EP3022214A1 - Polymerisierte ceriumoxidnanopartikel in einem aktiven oder bioaktiven netzwerk, schützende topische behandlungen, verfahren zur herstellung und verwendungen davon - Google Patents

Polymerisierte ceriumoxidnanopartikel in einem aktiven oder bioaktiven netzwerk, schützende topische behandlungen, verfahren zur herstellung und verwendungen davon

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Publication number
EP3022214A1
EP3022214A1 EP14758589.7A EP14758589A EP3022214A1 EP 3022214 A1 EP3022214 A1 EP 3022214A1 EP 14758589 A EP14758589 A EP 14758589A EP 3022214 A1 EP3022214 A1 EP 3022214A1
Authority
EP
European Patent Office
Prior art keywords
polymers
hase
nanoparticles
topical
ase
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP14758589.7A
Other languages
English (en)
French (fr)
Inventor
Sonia AMIGONI
Denis Josse
Thierry Devers
Arnaud ZENERINO
Frédéric GUITTARD
Elisabeth TAFFIN DE GIVENCHY
Cécile BIGNON
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre National de la Recherche Scientifique CNRS
Universite dOrleans
Universite de Nice Sophia Antipolis UNSA
Original Assignee
Centre National de la Recherche Scientifique CNRS
Universite dOrleans
Universite de Nice Sophia Antipolis UNSA
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Publication date
Application filed by Centre National de la Recherche Scientifique CNRS, Universite dOrleans, Universite de Nice Sophia Antipolis UNSA filed Critical Centre National de la Recherche Scientifique CNRS
Publication of EP3022214A1 publication Critical patent/EP3022214A1/de
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01F—COMPOUNDS OF THE METALS BERYLLIUM, MAGNESIUM, ALUMINIUM, CALCIUM, STRONTIUM, BARIUM, RADIUM, THORIUM, OR OF THE RARE-EARTH METALS
    • C01F17/00—Compounds of rare earth metals
    • C01F17/20—Compounds containing only rare earth metals as the metal element
    • C01F17/206—Compounds containing only rare earth metals as the metal element oxide or hydroxide being the only anion
    • C01F17/224—Oxides or hydroxides of lanthanides
    • C01F17/235—Cerium oxides or hydroxides
    • 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
    • A61K31/765—Polymers containing oxygen
    • A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0241—Containing particulates characterized by their shape and/or structure
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5115—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK  ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
    • C09C3/00—Treatment in general of inorganic materials, other than fibrous fillers, to enhance their pigmenting or filling properties
    • C09C3/10—Treatment with macromolecular organic compounds
    • 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
    • A61K2800/413—Nanosized, i.e. having sizes below 100 nm
    • 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
    • A61K2800/48—Thickener, Thickening system
    • 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
    • A61K2800/54—Polymers characterized by specific structures/properties
    • A61K2800/548—Associative polymers
    • 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
    • A61K2800/60—Particulates further characterized by their structure or composition
    • A61K2800/61—Surface treated
    • 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
    • A61K2800/60—Particulates further characterized by their structure or composition
    • A61K2800/61—Surface treated
    • A61K2800/614—By macromolecular compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/60—Particles characterised by their size
    • C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2006/00—Physical properties of inorganic compounds
    • C01P2006/60—Optical properties, e.g. expressed in CIELAB-values

Definitions

  • the present invention relates to organic / inorganic hybrid compounds formed by functionalized micro- or nanoparticles of ceria (CeO2) covalently grafted onto rheology-modifying polymers. More particularly, the invention relates to amino functionalized micro- or nanoparticles of ceria grafted to polymers to form an active or bioactive network. The invention also relates to protective topical agents comprising them, to their methods of synthesis and to their uses, in particular for protecting or decontaminating the skin.
  • Contamination by biological or chemical risk agents can be multiple.
  • Biological risk agents are usually bacteria, viruses or toxins.
  • Chemical risk agents are generally organophosphorus neurotoxic compounds, or vesicants.
  • Toxic chemicals can be classified according to several criteria such as their volatility, their military use or their effects hemotoxic, vesicant, suffocating, neurotoxic, incapacitating, neutralizing.
