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WO2016030609A1 - Antimicrobial composition - Google Patents

Antimicrobial composition Download PDF

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Publication number
WO2016030609A1
WO2016030609A1 PCT/FR2015/052220 FR2015052220W WO2016030609A1 WO 2016030609 A1 WO2016030609 A1 WO 2016030609A1 FR 2015052220 W FR2015052220 W FR 2015052220W WO 2016030609 A1 WO2016030609 A1 WO 2016030609A1
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WO
WIPO (PCT)
Prior art keywords
antimicrobial
composition according
composition
peptide
phase
Prior art date
Application number
PCT/FR2015/052220
Other languages
French (fr)
Inventor
Stéphane Boisgard
Daniel COLLETTA
Philippe Humbert
Jean-Marie Lefevre
Jacques Peyrot
Original Assignee
Dermaconcept Jmc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Dermaconcept Jmc filed Critical Dermaconcept Jmc
Priority to EP15759906.9A priority Critical patent/EP3193909A1/en
Publication of WO2016030609A1 publication Critical patent/WO2016030609A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/16—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/755—Polymers containing halogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A61K38/1729—Cationic antimicrobial peptides, e.g. defensins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns

Definitions

  • the present invention relates to a novel composition with antimicrobial properties, especially antiseptic, based on silver and an antimicrobial peptide, useful in human and veterinary medicine.
  • the skin constitutes both a living anatomical barrier and a zone of exchange between the body and its environment, the effectiveness of which determines the maintenance of a good homeostatic balance.
  • the skin is a real organ comprising several integrated layers, ranging from the superficial layer, the epidermis, to the deeper layers, the dermis and the hypodermis, where each of these layers performs functions allowing the whole to react. and adapt to his environment.
  • the epidermis mainly composed of keratinocytes, melanocytes and Langerhans cells, has a variable thickness depending on the different parts of the body, and constitutes the outer layer of the skin to ensure the body's protection vis-à-vis its environment outside.
  • the dermis is the thickest layer, traversed by nerve fibers and blood vessels, consisting mainly of collagen, elastin, proteoglycans and glycosaminoglycans, mainly synthesized by dermal fibroblasts.
  • Collagen fibers provide the mechanical strength and texture of the skin, elastin is responsible for its elasticity, glycosaminoglycans and proteoglycans play a major role in the structure and hydration of the skin.
  • the deepest layer of the skin forms the hypoderm, which contains fat-producing lipids that form a fat layer that protects muscles, bones, and internal organs from shock.
  • Changes in the structure of the epidermis such as an increase in moisture or the occurrence of skin irritations or wounds of various origins, or the evolution of a dermatosis, promote colonization and skin infection by pathogenic microorganisms.
  • the skin is constantly attacked by pathogenic microorganisms, but the horny layer of the epidermis, because of its pH, its relatively low water content and the presence of antibacterial peptides having a bactericidal action, acts as the first antimicrobial defense against these pathogenic microorganisms.
  • biofilm bacteria are resistant to most antibiotics and antiseptics, and it is therefore necessary to develop compositions that can effectively fight against pathogenic microorganisms as much as possible respecting cutaneous homeostasis, and not promoting the development of strains. resistant, dangerous for the man and his environment.
  • Silver is known as an antiseptic and has been used for years, especially in creams to treat neonatal infections and more broadly as an antiseptic effective against Gram-positive and Gram-negative, aerobic and anaerobic bacteria.
  • the active form is the Ag + silver ion which can be provided by various silver salts and complexes such as silver nitrate, chloride, or thiosulfate, or various carboxylates such as acetate, or complexes.
  • sulfonamide derivatives such as silver sulfadiazine.
  • the object of the present invention is to develop a novel composition which exhibits optimal antimicrobial properties.
  • the present invention relates to an antimicrobial composition comprising metallic silver, characterized in that it further comprises:
  • antibacterial composition means a composition that makes it possible to kill (bactericidal) or slow down (bacteriostatic) the growth of microbes such as bacteria (antibacterial activity), fungi (antimycotic activity), viruses (antiviral activity), and / or or or parasites (antiparasitic activity).
  • the combination of metallic silver with an antimicrobial peptide advantageously makes it possible to provide a composition with effective antimicrobial properties, and more particularly an antiseptic and disinfectant composition.
  • the antimicrobial composition according to the invention especially has a particularly effective application as a surgical disinfectant for the hands. It also meets the requirements of standard NF EN 12791 (December 2005) concerning surgical disinfectants for the hands.
  • the antimicrobial peptide is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N
  • the antimicrobial peptide of the invention may have an antimicrobial spectrum against Gram-positive and Gram-negative bacteria, and is preferably a cationic antimicrobial peptide.
  • the cationic peptides are thus positively charged, unlike so-called "non-cationic" peptides such as anionic peptides.
  • the cationic peptides may be positively charged to a pH of 7.
  • the antimicrobial peptide is an oligopeptide, which may in particular comprise less than 50 amino acids, and preferably between 2 and 30 amino acids, and even more preferably between 3 and 20 amino acids.
  • an antimicrobial peptide chosen from linear peptides with a helical structure, peptides comprising one or more disulfide bridges, linear peptides rich in certain amino acids, and one of their mixtures.
  • an antimicrobial peptide chosen from linear peptides with a helical structure, peptides comprising one or more disulfide bridges, linear peptides rich in certain amino acids, and one of their mixtures.
  • the synthetic peptides can also be used as omiganan pentachlorhydrate (indolicidin analogue), iseganan hydrochloride, a synthetic protectrin, and pexiganan acetate (magainin analogue).
  • the antimicrobial peptide of the invention can be coupled to a lipid. More particularly, the coupling may be carried out by covalent bonding with said lipid.
  • the coupling of the lipid by covalent bonding with the peptide is preferably done with at least one amino acid constituting the peptide.
  • the covalent bond may be, for example, an amide bond on the N-terminus of the peptide. Preferably, this covalent bond is not liposomal.
  • the lipid is preferably a linear or branched, saturated or unsaturated fatty acid, preferably containing 6 to 22 carbon atoms, such as, for example, oleic acid, linoleic acid, lauric acid and sapenic acid. , stearic acid or palmitic acid.
  • Their polymeric derivatives can also be used, for example polylactic acid.
  • the antimicrobial peptide may be preferably amphiphilic. This amphiphilic character is reinforced by coupling the peptide with said lipid.
  • the antimicrobial composition according to the present invention may comprise an effective amount of the antimicrobial peptide, such as for example between 0.001 and 20.0% by weight of antimicrobial peptide, preferably between 0.5 and 10.0% by weight of antimicrobial peptide, and even more preferably between 1.0% and 5.0% by weight of antimicrobial peptide, based on the total weight of the antimicrobial composition.
  • the antimicrobial composition may comprise between 0.5 and 10.0% by weight of antimicrobial peptide, relative to the total weight of the antimicrobial composition.
  • the antimicrobial composition can comprise between 1.0 and 5.0% by weight of antimicrobial peptide, based on the total weight of the antimicrobial composition.
  • the metallic silver of the invention is preferably in the form of metal particles or metal powder, these particles being especially of micrometric size.
  • the average diameter of the metal particles may range from 1 to 100 ⁇ m, and preferably from 1 to 20 ⁇ m.
  • This is called metallic silver in micronized form.
  • Metallic silver in micronized form advantageously facilitates its dispersion in the antimicrobial composition of the invention, which may be hydrophilic or lipophilic.
  • metal particles means unitary metal particles and / or agglomerates of unitary metal particles.
  • the mean diameter of the unit metal particles can range from 1 to 100 ⁇ m, and preferably from 1 to 20 ⁇ m.
  • the average diameter of the agglomerates of unitary particles may range from 1 to 100 ⁇ m, and preferably from 1 to 20 ⁇ m.
  • the unit particles that constitute the agglomerate may have an average diameter ranging from 10 to 200 nm, and preferably from 15 to 80 nm.
  • the metal particles of the invention may be a mixture of the particles according to the first variant and particles according to the second variant.
  • the diameter of the metal particles of the invention can be easily determined by techniques well known to those skilled in the art, and in particular by electron microscopy.
  • the metallic silver used in the invention is advantageously of greater than 99.5% purity, and preferably greater than 99.8%.
  • a form of metallic silver suitable in the context of the invention may advantageously be constituted by a porous structure, in particular of the micro-sponge type, this structure more particularly making it possible to gradually release silver ions.
  • the antimicrobial composition according to the present invention may comprise an effective amount of metallic silver, such as for example between 0.001 and 10% by weight of metallic silver, preferably between 0.001 and 5.0% by weight of metallic silver, and even more preferably between 0.01% and 1.0% by weight of metallic silver, based on the total weight of the antimicrobial composition.
  • metallic silver such as for example between 0.001 and 10% by weight of metallic silver, preferably between 0.001 and 5.0% by weight of metallic silver, and even more preferably between 0.01% and 1.0% by weight of metallic silver, based on the total weight of the antimicrobial composition.
  • the antimicrobial composition may comprise between 0.01 and 1.0% by weight of metallic silver, relative to the total weight of the antimicrobial composition.
  • the antimicrobial composition may comprise between 0.001 and 5.0% by weight of metallic silver, based on the total weight of the antimicrobial composition.
  • the antimicrobial composition of the invention may comprise a fluoropolymer, which may be selected from tetrafluoroethylene polymers.
  • a fluoropolymer which may be selected from tetrafluoroethylene polymers.
  • PTFE polytetrafluoroethylene
  • the fluoropolymer is an exfoliant, including a mild exfoliant, which has a protective function and lubrication.
  • the fluoropolymer of the invention is preferably in the form of particles or powder, these particles being in particular of micrometric size. More particularly, the average diameter of the fluoropolymer particles may range from 1 to 100 ⁇ m, and preferably from 1 to 20 ⁇ m. This is called fluorinated polymer in micronized form.
  • the fluoropolymer in micronized form advantageously facilitates its dispersion in the antimicrobial composition of the invention, which may be hydrophilic or lipophilic.
