measured by an immunohistochemical technique and / or a gene fusion technique, in particular fluorescent fusion, more particularly fusion with a green fluorescent protein.
[0070] According to a particular embodiment, the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4.
[0071] According to a particular embodiment, the endolysin comprises a sequence protein encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 5.
[0072] In particular, the protein sequence can be encoded by a nucleic acid sequence consisting of a reference nucleic acid sequence SEQ ID NO: 5.
[0073] According to a particular embodiment, the endolysin may further comprise a heterologous protein sequence.
[0074] The term "heterologous protein sequence" means a protein sequence, that is, an amino acid sequence or a nucleic acid sequence encoding the protein sequence, that is not naturally found to be functionally linked as a neighboring sequence to said first protein sequence. As used here, the term "heterologous" can mean "recombinant." "Recombinant" refers to a genetic entity distinct from that generally found in nature. Applied to a nucleotide sequence or a 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 distinct from a sequence or molecule found in nature.
[0075] Such methods of protein or nucleic recombination are well known to those skilled in the art.
[0076] According to a particular embodiment, the endolysin comprises a heterologous protein sequence including a lytic domain. In particular, said lytic domain exhibits peptidoglycan hydrolase activity.
[0077] A "peptidoglycan hydrolase activity," also defined herein as a "lytic activity," can be evaluated by methods well known to those skilled in the art. In one embodiment, the lytic activity can be evaluated by spectrophotometry by measuring the decrease in turbidity of cellular suspensions of the substrate. In particular, the lytic activity can be evaluated by spectrophotometry by measuring the decrease in turbidity of a suspension of S. aureus, the turbidity being quantified by measuring the OD595 by spectrophotometry (Libra S22, Biochrom). Preferably, 200 nM of a polypeptide encoded by a nucleic acid molecule such as identified herein are incubated with a suspension of S. aureus having an initial D060o of 1 ± 0.05, as evaluated by spectrophotometry (Libra S22, Biochrom), in PBS buffer pH 7.4, 120 mM sodium chloride for 30 min at 37 °C.The decrease in turbidity is calculated by subtracting the OD595 after 30 min of incubation from the OD595 before 30 min of incubation. In the context of this text, a protein sequence is said to contain a lytic domain when, using this assay, a decrease in turbidity of at least 10, 20, 30, 40, 50, or 60% is detected. In particular, a decrease in... less than 70% is detected. In particular, an endolysin is described comprising a domain that exhibits a lytic activity of at least 50, 60, 70, 80, 90, 100, 150 or 200% or more of a lytic activity of the S. aureus bacteriophage endolysin O2638a (Ply2638) encoded by the reference nucleic acid sequence SEQ ID NO: 5.
[0078] According to a particular embodiment, the lytic activity of endolysin is measured by spectrophotometry by measuring the decrease in turbidity of a suspension of S. aureus.
[0079] In one embodiment, endolysine may not be encoded by an amino acid sequence comprising or consisting of an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4.
[0080] In particular, the endolysin may not be encoded by a nucleic acid sequence comprising or consisting of the reference nucleic acid sequence SEQ ID NO: 5, encoding the endolysin ¢2638 bacteriophage of S. aureus.
[0081] According to a particular embodiment, the heterologous protein sequence comprises a lytic domain, said lytic domain comprising a second and a third protein sequence, said second protein sequence comprising an M23 endopeptidase domain and said third protein sequence comprising an amidase domain.
[0082] An endopeptidase domain such as used here cleaves in particular the pentaglycine cross-bridges (Trayer, HR and Buckley, CE (1970) Molecular properties of lysostaphin, a bacteriolytic agent specific to Staphylococcus aureus. J Biol. Chem. 245, 4842-4846) which are found in the cell wall of Staphylococcus genera, in particular in the cell wall of S. aureus, S. simulans and S. carnosus.
[0083] An amidase domain such as used here hydrolyzes in particular substrates containing gamma-glutamyl.
[0084] The functionality and activity of these domains in a polypeptide can be confirmed by characterizing the cleavage products during the incubation of said polypeptides containing any of these domains with a purified peptidoglycan.
[0085] According to a particular embodiment, the endopeptidase and / or amidase activity of endolysin is measured by characterization of the cleavage products.
[0086] According to a particular embodiment, the endopeptidase and / or amidase activity of endolysin can be measured by measuring the optical density of bacteria in the presence of endolysin. Such methods are described in particular in Park et al. (Characterization of an endolysin, LysBPS13, from a Bacillus cereus bacteriophage, FEMS Microbiol Lett. 2012 Jul;332(l):76-83) and in Grishin et al. (A Simple Protocol for the Determination of Lysostaphin Enzymatic Activity, Antibiotics (Basel). 2020 Dec 17;9(12):917).
[0087] In particular, each of the protein sequences and nucleotide sequences encoding the second or third domain is of bacterial or bacteriophage origin.
[0088] 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 of the bacteriophage <e>2638a from S. aureus and lysostaphin from S. simulans. In particular, one of the second and third protein sequences is derived from the endolysin of bacteriophage <e>2638a from S. aureus and the other sequence of the second and third protein sequences is derived from lysostaphin from S. simulans.
[0089] According to a particular embodiment, said second protein sequence comprises at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 6 and said third protein sequence comprises at least 80%, in particular 90%, more particularly 95% sequence identity with the reference amino acid sequence SEQ ID NO: 8.
[0090] According to a particular embodiment, said second protein sequence is encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 7 and said third protein sequence is encoded by a nucleic acid sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference nucleic acid sequence SEQ ID NO: 9.
[0091] According to a particular embodiment, said second protein sequence is encoded by a nucleic acid sequence consisting of the reference nucleic acid sequence SEQ ID NO: 7 and said third protein sequence is encoded by a nucleic acid sequence consisting of the reference nucleic acid sequence SEQ ID NO: 9.
[0092] According to a particular embodiment, the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 10 and SEQ ID NO: 11.
[0093] In particular, endolysin may comprise a protein sequence consisting of the reference amino acid sequence SEQ ID NO: 10.
[0094] According to a particular embodiment, the endolysin comprises a protein sequence encoded by a nucleic acid sequence comprising at least 80% in in particular at least 90%, more particularly at least 95% sequence identity with a reference nucleic acid sequence SEQ ID NO: 12. In particular, endolysin may comprise a protein sequence encoded by a nucleic acid sequence consisting of a reference nucleic acid sequence SEQ ID NO: 12.
[0095] An endolysin comprising a protein sequence encoded by a reference nucleic acid sequence SEQ ID NO: 12 differs from endolysin 2638a bacteriophage of S. aureus in that the endopeptidase M23 N-terminal domain is substituted by an endopeptidase M23 domain from the lysostaphin of S. Simulons.
[0096] Suitable endolysins according to the invention can be obtained by any method known to those skilled in the art for producing recombinant proteins. In particular, endolysins according to the invention can be obtained by introducing one or more gene(s) of interest, such as the nucleic acid sequences described above, into the genome of a host organism via a vector.
[0097] In another aspect, a nucleic acid construct is described comprising at least one of the nucleic acid sequences as defined above. This nucleic acid construct may comprise a first nucleic acid sequence encoding a polypeptide including a cell wall-binding domain, possibly further comprising a second and a third nucleic acid sequence as defined above.
[0098] An expression vector comprising such a nucleic acid construct is also described. In particular, an expression vector comprises a nucleotide sequence as mentioned above, which is functionally linked to one or more control sequences, which direct the production or expression of the encoded polypeptide in a cell, subject, or cell-free expression system.
[0099] An expression vector can be considered a recombinant expression vector. This vector can consist of a plasmid, a cosmid, a bacteriophage, or a virus that is transformed by the introduction of a nucleic acid molecule according to the invention. Such transformation vectors, depending on the host organism to be transformed, are well known to those skilled in the art and are widely described in the literature.
[0100] Another object described in this text is a method for transforming host organisms by integrating at least one nucleic acid sequence as described, this transformation being able to be carried out by any suitable means known and widely described in the specialized literature, more particularly by the vector described above.
[0101] In another aspect, a cell is described, which comprises a nucleic acid construct or an expression vector as defined above. A cell may be any microbial cell, prokaryotic or eukaryotic, that is suitable for the expression of an endolysin according to the invention. In a preferred embodiment, said cell is an E. coli cell. In a further preferred embodiment, said cell is an E. coli CLiblue MRF cell.
[0102] The endolysin obtained can then be purified according to purification methods known in the art such as column chromatography, high-performance liquid chromatography, etc.
[0103] In a particular embodiment, one or more of the protein sequences as defined herein may include a sequence encoding a tag to facilitate the purification of the endolysin obtained. In particular, said tag is selected from, but not limited to, a group consisting of a FLAG tag, a poly(His) tag, an HA tag, and a Myc tag. More preferably, said tag is a 6xHis tag. Even more preferably, said tag is an N-terminal 6xHis tag identical to SEQ ID NO: 13.
[0104] Endolysins and methods for obtaining them are described in particular in application WO 2012 / 150858 Al.
[0105] An endolysin derived from a suitable Staphylococcus aureus phage according to the invention may be present in the composition in freshly prepared form or in lyophilized form.
[0106] In the present text, "freshly prepared" is defined in particular as storage for no more than 2 days after its production at 1.63 mg / mL in a lyophilization buffer (50 mM Tris, 500 mM sucrose, 200 mM mannitol, 0.05% polysorbate 20 + 50% glycerol) at -20 °C followed by thawing immediately before evaluating the lytic activity in an assay as identified herein.
[0107] By "lyophilized" is meant an endolysin that has been dehydrated by lyophilization, which consists of freezing the protein and then dehydrating it to extract the water.
[0108] After lyophilization, a lyophilized endolysin can undergo a subsequent reconstitution step by the addition of water. In one embodiment, lyophilization and reconstitution can be carried out by dialysis against three changes of 300 mL of lyophilization buffer (50 mM phosphate or Tris, 500 mM sucrose, 200 mM mannitol, pH 7.4) aliquot and freezing in the gas phase of liquid nitrogen. Lyophilization can be carried out under standard conditions, in particular at -40 °C and under vacuum at 75 mTorr for 60 minutes, before raising the temperature for 5 hours to -10 °C and then raising it again for 60 minutes at -10 °C at the same vacuum levels. As a final step, the temperature is in particular raised to 25 °C for 10 hours. The samples are reconstituted by the addition of water.
[0109] A composition according to the invention may comprise an endolysine content derived from a Staphylococcus aureus phage ranging from 0.0001% to 0.1% by weight relative to the total weight of the composition, in particular from 0.0005% to 0.01% by weight relative to the total weight of the composition, more particularly from 0.001% to 0.005% by weight relative to the total weight of the composition. 4-hydroxyacetophenone
[0110] In particular, a composition according to the invention comprises 4-hydroxyacetophenone, one of its salts, in particular its basic salts, organic or mineral, one of its optical isomers, one of its geometric isomers or one of its solvates such as hydrates.
[0111] 4-Hydroxyacetophenone, also known as 4-hydroxyphenylethanone, p-acetophenol, p-hydroxyphenylmethylketone or piceol, has the following general formula (I):
[0113] 4-Hydroxyacetophenone plays the role of preservative, particularly in cosmetic compositions, in particular by inhibiting oxidation reactions.
[0114] By "organic or mineral base salt" is meant the base salts or alkali agents as defined below.Examples of basic salts include alkali metal hydroxides such as sodium, potassium, and lithium hydroxides; alkaline earth metal hydroxides such as calcium and magnesium hydroxides; hydroxides of other metals, such as aluminium and zinc hydroxides; ammonia and organic amines such as unsubstituted or hydroxysubstituted mono-, di-, or tri-alkylamines; dicyclohexylamines; tributylamines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-hydroxy-alkylamines) such as mono-, bis-, or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris-(hydroxymethyl)methylamine; N,N-di-alkyl-N-(hydroxyalkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine and lysine.
[0115] 4-Hydroxyacetophenone suitable according to the invention is in particular marketed under the name SymSave® HO, under CAS No. 99-93-4, by the company SYMRISE.