  • Organophosphorus compounds include pesticides (POPs) and organophosphorus neurotoxins (NOPs).
  • Organophosphorus pesticides replaced organochlorine compounds that were highly persistent despite the higher toxicity of POPs.
  • the first compounds such as parathion (O, O-diethyl and op-nitrophenyl phosphorothioate), malathion (S- (1,2-dicarbethoxyethyl) and O-dimethyl thiophosphate) and paraoxon (phosphate diethyl p-nitrophenyl) are potent cholinesterase inhibitors.
  • Organophosphorus pesticides are extremely toxic and cause serious intoxication especially in the agricultural sector.
  • the World Health Organization (WHO) has estimated that there are 1 million serious poisonings per year worldwide, with about 220,000 deaths. The risk of pesticide intoxication is high because of frequent contact during aerial and ground pesticide spraying and handling.
  • the first organophosphorus neurotoxins (NOPs) synthesized for use as chemical warfare agents were the G agents. They include, in particular, the GA or Tabun agent, the GB or Sarin agent and the GD or Soman agent. These are esters of derivatives of fluorophosphonic or phosphoramidic acids. Other organophosphorus neurotoxins (NOPs) are the V agents.
  • Exposure to excessive concentrations of these agents can cause a set of typical symptoms of hypercholinergic: intense bronchial, salivary, ocular and intestinal secretions, sweating, bradycardia, muscle contractions, tremors, paralysis, loss of consciousness, convulsions, dysfunction of the respiratory system that can lead to death.
  • the prevention of skin contamination is mainly achieved by wearing protective gear such as coveralls, masks or gloves.
  • protective gear such as coveralls, masks or gloves.
  • protective topical agents makes it possible to provide an alternative or additional protection against irritants and environmental aggressives, such as, for example, microorganisms, chemicals such as vesicants and organophosphorus compounds.
  • TP protection topicals
  • a second generation of protective topicals consists of the incorporation of active, organic or inorganic, which can neutralize chemical contaminants has also been developed.
  • Such topics are described in particular in Kcper 0.; Lucas E.; Klabunde K. J.; Development of reactive topical skin protectants against sulfur mustard and nerve agents, J. Appl. Toxicol. 1999, 19, 59-70; or in Saxena A .; Srivastava A.K .; Singh B .; Goyal A .; Removal of sulfur mustard, sarin and simulants on impregnated silica nanoparticles, J. Hazard. Mater. , 2012, 211-212, 226-232).
  • the Applicant has developed a new concept consisting of grafting micro- or nanoparticles, known in particular for their neutralizing effects vis-à-vis toxic and / or biological chemical agents, to polymers in particular modifying rheology, facilitating integration and homogeneous dispersion of micro- or nanoparticles in a topical formulation but also in preventing the release ⁇ micro- or nanoparticles.
  • the solution to the problem posed thus relates to a compound formed by functionalized microparticles or nanoparticles, covalently associated with rheological modifying polymers, characterized in that: - the functionalized microparticles or nanoparticles, micro- or are functionalized nanoparticles ceria (Ce0 2), having a nominal diameter of between 1 and 1500 nm;
  • the modifying polymers or rheology adapters are chosen from non-associative polymers or associative polymers.
  • the Applicant has been able to demonstrate, as illustrated in Example 7, that the compounds according to the invention make it possible to obtain excellent protective topical agents which limit the trans-brominated penetration of toxic agents, such as paraoxon.
  • the subject of the present invention is also a protective topical comprising a compound according to the invention, in a pharmaceutically and / or cosmetically acceptable medium.
  • Its fourth object is a compound or protective topical according to the invention, for its use in the prevention of cutaneous irritations or allergies.
  • Its fifth object is the use of a protective compound or topical agent according to the invention, for the protection or the skin decontamination, in particular due to biological and / or chemical risk agents.
  • Its sixth object is a method for synthesizing a compound according to the invention comprising the steps of:
  • the subject of the invention is methods for synthesizing the compounds according to the invention.
  • the compounds and topicals previously described can in particular be synthesized according to the various processes, the main stages of which are described in Examples 1 to 6.