  • the antimicrobial composition according to the present invention may comprise an effective amount of fluorinated polymer, such as for example between 0.001 and 10% by weight of fluoropolymer, preferably between 0.001 and 5.0% by weight of fluoropolymer, and still more preferably more preferred between 0.01% and 1.0% by weight of fluoropolymer, based on the total weight of the antimicrobial composition.
  • fluorinated polymer such as for example between 0.001 and 10% by weight of fluoropolymer, preferably between 0.001 and 5.0% by weight of fluoropolymer, and still more preferably more preferred between 0.01% and 1.0% by weight of fluoropolymer, based on the total weight of the antimicrobial composition.
  • the antimicrobial composition may comprise between 0.01 and 1.0% by weight of fluoropolymer, relative to the total weight of the antimicrobial composition.
  • the antimicrobial composition may comprise between 0.001 and 1.0% by weight of fluoropolymer, based on the total weight of the antimicrobial composition.
  • compositions can be advantageously added to the composition and chosen for example from a healing agent, an anti-inflammatory agent, an anti-infective agent and a vitamin such as vitamin A or E.
  • the healing agent may be, for example, a zinc salt, a carob seed extract rich in oligogalactomannans.
  • the anti-inflammatory drug may be a poly-saccharide such as Rhamnosoft ® or Teflose ® (Solabia) which inhibits cell adhesion and limits inflammatory reactions, or a Boswellia serrata gum extract (Soothex ® ) which acts by enzymatic inhibition. of synthesis of leukotrienes.
  • the complementary anti-infectives can be selected from a silanol and an antimicrobial peptide-forming activator such as caproyl methyl tyrosinate (Defensamide ®).
  • the antimicrobial composition does not substantially comprise hyaluronic acid. More particularly, the antimicrobial composition comprises less than 0.05% by weight of hyaluronic acid, and preferably 0% by weight of hyaluronic acid.
  • excipients and supports that can be used for the preparation of the compositions according to the present invention, as well as their amounts, are those commonly used in preparations for hygienic, dermatological and / or pharmaceutical use, and chosen according to the application chosen and the form of administration used.
  • emulsifiers By way of example, mention may be made of emulsifiers, thickeners, gelling agents, moisturizing agents, softeners, chelating agents, preservatives, solubilizers, suspending agents, washing bases, exfoliants and perfumes. .
  • the emulsifying agent may be chosen for example from high molecular weight carboxyvinyl polymers, cetyl alcohols, dimethylaminopropylamine derivatives such as cocamidopropyl betaine, polysorbates such as Polysorbate 20® or Tween 60® , esters. sorbitan and more particularly a stearate, a palmitate, or a sorbitan laurate such as Arlacel ® . Can still be used as emulsifier stearic or palmitic acid derivative, e.g., polyethylene glycol stearate, glyceryl stearate, PEG-100 ® (e.g.
  • Arlacel 165 ® a steareth or a ceteareth
  • a fatty alcohol such as a stearyl, caprylic or cetearyl alcohol, for example Montanov 68 ®
  • an emulsifiable silicone such as cyclomethicone.
  • Thickeners are incorporated in the composition to improve the fluidity. They can be chosen for example from among poly-acrylamides of the Carbopol type, acrylate / acrylic acid such as Aculyn ®, cross-linked acrylates such as Carbopol ® Ultrez, cellulose derivatives such as hydroxypropyl cellulose, or natural gums such as xanthan gum and tragacanth .
  • the moisturizing agents used in the composition may be chosen for example from propylene glycol, ethoxy diglycol, glycerin, butylene glycol and shea butter, and also fatty alcohols.
  • a suitable suspending agent is, for example, a clay such as bentonite or smectite.
  • Chelating agents are typically capable of trapping a metal ion from a system by forming a complex such that the metal ion can not easily participate or catalyze chemical reactions.
  • a chelating agent that can be used in the antimicrobial composition, mention may be made of N-hydroxysuccinimide, ethylene diamine tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), deferoxamine, hydroxamic acids and their salts, phytic acid, phytate, gluconic acid and its salts, transferrin, lactoferrin, furildioxime and a derivative thereof.
  • composition of the invention may be used in the composition of the invention, such as chlorphenesine, sodium levulinate, sodium anisate, phenoxy ethanol, methyl parahydroxybenzoate (methylparaben), ethyl para-hydroxybenzoate (ethylparaben) ), and Sebicide HB ® associating phenoxy ethanol and parahydroxybenzoates and having an extended antimicrobial spectrum.
  • preservatives such as chlorphenesine, sodium levulinate, sodium anisate, phenoxy ethanol, methyl parahydroxybenzoate (methylparaben), ethyl para-hydroxybenzoate (ethylparaben) ), and Sebicide HB ® associating phenoxy ethanol and parahydroxybenzoates and having an extended antimicrobial spectrum.
  • Exfoliants may also be added to the antimicrobial composition of the invention, such as alpha-hydroxy acids (AHAs) such as for example lactic acid, glycolic acid, mandelic acid, tartaric acid, malic acid or a derivative thereof, to facilitate the removal of dead cells and stimulate the formation of collagen and elastin.
  • AHAs alpha-hydroxy acids
  • Betahydroxy acids especially salicylic acid, can also be used as exfoliants.
  • compositions according to the present invention are prepared by the usual techniques, depending on the chosen form of administration, the a desired amount of metallic silver being mixed with the antimicrobial peptide, and optionally the fluoropolymer, and the carriers and excipients, in a physiologically acceptable medium.
  • physiologically acceptable means supports and excipients of a type commonly used in hygienic, dermatological and / or pharmaceutical compositions, in human or animal medicine, which are neutral with respect to the active ingredients used. , not showing any toxic effect and causing no harmful side effects on the skin, on the eye, and in the ear (ear cavity) and the mouth (oral cavity).
  • a cream in the case of a cream, it is possible to proceed by dispersing a fatty phase in an aqueous phase to obtain an oil-in-water emulsion, or conversely to prepare a water-in-oil emulsion, the active ingredients being in the aqueous phase. one or the other phase.
  • the antimicrobial composition according to the present invention can be advantageously used as a hygienic, dermatological and / or pharmaceutical composition, in human or animal medicine.
  • Topical application especially for external topical application
  • atrial, oral or ophthalmic application especially for atrial, oral or ophthalmic application.
  • the antimicrobial compositions of the invention may for example be in the form of aqueous or aqueous-alcoholic solutions, micellar lotions, spraying solutions, shampoos, dispersions, serums, wipes, patches, tulles or wound dressings. controlled release of gels (aqueous, anhydrous or lipophilic), oleogels (lipid gels), ointments, suspensions, ionic or nonionic vesicular dispersions, liquid or semi-liquid emulsions (for example a milk), solid or semi-solid.
  • the emulsions may be of the oil-in-water (O / W) or water-in-oil (W / O) type, for example gels or creams.
  • the antimicrobial composition of the invention can be used in many applications related to personal hygiene, whether in humans or animals, on the skin or mucous membranes.
  • the antimicrobial composition of the invention can be used as an antiseptic for the skin and its appendages.
  • the antimicrobial composition of the invention may be used as an antiseptic:
  • a cream which can be used for the hands, comprising the components listed in Table 1 below is prepared.
  • Emulsifying agent 1 4.00
  • Emulsifying agent 2 1.00
  • EDTA di-sodium ethylene diamine tetraacetic acid
  • Moisturizing agent is glycerin marketed by the company Interchimie;
  • Thickener is a xanthan gum marketed by Solvay / Rhodia under the reference Rhodicare T;
  • Emulsifier 1 is a mixture of glyceryl stearate and PEG-100 stearate, sold by Croda under the reference Arlacel 165;
  • Emulsifying agent 2 is cetyl alcohol marketed by BASF under the reference Lanette 16;
  • Fatty phase 1 is triglycerides of fatty acids (capric / caprylic triglycerides) marketed by Stearineries Dubois under the reference DUB MCT;
  • Fatty phase 2 is liquid paraffin marketed by Univar under the reference Marcol 82;
  • Metallic silver is micronized metallic silver with an average particle size of approximately 10 ⁇ m, marketed by Impag under the reference Microsilver BG;
  • Fluorinated polymer is micronized PTFE, sold by the company SAFIC / ALCAN under the reference Microslip 519L; and
  • An antimicrobial peptide is palmitoyl hexapeptide-26, which is a cationic oligopeptide produced by the reaction between palmitic acid and hexapeptide-26 based on alanine, arginine, glutamine, lysine and phenylalanine, this peptide being marketed by Infinitec under the Shield Bact peptide PF WP reference; this reference also comprises two preservatives of the sodium levulinate and sodium anisate type.
  • the preparation of the cream of Example 1 is carried out as follows by standard techniques well known to those skilled in the art, at room temperature unless otherwise indicated:
  • phase A Prepare phase A by moistening the xanthan gum previously wetted in glycerin, then add the rest of the ingredients of phase A, phase A being then raised to 75 ° C;
  • phase B by mixing the components of phase B, then bring it to 75 ° C;
  • a washing gel which can be used for the hands, comprising the components listed in Table 2 below is prepared. COMPONENTS%
  • Emulsifying agent 1 25,00
  • Moisturizing agent is glycerin marketed by the company Interchimie;
  • Thickener 1 is a xanthan gum marketed by the company Solvay / Rhodia under the reference Rhodicare T;
  • Thickener 2 is an acrylate copolymer marketed by the company Gattefossé under the reference Carbopol aqua SF1;
  • Emulsifier 1 is cocamidopropyl betaine marketed by BASF under the reference Dehyton K;
  • Metallic silver is micronized metallic silver with an average particle size of approximately 10 ⁇ m, marketed by Impag under the reference Microsilver BG; - Conservative 2 is phenoxy ethanol marketed by SCD under the reference Phenoxetol;
  • Exfoliant is polylactic acid marketed by the company SAFIC / ALCAN under the reference Ecoscrub 20PC;
  • Fluorinated polymer is micronized PTFE marketed by the company
  • An antimicrobial peptide is palmitoyl hexapeptide-26, which is a cationic oligopeptide produced by the reaction between palmitic acid and hexapeptide-26 based on alanine, arginine, glutamine, lysine and phenylalanine, this peptide being marketed by Infinitec under the Shield Bact peptide PF WP reference; this reference additionally comprises two preservatives of the sodium levulinate and sodium anisate type; and
  • 20% NaOH is 20% sodium hydroxide marketed by Arnaud.