[0116] The composition according to the invention comprises in particular a 4-hydroxyacetophenone content 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.
[0117] A composition according to the invention may comprise one or more endolysine(s) according to the invention and 4-hydroxyacetophenone according to the invention in an endolysine(s) / 4-hydroxyacetophenone mass ratio of between 0.0001 and 0.5 and in particular between 0.001 and 0.25, more particularly between 0.002 and 0.1.
[0118] A composition according to the invention may include at least water and optionally an organic solvent miscible in water, or a solvent not miscible in water such as an oil.
[0119] In particular, a composition according to the invention may comprise a quantity of water of at least 10% by weight relative to the total weight of the composition, in particular a quantity of water ranging from 10% to 98% by weight, more particularly from 20% to 95% by weight, notably from 30% to 90% by weight and more particularly from 35% to 85% by weight relative to the total weight of the composition.
[0120] The water may be sterile demineralized water and / or floral water and / or natural thermal or mineral water.
[0121] By "water-miscible organic solvent" according to the present invention, we mean an organic compound that is liquid at room temperature and miscible with water, the miscibility of which in water is greater than 50% by weight at 25 °C and atmospheric pressure.
[0122] Water-miscible organic solvents usable in the composition of the invention may in particular be volatile.
[0123] Among the water-miscible organic solvents that can be used in a composition of the invention, examples include lower monoalcohols having 2 to 5 carbon atoms such as ethanol and isopropanol, polyols such as propylene glycol, glycerol.
[0124] According to one embodiment, a composition according to the invention may be free of lower monoalcohols having from 2 to 5 carbon atoms.
[0125] Water-miscible organic solvents may be present in the composition according to the invention in a content ranging from 5% to 20% by weight relative to the total weight of the composition, preferably from 10% to 15% by weight relative to the total weight of the composition.
[0126] According to a particular embodiment, a composition according to the invention may comprise less than 2% by weight of ethanol, in particular less than 1% by weight, more particularly less than 0.5% by weight, relative to the total weight of the composition position, in particular less than 0.1% by weight of ethanol, and in particular may be free of ethanol. Additional ingredients
[0127] In addition to the aforementioned compounds, a composition according to the invention may of course include one or more ancillary ingredient(s).
[0128] Of course, a person skilled in the art will take care to choose one or more ancillary ingredient(s) such that the advantageous properties of the endolysine(s) of the invention are not, or substantially not, altered.
[0129] The ancillary ingredients are present in the compositions in a usual amount for each of them in a cosmetic composition, in particular in a usual amount for each of them allowing them to retain their cosmetic properties, more particularly in a usual amount for each of them allowing them, when each is the only ingredient of a composition according to the invention exhibiting this property, to retain their cosmetic property.
[0130] Thus, a composition according to the invention may comprise one or more of the following ancillary ingredients selected from surfactants; fats; colorants; preservatives; perfumes; pH adjusters such as organic acids like citric acid; antioxidants; hydrophilic gelling agents such as hydroxypropylmethylcellulose; amino acids such as arginine; carbohydrates; chelating agents; sugar alcohols; cosmetic actives; and mixtures thereof.
[0131] Of course, a person skilled in the art will take care to choose this or these possible ancillary ingredient(s) and / or their quantity in such a way that the advantageous properties of a composition according to the invention are not, or substantially not, altered by the envisaged addition.
[0132] The ancillary ingredient(s) other than those listed below may be present in the composition according to the invention in a concentration of between 0.001% and 20% by weight, in particular from 0.01% to 10% by weight, more particularly between 0.1% and 5% by weight relative to the total weight of the composition.
[0133] According to a particular embodiment, a composition according to the invention may include at least one ancillary ingredient selected from an oil, an aromatic alcohol of formula (II), an organic filler, a non-ionic surfactant, and mixtures thereof. Oil
[0134] A composition according to the invention may comprise at least one oil.
[0135] For the purposes of the present invention, "oil" means a liquid compound at 25 °C and atmospheric pressure (1.013105 Pa), immiscible with water.
[0136] By "immiscible" is meant that the mixture of the same quantity of water and oil, after stirring, does not lead to a stable solution comprising only one phase, under the aforementioned temperature and pressure conditions. The observation is made visually or, if necessary, using a phase-contrast microscope, on 100 g of the mixture obtained after sufficient Rayneri shaking to create a vortex within the mixture (for example, 200 to 1000 rpm); the resulting mixture being left to stand in a closed bottle for 24 hours at room temperature before observation.
[0137] The term "hydrocarbon oil" means an oil containing primarily hydrogen and carbon atoms and possibly one or more functional groups selected from among the hydroxyl, ester, ether, and carboxylic groups. A hydrocarbon oil therefore does not contain silicon or fluorine atoms.
[0138] By "siliconized oil" is meant an oil comprising at least one silicon atom, and in particular at least one Si-O group, and more particularly an organo-polysiloxane.
[0139] By "fluoridated oil" is meant an oil comprising at least one fluorine atom.
[0140] By "nonpolar hydrocarbon oil" is meant a hydrocarbon oil that does not comprising only carbon and hydrogen atoms, in particular non-aromatic (also called hydrocarbon).
[0141] By "polar hydrocarbon oil" is meant hydrocarbon oils comprising mainly hydrogen and carbon atoms and one or more functions selected from among the hydroxyl, ester, ether, carboxylic functions.
[0142] In particular, the composition according to the invention may include at least one oil selected from volatile oils and non-volatile oils, in particular excluding paraffin oils.
[0143] Volatile oils
[0144] By "volatile oil" is meant an oil (or non-aqueous medium) capable of evaporating upon contact with the skin in less than one hour, at room temperature and atmospheric pressure. The volatile oil is a volatile cosmetic oil, liquid at room temperature, having in particular a non-zero vapor pressure, at room temperature and atmospheric pressure, in particular, having a vapor pressure ranging from 0.13 Pa to 40,000 Pa (103 to 300 mm Hg), and in particular, ranging from 1.3 Pa to 13,000 Pa (0.01 to 100 mm Hg), and more particularly ranging from 1.3 Pa to 1300 Pa (0.01 to 10 mm Hg).
[0145] According to a particular embodiment of the invention, volatile oils are such that their flash points are below 120 °C and their vapor pressure is less than 5 Pa, more particularly those whose flash point is below 90 °C and whose vapor pressure is greater than 1 Pa, even more particularly those whose flash point is less than or equal to 60 °C and the vapor pressure is greater than 5 Pa and more particularly whose flash point is less than 60 °C and the vapor pressure is greater than 100 Pa.
[0146] The volatile oil(s) may be chosen from volatile hydrocarbon oils such as: - hydrocarbon oils having 8 to 16 carbon atoms, and in particular: a) C8-C16 branched alkanes such as isoalkanes (also called isoparaffins) such as C8-C9 Isoparaffin, C13-C16 Isoparaffin, isododecane, isodecane, isohexadecane, and for example oils sold under the trade names Isopars or Permetyls, alone or in mixtures, in particular isododecane (also called 2,2,4,4,6-pentamethylheptane), for example marketed by INEOS, more particularly isododecane; b) linear C6-C16 alkanes, alone or in mixtures, for example such as hexane, decane, undecane, tridecane, isoparaffins such as, or n-dodecane (C12) and n-tetradecane (C14) sold by Sasol respectively under the references PARAFOL 12-97 and PARAFOL 14-97, the undecane-tridecane mixture, the mixtures of n-undecane (Cl 1) and n-tridecane (Cl3) obtained in examples 1 and 2 of application WO 2008 / 155059 of the Cognis Company, and their mixtures as well as the mixtures of n-undecane (C11) and n-tridecane (Cl3) Cetiol Ultimate® of the BASF Company; c) cyclic, non-aromatic, volatile C5-C12 alkanes; - short chain esters having 3 to 8 carbon atoms in total, such as methyl acetate, ethyl acetate, propyl acetate, n-butyl acetate or isobutyl acetate for example sold by SOLVAY, DOW or OXEA; - volatile carbonate hydrocarbon oils of structure R'1-OC(O)-O-R'2 in which R'1 and R'2, identical or different, independently designate a linear, branched, or cyclic C4-C8 alkyl group, in particular a linear C4-C8 alkyl group. It may be preferable for R1 and R2 to be identical. In particular, R'1 and R'2 designate 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-O-R2 in which RI and R2, whether identical or different, independently designate a linear, branched, or cyclic C4-C8 alkyl group, in particular a linear or branched C4-C8 alkyl group. Preferably, RI and R2 should be identical. Examples of linear alkyl groups include butyl and pentyl groups. Examples of branched alkyl groups include 1-methylpropyl, 2-methylpropyl, β-butyl, and 1,1-dimethylpropyl.
[0147] In particular, the volatile hydrocarbon oil(s) are chosen from alkanes in C8-C16 in particular linear, and more particularly are chosen from among the alkanes in C9-C12, even more particularly are chosen from a mixture of alkanes in C9-C12 such as VEGELIGHT SILK® marketed by BioSynthls.
[0148] The volatile oil(s) may be chosen from silicone-coated volatile oils such as: - silicone oils comprising in particular, from 2 to 7 silicon atoms, these silicone oils possibly having alkyl or alkoxy groups having from 1 to 10 carbon atoms. As volatile silicone oils usable in the invention, we may mention, in particular, dimethicones of viscosity 5 and 6 cSt, cyclopentadime-thylsiloxane, dodecamethylpentasiloxane, cyclohexadimethylsiloxane, octamethyl cyclotetrasiloxane, decamethyl cyclopentasiloxane, dodecamethyl cyclohexasiloxane, heptamethyl hexyltrisiloxane, heptamethyloctyl trisiloxane, hexamethyl disiloxane, octamethyl trisiloxane, decamethyl tetrasiloxane, dodecamethyl pentasiloxane, and mixtures thereof. Examples include dodecamethyl-pentasiloxane such as the reference DM-FLUID-2cs marketed by SHIN-ETSU or cyclohexadimethylsiloxane such as the reference XIAMETER PMX-0246 CYCLOHEXASILOXANE marketed by DOW CHEMICAL.
[0149] Non-volatile oils
[0150] By "non-volatile oil" is meant an oil whose vapor pressure at 25°C and atmospheric pressure is non-zero and less than 2.66 Pa, more particularly less than 0.13 Pa. By way of example, the vapor pressure can be measured according to the static method or by the isothermal thermogravimetric effusion method, according to the vapor pressure of the oil (OECD standard 104).
[0151] The non-volatile oil or oils may be of natural or synthetic origin, in particular natural.