  • FIG. 1 is a schematic representation of telechelic and comb type compounds
  • FIG. 2 illustrates functionalization of ceria nanoparticles by (3-aminopropyl) triethoxysilane in anhydrous toluene;
  • FIG. 3 illustrates a synthetic scheme of non-associative polymers ASE-H and ASE-F;
  • FIG. 4 illustrates a synthetic scheme of associative polymers
  • FIG. 5 represents a macromer synthesis scheme intended to be integrated with HASE associative polymers
  • FIG. 6 represents studies of contact angles with olive oil on various polymers previously deposited on a glass plate
  • Fig. 7 shows studies of olive oil contact angles for various HASE-F-RF8 polymers at 3.3; 13.5 and 45.9 mol% of ⁇ macromers;
  • FIG. 8 represents a flow analysis for the polymers HASE-F-RF8 (3.3 mol% of macromer), (13.5 mol% of macromer) and (45.9 mol% of macromer);
  • FIG. 9 represents a topical evaluation study HASE-F-RF8
  • FIG. 10 represents an evaluation study of topical HASE-F-RF8 (13.5 mole% of macromer) / Si, HASE-F-RF8 (13.5 mole% of macromer) / Ce and HASE-F- RF8 (13.5 mole% macromer) vis-à-vis the transmembrane penetration of paraoxon;
  • FIG. 12 represents a study evaluating the efficacy of a formulation comprising a compound according to the invention with respect to the transmembrane penetration of paraoxon.
  • the compound according to the invention is a compound formed by functionalized microparticles or nanoparticles covalently associated with rheology-modifying polymers, characterized in that:
  • functionalized microparticles or nanoparticles are functionalized micro- or nanoparticles of ceria (Ce ⁇ 3 ⁇ 4), having a nominal diameter of between 1 and 1500 nm;
  • the modifying polymers or rheology adapters are chosen from non-associative polymers or associative polymers.
  • a nanoparticle is defined as being a nano-object whose three dimensions are at the nanoscale, that is to say a particle whose nominal diameter is less than 100 nm.
  • the nanoparticle according to the invention has a diameter of between 1 and 50 nm. More preferably, the nominal diameter of the nanoparticle is between 5 nm and 25 nm.
  • a microparticle according to the invention is in turn a micro-object whose three dimensions are at the micrometer scale, that is to say a particle whose nominal diameter is between 100 nm and 100000 nm.
  • the microparticle according to the invention has a nominal diameter of between 100 nm and 5000 nm. More preferably, the nominal diameter of the microparticle is between 100 nm and 1500 nm.
  • micro- or nanoparticles may be produced by various methods, in particular by chemical vapor phase synthesis, in the liquid phase, in a solid medium, in a mixed medium or by physicochemical methods such as evaporation / condensation.
  • the micro- or nanoparticles of ceria or cerium dioxide (Ce (1 ⁇ 2) can be synthesized in mixed medium by the sol-gel method.
  • the principle of the sol-gel process is based on the use of a succession of hydrolysis-condensation reactions, at a moderate temperature close to ambient, to prepare oxide networks which may in turn be heat-treated
  • the soluble metal species may also contain organic constituents which The first step in the sol-gel synthesis is the hydroxylation of the alkoxy metal, which occurs during the hydrolysis of the alkoxy group:
  • Step 1 hydrolysis: M '-OR' + H2O -> M '-OH + R'OH where M 'represents cerium; and R 'represents an alkyl organic group comprising from 1 to 5 carbon atoms, preferably from 2 to 3 carbon atoms.
  • the hydroxy reactive groups are then generated.
  • the solution obtained is called sol. They are then modified by polycondensation reactions via two competitive mechanisms: the formation of an oxygen bridge (oxolation) or a hydroxo bridge (olation). This corresponds to the formation of the mineral macromolecular network with elimination of water or alcohol:
  • M 'and R' are as defined above, i.e., M 'represents cerium; and R 'represents an alkyl organic group comprising from 1 to 5 carbon atoms, preferably from 2 to 3 carbon atoms.