  • Example 2 The preparation of the washing gel of Example 2 is carried out as follows by conventional techniques well known to those skilled in the art, at room temperature unless otherwise indicated:
  • phase A prepare phase A by moistening the xanthan gum previously wetted in glycerin, then add the rest of the ingredients of phase A;
  • Thickener 1 is an acrylate copolymer sold by the company Gattefossé under the reference Carbopol aqua SF1;
  • An antimicrobial peptide is palmitoyl hexapeptide-26, which is a cationic oligopeptide produced by the reaction between palmitic acid and hexapeptide-26 based on alanine, arginine, glutamine, lysine and phenylalanine, this peptide being marketed by Infinitec under the Shield Bact peptide PF WP reference; this reference additionally comprises two preservatives of the sodium levulinate and sodium anisate type;
  • Alcohol is denatured alcohol at 96.2 ° marketed by France Alcohol under the reference Alcohol 96.2 °;
  • Metallic silver is micronized metallic silver with an average particle size of approximately 10 ⁇ m, marketed by Impag under the reference Microsilver BG;
  • Moisturizing agent is glycerin marketed by the company Interchimie;
  • Example 3 20% NaOH is 20% sodium hydroxide marketed by Arnaud.
  • the preparation of the hydroalcoholic solution of Example 3 is carried out as follows by conventional techniques well known to those skilled in the art, at room temperature unless otherwise indicated:
  • phase A by adding them in their order of appearance in table 3, with simple stirring with a four-blade propeller;

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Abstract

The invention relates to an antimicrobial composition comprising metal silver, characterised in that it also comprises an antimicrobial peptide, and optionally a fluorinated polymer.

Description

Composition antimicrobienne  Antimicrobial composition
La présente invention concerne une nouvelle composition à propriétés antimicrobiennes, notamment antiseptique, à base d'argent et d'un peptide antimicrobien, utile en médecine humaine et vétérinaire. The present invention relates to a novel composition with antimicrobial properties, especially antiseptic, based on silver and an antimicrobial peptide, useful in human and veterinary medicine.
La peau constitue à la fois une barrière anatomique vivante et une zone d'échange entre le corps et son environnement, dont l'efficacité conditionne le maintien d'un bon équilibre homéostasique. La peau est un véritable organe comprenant plusieurs couches intégrées, allant de la couche superficielle, l'épiderme, jusqu'aux couches plus profondes, le derme et l'hypoderme, où chacune de ces couches remplit des fonctions permettant à l'ensemble de réagir et de s'adapter à son environnement.  The skin constitutes both a living anatomical barrier and a zone of exchange between the body and its environment, the effectiveness of which determines the maintenance of a good homeostatic balance. The skin is a real organ comprising several integrated layers, ranging from the superficial layer, the epidermis, to the deeper layers, the dermis and the hypodermis, where each of these layers performs functions allowing the whole to react. and adapt to his environment.
L'épiderme, principalement composé de kératinocytes, de mélanocytes et des cellules de Langerhans, a une épaisseur variable selon les différentes parties du corps, et constitue la couche externe de la peau pour assurer la protection du corps vis-à-vis de son environnement extérieur. Le derme est la couche la plus épaisse, traversée par des fibres nerveuses et des vaisseaux sanguins, se composant principalement de collagène, d'élastine, de protéoglycanes et de glycosaminoglycanes, principalement synthétisés par les fibroblastes dermiques. Les fibres de collagène assurent la résistance mécanique et la texture de la peau, l'élastine est responsable de son élasticité, les glycosaminoglycanes et les protéoglycanes jouent un rôle majeur de structure et d'hydratation de la peau. La couche la plus profonde de la peau forme l'hypoderme, contenant les adipocytes qui produisent des lipides assurant la formation d'une couche grasse protégeant les muscles, les os et les organes internes contre les chocs.  The epidermis, mainly composed of keratinocytes, melanocytes and Langerhans cells, has a variable thickness depending on the different parts of the body, and constitutes the outer layer of the skin to ensure the body's protection vis-à-vis its environment outside. The dermis is the thickest layer, traversed by nerve fibers and blood vessels, consisting mainly of collagen, elastin, proteoglycans and glycosaminoglycans, mainly synthesized by dermal fibroblasts. Collagen fibers provide the mechanical strength and texture of the skin, elastin is responsible for its elasticity, glycosaminoglycans and proteoglycans play a major role in the structure and hydration of the skin. The deepest layer of the skin forms the hypoderm, which contains fat-producing lipids that form a fat layer that protects muscles, bones, and internal organs from shock.
Les changements dans la structure de l'épiderme, tels qu'une augmentation de l'humidité ou l'existence d'irritations ou de plaies cutanées d'origines diverses, ou l'évolution d'une dermatose, favorisent la colonisation et l'infection de la peau par les micro-organismes pathogènes.  Changes in the structure of the epidermis, such as an increase in moisture or the occurrence of skin irritations or wounds of various origins, or the evolution of a dermatosis, promote colonization and skin infection by pathogenic microorganisms.
Ainsi, la peau est constamment attaquée par des microorganismes pathogènes, mais la couche cornée de l'épiderme, en raison de son pH, de sa teneur en eau relativement faible et de la présence de peptides antibactériens ayant une action bactéricide, joue le rôle de première défense antimicrobienne contre ces micro-organismes pathogènes. Thus, the skin is constantly attacked by pathogenic microorganisms, but the horny layer of the epidermis, because of its pH, its relatively low water content and the presence of antibacterial peptides having a bactericidal action, acts as the first antimicrobial defense against these pathogenic microorganisms.
La plupart des colonies bactériennes se transforment en biofilms, structure membranaire de survie microbienne, détournant les facteurs de croissance et de cicatrisation en créant une inflammation qui empêche le processus de défense antimicrobienne d'agir efficacement. En raison de l'utilisation très répandue, et parfois excessive, d'antibiotiques, les bactéries ont développé une résistance aux antibiotiques qui limitent et même annulent leurs effets antibactériens. Les bactéries des biofilms résistent à la plupart des antibiotiques et des antiseptiques, et il est donc nécessaire de mettre au point des compositions susceptibles de lutter efficacement contre les microorganismes pathogènes respectant le plus possible l'homéostasie cutanée, et ne favorisant pas le développement de souches résistantes, dangereuses pour l'homme et son environnement.  Most bacterial colonies are transformed into biofilms, a microbial membrane-survival structure, diverting growth and healing factors, creating inflammation that prevents the antimicrobial defense process from acting effectively. Because of the widespread, and sometimes excessive, use of antibiotics, bacteria have developed antibiotic resistance that limits and even nullifies their antibacterial effects. The biofilm bacteria are resistant to most antibiotics and antiseptics, and it is therefore necessary to develop compositions that can effectively fight against pathogenic microorganisms as much as possible respecting cutaneous homeostasis, and not promoting the development of strains. resistant, dangerous for the man and his environment.
L'argent est connu comme antiseptique et a été utilisé pendant des années, notamment dans des crèmes pour traiter des infections néonatales et plus largement comme antiseptique efficace contre les bactéries Gram positif et Gram négatif, aérobies et anaérobies. La forme active est l'ion argent Ag+ qui peut être apporté par divers sels et complexes d'argent tels que le nitrate, le chlorure, ou le thiosulfate d'argent, ou encore divers carboxylates tels que l'acétate, ou des complexes dérivés de sulfamides comme la sulfadiazine argentique. Silver is known as an antiseptic and has been used for years, especially in creams to treat neonatal infections and more broadly as an antiseptic effective against Gram-positive and Gram-negative, aerobic and anaerobic bacteria. The active form is the Ag + silver ion which can be provided by various silver salts and complexes such as silver nitrate, chloride, or thiosulfate, or various carboxylates such as acetate, or complexes. sulfonamide derivatives such as silver sulfadiazine.
On peut également citer le document FR-2 978 664 qui décrit l'utilisation d'argent métallique associé à de l'acide hyaluronique, dans une composition antiseptique utile en dermatologie et en ophtalmologie.  One can also cite the document FR-2 978 664 which describes the use of metallic silver associated with hyaluronic acid, in an antiseptic composition useful in dermatology and ophthalmology.
Le but de la présente invention est de mettre au point une nouvelle composition qui présente des propriétés antimicrobiennes optimales.  The object of the present invention is to develop a novel composition which exhibits optimal antimicrobial properties.
La présente invention a pour objet une composition antimicrobienne comprenant de l'argent métallique, caractérisée en ce qu'elle comprend en outre :  The present invention relates to an antimicrobial composition comprising metallic silver, characterized in that it further comprises:
- un peptide antimicrobien, et  an antimicrobial peptide, and
- optionnellement un polymère fluoré. On entend par « composition antimicrobienne » une composition qui permet de tuer (bactéricide) ou de ralentir (bactériostatique) la croissance des microbes tels les bactéries (activité antibactérienne), les mycètes (activité antimycosique), les virus (activité antivirale), et/ou les parasites (activité antiparasitaire). optionally a fluoropolymer. The term "antimicrobial composition" means a composition that makes it possible to kill (bactericidal) or slow down (bacteriostatic) the growth of microbes such as bacteria (antibacterial activity), fungi (antimycotic activity), viruses (antiviral activity), and / or or parasites (antiparasitic activity).
L'association d'argent métallique avec un peptide antimicrobien permet avantageusement de proposer une composition aux propriétés antimicrobiennes efficaces, et plus particulièrement une composition antiseptique et désinfectante.  The combination of metallic silver with an antimicrobial peptide advantageously makes it possible to provide a composition with effective antimicrobial properties, and more particularly an antiseptic and disinfectant composition.