[0152] Among the non-volatile oils, we can mention: - non-volatile fluorinated oils can be chosen in particular from fluorinated polyethers, as well as from fluorosilicone oils, fluorinated silicones as described in document EP-A-847752; - Non-volatile silicone oils can in particular be chosen from among the non-volatile silicones with the following INCI names: dimethicone, dimethiconol, trimethyl pentaphenyl trisiloxane, tetramethyl tetraphenyl trisiloxane, diphenyl dimethicone, tri-methylsiloxyphenyl dimethicone, phenyltrimethicone, diphenylsiloxy phenyl tri-methicone; as well as their mixtures. These products are marketed under the names PH-1555 HRI Cosmetic Fluid (Trimethyl Pentaphenyl Trisiloxane), Dow Corning 556 Cosmetic Grade Fluid (Phenyltrimethicone) by Dow Corning; Diphenyl Dimethicone such as products KF-54, KF54HV, KF-50-300CS, KF-53d, KF-50-100CS or Diphe- nylsiloxy Phenyl Trimethicone KF56 A marketed by Shin Etsu, marketed by Shin Etsu; the products Belsil PDM 1000, Belsil PDM 20 marketed by Wacker Chemie (Trimethylsiloxy Phenyl Dimethicone), alone or in mixtures;- Non-volatile, non-polar hydrocarbon oils, which may be selected from linear or branched compounds of mineral or synthetic origin, such as: i) squalane, such as NEOSSANCE SQUALANE, marketed by AMYRIS, and isoeicosane; ii) mixtures of linear, saturated hydrocarbons, particularly C14-C30, and more specifically C15-C28, such as mixtures with INCI names such as: (C15-C19)alkane, (C18-C21)alkane, (C21-C28)alkane, such as Gemseal 40, Gemseal 60, and Gemseal 120, marketed by Total, Emogreen L19, and Emogreen L15, marketed by SEPPIC; iii) polybutenes, hydrogenated or non-hydrogenated, such as products from the Indopol range marketed by the company INEOS Oligomers, the products with the INCI name HYDROGENATED POLY-ISOBUTENE;(iv) polyisobutenes, hydrogenated or not, in particular hydrogenated polyisobutenes such as, for example, the non-volatile compounds of the Parléam® range marketed by NIPPON OIL FATS, (v) polydecenes, hydrogenated or not, such as, for example, non-volatile compounds of the PURESYN® range marketed by ExxonMobil, (vi) decene / butene copolymers, butene / isobutene copolymers and (vii) mixtures thereof; - non-volatile polar hydrocarbon oils that can be chosen from: (i) Fatty alcohols, saturated, unsaturated, linear or branched, in the C10-C26 range, liquid at room temperature (25°C), in particular mono-alcohols. In particular, C10-C26 alcohols are fatty alcohols, especially branched ones when they comprise at least 16 carbon atoms; in particular, fatty alcohols comprise from 10 to 24 carbon atoms, and more particularly from 12 to 22 carbon atoms, such as, in particular, lauric, isostearyl, oleic alcohols, 2-butyloctanol, 2-undecyl pentadecanol, 2-hexyldecyl alcohol, isocetyl alcohol, octyldodecanol and mixtures thereof; ii) triglycerides consisting of esters of fatty acids and glycerol, in particular whose fatty acids may have chain lengths ranging from C4 to C36, and especially from C18 to C36, these oils being linear or branched, saturated or unsaturated;Examples include heptanoic or octanoic triglycerides, caprylic / capric acid triglycerides; vegetable oils such as wheat germ, sunflower, grapeseed, sesame, corn, apricot kernel, castor, shea, avocado, olive, soybean, sweet almond, palm, rapeseed, cottonseed, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, squash, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, candlenut, passionflower, rosehip, peanut, and others; coconut, argan, passionflower, kaya; the liquid fraction of shea butter, and the liquid fraction of cocoa butter; as well as mixtures thereof; iii) linear aliphatic hydrocarbon esters of formula RC(O)-OR' in which RC(O)-O- represents the carboxylic acid remainder comprising 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. Examples of such esters include isoamyl laurate, cetostearyl octanoate, isopropyl stearate or isostearate, ethyl palmitate, 2-ethylhexyl palmitate, isostearyl isostearate, octyl stearate, isostearyl heptanoate, and octanoates, decanoates, or ricinoleates of alcohols or polyalcohols such as propylene glycol dioctanoate, cetyl octanoate, coco caprylate caprate, tridecyl octanoate, 2-ethylhexyl palmitate, and alkyl benzoate.polyethylene glycol diheptanoate, propylene glycol diethyl 2-hexanoate and mixtures thereof, hexyl laurate, neopentanoic acid esters such as isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyl-2-docecyl neopentanoate, isononanoic acid esters such as isononyl isononanoate, isotridecyl isononanoate, octyl isononanoate, oleyl erucate; lauroyl isopropyl sarcosinate, diisopropyl sebacate, isocetyl stearate, isodecyl neopentanoate, isostearyl behenate, myristyl myristate; and mixtures thereof; , (iv) hydroxylated esters such as polyglycerol-2 triisostearate; (v) aromatic esters such as tridecyl trimellitate, C12-C15 alcohol benzoate, 2-phenyl ethyl ester of benzoic acid, butyl octyl salicylate; (vi) linear fatty acid esters with a total carbon number from 35 to 70 such as pentaerythrityl tetrapelargonate; vii) C24-C28 branched fatty alcohol or fatty acid esters such as triisoarachidyl citrate, pentaerythrityl tetraisononanoate, glyceryl triisostearate, glyceryl tridecyl-2 tetradecanoate, pentaerythrityl tetraisostearate, polyglyceryl-2 tetraisostearate or pentaerythrityl tetradecanoate; (viii) polyesters obtained by condensation of unsaturated fatty acid dimers and / or trimers and diols, such as those with the INCI name dilinoleic acid / butanediol copolymer and dilinoleic acid / propanediol copolymer; polyesters obtained by condensation of fatty acid dimers and diol dimers, such as dilinoleyl dimer and dilinoleate; (ix) synthetic ethers of formula R1-O-R2, in which RI and R2, whether identical or different, independently designate a linear, branched, or C6-C24 alkyl group. cyclic, in particular a C6-C18 alkyl group, and more particularly a C8-C12 alkyl group. It may be preferable for RI and R2 to be identical. Examples of linear alkyl groups include hexyl, heptyl, octyl, nonyl, decyl, undodyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, behenyl, docosyl, tricosyl, and tetracosyl.Examples of branched alkyl groups include 1,1-dimethylpropyl, 3-methylhexyl, 5-methylhexyl, ethylhexyl, 2-ethylhexyl, 5-methyloctyl, 1-ethylhexyl, 1-butylpentyl, 2-butyloctyl, isotridecyl, 2-pentylnonyl, 2-hexyldecyl, isostearyl, 2-heptylundecyl, 2-octyldodecyl, 1,3-dimethylbutyl, 1-(l-methylethyl)-2-methylpropyl, 1,1,3,3-tetramethylbutyl, 3,5,5-trimethylhexyl, and 1-(2-methylpropyl)-3-methylbutyl. a 3,7-dimethyloctyl group, and a 2-(1,3,3-trimethylbutyl)-5,7,7-trimethyloctyl group. Examples of cyclic alkyl groups include a cyclohexyl group, a 3-methylcyclohexyl group, and a 3,3,5-trimethylcyclohexyl group., dilaury ether, diisostearyl ether, dioctyl ether, no-nylphenyl ether, dodecyl dimethyl butyl ether, cetyl dimethyl butyl ether, cetyl isobutyl ether and mixtures thereof. Among the non-volatile ether oils, dicaprylyl ether, such as CETIOL OE marketed by BASF, can be cited; . x) Carbonates of the formula R8-OC(O)-O-R9, with R8 and R9, identical or different, represent an alkyl chain from C4 to C12, and in particular from C6 to C10, linear or branched; carbonate oils can be dicaprylyl carbonate (or dioctyl carbonate), marketed under the name Cetiol CC® by BASF, di(ethyl-2-hexyl) carbonate, marketed under the name TEGOSOFT DEC® by Evonik, dipropylheptyl carbonate (Cetiol 4 Ail from BASF), dibutyl carbonate; di-neopentyl carbonate; dipentyl carbonate; dineoheptyl carbonate; di-heptyl carbonate; di-isononyl carbonate; or di-nonyl carbonate; and more particularly dioctyl carbonate; xi) vinylpyrrolidone copolymers such as vinylpyrrolidone / 1-hexadecene copolymer (INCI name); xii) higher C6-C26 fatty acids that are liquid at room temperature (25°C) such as oleic acid, linoleic acid, linolenic acid, or isostearic acid; and xiii) mixtures thereof.
[0153] According to a particular embodiment, the composition comprises at least one oil selected from C8-C16 alkane hydrocarbon volatile oils, the oils non-volatile silicone oils, non-polar non-volatile hydrocarbon oils with the exception of paraffin oils, polar non-volatile hydrocarbon oils as defined above, and their mixtures, more particularly selected from polar non-volatile hydrocarbon oils and their mixtures.
[0154] According to a particular embodiment, the composition comprises at least one oil selected from polar hydrocarbon non-volatile oils, more particularly, the composition according to the invention comprises at least one oil selected from polar hydrocarbon non-volatile oils and does not comprise non-polar hydrocarbon non-volatile oils, even more particularly the composition according to the invention comprises at least one oil selected from polar hydrocarbon non-volatile oils and does not comprise non-polar hydrocarbon non-volatile oils, fluorinated non-volatile oils, siliconed non-volatile oils, or volatile oils.
[0155] According to a particular embodiment, the polar non-volatile hydrocarbon oils are selected from: (i) Fatty alcohols, saturated, unsaturated, linear or branched, of C10-C26, liquid at room temperature (25°C), in particular mono-alcohols. In particular, C10-C26 alcohols are fatty alcohols, especially branched ones when they comprise at least 16 carbon atoms; more particularly, a fatty alcohol comprises from 10 to 24 carbon atoms, and even more particularly from 12 to 22 carbon atoms, such as, in particular, lauric, isostearyl, oleic alcohol, 2-butyloctanol, 2-undecyl pentadecanol, 2-hexyldecyl alcohol, isocetyl alcohol, octyldodecanol and mixtures thereof; ii) triglycerides consisting of esters of fatty acids and glycerol, in particular whose fatty acids can have chain lengths ranging from C4 to C36, and especially from C18 to C36, these oils being linear or branched, saturated or unsaturated; examples include heptanoic or octanoic triglycerides, caprylic / capric acid triglycerides; vegetable oils such as wheat germ, sunflower, grapeseed, sesame, corn, apricot kernel, castor, shea, avocado, olive, soybean, sweet almond, palm, rapeseed, cottonseed, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, squash, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, candlenut, passionflower, rosehip, peanut, coconut, argan, passionflower, kaya; the liquid fraction of shea butter, and the liquid fraction of cocoa butter;as well as mixtures thereof; iii) linear aliphatic hydrocarbon esters of formula RC(O)-OR' in which RC(O)-O- represents the carboxylic acid residue containing from 2 to 40 carbon atoms, and R' represents a hydrocarbon chain containing from 1 to 40 carbon atoms, aliphatic hydrocarbon esters of alkylene glycol, in par in particular ethylene glycol or propylene glycol; the total number of carbon atoms advantageously being at least 10. Examples of such esters include isoamyl laurate, cetostearyl octanoate, isopropyl stearate or isostearate, ethyl palmitate, 2-ethylhexyl palmitate, isostearyl isostearate, octyl stearate, isostearyl heptanoate, and octanoates, decanoates, or ricinoleates of alcohols or polyalcohols such as propylene glycol dioctanoate, cetyl octanoate, coco-caprylate caprate, tridecyl octanoate, ethyl 2-hexyl palmitate, alkyl benzoate, and polyethylene diheptanoate. glycol, propylene glycol 2-diethyl hexanoate and mixtures thereof, hexyl laurate, neopentanoic acid esters such as isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyl-2-docecyl neopentanoate,esters of isononanoic acid such as isononyl isononanoate, isotridecyl isononanoate, octyl isononanoate, oleyl erucate; lauroyl isopropyl sarcosinate, diisopropyl sebacate, isocetyl stearate, isodecyl neopentanoate, isostearyl behenate, myristyl myristate; and mixtures thereof; ix) synthetic ether of formula R1-O-R2 in which RI and R2, identical or different, independently denote a linear, branched, or cyclic C6-C24 alkyl group, in particular a C6-C18 alkyl group, and more particularly a C8-C12 alkyl group. It may be preferable for RI and R2 to be identical. Examples of linear alkyl groups include hexyl, heptyl, octyl, nonyl, decyl, undodyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, behenyl, docosyl, tricosyl, and tetracosyl groups.Examples of branched alkyl groups include 1,1-dimethylpropyl, 3-methylhexyl, 5-methylhexyl, ethylhexyl, 2-ethylhexyl, 5-methyloctyl, 1-ethylhexyl, 1-butylpentyl, 2-butyloctyl, isotridecyl, 2-pentylnonyl, 2-hexyldecyl, isostearyl, 2-heptylundecyl, 2-octyldodecyl, 1,3-dimethylbutyl, 1-(l-methylethyl)-2-methylpropyl, 1,1,3,3-tetramethylbutyl, 3,5,5-trimethylhexyl, and 1-(2-methylpropyl)-3-methylbutyl. a 3,7-dimethyloctyl group, and a 2-(1,3,3-trimethylbutyl)-5,7,7-trimethyloctyl group. Examples of cyclic alkyl groups include a cyclohexyl group, a 3-methylcyclohexyl group, and a 3,3,5-trimethylcyclohexyl group., dilaurylether, diisostearylether, dioctylether, no-nylphenylether, dodecyl dimethylbutylether, cetyl dimethylbutylether, cetyl . isobutyl ether and their mixtures. Among the non-volatile ether oils, we can mention dicaprylyl ether, such as the reference CETIOL OE marketed by BASF; x) Carbonates of the formula R8-OC(O)-O-R9, with R8 and R9, identical or different, represent an alkyl chain from C4 to Cl2, and in particular from C6 to C10, linear or branched; carbonate oils can be dicaprylyl carbonate (or dioctyl carbonate), marketed under the name Cetiol CC® by BASF, di(ethyl-2-hexyl) carbonate, marketed under the name TEGOSOFT DEC® by Evonik, dipropylheptyl carbonate (Cetiol 4 Ail from BASF), dibutyl carbonate; di-neopentyl carbonate; dipentyl carbonate; dineoheptyl carbonate; di-heptyl carbonate; di-isononyl carbonate; or di-nonyl carbonate; and more particularly dioctyl carbonate; More specifically, non-volatile polar hydrocarbon oils are selected from among the following: ii) triglycerides consisting of esters of fatty acids and glycerol, in particular whose fatty acids can have chain lengths ranging from C4 to C36, and especially from C18 to C36, these oils being linear or branched, saturated or unsaturated; examples include heptanoic or octanoic triglycerides, caprylic / capric acid triglycerides; vegetable oils such as wheat germ, sunflower, grapeseed, sesame, corn, apricot kernel, castor, shea, avocado, olive, soybean, sweet almond, palm, rapeseed, cottonseed, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, squash, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, candlenut, passionflower, rosehip, peanut, coconut, argan, passionflower, kaya; the liquid fraction of shea butter, and the liquid fraction of cocoa butter;as well as mixtures thereof.