  • the gel corresponds to the formation of a three-dimensional network of Van der Waals bonds.
  • micro- or nanoparticles that can be used according to the invention preferably have a mean nominal diameter of between 1 and 1500 nm.
  • the ceria micro- or nanoparticles have a mean nominal diameter of between 1 and 300 nm.
  • their average nominal diameter is between 5 and 150 nm. More preferably, their mean nominal diameter is between 8 and 10 nm.
  • micro- or nanoparticles may be functionalized for example by primary or secondary amine functional groups, epoxy functions, alcohol functional groups and thiol functions.
  • ceria micro- or nanoparticles are functionalized amine.
  • FIG. 1 A general diagram of the amino functionalization of the micro- or nanoparticles is illustrated in FIG.
  • Example 1 The detail of synthesis routes of ceria nanoparticles is described in Example 1.
  • the level of amine functions on the functionalized micro- or nanoparticles amine is between 0.1 and 10 meq / g of micro- or nanoparticles.
  • the number of NH 2 functions obtained is in meq / g of micro- or nano-particles and is calculated according to the following equation: Molar Mass of Nitrogen
  • the level of amine functions on the functionalized micro- or nanoparticles amine is between 0.1 and 4 meq / g of micro- or nanoparticles. More preferably, the level of amino functions on the micro- or nanoparticles is about 0.5 or 2.5 meq / g of micro- or nanoparticles.
  • micro- or nanoparticles according to the invention are functionalized amine, in order to react on the acid functions of the polymers.
  • the modifying polymers or rheology adapters according to the invention are already used, alone, for their rheological properties in fields such as cosmetics or paint.
  • hydrocarbon or fluorocarbon polymers synthesized for example by emulsion polymerization.
  • IR infrared
  • NMR nuclear magnetic resonance
  • the polymers that can be used belong to two different classes: non-associative polymers and associative polymers.
  • non-associative polymers or alkali-swellable emulsion-capable emulsions (ASE) usable according to the invention are already widely used, alone, as thickeners in latex coatings, paints and adhesives.
  • They consist mainly of acrylic or methacrylic acid monomers and of C1-C4 alkyl acrylate, preferentially ethyl acrylate.
  • the non-associative polymers ASE can be optimized by crosslinking.
  • the crosslinking phenomenon makes it possible to physically densify the polymer network, which reduces the possibility of movement of the molecules and therefore increases the viscosity.
  • the non-associative polymers according to the invention may comprise a hydrocarbon chain (ASE-H) and / or a fluorocarbon chain (ASE-F).
  • ASE-H hydrocarbon chain
  • ASE-F fluorocarbon chain
  • non-associative polymers ASE-H correspond to the following general formula (I):
  • - Ri and R2 represent a hydrogen atom or a methyl group -CH 3 ;
  • R3 is [Q] di- (CH 2) n -H wherein n is between 1 and 30, dl represents 0 or 1, and Q represents -C (0) -0 or -C (0) - NH-;
  • R3 represents [Q] d2-oi, wherein:
  • a and b are integers, identical or different, greater than 1.
  • a is between 1 and 10,000 and b is between 1 and 20000.
  • the polymers are composed of different monomers or macromers, at given molar concentrations, which vary according to the values of a, b and / or c.
  • sequence of different monomers or macromers in the polymers obtained is variable and is not fixed in the formulas (I), (II), (III), (V), (VI), (VII) and (VIII). - "-v ⁇ / WV u I
  • the ASE hydrocarbon chain polymers include acrylic and / or methacrylic acid monomers and C 1 -C 4 alkyl acrylates.
  • ASE hydrocarbon chain polymers comprise:
  • the ASE-H polymers comprise the following monomers:
  • the ASE hydrocarbon chain polymers (ASE-H) have particularly advantageous thickening properties when the methacrylic acid / ethyl acrylate ratio is between 0.1 and 0.5. The most preferred ratio is 0.21.
  • non-associative ASE polymers according to the invention may also comprise a fluorocarbon chain (ASE-F).