La composition antimicrobienne selon l'invention a notamment une application particulièrement efficace en tant que désinfectant chirurgical pour les mains. Elle satisfait d'ailleurs aux conditions de la norme NF EN 12791 (décembre 2005) concernant les désinfectants chirurgicaux pour les mains.  The antimicrobial composition according to the invention especially has a particularly effective application as a surgical disinfectant for the hands. It also meets the requirements of standard NF EN 12791 (December 2005) concerning surgical disinfectants for the hands.
Les essais de désinfection des mains réalisés par la Demanderesse avec des compositions antimicrobiennes selon l'invention ont mis en évidence une efficacité antiseptique répondant à cette norme.  The hand disinfection tests carried out by the Applicant with antimicrobial compositions according to the invention have demonstrated an antiseptic efficacy meeting this standard.
Le peptide antimicrobien The antimicrobial peptide
Le peptide antimicrobien de l'invention peut présenter un spectre antimicrobien contre les bactéries Gram-positif et Gram-négatif, et est de préférence un peptide antimicrobien cationique. Les peptides cationiques sont ainsi chargés positivement, contrairement aux peptides dits « non- cationiques » tels que les peptides anioniques. De préférence, les peptides cationiques peuvent être chargés positivement à un pH égal à 7.  The antimicrobial peptide of the invention may have an antimicrobial spectrum against Gram-positive and Gram-negative bacteria, and is preferably a cationic antimicrobial peptide. The cationic peptides are thus positively charged, unlike so-called "non-cationic" peptides such as anionic peptides. Preferably, the cationic peptides may be positively charged to a pH of 7.
Plus particulièrement, le peptide antimicrobien est un oligopeptide, pouvant notamment comprendre moins de 50 acides aminés, et de préférence entre 2 et 30 acides aminés, et encore plus préférentiellement entre 3 et 20 acides aminés.  More particularly, the antimicrobial peptide is an oligopeptide, which may in particular comprise less than 50 amino acids, and preferably between 2 and 30 amino acids, and even more preferably between 3 and 20 amino acids.
Dans la présente invention, on peut utiliser par exemple un peptide antimicrobien choisi parmi les peptides linéaires à structure en hélice, les peptides comportant un ou plusieurs ponts disulfure, les peptides linéaires riches en certains acides aminés, et un de leurs mélanges. A titre d'exemple, on peut citer les dérivés de la magainine, de la protégrine, de l'indolicidine et de l'histatine. Les peptides synthétiques peuvent également être utilisés comme le pentachlorhydrate d'omiganan (analogue de l'indolicidine), le chlorhydrate d'iseganan, une protégrine synthétique, et l'acétate de pexiganan (analogue de la magainine). In the present invention, it is possible to use, for example, an antimicrobial peptide chosen from linear peptides with a helical structure, peptides comprising one or more disulfide bridges, linear peptides rich in certain amino acids, and one of their mixtures. By way of example, mention may be made of the derivatives of magainine, proteine, indolicidin and histatin. The synthetic peptides can also be used as omiganan pentachlorhydrate (indolicidin analogue), iseganan hydrochloride, a synthetic protectrin, and pexiganan acetate (magainin analogue).
Le peptide antimicrobien de l'invention peut être couplé à un lipide. Plus particulièrement, le couplage peut s'effectuer par liaison covalente avec ledit lipide. Le couplage du lipide par liaison covalente avec le peptide se fait de préférence avec l'un au moins des acides aminés constituant le peptide. La liaison covalente peut être par exemple une liaison amide sur l'extrémité N- terminale du peptide. De préférence, cette liaison covalente n'est pas liposomiale.  The antimicrobial peptide of the invention can be coupled to a lipid. More particularly, the coupling may be carried out by covalent bonding with said lipid. The coupling of the lipid by covalent bonding with the peptide is preferably done with at least one amino acid constituting the peptide. The covalent bond may be, for example, an amide bond on the N-terminus of the peptide. Preferably, this covalent bond is not liposomal.
Le lipide est de préférence un acide gras, linéaire ou ramifié, saturé ou insaturé, comportant de préférence 6 à 22 atomes de carbone, tel que par exemple l'acide oléique, l'acide linoléique, l'acide laurique, l'acide sapiénique, l'acide stéarique ou l'acide palmitique. Leurs dérivés polymériques peuvent également être utilisés comme par exemple l'acide polylactique.  The lipid is preferably a linear or branched, saturated or unsaturated fatty acid, preferably containing 6 to 22 carbon atoms, such as, for example, oleic acid, linoleic acid, lauric acid and sapenic acid. , stearic acid or palmitic acid. Their polymeric derivatives can also be used, for example polylactic acid.
Le peptide antimicrobien peut être de préférence amphiphile. Ce caractère amphiphile est renforcé en couplant le peptide avec ledit lipide.  The antimicrobial peptide may be preferably amphiphilic. This amphiphilic character is reinforced by coupling the peptide with said lipid.
Dans le cadre de l'invention, on peut citer à titre d'exemple comme peptide antimicrobien cationique disponible dans le commerce le produit référencé Oligopeptide-10 de chez Grant Industries ou le produit référencé Shield Bact Peptide de chez Infinitec qui est un hexapeptide couplé à l'acide palmitique comprenant des ponts disulfure. Le produit référencé Shield Bact Peptide Solution PF-WP de chez Infinitec, comprenant des conservateurs tels que du levulinate de sodium et de l'anisate de sodium, peut également être utilisé.  In the context of the invention, mention may be made, by way of example, as a commercially available cationic antimicrobial peptide, the product referenced Oligopeptide-10 from Grant Industries or the product referenced Shield Bact Peptide from Infinitec which is a hexapeptide coupled to palmitic acid comprising disulfide bridges. The product referenced Shield Bact Peptide Solution PF-WP from Infinitec, including preservatives such as sodium levulinate and sodium anisate, can also be used.
La composition antimicrobienne selon la présente invention peut comprendre une quantité efficace du peptide antimicrobien, telle que par exemple entre 0,001 et 20,0% en poids de peptide antimicrobien, de préférence entre 0,5 et 10,0% en poids de peptide antimicrobien, et de façon encore plus préférée entre 1,0% et 5,0% en poids de peptide antimicrobien, par rapport au poids total de la composition antimicrobienne. Pour des applications cutanées, la composition antimicrobienne peut comprendre entre 0,5 et 10,0% en poids de peptide antimicrobien, par rapport au poids total de la composition antimicrobienne. The antimicrobial composition according to the present invention may comprise an effective amount of the antimicrobial peptide, such as for example between 0.001 and 20.0% by weight of antimicrobial peptide, preferably between 0.5 and 10.0% by weight of antimicrobial peptide, and even more preferably between 1.0% and 5.0% by weight of antimicrobial peptide, based on the total weight of the antimicrobial composition. For cutaneous applications, the antimicrobial composition may comprise between 0.5 and 10.0% by weight of antimicrobial peptide, relative to the total weight of the antimicrobial composition.
Pour des applications muqueuses, la composition antimicrobienne peut comprendre entre 1,0 et 5,0% en poids de peptide antimicrobien, par rapport au poids total de la composition antimicrobienne.  For mucosal applications, the antimicrobial composition can comprise between 1.0 and 5.0% by weight of antimicrobial peptide, based on the total weight of the antimicrobial composition.
L'argent métallique Metallic silver
L'argent métallique de l'invention est de préférence sous forme de particules métalliques ou poudre métallique, ces particules étant notamment de taille micrométrique.  The metallic silver of the invention is preferably in the form of metal particles or metal powder, these particles being especially of micrometric size.
Plus particulièrement, le diamètre moyen des particules métalliques peut aller de 1 à 100 pm, et de préférence de 1 à 20 pm. On parle alors d'argent métallique sous forme micronisée. L'argent métallique sous forme micronisée permet avantageusement de faciliter sa dispersion dans la composition antimicrobienne de l'invention, qui peut être hydrophile ou lipophile.  More particularly, the average diameter of the metal particles may range from 1 to 100 μm, and preferably from 1 to 20 μm. This is called metallic silver in micronized form. Metallic silver in micronized form advantageously facilitates its dispersion in the antimicrobial composition of the invention, which may be hydrophilic or lipophilic.
Dans la présente invention, on entend par « particules métalliques » des particules métalliques unitaires et/ou des agglomérats de particules métalliques unitaires.  In the present invention, the term "metal particles" means unitary metal particles and / or agglomerates of unitary metal particles.
Selon une première variante, le diamètre moyen des particules métalliques unitaires peut aller de 1 à 100 pm, et de préférence de 1 à 20 pm.  According to a first variant, the mean diameter of the unit metal particles can range from 1 to 100 μm, and preferably from 1 to 20 μm.
Selon une deuxième variante, le diamètre moyen des agglomérats de particules unitaires peut aller de 1 à 100 pm, et de préférence de 1 à 20 pm. Dans ce cas, les particules unitaires qui constituent l'agglomérat peuvent avoir un diamètre moyen pouvant aller de 10 à 200 nm, et de préférence de 15 à 80 nm.  According to a second variant, the average diameter of the agglomerates of unitary particles may range from 1 to 100 μm, and preferably from 1 to 20 μm. In this case, the unit particles that constitute the agglomerate may have an average diameter ranging from 10 to 200 nm, and preferably from 15 to 80 nm.
Selon une troisième variante, les particules métalliques de l'invention peuvent être un mélange des particules selon la première variante et des particules selon la deuxième variante.  According to a third variant, the metal particles of the invention may be a mixture of the particles according to the first variant and particles according to the second variant.
Le diamètre des particules métalliques de l'invention peut être facilement déterminé par des techniques bien connues de l'homme du métier, et notamment par microscopie électronique. L'argent métallique utilisé dans l'invention est avantageusement de pureté supérieure à 99,5%, et de préférence supérieure à 99,8%. The diameter of the metal particles of the invention can be easily determined by techniques well known to those skilled in the art, and in particular by electron microscopy. The metallic silver used in the invention is advantageously of greater than 99.5% purity, and preferably greater than 99.8%.