[0156] According to a particular embodiment, the composition comprises at least one oil selected from the group consisting of: - non-volatile polar hydrocarbon triglyceride oils consisting of fatty acid esters and glycerol, in particular those whose fatty acids may have chain lengths ranging from C4 to C36, and especially from C8 to C36, these oils being linear or branched, saturated or unsaturated, selected from soybean oil, jojoba seed oil, shea butter olein, capric acid and caprylic acid triglycerides, and mixtures thereof, - volatile C8-C16 alkane oils, such as C9-C12 alkanes and isoparaffin, - non-volatile, non-polar oils such as squalane, - non-volatile polar hydrocarbon oils of the synthetic ether type with the formula R1-O-R2, in which RI and R2, whether identical or different, designate inde pendant a linear, branched or cyclic C6-C24 alkyl group, in particular a C6-C18 alkyl group, and more particularly a C8-C12 alkyl group, such as dicaprylyl ether, - non-volatile silicone oils such as dimethicone, - non-volatile polar hydrocarbon oils such as fatty alcohols, saturated, unsaturated, linear or branched, in C10-C26, liquid at room temperature (25°C) such as octyldodecanol, - non-volatile polar hydrocarbon oils of the carbonate type with the formula R8-OC(O)-O-R9, with R8 and R9, identical or different, represent an alkyl chain in C4 to C12, in particular from C6 to C10, linear or branched such as dicaprylyl carbonate and - their mixtures.
[0157] 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.
[0158] 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.
[0159] According to a particular embodiment, the composition is devoid of paraffin oils, i.e. the composition comprises 0% paraffin oils.
[0160] The oils according to the invention can advantageously be present in a composition according to the invention in a usual content for a cosmetic composition, in particular in a usual content enabling them to play their cosmetic role in a composition of the invention, in particular in a cosmetic composition according to the invention, more particularly in a usual content enabling them to play their cosmetic role when they are the only ones to play this role in a composition according to the invention.
[0161] Oil can play various cosmetic roles, such as acting as a consistency factor, improving the stability of an emulsion in cold conditions, or providing a smooth appearance to the composition, particularly in the case of an emulsion. It can also help facilitate the spreading and gliding of the composition on the skin, as well as its penetration. Finally, oil can act on the skin through its occlusive effect, its lubricating effect (to the touch), or its emollient / moisturizing effect.
[0162] 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, and more specifically from 10% to 30% by weight relative to the total weight of the composition.
[0163] By total oil content, we mean the sum of the contents of each of the oils mentioned above, present in the composition, or, when only one of these oils is present in the composition, we mean the content of that oil. Aromatic alcohols
[0164] A composition according to the invention may, in addition, comprise at least one aromatic alcohol of formula (II), one of its salts, in particular its basic salts, organic or mineral, one of its optical isomers, one of its geometric isomers or one of its solvates such as hydrates:
[0165] [Chem.2] in which - R1 represents a group chosen from the group consisting of: a) linear or branched hydroxy(CrC4)alkyl, in particular a hydroxy(CrC2)alkyl group, b) a group chosen from -OR5, -C(O)OR6, and -(CH2)nC(H)(R7)-C(O)R8, with : R5 representing a linear or branched (C3-C4)alkyl group, possibly substituted by one or more hydroxyl (OH) group(s), R6 representing a linear or branched (Ci-C4)alkyl group, a phenyl or a benzyl, possibly substituted by one or more hydroxyl group(s), R7 representing a hydrogen atom or a linear or branched (Ci-C4)alkyl group such as methyl or ethyl, in particular R7 representing a hydrogen atom; R8 representing a hydrogen atom, or a (CrCi2)alkyl group, linear or branched, in particular linear, possibly substituted by one or more hydroxyl group(s), or a (C2-Ci2)alkenyl group, linear or branched, in particular linear, possibly substituted by one or more hydroxyl group(s), n is equal to 0, 1 or 2, in particular n is equal to 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 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 carries or represents a hydroxyl group.
[0166] More particularly, the aromatic alcohol(s) of formula (II) of the invention are such that: - when R1 represents a -C(O)OR6 group then R2 is a -OH group; - when R1 represents a group -(CH2)n -C(H)(R7)-C(O)R8 then R2 is a group -OH.
[0167] In particular, the aromatic alcohol may have the following formula (II):
[0168] [Chem.3] in which R1 is chosen from the group consisting of a group: i) linear or branched hydroxy(Ci-C4)alkyl, in particular a hydroxy(CrC2)alkyl group such as hydroxymethyl or hydroxyethyl, ii) a -OR5 group with R5 representing a (C3-C4)hydroxyalkyl group, in particular -OR5 representing -O-CH2-CH(OH)-CH2OH, iii) a -C(O)OR6 group with R6 representing a linear or branched (CrC4)alkyl group, in particular R6 representing a methyl, ethyl, propyl, ispropyl, butyl, isobutyl, or benzyl group, and (iv) a -CH2-CH2-C(O)R8 group with R8 representing a (Ci-C6)alkyl group, linear or branched, in particular -CH2-CH2-C(O)R8 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, 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 carries or represents a hydroxyl group.
[0169] Such compounds act in particular as preservatives, especially in cosmetic compositions. Some also act as perfumes, especially in cosmetic compositions.
[0170] By "organic or mineral base salt" is meant the salts of bases or of alkali agents as defined below.Examples of basic salts include alkali metal hydroxides such as sodium, potassium, and lithium hydroxides; alkaline earth metal hydroxides such as calcium and magnesium hydroxides; hydroxides of other metals, such as aluminium and zinc hydroxides; ammonia and organic amines such as unsubstituted or hydroxysubstituted mono-, di-, or tri-alkylamines; dicyclohexylamines; tributylamines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-hydroxy-alkylamines) such as mono-, bis-, or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris-(hydroxymethyl)methylamine; N,N-di-alkyl-N-(hydroxyalkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine and lysine.
[0171] For the purposes of the present invention, "alkyl group", "alkyl group" or "alkyl radical" means a monovalent saturated hydrocarbon radical, linear or branched, in particular methyl, ethyl, propyl, isopropyl, butyl, tert-butyl radicals, substituted or unsubstituted.
[0172] The term "hydroxyalkyl group" means a saturated hydrocarbon group, linear or branched, comprising at least one -OH group. A hydroxy(Ci-C4)alkyl group is a saturated Ci-C4 hydrocarbon radical, linear or branched, comprising at least one -OH group, in particular comprising a single -OH group. A hydroxy(Ci-C2)alkyl group is a saturated Ci-C2 hydrocarbon radical, linear or branched, comprising at least one -OH group, in particular comprising a single -OH group.
[0173] According to a particular embodiment, the hydroxy(CrC4)alkyl group is selected from the group consisting of a hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, l-(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 a hydroxymethyl or a 2-hydroxyethyl.
[0174] By "halogen atom" is meant one of the chemical elements of the 17th group of the The periodic table of elements includes fluorine, chlorine, bromine, and iodine. Specifically, the halogen atom is chlorine.
[0175] According to a particular embodiment, R1 is chosen from the group consisting of (C i-C2)hydroxyalkyl, 2-hydroxyethyl, hydroxymethyl, an -O-CH2 -CH(OH)-CH2OH group, an -CH2-CH2-C(O)-CH3 group, and a -C(O)-OCH3 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 chosen from the group consisting of a hydrogen atom and an -O-C2-H5 group; and R4 is a hydrogen atom.
[0176] 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.
[0177] According to a particular embodiment, R1 represents a 2-hydroxyethyl, R2 represents a hydrogen atom, R3 represents a hydrogen atom and R4 represents a hydrogen atom.
[0178] 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.
[0179] According to a particular embodiment, R1 represents an -OR5 group with R5 representing a linear or branched (C3-C4) alkyl group substituted by 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 by two hydroxyl groups, R2 represents a halogen atom, R3 represents a hydrogen atom, and R4 represents a hydrogen atom.
[0180] According to a particular embodiment, R1 represents a -O-CH2 -CH(OH)-CH2OH group, R2 represents a chlorine atom, R3 represents a hydrogen atom and R4 represents a hydrogen atom.
[0181] According to a particular embodiment, R1 represents a -(CH2)nC(H)(R)7-C(O)R8 group, with R7 representing a hydrogen atom or a methyl or ethyl group, and R8 representing a linear (CrCi2)alkyl group optionally substituted by a hydroxyl group or a (C2-Ci2)alkenyl group optionally substituted by a hydroxyl group, and n is as defined above, 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)R8 group, R8 representing a linear (Ci-C12)alkyl group, in particular a (Ci- C6) linear alkyl such as a methyl, R2 represents a hydroxyl group, R3 represents a -OC2H5 group, and R4 represents a hydrogen atom.
[0182] According to a particular embodiment, R1 represents a -C(O)OR6 group, with R6 representing a linear or branched (Ci-C4)alkyl group, a phenyl or a benzyl, optionally substituted by one or more hydroxyl group(s), R2 represents a hydroxyl group, R3 represents a hydrogen atom and R4 represents a hydrogen atom.
[0183] According to a particular embodiment, R1 represents a -C(O)-OCH3 group, R2 represents a hydroxyl group, R3 represents a hydrogen atom and R4 represents a hydrogen atom.
[0184] According to a particular embodiment, the aromatic alcohol of formula (II) is selected from the group consisting of phenylethyl alcohol; benzyl alcohol; chlorphenesin (also called 3-(4-Chlorophenoxy)-1,2-propanediol); zingerone; ethylzingerone (also called 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one); vanillin; parabens in particular (Ci-C6)alkylparabens or arylparabens in particular methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben or benzylparaben; their salts and mixtures thereof.
[0185] According to a particular embodiment, the aromatic alcohol of formula (II) is selected from the group consisting of phenylethyl alcohol; benzyl alcohol; chlorphenesin (also called 3-(4-Chlorophenoxy)-1,2-propanediol); zingerone; ethylzingerone (also called 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one); parabens, in particular methylparaben; their salts, and mixtures thereof.
[0186] The composition according to the invention includes 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.
[0187] By 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 that aromatic alcohol of formula (II). Organic bulking agents
[0188] A composition according to the invention may further comprise one or more organic filler(s).