  • ASE-F fluorocarbon chain
  • non-associative polymers ASE-F have the following general formula (II):
  • R1, R2 and R4 represent a hydrogen atom or a methyl group -CH 3 ;
  • R3 is [Q] di _ (CH 2) n -H wherein n is between 1 and 30, dl represents 0 or 1, and Q represents -C (0) -0 or-C. (O ) - NH-;
  • R3 represents [Q] d2-a, wherein:
  • -CN -CH 2 CH 2 -N + (CH 3 ) 2 (CH 2 CO 2 " ); -CH 2 CH 2 -NH-C (CH 3 ) 3 ; -CH 2 CH 2 -N (CH 3 ) 2 ; pyrrolidinone; caprolactam; - R3 represents [Q] of i- (CH 2) n - (C3 ⁇ 4) pX wherein n is conpris between 1 and 30, dl represents 0 or 1, Q represents -C (0) -0 or - C (O) - NH-, X is a fluorine atom F and p is from 1 to 12; and wherein the indices a and c are integers, identical or different, greater than 1 and b is greater than or equal to 0; preferably, a is between 1 and 10000, b is between 0 and 5000 and c is between 1 and 8000.
  • ASE-F polymers are preferably composed of monomers:
  • AM methacrylic acid
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • MTFE trifluoroethyl acrylate or of 2-perfluorobutylethyl acrylate or of 2-perfluorohexylethyl acrylate or of 2-perfluorooctylethyl acrylate
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • ASE fluorocarbon chain polymers are composed of the following monomers:
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • 2-perfluorobutylethyl acrylate or of 2-perfluorohexylethyl acrylate or of 2-acrylate acrylate perfluorooctylethyl from 10 to 55 mol% of 2,2,2-trifluoroethyl methacrylate (MTFE) or of trifluoroethyl acrylate or of 2-perfluorobutylethyl acrylate or of 2-perfluorohexylethyl acrylate or of 2-acrylate acrylate perfluorooctylethyl.
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • the fluorocarbon chain ASE polymers include methacrylic acid (MA), ethyl acrylate (AE), and 2,2,2-trifluoroethyl methacrylate (MTFE) monomers.
  • ASE hydrocarbon chain polymers comprise:
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • the ASE fluorocarbon chain polymers have particularly advantageous thickening properties when the ratio of the acidic monomers methacrylic acid (AM) / ethyl acrylate (AE) is between 7 and 0.1.
  • a general formula of polymers ASE-H and ASE-F that can be used according to the invention is illustrated in FIG. 3.
  • a route of synthesis of the polymers ASE-H and ASE-F is detailed in example 2, and is summarized in FIG. Figure 3, wherein the indices a, b and c are integers, identical or different, greater than 1.
  • a is between 1 and 10000;
  • b is between 1 and 5000 and c is between 1 and 8000.
  • the associative polymers that may be used according to the invention consist of a hydrophilic macromolecular structure on which hydrophobic groups are present. These hydrophobic groups are often short-chain (having from 1 to 6 carbon atoms) or long-chain (having more than 6 carbon atoms) chains capable of forming aggregates, clusters, of micellar type from a so-called critical aggregation concentration. These aggregates are called hydrophobic junctions.
  • HEUR hydrophobic ethylene oxide-urethane-based urethanes
  • Telechelic polymers are linear chains of polymers containing hydrophobic groups at the end of the chain.
  • Comb type polymers are polymers containing hydrophobic chains along the backbone.
  • HASE polymers are generally copolymers of methacrylic acid (AM), ethyl acrylate (AE) and an amount of hydrophobic groups, which are macromonomers or macromers. Despite the presence of hydrophobic groups, which are long hydrocarbon chains, HASE polymers are soluble in aqueous medium which makes them particularly interesting.
  • the HASE polymers are generally prepared by emulsion polymerization at a low pH, which makes it possible to obtain polymers with molar masses of between 300000 and 1800000 g / mol.
  • the rheological properties of the HASE polymers showed that the viscosity was highly pH dependent. In the pH range of 2.4 to 4.5, the polymer backbone folds to form a compact coil due to the low quality of the solvent.