Une forme d'argent métallique appropriée dans le cadre de l'invention peut être avantageusement constituée par une structure poreuse, notamment du type micro-éponge, cette structure permettant plus particulièrement de libérer progressivement des ions argent.  A form of metallic silver suitable in the context of the invention may advantageously be constituted by a porous structure, in particular of the micro-sponge type, this structure more particularly making it possible to gradually release silver ions.
Dans le cadre de l'invention, on peut citer à titre d'exemple comme argent métallique disponible dans le commerce le produit référencé MicroSilver BG de chez Impag, constituait de particules d'argent métallique dont le diamètre moyen est d'environ 10 pm.  In the context of the invention, mention may be made, by way of example, as a commercially available metallic silver, the product referenced MicroSilver BG from Impag, constituted particles of metallic silver, the average diameter of which is approximately 10 μm.
La composition antimicrobienne selon la présente invention peut comprendre une quantité efficace d'argent métallique, telle que par exemple entre 0,001 et 10% en poids d'argent métallique, de préférence entre 0,001 et 5,0% en poids d'argent métallique, et de façon encore plus préférée entre 0,01% et 1,0% en poids d'argent métallique, par rapport au poids total de la composition antimicrobienne.  The antimicrobial composition according to the present invention may comprise an effective amount of metallic silver, such as for example between 0.001 and 10% by weight of metallic silver, preferably between 0.001 and 5.0% by weight of metallic silver, and even more preferably between 0.01% and 1.0% by weight of metallic silver, based on the total weight of the antimicrobial composition.
Pour des applications cutanées, la composition antimicrobienne peut comprendre entre 0,01 et 1,0% en poids d'argent métallique, par rapport au poids total de la composition antimicrobienne.  For cutaneous applications, the antimicrobial composition may comprise between 0.01 and 1.0% by weight of metallic silver, relative to the total weight of the antimicrobial composition.
Pour des applications muqueuses, la composition antimicrobienne peut comprendre entre 0,001 et 5,0% en poids d'argent métallique, par rapport au poids total de la composition antimicrobienne.  For mucosal applications, the antimicrobial composition may comprise between 0.001 and 5.0% by weight of metallic silver, based on the total weight of the antimicrobial composition.
Le polymère fluoré The fluoropolymer
La composition antimicrobienne de l'invention peut comprendre un polymère fluoré, qui peut être choisi parmi les polymères de tétrafluoroéthylène. A titre d'exemple préféré, on peut citer le polytétrafluoroéthylène (PTFE).  The antimicrobial composition of the invention may comprise a fluoropolymer, which may be selected from tetrafluoroethylene polymers. By way of preferred example, mention may be made of polytetrafluoroethylene (PTFE).
Le polymère fluoré est un exfoliant, notamment un exfoliant doux, qui a une fonction de protection et de lubrification.  The fluoropolymer is an exfoliant, including a mild exfoliant, which has a protective function and lubrication.
Le polymère fluoré de l'invention est de préférence sous forme de particules ou poudre, ces particules étant notamment de taille micrométrique. Plus particulièrement, le diamètre moyen des particules de polymère fluoré peut aller de 1 à 100 pm, et de préférence de 1 à 20 pm. On parle alors de polymère fluoré sous forme micronisée. Le polymère fluoré sous forme micronisée permet avantageusement de faciliter sa dispersion dans la composition antimicrobienne de l'invention, qui peut être hydrophile ou lipophile. The fluoropolymer of the invention is preferably in the form of particles or powder, these particles being in particular of micrometric size. More particularly, the average diameter of the fluoropolymer particles may range from 1 to 100 μm, and preferably from 1 to 20 μm. This is called fluorinated polymer in micronized form. The fluoropolymer in micronized form advantageously facilitates its dispersion in the antimicrobial composition of the invention, which may be hydrophilic or lipophilic.
Dans le cadre de l'invention, on peut citer à titre d'exemple comme polymère fluoré disponible dans le commerce le produit référencé Microslip 519L de chez SAFIC/ALCAN, qui est une poudre de PTFE avec une taille de particules de 5,0-6,0pm.  In the context of the invention, mention may be made, by way of example, as a fluoropolymer available commercially, the product referenced Microslip 519L from Safic / Alcan, which is a PTFE powder with a particle size of 5.0- 6,0pm.
La composition antimicrobienne selon la présente invention peut comprendre une quantité efficace de polymère fluoré, telle que par exemple entre 0,001 et 10% en poids de polymère fluoré, de préférence entre 0,001 et 5,0% en poids de polymère fluoré, et de façon encore plus préférée entre 0,01% et 1,0% en poids de polymère fluoré, par rapport au poids total de la composition antimicrobienne.  The antimicrobial composition according to the present invention may comprise an effective amount of fluorinated polymer, such as for example between 0.001 and 10% by weight of fluoropolymer, preferably between 0.001 and 5.0% by weight of fluoropolymer, and still more preferably more preferred between 0.01% and 1.0% by weight of fluoropolymer, based on the total weight of the antimicrobial composition.
Pour des applications cutanées, la composition antimicrobienne peut comprendre entre 0,01 et 1,0% en poids de polymère fluoré, par rapport au poids total de la composition antimicrobienne.  For cutaneous applications, the antimicrobial composition may comprise between 0.01 and 1.0% by weight of fluoropolymer, relative to the total weight of the antimicrobial composition.
Pour des applications muqueuses, la composition antimicrobienne peut comprendre entre 0,001 et 1,0% en poids de polymère fluoré, par rapport au poids total de la composition antimicrobienne.  For mucosal applications, the antimicrobial composition may comprise between 0.001 and 1.0% by weight of fluoropolymer, based on the total weight of the antimicrobial composition.
Autres actifs other assets
Divers actifs secondaires peuvent être avantageusement ajoutés à la composition et choisis par exemple parmi un agent cicatrisant, un antiinflammatoire, un anti-infectieux et une vitamine telle que la vitamine A ou E.  Various secondary active agents can be advantageously added to the composition and chosen for example from a healing agent, an anti-inflammatory agent, an anti-infective agent and a vitamin such as vitamin A or E.
L'agent cicatrisant peut être par exemple un sel de zinc, un extrait de graine de caroube riche en oligogalactomannanes.  The healing agent may be, for example, a zinc salt, a carob seed extract rich in oligogalactomannans.
L'anti-inflammatoire peut être un poly-saccharide tel que Rhamnosoft® ou Teflose® (Solabia) qui inhibe l'adhésion cellulaire et limite les réactions inflammatoires, ou un extrait de gomme de Boswellia serrata (Soothex®) qui agit par inhibition enzymatique de la synthèse des leukotriènes. L'anti-infectieux complémentaire peut être choisi parmi un silanol et un activateur de formation de peptide antimicrobien tel que le méthyl caproyl tyrosinate (Defensamide®). The anti-inflammatory drug may be a poly-saccharide such as Rhamnosoft ® or Teflose ® (Solabia) which inhibits cell adhesion and limits inflammatory reactions, or a Boswellia serrata gum extract (Soothex ® ) which acts by enzymatic inhibition. of synthesis of leukotrienes. The complementary anti-infectives can be selected from a silanol and an antimicrobial peptide-forming activator such as caproyl methyl tyrosinate (Defensamide ®).
Dans un mode de réalisation particulier, la composition antimicrobienne ne comprend sensiblement pas d'acide hyaluronique. Plus particulièrement, la composition antimicrobienne comprend moins de 0,05% en poids d'acide hyaluronique, et de préférence 0% en poids d'acide hyaluronique. Excipients et supports  In a particular embodiment, the antimicrobial composition does not substantially comprise hyaluronic acid. More particularly, the antimicrobial composition comprises less than 0.05% by weight of hyaluronic acid, and preferably 0% by weight of hyaluronic acid. Excipients and supports
Les excipients et supports utilisables pour la préparation des compositions conformes à la présente invention, ainsi que leurs quantités, sont ceux couramment utilisés dans les préparations à usage hygiénique, dermatologique et/ou pharmaceutique, et choisis en fonction de l'application retenue et de la forme d'administration utilisée.  The excipients and supports that can be used for the preparation of the compositions according to the present invention, as well as their amounts, are those commonly used in preparations for hygienic, dermatological and / or pharmaceutical use, and chosen according to the application chosen and the form of administration used.
A titre d'exemple, on peut citer des émulsionnants, des épaississants, des gélifiants, des agents hydratants, des adoucissants, des agents chélatants, des conservateurs, des solubilisants, des agents de suspension, des bases lavantes, des exfoliants, et des parfums.  By way of example, mention may be made of emulsifiers, thickeners, gelling agents, moisturizing agents, softeners, chelating agents, preservatives, solubilizers, suspending agents, washing bases, exfoliants and perfumes. .
L'agent émulsionnant peut être choisi par exemple parmi des polymères carboxyvinyliques à haut poids moléculaire, des alcools cétyliques, des dérivés de la diméthylaminopropylamine tels que la bétaïne de cocamidopropyle, des polysorbates tels que le Polysorbate 20® ou le Tween 60®, des esters de sorbitan et plus particulièrement un stéarate, un palmitate, ou un laurate de sorbitan tel que l'Arlacel®. On peut encore utiliser comme agent émulsionnant un dérivé d'acide stéarique ou palmitique, par exemple le stéarate de polyéthylène glycol, le stéarate de glycéryle, le stéarate de PEG-100® (par exemple Arlacel 165®), un stéareth ou un cétéareth, un alcool gras tel qu'un alcool stéarylique, caprylique, ou cétéarylique, par exemple le Montanov 68®, ou encore une silicone émulsionnable telle que la cyclométhicone. The emulsifying agent may be chosen for example from high molecular weight carboxyvinyl polymers, cetyl alcohols, dimethylaminopropylamine derivatives such as cocamidopropyl betaine, polysorbates such as Polysorbate 20® or Tween 60® , esters. sorbitan and more particularly a stearate, a palmitate, or a sorbitan laurate such as Arlacel ® . Can still be used as emulsifier stearic or palmitic acid derivative, e.g., polyethylene glycol stearate, glyceryl stearate, PEG-100 ® (e.g. Arlacel 165 ®), a steareth or a ceteareth, a fatty alcohol such as a stearyl, caprylic or cetearyl alcohol, for example Montanov 68 ® , or an emulsifiable silicone such as cyclomethicone.