[0189] For the purposes of this invention, "organic filler" means colorless or white solid particles of any shape, of organic, natural or synthetic origin, which are insoluble and scattered throughout the middle of the composition.
[0190] The composition according to the invention may further comprise at least one organic filler selected from an unmodified starch, an N-acylated amino acid, their salts, and mixtures thereof.
[0191] Unmodified starches
[0192] The composition according to the present invention may comprise one or more unmodified starch(es).
[0193] For the purposes of this invention, "unmodified starch" means native starch or starch that has not undergone any chemical or physical modification, in particular by one or more of the following reactions: pregelatinization, oxidation, crosslinking, esterification, etherification, amidification, heat treatments.
[0194] The unmodified starch molecules usable in the present invention can originate from all plant sources of starch, in particular cereals and tubers; more particularly they can be starches from maize, rice, cassava, barley, potato, wheat, sorghum, peas, oats.
[0195] According to a particular embodiment, the unmodified starch is selected from maize starches, rice starches, potato starches, and mixtures thereof, in particular the unmodified starch is selected from maize or potato starches.
[0196] 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.
[0197] According to a particular embodiment, the unmodified starch used in the composition of the present invention is a corn starch such as that marketed under the name BEAUTE-BY-ROQUETTE ST005 by the company ROQUETTE.
[0198] 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.
[0199] N-acylated amino acids and their salts
[0200] A composition according to the present invention may comprise one or more N-acylated amino acids, their salts, and mixtures thereof.
[0201] The term "salt" of an N-acylated amino acid according to the invention means a salt formed by an inorganic or organic acid or an inorganic or organic base.
[0202] Examples of acid salts include sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, isonicotinate, lactate, salicylate, tartrate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gen- tisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, glutamate and aspartate.
[0203] Examples of base salts include alkali metal hydroxides such as sodium, potassium and lithium; alkaline earth metal hydroxides such as calcium and magnesium; hydroxides of other metals, such as aluminium and zinc; ammonia and organic amines such as unsubstituted or hydroxysubstituted mono-, di- or tri-alkylamines; dicyclohexylamines; tributylamines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris-(2-hydroxy-alkylamines) such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris-(hydroxymethyl)methylamine, N,N-di-alkyl-N-(hydroxyalkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine and lysine.
[0204] N-acylated amino acids suitable as an organic filler according to the invention comprise at least one acyl group having from 8 to 22 carbon atoms, in particular a 2-ethyl hexanoyl, caproyl, lauroyl, myristoyl, palmitoyl, stearoyl or cocoyl group, in particular lauroyl.
[0205] The amino acid may be, for example, lysine, glutamic acid or alanine, preferably lysine.
[0206] The amino acid can be of D or L configuration, in particular L.
[0207] According to a particular embodiment of the invention, the C8-C22 N-acylated amino acids are selected from lauroyl lysine, its salts and mixtures thereof, in particular N-lauroyl-L-lysine, its salts and mixtures thereof.
[0208] N-lauroyl-L-lysine is marketed in particular under the name AMIHOPE LL® by the company AJINOMOTO.
[0209] The N-acylated amino acid(s) and their salts may be present in the composition according to the invention in a content ranging from 0.1% to 15% by weight, in particular from 1% to 10% by weight, more particularly from 2% to 4% by weight, such as 3% by weight, relative to the total weight of the composition.
[0210] 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.
[0211] A composition according to the invention may comprise one or more endolysins according to the invention and one or more organic filler(s) in an endolysin / organic filler mass ratio of between 0.0001 and 0.04, and in particular between 0.0002 and 0.004, more particularly between 0.0006 and 0.002. Non-ionic surfactants
[0212] The composition according to the invention may further comprise at least one non-ionic surfactant, in particular selected from non-ionic surfactants comprising one or more carbohydrate residue(s), non-ionic surfactants of the C6-C30 fatty acid alkanolamides type.
[0213] For the purposes of this invention, "surfactant" means any compound that modifies the surface tension between two surfaces. Surfactant compounds are amphiphilic molecules, meaning they have two parts with different polarities: one lipophilic (attracting fats) is nonpolar, and the other hydrophilic (miscible in water) is polar. They thus allow the solubilization of two immiscible phases by interacting with the nonpolar (i.e., lipophilic, and therefore hydrophobic) phase through its hydrophobic part, while interacting with the polar phase through its hydrophilic part.
[0214] By "non-ionic surfactant" is meant a surfactant that does not have a net charge (does not ionize in water).
[0215] Non-ionic surfactant comprising one or more carbohydrate residue(s)
[0216] The composition according to the invention may further comprise at least one non-ionic surfactant comprising one or more carbohydrate residue(s).
[0217] For the purposes of this invention, "carbohydrate" means a sugar-type compound or carbohydrate, corresponding to a molecule essentially composed of carbon, hydrogen, and oxygen atoms.
[0218] According to a particular embodiment, the carbohydrate residue(s) is / are monosaccharides comprising 5 to 6 carbon atoms, more particularly chosen from glucose, fructose, xylose or galactose, even more particularly glucose.
[0219] According to a particular embodiment, the non-ionic surfactant(s) comprising one or more carbohydrate residue(s) is / are chosen from among: (i) esters of sugar(s) and fatty acid(s) such as (poly)esters of glycerol of glucose or alkylglucose and fatty acid having a hydrocarbon chain, linear or branched, saturated or unsaturated, in C6-C22, in particular in Cl6-20; (ii) sugar(s) and fatty alcohol(s) ethers such as alkyl(poly)glycosides; and (iii) mixtures thereof.
[0220] According to a particular embodiment, the non-ionic surfactant(s) comprising one or more carbohydrate residue(s) is / are chosen from among alkyl(poly)glycoside and (poly)esters of glycerol, glucose or alkylglucose and fatty acid having a hydrocarbon chain, linear or branched, saturated or unsaturated, in C6-C22, in particular in C16-20, and mixtures thereof. - Alkyl(poly)glycoside
[0221] Non-ionic surfactants of the alkyl(poly)glycoside type are notably represented by the following general formula (III):
[0222] [Chem 4]
[0223] R*O-(R2O)t-(G)v (III) in which: - R1 represents a linear or branched alkyl or alkenyl radical comprising 6 to 24 carbon atoms, in particular 8 to 20 carbon atoms, or an alkylphenyl radical whose linear or branched alkyl radical comprises 6 to 24 carbon atoms, in particular 8 to 20 carbon atoms; - R2 represents an alkylene radical with 2 to 4 carbon atoms, - G represents a sugar motif with 5 to 6 carbon atoms, -1 designates a value from 0 to 10, in particular from 0 to 4, - v designates a value from 1 to 15, in particular from 1 to 4.
[0224] According to a particular embodiment, the alkyl(poly)glycoside surfactants are compounds of the formula described above in which: - R1 designates a saturated or unsaturated, linear or branched alkyl radical comprising 8 to 20 carbon atoms, - R2 represents an alkylene radical with 2 to 4 carbon atoms, -1 denotes a value ranging from 0 to 3, in particular equal to 0, - G designates glucose, fructose or galactose, in particular glucose; - the degree of polymerization, i.e. the value of v, can range from 1 to 15, in particular from 1 to 4; the average degree of polymerization being more particularly between 1 and 2.
[0225] The glycosidic bonds between the sugar motifs are generally of type 1-6 or 1-4, in particular of type 1-4.
[0226] Examples of alkyl(poly)glycosides include caprylyl / capryl glucoside, such as the product marketed under the name ORAMIX CG 110L® by SEPPIC; decyl glucoside, marketed under the name SORBITHIX L-100® by APPLECHEM; arachidylglucoside, possibly in a mixture with arachidyl alcohol and behenyl alcohol, marketed for example under the name MONTANOV 202® by SEPPIC; ce-tylstearyl glucoside, possibly in a mixture with cetylstearyl alcohol, marketed for example under the name MONTANOV 68MB® by SEPPIC, under the name EMULGADE PL 68 / 50® by BASF and under the names TEGO CARE CG 90 MB® by EVONIK GOLDSCHMIDT; cocoglucoside, such as the product marketed under the name LAMESOFT PO65® by BASF; octyldodecyl xyloside marketed for example under the names FLUIDANOV 20X by the company SEPPIC.
[0227] The alkyl(poly)glycoside can be used in mixture with at least one fatty alcohol, in particular a fatty alcohol having from 6 to 24 carbon atoms, and more particularly from 8 to 20 carbon atoms.
[0228] For example, it is possible to jointly implement a fatty alcohol and an alkyl(poly)glycoside whose alkyl part is identical to that of the selected fatty alcohol.
[0229] Fatty alcohol / alkyl polyglycoside emulsifying mixtures as defined above are known as such. They are described in particular in applications WO 92 / 06778, WO 95 / 13863 and WO 98 / 47610 and prepared according to the preparation processes indicated in those documents.
[0230] Among fatty alcohol / alkyl(poly)glycoside mixtures, examples include products sold by SEPPIC under the MONTANOV® brand, such as the following mixtures: - Arachidyl alcohol and behenyl alcohol / arachidylglucoside - MONTANOV 202® - Cetylstearyl alcohol / Cetylstearylglucoside - MONTANOV 68MB®.
[0231] In a particular embodiment, the composition according to the invention comprises an alkyl(poly)glycoside type surfactant selected from caprylyl / capryl glucoside, arachidyl glucoside, and mixtures thereof.
[0232] In a particular embodiment, the composition according to the invention does not comprise decyl glucoside.
[0233] - (polv)Glycerol esters of glucose or alkvlglucose and fatty acid
[0234] Glycerol (poly)esters of glucose or alkylglucose and fatty acid having a hydrocarbon chain, linear or branched, saturated or unsaturated, in C6-C22 are in particular glycerol (poly)esters of alkylglucose and fatty acid having a linear hydrocarbon chain saturated in C6-C22, in particular in Cl6-20, more particularly in Cl8.
[0235] Among the (poly)esters of glycerol of glucose or alkylglucose and fatty acid having a hydrocarbon chain, linear or branched, saturated or unsaturated, in C6-C22, polyglyceryl-3 methylglucose distearate is particularly preferred.
[0236] Among the commercial products, we can mention the product sold by the company, EVONIK GOLDSCHMIDT under the names TEGO CARE 450.
[0237] The nonionic surfactant(s) comprising one or more carboxyhydrate residue(s) may be present in the composition according to the invention in a content ranging from 0.01 to 10% by weight, in particular in a content ranging from 0.05 to 8% by weight, more particularly in a content ranging from 0.1 to 5% by weight relative to the total weight of the composition, more particularly in a content ranging from 0.2 to 3% by weight relative to the total weight of the composition.
[0238] A composition according to the invention may comprise one or more endolysine(s) according to the invention and one or more non-ionic surfactant(s) comprising one or more carbohydrate residue(s) according to the invention in a mass ratio of endolysine(s) / non-ionic surfactant(s) comprising one or more carbohydrate residue(s) of between 0.0001 and 0.5 and in particular between 0.0002 and 0.1, more particularly between 0.0004 and 0.05, even better between 0.0006 and 0.02.
[0239] C6-C30 fatty acid alkanolamides
[0240] The composition according to the invention may further contain at least one non-ionic surfactant selected from C6-C30 fatty acid alkanolamides.
[0241] Such surfactants may be selected from mono-alkanolamides and diale anolamides of formula (IV):
[0242] [Chem 5]
[0243] R'CONR2R3 (IV) in which: R1 is a linear or branched hydrocarbon group, saturated or unsaturated, having from 6 to 30 carbon atoms, R2 and R3, independently, are hydrogen or a linear or branched, saturated or unsaturated alkanol group having 1 to 10 carbon atoms, provided that only one of R2 or R3 is hydrogen.