  • the polymer solution is milky and consists of insoluble colloidal particles. At pH 6, the viscosity increases sharply and then remains constant until pH 11, the carboxyl groups on the backbone of the polymer dissolve and the solution becomes transparent.
  • the polymer chain then resembles a polyelectrolyte which causes the extension of the polymer backbone due to the mutual repulsion of the carboxylates and the increase of the hydrodynamic volume. At the same time, a large number of inter and intramolecular associations between the hydrophobic groups are formed, which leads to the construction of a network within the aqueous medium.
  • HASE polymers combine the properties of polyelectrolytes and the properties of uncharged associative polymers. Above pH 11, the viscosity decreases slowly due to the protective effect of the charge. Other factors may vary the dynamic nature of the polymer and the structure of the HASE polymers, such as in particular the concentration of salts in the medium. When this is important, the viscosity decreases significantly.
  • the negative effect of the addition of salts can be compensated by the addition of a surfactant.
  • the concentration of surfactant can vary the viscosity of the medium. Concentration growth by a nonionic surfactant increases the viscosity of the medium, while anionic surfactant increases the viscosity to a critical concentration where it drops.
  • the viscosity of the medium can also be decreased as the temperature increases.
  • Monovalent neutralizers may also be recommended. Indeed, when using di- or trivalent basic molecule thus having the power to neutralize more than one carboxylic acid function, there may be a reduction in the ability of the polymer to unfold and unfold completely.
  • an organic solvent can reduce the viscosity of the medium by breaking the hydrophobic associations within the aqueous medium and by solubilizing the hydrophobic groups.
  • the polymers according to the invention are HASE polymers with hydrocarbon chain macromers (HASE-H-RH or HASE-F-RH) or a fluorocarbon chain (HASE-F-RF).
  • the associative polymers HASE with macromers having a hydrocarbon chain (HASE-H-RH or HASE-F-RH) or a fluorocarbon chain (HASE-F ⁇ RF) according to the invention:
  • R2 and R6 represent a hydrogen atom or a methyl group
  • R5 represents [Q] d i- (CH 2 ) n - (CX 2 ) p X in which n is between 1 and 30, d1 corresponds to 0 or 1, and Q corresponds to -C (0) -0 or - C (O) -NH-;
  • p is between 1 and 12;
  • R5 represents [Q] d2 ⁇ a, wherein:
  • R7 represents ⁇ [Q '] d 3 (OCH 2 CH 2 ) q - [Q "] d4- (CH 2 ) n (CX 2 ) pX in which Q' corresponds to -CH 2 , C (O), OC (O) or -NH-C (O), n is 1 to 30, q is 1 to 150, d3 and d4 are 0 and / or 1, Q "is -OC (O) or -NH-C (O); and
  • p is between 1 and 12;
  • indices a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0.
  • a is between 1 and 10,000; b is 0 to 10000 and c is 1 to 5000.
  • the H7ASE-H-RH hydrocarbon-chain polymers are composed of monomers of methacrylic acid (AM), of C1-C4 alkyl acrylates and of a macromer which is an ester of general formula (IV ):
  • q denotes a number between 5 and 10 and n is between 6 and 30 carbon atoms.
  • the HASE-H-RH polymers comprise monomers of methacrylic acid (AM), of ethyl acrylate (AE), and of a macromer which is an ester of general formula (IV) as defined above, and therefore correspond to the following general formula (V):
  • q denotes a number between 5 and 10;
  • n is between 1 and 30;
  • a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0; preferably, a is between 1 and 10,000, b is between 0 and 10,000 and c is between 1 and 5000. More preferably, the HASE-H-RH polymers have the general formula (V) and include:
  • the particularly preferred HASE-H-RH polymers have the formula (V) above, and are such that:
  • HASE-H-RH4 polymer 6 carbon atoms
  • HASE-H-RH6 polymer 8 carbon atoms
  • HASE-H-RH8 polymer 10 carbon atoms
  • the ethyl acrylate monomer (AE) of the HASE-H-RH polymer of the formula (V) above can be replaced by a methacrylate monomer of 2.2.2. trifluoroethyl (MTFE) and therefore corresponds to a HASE-F-RH polymer which corresponds to the following general formula (VI):
  • q denotes a number between 5 and 10;
  • n is between 6 and 30 carbon atoms
  • a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0; preferably, a is between 1 and 10,000, b is between 0 and 10,000 and c is between 1 and 5000.