Les épaississants (ou gélifiants) sont incorporés dans la composition pour en améliorer la fluidité. Ils peuvent être choisis par exemple parmi les poly-acrylamides du type Carbopol, des copolymères acrylate/acide acrylique comme l'Aculyn®, des acrylates réticulés comme un Carbopol Ultrez®, des dérivés de cellulose comme l'hydroxypropyl cellulose, ou les gommes naturelles comme la gomme xanthane et la gomme adragante. Thickeners (or gelling agents) are incorporated in the composition to improve the fluidity. They can be chosen for example from among poly-acrylamides of the Carbopol type, acrylate / acrylic acid such as Aculyn ®, cross-linked acrylates such as Carbopol ® Ultrez, cellulose derivatives such as hydroxypropyl cellulose, or natural gums such as xanthan gum and tragacanth .
Les agents hydratants utilisés dans la composition peuvent être choisis par exemple parmi le propylène glycol, l'éthoxy diglycol, la glycérine, le butylène glycol et le beurre de Karité, ainsi que les alcools gras. Un agent de suspension approprié est par exemple une argile telle que bentonite ou smectite.  The moisturizing agents used in the composition may be chosen for example from propylene glycol, ethoxy diglycol, glycerin, butylene glycol and shea butter, and also fatty alcohols. A suitable suspending agent is, for example, a clay such as bentonite or smectite.
Les agents chélatants sont classiquement capables de piéger un ion métal d'un système en formant un complexe de telle façon que l'ion métal ne peut facilement participer ou catalyser des réactions chimiques. A titre d'exemple d'agent chélatant pouvant être utilisé dans la composition antimicrobienne, on peut citer le N-hydroxysuccinimide, l'acide éthylène diamine tétraacétique (EDTA), l'acide nitrilotriacétique (NTA), la déféroxamine, les acides hydroxamiques et leurs sels, l'acide phytique, le phytate, l'acide gluconique et ses sels, la transferrine, la lactoferrine, furildioxime et un de leurs dérivés.  Chelating agents are typically capable of trapping a metal ion from a system by forming a complex such that the metal ion can not easily participate or catalyze chemical reactions. As an example of a chelating agent that can be used in the antimicrobial composition, mention may be made of N-hydroxysuccinimide, ethylene diamine tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), deferoxamine, hydroxamic acids and their salts, phytic acid, phytate, gluconic acid and its salts, transferrin, lactoferrin, furildioxime and a derivative thereof.
Divers conservateurs peuvent être utilisés dans la composition de l'invention, tels que la chlorphenesine, le levulinate de sodium, l'anisate de sodium, le phénoxy éthanol, le parahydroxybenzoate de méthyle (méthylparaben), le para-hydroxybenzoate d'éthyle (éthylparaben), et le Seppicide HB® associant du phénoxy éthanol et des parahydroxybenzoates et présentant un spectre antimicrobien étendu. Various preservatives may be used in the composition of the invention, such as chlorphenesine, sodium levulinate, sodium anisate, phenoxy ethanol, methyl parahydroxybenzoate (methylparaben), ethyl para-hydroxybenzoate (ethylparaben) ), and Sebicide HB ® associating phenoxy ethanol and parahydroxybenzoates and having an extended antimicrobial spectrum.
Des exfoliants peuvent également être ajoutés à la composition antimicrobiennes de l'invention, tels que des alpha-hydroxy acides (AHA) comme par exemple l'acide lactique, l'acide glycolique, l'acide mandélique, l'acide tartrique, l'acide malique ou un de leurs dérivés, pour faciliter l'élimination des cellules mortes et stimuler la formation de collagène et d'élastine. Des acides bêta-hydroxylés, en particulier l'acide salicylique, peuvent également être utilisés comme exfoliants.  Exfoliants may also be added to the antimicrobial composition of the invention, such as alpha-hydroxy acids (AHAs) such as for example lactic acid, glycolic acid, mandelic acid, tartaric acid, malic acid or a derivative thereof, to facilitate the removal of dead cells and stimulate the formation of collagen and elastin. Betahydroxy acids, especially salicylic acid, can also be used as exfoliants.
Les compositions conformes à la présente invention sont préparées par les techniques usuelles, en fonction de la forme d'administration choisie, la quantité voulue d'argent métallique étant mélangée avec le peptide antimicrobien, et optionnellement le polymère fluoré, et les supports et excipients, dans un milieu physiologiquement acceptable. The compositions according to the present invention are prepared by the usual techniques, depending on the chosen form of administration, the a desired amount of metallic silver being mixed with the antimicrobial peptide, and optionally the fluoropolymer, and the carriers and excipients, in a physiologically acceptable medium.
Par physiologiquement acceptable, au sens de la présente invention, on entend des supports et excipients d'un type couramment utilisé dans les compositions hygiéniques, dermatologiques et/ou pharmaceutiques, en médecine humaine ou animale, neutres vis-à-vis des principes actifs utilisés, ne présentant pas d'effet toxique et n'occasionnant aucun effet secondaire néfaste sur la peau, sur l'œil, et dans l'oreille (cavité auriculaire) et la bouche (cavité buccale).  For the purposes of the present invention, the term "physiologically acceptable" means supports and excipients of a type commonly used in hygienic, dermatological and / or pharmaceutical compositions, in human or animal medicine, which are neutral with respect to the active ingredients used. , not showing any toxic effect and causing no harmful side effects on the skin, on the eye, and in the ear (ear cavity) and the mouth (oral cavity).
Par exemple, dans le cas d'une crème, on peut procéder par dispersion d'une phase grasse dans une phase aqueuse pour obtenir une émulsion huile dans eau, ou inversement pour préparer une émulsion eau dans huile, les principes actifs étant dans l'une ou l'autre phase.  For example, in the case of a cream, it is possible to proceed by dispersing a fatty phase in an aqueous phase to obtain an oil-in-water emulsion, or conversely to prepare a water-in-oil emulsion, the active ingredients being in the aqueous phase. one or the other phase.
Applications applications
La composition antimicrobienne selon la présente invention peut être utilisée avantageusement comme composition hygiénique, dermatologique et/ou pharmaceutique, en médecine humaine ou animale.  The antimicrobial composition according to the present invention can be advantageously used as a hygienic, dermatological and / or pharmaceutical composition, in human or animal medicine.
Elle peut se présenter sous toutes les formes galéniques usuelles pour une application topique (notamment pour application topique externe), comme pour une application auriculaire, buccale ou ophtalmique.  It may be in any of the usual dosage forms for topical application (especially for external topical application), as for atrial, oral or ophthalmic application.
Les compositions antimicrobiennes de l'invention peuvent se présenter par exemple sous forme de solutions aqueuses ou hydro-alcooliques, de lotions micellaires, de solutions pour pulvérisation, de shampooings, de dispersions, de sérums, de lingettes, de patchs, tulles ou pansements à libération contrôlée, de gels (aqueux, anhydres ou lipophiles), d'oléogels (gels lipidiques), de pommades, de suspensions, de dispersions vésiculaires ioniques ou non ioniques, d'émulsions liquides ou semi-liquides (par exemple un lait), solide ou semi-solide. Les émulsions peuvent être du type huile dans eau (H/E) ou eau dans huile (E/H), par exemple des gels ou des crèmes. La composition antimicrobienne de l'invention peut être utilisée dans de nombreuses applications liées à l'hygiène corporelle, que ce soit chez l'homme ou l'animal, sur la peau ou les muqueuses. The antimicrobial compositions of the invention may for example be in the form of aqueous or aqueous-alcoholic solutions, micellar lotions, spraying solutions, shampoos, dispersions, serums, wipes, patches, tulles or wound dressings. controlled release of gels (aqueous, anhydrous or lipophilic), oleogels (lipid gels), ointments, suspensions, ionic or nonionic vesicular dispersions, liquid or semi-liquid emulsions (for example a milk), solid or semi-solid. The emulsions may be of the oil-in-water (O / W) or water-in-oil (W / O) type, for example gels or creams. The antimicrobial composition of the invention can be used in many applications related to personal hygiene, whether in humans or animals, on the skin or mucous membranes.
Plus particulièrement, la composition antimicrobienne de l'invention peut être utilisée comme antiseptique pour la peau et ses annexes.  More particularly, the antimicrobial composition of the invention can be used as an antiseptic for the skin and its appendages.
Préférentiellement, la composition antimicrobienne de l'invention peut être utilisée comme antiseptique :  Preferably, the antimicrobial composition of the invention may be used as an antiseptic:
- pour le corps, notamment pour les mains et/ou les pieds ;  - for the body, especially for the hands and / or the feet;
- pour la cavité buccale ;  - for the oral cavity;
- pour la cavité auriculaire, ou plus généralement pour tout traitement antimicrobien de type oto-rhino-laryngologiste (ORL) ; et/ou  for the atrial cavity, or more generally for any antimicrobial treatment of the otorhinolaryngologist (ENT) type; and or
- pour l'œil, ou plus généralement pour tout traitement antimicrobien de type ophtalmique.  - for the eye, or more generally for any antimicrobial treatment of the ophthalmic type.
D'autres caractéristiques et avantages de la présente invention apparaîtront à la lumière des exemples qui vont suivre, lesdits exemples étant donnés à titre illustratif et nullement limitatif.  Other features and advantages of the present invention will emerge in the light of the examples which follow, said examples being given by way of illustration and in no way limiting.
Dans tous les exemples de compositions qui suivent, les quantités sont exprimées en pourcentage en poids, sauf indication contraire.  In all of the following examples of compositions, the amounts are expressed as percentages by weight unless otherwise indicated.