[0244] Examples of this type of surfactant include lauric acid monoethanolamide, lauric acid diethanolamide, lauric acid monopropanolamide, lauric acid monoisopropanolamide, myristic acid monoethanolamide, myristic acid diethanolamide, palmitic acid monoethanolamide, stearic acid monoethanolamide (stearamide MEA), oleic acid monoethanolamide, oleic acid diethanolamide, oleic acid monoisopropanolamide, coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid monopropanolamide, coconut oil fatty acid monoisopropanolamide (cocamide MIPA), erucic acid diethanolamide, palm vegetable oil fatty acid monoethanolamide, and mixtures thereof.
[0245] According to a particular embodiment in formula (IV), R1 is a linear or branched, saturated or unsaturated hydrocarbon group having from 8 to 18 carbon atoms,
[0246] R2 and R3, independently, are hydrogen or a linear or branched, saturated or unsaturated alkanol group having from 2 to 5 carbon atoms, provided that only one of R2 or R3 is hydrogen.
[0247] According to a particular embodiment, in formula (IV), R2 is hydrogen, and R3 is a linear or branched saturated alkanol group having 2 to 5 carbon atoms.
[0248] According to a particular embodiment, the appropriate C6-C30 fatty acid alkanolamide of formula (IV) is selected 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.
[0249] Such products are available, for example, coconut oil fatty acid monoethanolamide (cocamide MEA) marketed under the name COMPERLAN® 100 by COGNIS (BASF), coconut oil fatty acid monoisopropanolamide (cocamide MIPA) marketed under the trade name EMPILAN® CIS by Innospec active Chemicals.
[0250] According to a particular embodiment, said C6-C30 fatty acid alkanolamide is cocamide mono-isopropanolamine.
[0251] The C6-C30 fatty acid alkanolamide according to the present invention may be present in an amount from 0.5% to 10% by weight, more particularly from 0.1% to 5% by weight, relative to the total weight of the composition.
[0252] According to a particular embodiment, a composition according to the invention comprises less than 2% by weight relative to the total weight of the composition of solid fatty acid(s) at room temperature (25°C), more particularly a composition according to the invention comprises less than 1% by weight relative to the total weight of the composition of solid fatty acid(s) at room temperature (25°C), i.e. even is free (0% by weight relative to the total weight of the composition) of solid fatty acid at room temperature (25°C), and in particular does not comprise stearic acid.
[0253] According to a particular embodiment, a composition according to the invention comprises less than 0.5% by weight relative to the total weight of the composition of benzoic acid, and / or its salts, in particular alkali or alkaline earth metal benzoates such as sodium benzoate, of sorbic acid and / or its salts in particular alkali or alkaline earth salt sorbate including potassium sorbate, more particularly less than 0.1% by weight or even free (0% by weight relative to the total weight of the composition) of benzoic acid and / or its salts including sodium benzoate, and of sorbic acid and / or its salts including potassium sorbate.
[0254] According to a particular embodiment, a composition according to the invention comprises less than 0.1% by total weight relative to the total weight of the composition of carrageenan, gellan gum, scleroglucan gum, acacia gum, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soy lecithin, sodium alginate, poly- acrylamidomethyl propane sulfonic 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 (0% by weight relative to the total weight of the composition) from carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soy lecithin, sodium alginate, polyacrylamidomethyl propane sulfonic acid, carbomer, cellulose, sodium polyacrylate, konjac gum, agar, and caesalpinia spinosa gum.
[0255] According to a particular embodiment, a composition according to the invention comprises less than 0.5% by total 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).
[0256] According to a particular embodiment, a composition according to the invention comprises an amount less than or equal to 0.5% by total 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).
[0257] According to a particular embodiment, a composition according to the invention comprises an amount less than or equal to 0.5% by total 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).
[0258] According to a particular embodiment, a composition according to the invention comprises an amount less than or equal to 0.5% by total weight relative to the total weight of the composition of zwitteronic surfactant, more particularly is free of zwitteronic surfactant (0% by weight relative to the total weight of the composition).
[0259] According to a particular embodiment, a composition according to the invention comprises less than 0.5% by total weight relative to the total weight of the composition of anionic, cationic, amphoteric and zwitterionic surfactant, more particularly less than 0.1% by total weight relative to the total weight of the composition of anionic, cationic, amphoteric and zwitterionic surfactant, even more particularly less than 0.01% by total weight relative to the total weight of the composition of anionic, cationic, amphoteric and zwitterionic surfactant, better according to a particular embodiment the composition is free of anionic, cationic, amphoteric, and zwitterionic (0% by weight relative to the total weight of the composition).
[0260] According to a particular embodiment, a composition according to the invention comprises less than 0.5% by total 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 co-coamphodiacetate, polyglycerol esters and fatty acids such as polyglyceryl-4-isostearate, polyglyceryl-4-diisostearate polyhydroxy stearate sebacate, and sodium stearate, glyceryl stearate citrate, alkyl sulfate such as sodium lauryl sulfate, alkyl ether sulfate such as sodium laureth sulfate, disodium cocoamphodiacetate, polyglycerol esters and fatty acids such as polyglyceryl-4-isostearate and polyglyceryl-4-diisostearate polyhydroxystearate sebacate, and sodium stearate.
[0261] According to a particular embodiment, a composition according to the invention comprises an amount less than 1% by weight relative to the total weight of the composition of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica, more particularly comprises an amount less than 0.5% by weight relative to the total weight of the composition of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica, or is even free (0% by weight relative to the total weight of the composition) of kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica.
[0262] According to a particular embodiment, a composition according to the invention comprises an amount less than 0.1% by weight relative to the total weight of the composition of solid fatty acid at room temperature (25°C), and in particular does not comprise stearic acid; of benzoic acid, and / or its salts, in particular alkali or alkaline earth metal benzoates such as sodium benzoate, of sorbic acid and / or its salts in particular alkali or alkaline earth salt sorbate including potassium sorbate; in carrageenan, gellan gum, scleroglucan gum, gum arabic, pectin, xanthan gum, guar gum such as hydroxypropyl guar, hydrogenated soy lecithin, sodium alginate, polyacrylamidomethyl propane sulfonic acid, carbomer, sodium polyacrylate, konjac gum, agar, and caesalpinia spinosa gum;in glyceryl stearate citrate, in alkyl sulfate such as sodium lauryl sulfate, in alkyl ether sulfate such as sodium laureth sulfate, in disodium cocoamphodiacetate, in polyglycerol and fatty acid esters such as polyglyceryl-4-isostearate and polyglyceryl-4-diisostearate polyhydroxystearate sebacate, and in sodium stearate; in kaolin, perlite, titanium dioxide, talc, cellulose, boron nitride, maltodextrin and mica. ;
[0263] According to one embodiment, a composition according to the invention comprises hydroxypropylmethylcellulose.
[0264] According to a particular embodiment, a composition according to the invention comprises water.
[0265] According to a particular embodiment, a composition according to the invention comprises propylene glycol.
[0266] According to a particular embodiment, a composition according to the invention comprises water, propylene glycol and hydroxypropylmethylcellulose.
[0267] A composition according to the invention can be presented in all the galenic forms normally used in the cosmetic field.
[0268] It may be in particular in the form of an aqueous, hydroalcoholic, or possibly gelled solution; a lotion-type dispersion, possibly two-phase; an oil-in-water or water-in-oil or multiple oil-in-water emulsion; a gel, particularly an aqueous gel; or a dispersion of oils in an aqueous phase, particularly using spherules, these spherules being polymeric particles or, preferably, ionic and / or non-ionic lipid vesicles. In particular, a composition according to the invention may be in the form of a gel, particularly an aqueous gel. It may also be an anhydrous composition.An anhydrous composition is defined as a composition containing less than 10% water by weight, in particular less than 5% water by weight, more specifically less than 2% water by weight, or even less than 0.5% water, and notably free of water, the water not being added during the preparation of the composition but corresponding to the residual water provided by the mixed ingredients. The composition may have a more or less fluid liquid consistency.
[0269] A composition according to the invention is particularly suitable for topical administration.
[0270] Thus, a composition according to the invention may include all the constituents usually employed in the envisaged topical application and administration.
[0271] A composition according to the invention may advantageously be in the form of an emulsion, in particular obtained by dispersing an aqueous phase in an oily phase (W / O) or an oily phase in an aqueous phase (W / O), of liquid or semi-liquid consistency such as milk, or of soft consistency, or even as a multiple emulsion (W / O / O or W / O / O). These compositions are prepared according to known conventional methods.
[0272] More particularly, a composition according to the invention may be intended for topical application and, in particular, may be in the form of an emulsion, especially an oil-in-water emulsion. In particular, such an emulsion is not intended to be rinsed off after application.
[0273] A composition according to the invention is more particularly intended to be applied to skin.
[0274] In particular, skin means the skin of the face, scalp, décolletage, neck, arms or forearms, or more preferably, the skin of the face (in particular the forehead, nose, cheeks, chin), décolletage and neck.
[0275] The composition may alternatively be in the form of a face and / or body care or makeup product, and be packaged for example as a cream in a jar or as a fluid in a tube or pump bottle or dropper bottle.
[0276] The composition according to the invention can be manufactured by any known process generally used in the cosmetic field.
[0277] The ingredients are mixed before shaping, in the order and under conditions easily determined by those skilled in the art.
[0278] According to a particular embodiment of the invention, other agents intended to enhance the appearance and / or texture of the skin may also be added to the composition according to the invention. Uses and processes
[0279] According to one aspect of it, the present invention relates to the cosmetic use, in particular topical, of a composition according to the invention to prevent and / or treat a skin disorder related to colonization by Staphylococcus aureus in an individual in need, and in particular to prevent and / or treat acne and / or eczema in an individual in need.
[0280] According to yet another aspect of it, the present invention relates to a non-therapeutic cosmetic process for the care of keratinous materials, in particular of the skin, comprising the topical application on these keratinous materials of a composition according to the invention.
[0281] Skin may in particular be skin with acne or at risk of developing acne and / or skin with eczema or at risk of developing eczema.
[0282] The cosmetic uses and processes considered according to the invention are non-therapeutic.
[0283] The cosmetic uses and processes of the invention are more particularly implemented by topically administering a composition according to the invention.
[0284] Topical administration consists of the external application to the skin of cosmetic compositions according to the usual techniques for using these compositions.
[0285] By way of illustration, the cosmetic use or process according to the invention can be implemented by topical application, for example daily, of at least one composition according to the invention, which can, for example, be formulated in the form of a cream, Cleansing gel, serum, lotion, emulsion or milk, particularly in gel form.
[0286] The application may be repeated, for example, 1 to 2 times daily for one or more days and generally for a prolonged period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with one or more breaks if necessary.
[0287] According to one embodiment, the application is daily (once a day) and generally over a prolonged period of at least 3 days, at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of interruption.
[0288] According to one embodiment, the cosmetic treatment process according to the invention may comprise a single application.
[0289] Throughout the description, including the claims, the expressions "between ... and ..." and "ranging from ... to ..." shall be understood to include bounds, unless otherwise specified.
[0290] The following examples illustrate the present invention without limiting its scope.
[0291] In the examples, unless otherwise indicated, the temperature is ambient temperature (25°C), expressed in degrees Celsius, and the pressure is atmospheric pressure. Examples
[0292] Preparation of the working suspension of Staphylococcus aureus (S. aureus} from an ATCC 6538 lyophilisate (according to the recommendations of standard NF EN 12353).
[0293] The lyophilized powder is rehydrated in Trypticase soy broth, inoculated onto Trypticase soy agar (TSA plates) and then incubated for 24 hours at 32.5°C. The cells are then recovered and resuspended in a commercial cryoprotectant solution with cryobeads for storage at -80°C for up to 14 months (long-term storage stock).
[0294] From a cryo-bead of this -80°C stock, a subculture is performed on a TSA slant agar plate, 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 on Trypticase soy agar and then incubating for 24 hours at 35°C. The working suspension is prepared by suspending the cells of this working culture in a trypton salt diluent. This suspension is calibrated between 1 and 3 x 10⁸ CFU (colony-forming units) / mL by absorbance measurement at 620 nm.
[0295] Evaluation of the antimicrobial activity of the samples against S. aureus
[0296] Three formulas were prepared according to the information provided in Table 1 below.