Exemple 1 : Example 1
On prépare une crème, pouvant être utilisée pour les mains, comprenant les composants listés dans le tableau 1 ci-dessous.  A cream, which can be used for the hands, comprising the components listed in Table 1 below is prepared.
COMPOSANTS % en poids COMPONENTS% by weight
Phase A :  Phase A:
Eau 76,42  Water 76.42
Agent chélatant 0,10  Chelating agent 0.10
Agent hydratant 3,00  Moisturizing agent 3.00
Epaississant 0,20  Thickener 0.20
Conservateur 1 0,25  Conservative 1 0.25
Phase B :  Phase B:
Agent émulsionnant 1 4,00  Emulsifying agent 1 4.00
Agent émulsionnant 2 1,00  Emulsifying agent 2 1.00
Phase grasse 1 6,00 Phase grasse 2 4,00 Fat phase 1 6,00 Fat phase 2 4.00
Phase C :  Phase C:
Argent métallique 0,03  0.03 Metallic silver
Agent hydratant 2,00  Moisturizing agent 2.00
Phase D :  Phase D:
Conservateur 2 0,60  Conservative 2 0.60
Phase E :  Phase E:
Polymère fluoré 0,40  Fluoropolymer 0.40
Phase F :  Phase F:
Peptide antimicrobien 2,00  Antimicrobial Peptide 2.00
Tableau 1  Table 1
L'origine des composants du tableau 1 est la suivante : The origin of the components of Table 1 is as follows:
- Agent chélatant est de l'acide éthylène diamine tétraacétique (EDTA) di-sodium, commercialisé par la société Univar sous la référence Dissolvine Na2 ;  - Chelating agent is di-sodium ethylene diamine tetraacetic acid (EDTA), sold by the company Univar under the reference Dissolvin Na2;
- Agent hydratant est de la glycérine commercialisée par la société Interchimie ;  - Moisturizing agent is glycerin marketed by the company Interchimie;
- Epaississant est une gomme xanthane commercialisée par la société Solvay/Rhodia sous la référence Rhodicare T ;  Thickener is a xanthan gum marketed by Solvay / Rhodia under the reference Rhodicare T;
- Conservateur 1 est de la chlorphenesine commercialisée par la société Arnaud sous la référence Chlorphenesin ;  Conservative 1 is chlorphenesine marketed by Arnaud under the reference Chlorphenesin;
- Agent émulsionnant 1 est un mélange de stéarate de glycéryle et de stéarate de PEG-100, commercialisé par la société Croda sous la référence Arlacel 165 ;  Emulsifier 1 is a mixture of glyceryl stearate and PEG-100 stearate, sold by Croda under the reference Arlacel 165;
- Agent émulsionnant 2 est de l'alcool cétylique commercialisé par la société BASF sous la référence Lanette 16 ;  - Emulsifying agent 2 is cetyl alcohol marketed by BASF under the reference Lanette 16;
- Phase grasse 1 est des triglycérides d'acides gras (capric/caprylic triglycérides) commercialisés par la société Stearineries Dubois sous la référence DUB MCT ;  Fatty phase 1 is triglycerides of fatty acids (capric / caprylic triglycerides) marketed by Stearineries Dubois under the reference DUB MCT;
- Phase grasse 2 est de la paraffine liquide commercialisée par la société Univar sous la référence Marcol 82 ; - Argent métallique est de l'argent métallique micronisé dont la taille de particules moyenne est d'environ 10 pm, commercialisé par la société Impag sous la référence Microsilver BG ; Fatty phase 2 is liquid paraffin marketed by Univar under the reference Marcol 82; Metallic silver is micronized metallic silver with an average particle size of approximately 10 μm, marketed by Impag under the reference Microsilver BG;
- Conservateur 2 est du phénoxy éthanol commercialisé par la société SCD sous la référence Phenoxetol ;  - Conservative 2 is phenoxy ethanol marketed by SCD under the reference Phenoxetol;
- Polymère fluoré est du PTFE micronisé, commercialisé par la société SAFIC/ALCAN sous la référence Microslip 519L ; et  Fluorinated polymer is micronized PTFE, sold by the company SAFIC / ALCAN under the reference Microslip 519L; and
- Peptide antimicrobien est le palmitoyl hexapeptide-26 qui est un oligopeptide cationique produit de la réaction entre l'acide palmitique et l'hexapeptide-26 à base d'alanine, d'arginine, de glutamine, de lysine et de phénylalanine, ce peptide étant commercialisé par la société Infinitec sous la référence Shield Bact peptide PF WP ; cette référence comprend en outre deux conservateurs du type levulinate de sodium et anisate de sodium. La préparation de la crème de l'exemple 1 est réalisée comme suit par des techniques classiques bien connues de l'homme du métier, à température ambiante sauf indication contraire :  An antimicrobial peptide is palmitoyl hexapeptide-26, which is a cationic oligopeptide produced by the reaction between palmitic acid and hexapeptide-26 based on alanine, arginine, glutamine, lysine and phenylalanine, this peptide being marketed by Infinitec under the Shield Bact peptide PF WP reference; this reference also comprises two preservatives of the sodium levulinate and sodium anisate type. The preparation of the cream of Example 1 is carried out as follows by standard techniques well known to those skilled in the art, at room temperature unless otherwise indicated:
- préparer la phase A en hydratant la gomme xanthane préalablement mouillée dans la glycérine, puis ajouter le reste des ingrédients de la phase A, la phase A étant ensuite portée à 75°C ;  - Prepare phase A by moistening the xanthan gum previously wetted in glycerin, then add the rest of the ingredients of phase A, phase A being then raised to 75 ° C;
- préparer la phase B en mélangeant les composants de la phase B, puis la porter à 75°C ;  - prepare phase B by mixing the components of phase B, then bring it to 75 ° C;
- réaliser une émulsion sous vive agitation (mélangeur de type Turrax, puis agitation de type défloculeuse) en versant la phase B dans la phase A ;  - Make an emulsion with vigorous stirring (Turrax type mixer, then deflocculating type of agitation) by pouring phase B into phase A;
- refroidir sous agitation à 40°C, puis ajouter la phase C préalablement mélangée (mélangeur de type Turrax) ; et  - Cool with stirring at 40 ° C, then add the previously mixed phase C (Turrax type mixer); and
- ajouter successivement les phases D, E et F sous agitation de type défloculeuse. Exemple 2 :  successively adding the phases D, E and F with deflocculating stirring. Example 2
On prépare un gel lavant, pouvant être utilisé pour les mains, comprenant les composants listés dans le tableau 2 ci-dessous. COMPOSANTS % A washing gel, which can be used for the hands, comprising the components listed in Table 2 below is prepared. COMPONENTS%
Phase A :  Phase A:
Eau 56,95  Water 56.95
Agent hydratant 3,00  Moisturizing agent 3.00
Epaississant 1 0,10  Thickener 1 0.10
Epaississant 2 5,00  Thickener 2 5.00
Conservateur 1 0,25  Conservative 1 0.25
Phase B :  Phase B:
Agent émulsionnant 1 25,00  Emulsifying agent 1 25,00
Phase C :  Phase C:
Argent métallique 0,10  Metallic silver 0,10
Agent hydratant 2,00  Moisturizing agent 2.00
Phase D :  Phase D:
Conservateur 2 0,30  Conservative 2 0.30
Phase E :  Phase E:
Exfoliant 3,00  Exfoliant 3.00
Polymère fluoré 0,10  Fluoropolymer 0.10
Phase F :  Phase F:
Peptide antimicrobien 3,00  Antimicrobial Peptide 3.00
Phase G :  Phase G:
NaOH 20% 1,20  20% NaOH 1.20
Tableau 2  Table 2
L'origine des composants du tableau 2 est la suivante : The origin of the components in Table 2 is as follows:
- Agent hydratant est de la glycérine commercialisée par la société Interchimie ;  - Moisturizing agent is glycerin marketed by the company Interchimie;
- Epaississant 1 est une gomme xanthane commercialisée par la société Solvay/Rhodia sous la référence Rhodicare T ;  Thickener 1 is a xanthan gum marketed by the company Solvay / Rhodia under the reference Rhodicare T;
- Epaississant 2 est un copolymère d'acrylate commercialisé par la société Gattefossé sous la référence Carbopol aqua SF1 ;  Thickener 2 is an acrylate copolymer marketed by the company Gattefossé under the reference Carbopol aqua SF1;
- Conservateur 1 est de la chlorphenesine commercialisée par la société Arnaud sous la référence Chlorphenesin ;  Conservative 1 is chlorphenesine marketed by Arnaud under the reference Chlorphenesin;
- Agent émulsionnant 1 est de la bétaine de cocamidopropyle commercialisée par la société BASF sous la référence Déhyton K ;  Emulsifier 1 is cocamidopropyl betaine marketed by BASF under the reference Dehyton K;
- Argent métallique est de l'argent métallique micronisé dont la taille de particules moyenne est d'environ 10 pm, commercialisé par la société Impag sous la référence Microsilver BG ; - Conservateur 2 est du phénoxy éthanol commercialisé par la société SCD sous la référence Phenoxetol ; Metallic silver is micronized metallic silver with an average particle size of approximately 10 μm, marketed by Impag under the reference Microsilver BG; - Conservative 2 is phenoxy ethanol marketed by SCD under the reference Phenoxetol;
- Exfoliant est de l'acide polylactique commercialisé par la société SAFIC/ALCAN sous la référence Ecoscrub 20PC ;  - Exfoliant is polylactic acid marketed by the company SAFIC / ALCAN under the reference Ecoscrub 20PC;
- Polymère fluoré est du PTFE micronisé, commercialisé par la société Fluorinated polymer is micronized PTFE marketed by the company
SAFIC/ALCAN sous la référence Microslip 519L ; SAFIC / ALCAN under the reference Microslip 519L;
- Peptide antimicrobien est le palmitoyl hexapeptide-26 qui est un oligopeptide cationique produit de la réaction entre l'acide palmitique et l'hexapeptide-26 à base d'alanine, d'arginine, de glutamine, de lysine et de phénylalanine, ce peptide étant commercialisé par la société Infinitec sous la référence Shield Bact peptide PF WP ; cette référence comprend en outre deux conservateurs du type levulinate de sodium et anisate de sodium ; et  An antimicrobial peptide is palmitoyl hexapeptide-26, which is a cationic oligopeptide produced by the reaction between palmitic acid and hexapeptide-26 based on alanine, arginine, glutamine, lysine and phenylalanine, this peptide being marketed by Infinitec under the Shield Bact peptide PF WP reference; this reference additionally comprises two preservatives of the sodium levulinate and sodium anisate type; and
- NaOH 20% est de l'hydroxyde de sodium 20% commercialisé par la société Arnaud.  20% NaOH is 20% sodium hydroxide marketed by Arnaud.