[0297] [Tables 1] INCI NAME Formula a (not in invention) Formula b (according to invention) Formula c (not in invention) Base formula: -WATER -PROPYLENE GLYCOL (PROPYLENE GLYCOL USP / EP from DOW) -HYDROXYPROPYL METHYL-CELLULOSE Qsp 100 Qsp 100 Qsp 100 Endolysin of sequence SEQ ID NO: 10 0% 0.002565% 0.002565% 4-HYDROXYACETOPHENONE (SYMSAVE H 0 from SYMRISE) 0.3% 0.3% 0% SODIUM BENZOATE 0% 0% 0.5%
[0298] Table 1
[0299] The first formula (formula a), outside the scope of this invention, comprises The first formula (formula b), according to the invention, comprises 4-hydroxyacetophenone but is devoid of endolysine according to the invention. The second formula (formula b), according to the invention, comprises 4-hydroxyacetophenone as well as an endolysine according to the invention. Finally, the third formula (formula c), which is not part of the invention, comprises another cosmetic preservative, sodium benzoate, instead of 4-hydroxyacetophenone, as well as an endolysine according to the invention.
[0300] [Tables2] INCI NAME Formula d (not in invention) Formula e (not in invention) Formula f (according to invention) Base formula: Water Paraffin oil Vaseline Glycerin Ceteareth-20 Cetearyl alcohol Qsp 100 Qsp 100 Qsp 100 Endolysin sequence SEQ ID NO: 10 0% 0.003325% 0.003325% 4-HYDROXYACETOPHENON E (SYMSAVE HO from SYMRISE) 0% 0% 0.3%
[0301] Table 2
[0302] The fourth formula (formula d), not part of the invention, does not include either 4-hydroxyacetophenone or endolysine according to the invention. The fifth formula (formula e), not part of the invention, includes endolysine according to the invention but does not include 4-hydroxyacetophenone. The sixth formula (formula f), according to the invention, includes 4-hydroxyacetophenone as well as endolysine according to the invention.
[0303] At T=1 week and / or T=8 weeks after the manufacture of compositions a, b and c, and at T=1 week and T=3 months after the manufacture of compositions d, e and f, 20 gram aliquots of each composition are inoculated with 0.2 mL of a calibrated suspension of S. aureus. After homogenization, the level of microorganisms present in the product represents an S. aureus concentration of 10⁶ CFU per gram of product, i.e., a 1% inoculation of a suspension at 10⁸ CFU per mL (the inoculum level is determined by spreading the suspension on Trypticase soy agar plates and incubating for 24 h at 35°C). After 30 and 60 minutes of contact at room temperature (20°C ± 3°C), 1 gram of the mixture is weighed, then 9.0 mL of Eugon LT100 supp broth is added and mixed until completely homogenized. This mixture is then serially diluted in Eugon LT100 supp broth to a 1 / 100th dilution.
[0304] The dilutions are spread onto Trypticase soy agar plates and incubated at 35°C for 48 hours until the surviving colonies of S. aureus are counted.
[0305] Antimicrobial activity on S. aureus is expressed as a logarithmic reduction from the initial rate and associated with the activity of the active compound endolysin of sequence SEQ ID NO: 10 by comparing the counts of surviving S. aureus in formula with and without endolysin, in the presence of each of the compounds tested.
[0306] This method is an adaptation of the challenge test method described in the standard "ISO 11930 Cosmetics - Microbiology - Evaluation of the antimicrobial protection of a cosmetic product".
[0307] The preservatives are present in the compositions of this example in a usual amount for each of them in a cosmetic composition, in particular in a usual amount for each of them enabling them to play their role as cosmetic preservatives. Results and conclusions
[0308] The results are expressed as the logarithmic reduction of Staphylococcus aureus relative to the inoculated level. The reductions thus range from 0 log (no antimicrobial activity observed under the tested condition, i.e., complete loss of endolysin activity) to -5.4 log (maximum decrease observed under the test conditions, i.e., maintenance of endolysin activity under the tested conditions). The tested composition is therefore particularly active when the values approach -5.4.
[0309] The evaluation of the antimicrobial activity of endolysin is taken at T= 1 week and at T=8 weeks from the date of manufacture of the formulas for formulas a, b and c and at T= 1 week and at T=3 months for formulas d, e and f. This evaluation is carried out according to the protocol described above, i.e. the measurement of the activity of endolysin in formula after t=30 minutes of contact and t=1 hour of contact S. aureus / formula.
[0310] For each measurement, the Log of reduction was measured after 30min (t30min) and then after Ih of contact (tlh).
[0311] The results are provided in Table 3 below.
[0312] [Tables3] Preservative content (%) 0.3 Endolysin SEQ ID NO: 10 (%) Initial pH Formula age Log reduction t30min Log reduction tlh Formula ea 0 5.6 1 week 0.0 0.0 Formula eb 0.002565 5.9 1 week -5.4 -5.4 8 weeks -4.4 -5.4 Formula ec 0.5 0.002565 7.4 1 week -1.1 -1.7
[0313] Table 3
[0314] The results show that the association of 4-hydroxyacetophenone with endolysin of sequence SEQ ID NO: 10 maintains the antibacterial activity against S. aureus of the endolysin after 1 week and even after 8 weeks of storage of the composition.
[0315] Conversely, a composition outside the invention comprising sodium benzoate as a preservative does not allow endolysin to maintain its destructive activity against S. aureus, after only one week of storage of the formula.
[0316] [Tables4] 4-Hydroxyacetophenone Level (%) Endolysin SEQ ID NO: 10 (%) Formula Age Log of Reduction t30min Log of Reduction tlh Formula ed 0.3 0 1 week 0.0 0.0 Formula ee 0 0.003325 1 week -3.4 -4.1 3 months -0.8 -1.9 Formula ef 0.3 0.003325 1 week -3.6 -3.9 3 months -3.8 -3.0
[0317] Table 4
[0318] The results show that the formula d (without endolysin and with the 4-hydroxyacetophenone) has no significant antimicrobial activity on S. aureus demonstrating that the antimicrobial effect observed for formulas e and f is due to endolysin. The results obtained with formulas e and f show that the addition of 4-hydroxyacetophenone to the endolysin of sequence SEQ ID NO: 10 significantly improves the stability of the endolysin's antibacterial activity against S. aureus after 3 months of storage. Sequence listing
[0319] SEP ID NO: 1 CBD-2638 (protein)
[0320] WKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYD EQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK
[0321] SEP ID NO: 2 CBD-2638 (nucleic acid)
[0322] TGGAAACAGAATAAAGATGGCATTTGGTATAAAGCTGAACATGCTTCGTT CACAGTGACAGCACCAGAGGGAATTATCCAAGATACAAAGGTCCTTGGA CTGGTCACCCACAAGCTGGTGTTACAAAAAAGGTCAAACGATTAAATATG ATGAGGTTCAAAAATTTGACGGTCATGTTTGGGTATCGTGGGAAACGTTTG AGGGCGAAACTGTATACATGCCGGTACGCACATGGGACGCTAAACTGGT AAAGTTGGTAAGTTGTGGGGCGAAATTAAATAA
[0323] SEP ID NO: 3 Ply2638 (protein)
[0324] MLTAIDYLTKKGWKISSDPRTYDGYPKNYGYRNYHENGINYDEFCGGYHRA FDVYSNETNDVPAVTSGTVIEANDYGNFGGTFVIRDANDNDWIYGHLQRGSM RFVVGDKVNQGDIIGLQGNSNYDNPMSVKHLDAKQLQQLQLCVK AMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKITAPKPSIQGVVIHND YGSMTPSQYLPWLYARENNGTHVNGWASVYANRNEVLWYHPTDYVEWHCG NQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAADVMKSYGLPNSYGVVIHND YGSMTPSQYLPWLYARENNGTHVNGWASVYANRNLWYHPTDYVEWHCG VRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYFIKRIKHYDGGKLE VSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIWYKAEHASFTVTAP EGIITRYKGPWTGHPQAGVLQKGQTIKYDEVKVKVKVGWWTFWFWFWFW MPVRTWDACTGKVGKLWGEIK
[0325] SEP ID NO: 4 Ply2638 (protein)
[0326] MRGSHHHHHHGSMLTAIDYLTKKGWKISSDPRTYDGYPKNYGYRNYHENG INYDEFCGGYHRAFDVYSNETNDVPAVTSGTVIEANDYGNFGGTFVIRDANDN DWIYGHLQRGSMRFVVGDKVNQGDIIGLQGNSNYYDNPMSVHLHLQLRPKD AKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSNHIKGNKIT APKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVYANRNEVL WYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLKVAAD VMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNINKMKDYF IKRIKHYYDGGKLEVSKAATIKQSDVKQEVKKQEAKQIVKATDWKQNKDGIW YKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEVQKFDGHVW VSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK
[0327] SEP ID NO: 5 Ply2638 (nucléique)
[0328] ATGCTAACTGCTATTGACTATCTTACGAAAAAAGGTTGGAAATATCATC TGACCCTCGCACTTACGATGGTTACCCTAAAAAACTACGGCTACAGAAATTA CCATGAAAACGGCATTAATTATGATGAGTTTTGTGGTGGTTATCATATAGACG TTTTGATGTTTACAGTAACGAAACTAAACGACGTGCCTGCTGTTACTAGCGG AACAGTTATTGAAGCAAACGATTACGGTAATTTTGGTGGTACATTCGTTAT TAGAGAGGCTAACGATAACGATTGGATATATGGGCATCTACAACGTGGCTC AATGCGATTTGTTGTAGGCGACAAAGTCAATCAAGGTGACATTATTGGTT ACAAAGGTAATAGCAACTATTACGACAATCCTATGAGTGTACATTTACATTT ACAATTACGCCCTAAAAGAGCAAAGAAAGATGAAAATCACAAGTATGTA GTGGTTGGCTATGGAAAAATATGACATTACAAATTTAAATGCTAAACAAG ATAAATCAAAGAATGGGAGCGTGGAAAAGGTTGAAACATATCTATTCAAAC CATATTAAAGGTAACAAGATTACAGCACCAAAAACTAGTATTCAAGGTGTG GTCATCCACAATGATTATGGTAGTATGACACCTAGTCAATACTTACCATGG TTATATGCACGTGAGAATAACGGTACACACGTTAACGGTTGGGCTAGTGTT TATGCAAATAGAAACGAAGTGCTTTGGTATCATCCGACAGACTACGTAGAG TGGCATGTGGTAATCAATGGGCAAATGCTAACTTAATCGGATTTGAAGTG TGTGAGTCGTATCCTGGTAGAATCTCGGACAAATTATTCTTAGAAATGAA GAAGCGACATTGAAAGTAGCTGCGGATGTGAATGAAGTCGTACGGATTACC AGTTAATCGCAACACTGTACGTCTGCATAACGAATTCTTCGGAACTTCTTGTCCACATCGTTCGTGGGACTTGCATGTTGGCAAAGGTGAGCCTTACACAACT ACTAATATTAATAAAATGAAAGACTACTTCATCAAACGCATCAAACAATTA TATGACGGTGGAAAGCTAGAAGTAAGCAAAGCAGCAACTATCAAACAATC TGACGTTAAGCAAGAAGTTAAAAAGCAAGCAAACAAATCAATC CAACAGATTGGAAACAGAATAAGATGGCATTTGGTATAAAGCTGAACAT GCTTCGTTCACAGTGACAGCACCAGAGGGAATTATCCAAGATACAAAGG TCCTTGGACTGGTCACCCAAGCTGGTGTTACAAAAGGTCAAACGATTAATATGATGAGGTTCAAAAATTTGATTGGGGGGGGTT AACGTTTGAGGGCGAAACTGTATACATGCCGGTACGCACATGGGACGCTA AAACTGGTAAAGTTGGTAAGTTGTGGGGCGAAATTAAATAA