La préparation du gel lavant de l'exemple 2 est réalisée comme suit par des techniques classiques bien connues de l'homme du métier, à température ambiante sauf indication contraire : The preparation of the washing gel of Example 2 is carried out as follows by conventional techniques well known to those skilled in the art, at room temperature unless otherwise indicated:
- préparer la phase A en hydratant la gomme xanthane préalablement mouillée dans la glycérine, puis ajouter le reste des ingrédients de la phase A ;  - prepare phase A by moistening the xanthan gum previously wetted in glycerin, then add the rest of the ingredients of phase A;
- ajouter la phase B ;  - add phase B;
- ajouter la phase C préalablement mélangée (mélangeur de type Turrax) ;  add the previously mixed phase C (Turrax mixer);
- ajouter la phase D ;  - add phase D;
- ajouter les composants de la phase E l'un après l'autre dans leur ordre d'apparition dans le tableau 2;  - add the components of phase E one after the other in their order of appearance in table 2;
- ajouter la phase F ; et  - add phase F; and
- ajuster le pH avec la phase G, pour obtenir un pH compris entre 5,8 et 6,2.  - adjust the pH with phase G, to obtain a pH between 5.8 and 6.2.
Exemple 3 : Example 3
On prépare une solution hydro-alcoolique, pouvant être utilisée pour les mains, comprenant les composants listés dans le tableau 3 ci-dessous. COMPOSANTS % A hydroalcoholic solution, which can be used for the hands, comprising the components listed in Table 3 below is prepared. COMPONENTS%
Phase A :  Phase A:
Eau 9,80  Water 9.80
Epaississant 1 10,00  Thickener 1 10.00
Peptide antimicrobien 3,00  Antimicrobial Peptide 3.00
Phase B :  Phase B:
Alcool 70,00  Alcohol 70,00
Phase C :  Phase C:
Argent métallique 0,20  Metallic silver 0,20
Agent hydratant 5,00  Moisturizing agent 5.00
Phase D :  Phase D:
NaOH 20% 2,00  NaOH 20% 2.00
Tableau 3  Table 3
L'origine des composants du tableau 3 est la suivante : The origin of the components of Table 3 is as follows:
- Epaississant 1 est un copolymère d'acrylate commercialisé par la société Gattefossé sous la référence Carbopol aqua SF1 ;  Thickener 1 is an acrylate copolymer sold by the company Gattefossé under the reference Carbopol aqua SF1;
- Peptide antimicrobien est le palmitoyl hexapeptide-26 qui est un oligopeptide cationique produit de la réaction entre l'acide palmitique et l'hexapeptide-26 à base d'alanine, d'arginine, de glutamine, de lysine et de phénylalanine, ce peptide étant commercialisé par la société Infinitec sous la référence Shield Bact peptide PF WP ; cette référence comprend en outre deux conservateurs du type levulinate de sodium et anisate de sodium ;  An antimicrobial peptide is palmitoyl hexapeptide-26, which is a cationic oligopeptide produced by the reaction between palmitic acid and hexapeptide-26 based on alanine, arginine, glutamine, lysine and phenylalanine, this peptide being marketed by Infinitec under the Shield Bact peptide PF WP reference; this reference additionally comprises two preservatives of the sodium levulinate and sodium anisate type;
- Alcool est de l'alcool dénaturé à 96,2° commercialisé par la société France Alcool sous la référence Alcool 96,2° ;  Alcohol is denatured alcohol at 96.2 ° marketed by France Alcohol under the reference Alcohol 96.2 °;
- Argent métallique est de l'argent métallique micronisé dont la taille de particules moyenne est d'environ 10 pm, commercialisé par la société Impag sous la référence Microsilver BG ;  Metallic silver is micronized metallic silver with an average particle size of approximately 10 μm, marketed by Impag under the reference Microsilver BG;
- Agent hydratant est de la glycérine commercialisée par la société Interchimie ;  - Moisturizing agent is glycerin marketed by the company Interchimie;
- NaOH 20% est de l'hydroxyde de sodium 20% commercialisée par la société Arnaud. La préparation de la solution hydro-alcoolique de l'exemple 3 est réalisée comme suit par des techniques classiques bien connues de l'homme du métier, à température ambiante sauf indication contraire : 20% NaOH is 20% sodium hydroxide marketed by Arnaud. The preparation of the hydroalcoholic solution of Example 3 is carried out as follows by conventional techniques well known to those skilled in the art, at room temperature unless otherwise indicated:
- préparer la phase A en les ajoutant dans leur ordre d'apparition dans le tableau 3, sous simple agitation avec une hélice à quatre pales ;  prepare phase A by adding them in their order of appearance in table 3, with simple stirring with a four-blade propeller;
- ajouter la phase B sous la même agitation ;  add phase B under the same agitation;
- ajouter la phase C préalablement mélangée (mélangeur de type Turrax) ; et  add the previously mixed phase C (Turrax mixer); and
- ajuster le pH avec la phase D, pour obtenir un pH compris entre 5,0 et 7,0.  - adjust the pH with phase D, to obtain a pH between 5.0 and 7.0.

Claims

REVENDICATIONS
1. Composition antimicrobienne comprenant de l'argent métallique sous forme de particules métalliques de taille micrométrique, caractérisée en ce qu'elle comprend en outre un peptide antimicrobien cationique.  An antimicrobial composition comprising metallic silver in the form of micrometric metal particles, characterized in that it further comprises a cationic antimicrobial peptide.
2. Composition selon la revendication 1, caractérisée en ce que le peptide antimicrobien est un oligopeptide. 2. Composition according to claim 1, characterized in that the antimicrobial peptide is an oligopeptide.
3. Composition selon la revendication 2, caractérisée en ce que l'oligopeptide comprend moins de 50 acides aminés. 3. Composition according to claim 2, characterized in that the oligopeptide comprises less than 50 amino acids.
4. Composition selon l'une quelconque des revendications précédentes, caractérisée en ce que le peptide antimicrobien est couplé à un lipide. 4. Composition according to any one of the preceding claims, characterized in that the antimicrobial peptide is coupled to a lipid.
5. Composition selon l'une quelconque des revendications précédentes, caractérisé en ce que le peptide présente un spectre antimicrobien contre les bactéries Gram-positif et Gram-négatif. 5. Composition according to any one of the preceding claims, characterized in that the peptide has an antimicrobial spectrum against Gram-positive and Gram-negative bacteria.
6. Composition selon l'une quelconque des revendications précédentes, caractérisée en ce que la composition antimicrobienne comprend de 0,001 à 20,0% en poids de peptide antimicrobien. 6. Composition according to any one of the preceding claims, characterized in that the antimicrobial composition comprises from 0.001 to 20.0% by weight of antimicrobial peptide.
7. Composition selon l'une quelconque des revendications précédentes, caractérisée en ce que l'argent métallique est constitué par une structure poreuse. 7. Composition according to any one of the preceding claims, characterized in that the metallic silver is constituted by a porous structure.
8. Composition selon l'une quelconque des revendications précédentes, caractérisée en ce que le diamètre moyen des particules métalliques va de 1 à 100 pm, et de préférence de 1 à 20 pm. 8. Composition according to any one of the preceding claims, characterized in that the average diameter of the metal particles ranges from 1 to 100 μm, and preferably from 1 to 20 μm.
9. Composition selon l'une quelconque des revendications précédentes, caractérisée en ce que la composition antimicrobienne comprend de 0,001 à 10,0% en poids d'argent métallique. 9. Composition according to any one of the preceding claims, characterized in that the antimicrobial composition comprises from 0.001 to 10.0% by weight of metallic silver.
10. Composition selon l'une quelconque des revendications précédentes, caractérisée en ce que la composition antimicrobienne comprend en outre un polymère fluoré. 10. Composition according to any one of the preceding claims, characterized in that the antimicrobial composition further comprises a fluoropolymer.
11. Composition selon la revendication 10, caractérisée en ce que le polymère fluoré est le polytétrafluoroéthylène (PTFE). 11. Composition according to claim 10, characterized in that the fluoropolymer is polytetrafluoroethylene (PTFE).
12. Composition selon la revendication 10 ou 11, caractérisée en ce que la composition antimicrobienne comprend de 0,001 à 10,0% en poids de polymère fluoré. 12. Composition according to claim 10 or 11, characterized in that the antimicrobial composition comprises from 0.001 to 10.0% by weight of fluoropolymer.
13. Composition selon l'une quelconque des revendications 1 à 12, pour son application pharmaceutique dans le traitement antiseptique du corps, notamment des mains et/ou des pieds. 13. Composition according to any one of claims 1 to 12, for its pharmaceutical application in the antiseptic treatment of the body, including the hands and / or feet.
14. Composition selon l'une quelconque des revendications 1 à 12, pour son application pharmaceutique dans le traitement antiseptique de la cavité buccale et/ou auriculaire. 14. Composition according to any one of claims 1 to 12, for its pharmaceutical application in the antiseptic treatment of the oral cavity and / or auricle.
15. Composition selon l'une quelconque des revendications 1 à 12, pour son application pharmaceutique dans le traitement antiseptique de l'œil . 15. Composition according to any one of claims 1 to 12, for its pharmaceutical application in the antiseptic treatment of the eye.
PCT/FR2015/052220 2014-08-27 2015-08-18 Antimicrobial composition WO2016030609A1 (en)

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