[0329] SEP ID NO: 6 M23-LST (protein)
[0330] AATHEHSAQWLNNYKGYGYGPYPLGINGGMHYGVDFFMNIGTPVKAISS GKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVKAGQIIIG WSGSTGYSTAPHLHFQRMVNSTAQDPFLKSAGDPFLK
[0331] SEP ID NO: 7 M23-LST (nucleic)
[0332] GCTGCAACACATGAACATTCAGCACAATGGTTGAATAATTACAAAAAAG GATATGGTTACGGTCCTTATCCATTAGGTATAAATGGCGGTATGCACTACG GAGTTGATTTTTTTGAATATTGGAACACAGTAAAAGCTATTTCAAGCG GAAAAATAGTTGAAGCTGGTTGGAGTAATTACGGAGGAGGTAATCAAATA GGTCTTATTGAAAATGGAGTGCATAGACAATGGTATATGCATCTAAGT AAATATAATGTTAAAGTAGGATTATGTCAAAGCTGGTCAAAATAATCGGT TGGTCTGGAAGCACTGGTTATTTACCCATCCATCCTATCTATCAATA ATGGTTAATTCATTTTCAAATTCAACTGCCCAAGATCCAATGCCTTTCTTAA A GAGCGCAGGATAT
[0333] SEP ID NO: 8 Ami-2638 (protein)
[0334] NKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVYANR NEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEATLK VAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVTNKTGTTKGNI MKDYFIKRIKHYDG
[0335] SEP ID NO: 9 Ami-2638 (nucleic acid)
[0336] GGTAACAAGATTACAGCACCAAAACCTAGTATTCAAGGTGTGGTCATCCA CAATGATTATGGTAGTATGACACCTAGTCAATACTTACCATGGTTATATGC ACGTGAGAATAACGGTACACACGTTAACGGTTGGGCTAGTGTTTATGCAAA TAGAAACGAAGTCAGCTACCTACCTAGTTGATTGAGTTGAGGTCACGTAACGGTT TGGTAATCAATGGGCAAATGCTAACTTAATCGGATTTGAAGTGTGTGAGTC GTATCCTGGTAGAATCTCGGACAAATTATTCTTAGAAAATGAAGAAGCGAC ATTGAAAGTAGCTGCGGATGTGATGAAGTCCGTACGGATTACCAGTTAATCG CACACACTGTACGTCTCTGATCGATCGATTCCTTCCTTTCTTTC TCGTGGGACTTGCATGTTGGCAAAGGTGAGCCTTACAACTACTATATT AATAAAATGAAAGACTACTTCATCAAACGCATCAAACATTATTATGACGGT
[0337] SEP ID NO: 10 M23-LST Ami2638 CBD2638 (proteique)
[0338] AATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVIGVDFFSFMNIGT GKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVKVGDYVKAGQIIG WSGSTGYSTAPHLHFQRMVNSFSNSTAQDPMPFLKSAGYGKAGGTVTPTPNT GELLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKNGSVKELKHIYSN HIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENNGTHVNGWASVY ANRNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPGRISDKLFLENEEA TLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDLHVGKGEPYTTTNI NKMKDYFIKRIKHYYDGGKLEVSKAATIKQSDVKQEVKKQEAKQIVKATDW KQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGVLQKGQTIKYDEV QKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWGEIK
[0339] SEOIDNO: 11 M23-LST Ami2638 CBD2638 (protéique)
[0340] MRGSHHHHHHGSAATHEHSAQWLNNYKKGYGYGPYPLGINGGMHYGVDF FMNIGTPVKAISSGKIVEAGWSNYGGGNQIGLIENDGVHRQWYMHLSKYNVK VGDYVKAGQIIGWSGSTGYSTAPHLHFQRMVNSFSNSTAQDPMPFLKSAGYG KAGGTVTPTPNTGELLRPKDAKKDEKSQVCSGLAMEKYDITNLNAKQDKSKN GSVKELKHIYSNHIKGNKITAPKPSIQGVVIHNDYGSMTPSQYLPWLYARENN GTHVNGWASVYANRNEVLWYHPTDYVEWHCGNQWANANLIGFEVCESYPG RISDKLFLENEEATLKVAADVMKSYGLPVNRNTVRLHNEFFGTSCPHRSWDL HVGKGEPYTTTNINKMKDYFIKRIKHYYDGGKLEVSKAATIKQSDVKQEVKK QEAKQIVKATDWKQNKDGIWYKAEHASFTVTAPEGIITRYKGPWTGHPQAGV LQKGQTIKYDEVQKFDGHVWVSWETFEGETVYMPVRTWDAKTGKVGKLWG EIK
[0341] SEP ID NO: 12 M23-LST Ami2638 CBD2638 (nucléique)
[0342] GCTGCAACACATGAACATTCAGCACAATGGTTGAATAATTACAAAAAAG GATATGGTTACGGTCCTTATCCATTAGGTATAAATGGCGGTATGCACTACG GAGTTGATTTTTTTATGAATATTGGAACACCAGTAAAAGCTATTTCAAGCG GAAAAATAGTTGAAGCTGGTTGGAGTAATTACGGAGGAGGTAATCAAATA GGTCTTATTGAAAATGATGGAGTGCATAGACAATGGTATATGCATCTAAGT AAATATAATGTTAAAGTAGGAGATTATGTCAAAGCTGGTCAAATAATCGGT TGGTCTGGAAGCACTGGTTATTCTACAGCACCACATTTACACTTCCAAAGA ATGGTTAATTCATTTTCAAATTCAACTGCCCAAGATCCAATGCCTTTCTTAA AGAGCGCAGGATATGGAAAAGCAGGTGGTACAGTAACTCCAACGCCGAAT ACAGGTGAGCCTTACGCCCTAAAGACGCAAAGAAAGATGAAAAATCACA AGTATGTAGTGGTTTGGCTATGGAAAAATATGACATTACAAATTTAAATGC TAAACAAGATAAATCAAAGAATGGGAGCGTGAAAGAGTTGAAACATATCT ATTCAAACCATATTAAAGGTAACAAGATTACAGCACCAAAACCTAGTATTC AAGGTGTGGTCATCCACAATGATTATGGTAGTATGACACCTAGTCAATACT TACCATGGTTATATGCACGTGAGAATAACGGTACACACGTTAACGGTTGGG CTAGTGTTTATGCAAATAGAAACGAAGTGCTTTGGTATCATCCGACAGACT ACGTAGAGTGGCATTGTGGTAATCAATGGGCAAATGCTAACTTAATCGGAT TTGAAGTGTGTGAGTCGTATCCTGGTAGAATCTCGGACAAATTATTCTTAG AAAATGAAGAAAGCGACATTGAAAGTAGCTGCGGATGTGATGAAGTCGTACGGATTACCAGTTAATCGCAACACTGTACGTCTGCATAACGAATTCTTCGGA ACTTCTTGTCCACATCGTTCGTGGGACTTGCATGTTGGCAAAGGTGAGCCTT ACACAACTACTAATATTAATAAAATGAAAGACTACTTCATCAAACGCATCA AACATTATTATGACGGTGGAAAGCTAGAAGTAAGCAAAGCAGCAACTATC AAACAATCTGACGTTAAGCAAGAAGTTAAAAAGCAAGAAGCAAAACAAAT TGTGAAAGCAACAGATTGGAAACAGAATAAAGATGGCATTTGGTATAAAG CTGAACATGCTTCGTTCACAGTGACAGCACCAGAGGGAATTATCACAAGAT ACAAAGGTCCTTGGACTGGTCACCCACAAGCTGGTGTATTACAAAAAGGTC AAACGATTAAATATGATGAGGTTCAAAAATTTGACGGTCATGTTTGGGTAT CGTGGGAAACGTTTGAGGGCGAAACTGTATACATGCCGGTACGCACATGG GACGCTAAAACTGGTAAAGTTGGTAAGTTGTGGGGGCGAAATTAAATAA.
[0343] SEP ID NO: 13 Etiquette 6xHis N-terminal
[0344] MRGSHHHHHHGS < / e> < / e> < / e> < / e>
Claims
Claims
1. Composition, in particular cosmetic, comprising, in a physiologically acceptable medium: (i) at least one endolysin derived from a Staphylococcus aureus phage; and (ii) 4-hydroxyacetophenone, one of its salts, in particular its basic salts, organic or mineral, one of its optical isomers, one of its geometric isomers, or one of its solvates such as hydrates.
2. The composition of claim 1, wherein the endolysin comprises a first protein sequence comprising a cell wall binding domain of species of the genus Staphylococcus.
3. A composition according to claim 2, wherein the first protein sequence is derived from bacteriophage endolysin <e>2638a of S. aureus.
4. A composition according to claim 2 or 3, wherein the first protein sequence comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO:
1.
5. A composition according to any one of claims 1 to 3, wherein the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 3 and SEQ ID NO:
4.
6. A composition according to any one of claims 2 to 4, wherein said endolysin further comprises a heterologous protein sequence.
7. The composition of claim 6, wherein the heterologous protein sequence comprises a lytic domain, said lytic domain comprising a second and a third protein sequence, said second protein sequence comprising an M23 endopeptidase domain and said third protein sequence comprising an amidase domain.
8. A composition according to claim 7, wherein said second and third protein sequences are derived, independently of one another, from an enzyme selected from the group consisting of endolysin bacteriophage <e>2638a of S. aureus and the lysostaphin of S. simulated s, in particular one of the second and third protein sequences from the endolysin of the bacteriophage <e>2638a from S. aureus and the other sequence from the second and third protein sequences from lysostaphin from S. simulans.
9. A composition according to claim 7 or 8, wherein said second protein sequence comprises at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with the reference amino acid sequence SEQ ID NO: 6 and said third protein sequence comprises at least 80%, in particular 90%, more particularly 95% sequence identity with the reference amino acid sequence SEQ ID NO:
8.
10. A composition according to any one of claims 1 to 3 and 5 to 8, wherein the endolysin comprises a protein sequence comprising at least 80%, in particular at least 90%, more particularly at least 95% sequence identity with an amino acid sequence selected from the group consisting of the reference amino acid sequences SEQ ID NO: 10, and SEQ ID NO: 11, in particular the endolysin comprises a protein sequence consisting of the reference amino acid sequence SEQ ID NO:
10.
11. A composition according to any one of claims 1 to 10, wherein the endolysin derived from a Staphylococcus aureus phage is present in a content ranging from 0.0001% to 0.1% by weight relative to the total weight of the composition, in particular from 0.0005% to 0.01% by weight relative to the total weight of the composition, more particularly from 0.001% to 0.005% by weight relative to the total weight of the composition.
12. Composition according to any one of claims 1 to 11, comprising a 4-hydroxyacetophenone content 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.
13. Composition according to any one of claims 1 to 12, in which the endolysin(s) and the 4-hydroxyacetophenone are present in an endolysin(s) / 4-hydroxyacetophenone mass ratio of between 0.0001 and 0.5 and in particular of between 0.001 and 0.1, more particularly of between 0.002 and 0.
04.
14. A composition according to any one of claims 1 to 13, the com- position being suitable for topical administration.
15. Composition according to any one of claims 1 to 14 for its use in the prevention and / or treatment of a skin disorder linked to colonization by Staphylococcus aureus in an individual in need thereof, in particular for the prevention and / or treatment of acne and / or eczema in an individual in need thereof.
16. A composition for use according to claim 15, wherein the composition is suitable for topical administration.
17. Non-therapeutic cosmetic process for the care of keratin materials, in particular the skin, in particular acne-prone skin, comprising the topical application to these keratin materials of a composition according to any one of claims 1 to 14.
18. Use of 4-hydroxyacetophenone, one of its salts, in particular its basic, organic or mineral salts, one of its optical isomers, one of its geometric isomers, or one of its solvates such as hydrates, for increasing the stability of the enzymatic activity of an en-dolysin derived from a Staphylococcus aureus phage, in particular as defined according to any one of claims 2 to 10.
19. Use according to claim 18, in which 4-hydroxyacetophenone, one of its salts, in particular its basic salts, organic or inorganic, one of its optical isomers, one of its geometric isomers, or one of its solvates such as hydrates, is present in a composition as defined according to any one of claims 1 to 14.< / e> < / e> < / e>