  • HASE-F-RH polymers have the general formula (VI) above and include:
  • AM methacrylic acid
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • the particularly preferred HASE-F-RH polymers have the formula (VI) above, and are such that:
  • HASE-F-RH4 polymer 6 carbon atoms
  • HASE-F-RH6 polymer 8 carbon atoms
  • HASE-F-RH8 polymer 10 carbon atoms
  • the Applicant has, moreover, been able to demonstrate that the substitution of hydrocarbon chains by fluorocarbons on the macromer was possible in a HASE skeleton.
  • the rheology-modifying polymer according to the invention can disperse the micro- or nanoparticles while providing the hydrophobicity and oleophobicity necessary for protection against chemical agents.
  • HASE-F HASE fluorinated-chain polymers
  • R2 represent a hydrogen atom or a methyl group
  • R5 represents [Q] d i ⁇ (CH 2 ) n - (CX2) pX in which n is between 1 and 30, d1 corresponds to 0 or 1, and Q corresponds to -C (O) -0 or - C (O) -NH-;
  • q represents a number between 1 and 150
  • n is an integer from 1 to 30;
  • p is an integer from 1 to 12;
  • indices a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0; preferably, a is between 1 and 10,000, b is between 0 and 10,000 and c is between 1 and 5000.
  • HASE-F polymers have the following general formula (VIII):
  • q denotes a number between 5 and 10;
  • n is an integer from 1 to 30;
  • p is an integer from 1 to 12;
  • a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0; preferably, a is between 1 and 10,000, b is between 0 and 10,000 and c is between 1 and 5000.
  • the HASE-F polymers correspond to the general formula (VIII) above in which: - q equals 5, 7 or 9;
  • p 4, 6 or 8;
  • a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0; preferably, a is between 1 and 10,000, b is between 0 and 10,000 and c is between 1 and 5000. More preferably, the H7ASE-F polymers corresponding to the general formula (VIII) comprise the following monomers:
  • the particularly preferred HASE-F polymers have the formula (VIII) above, and are such that:
  • HASE-F-RF4 polymer q equals 5 and p equals 4 (hereinafter referred to as HASE-F-RF4 polymer);
  • HASE-F-RF6 polymer q equals 7 and p equals 6 (hereinafter referred to as HASE-F-RF6 polymer);
  • HASE-F-RF8 polymer q equals 7 and p equals 6 (hereinafter referred to as HASE-F-RF8 polymer);
  • the HASE polymers described above can be synthesized by the same method as for the ASE polymers.
  • the details of a synthetic route of the polymers HASE-H and HASE-F are detailed in Example 3.
  • the modifying polymers or rheology adapters that can be used in the compounds according to the invention are chosen from: i) from non-associative polymers ASE-H of the following general formula (I): (I)
  • - Ri and R2 represent a hydrogen atom or a methyl group -CH 3 ;
  • R 3 represents [Q] n - (CH 2 ) n -H in which n is between 1 and 30, dl corresponds to 0 or 1, and Q corresponds to -C (O) -O or -C (O) - NH-;
  • R3 is [Q] d2 _ a wherein:
  • indices a and b are integers, identical or different, greater than 1; or ii) among non-associative polymers ASE-F of general formula (II)
  • R1, R2 and R4 represent a hydrogen atom or a methyl group -CH 3 ;
  • R3 represents [Q] ⁇ a . - (CH 2 ) n -H wherein n is between 1 and 30, dl is 0 or 1, and Q is -C (O) -O or -C (O) - NH-;
  • R3 is [Q] d2 _ a wherein:
  • Q is -C (O) -O or -C (O) -NH-; and • a corresponds to -C (CH 3 ) 3 ; -CH (CH 3 ) 2 ; -C (CH 3 ) 2 -CH 2 -C (CH 3 ) 3; -CN; -CH 2 CH 2 N + (CH 3) 2 (CH 2 C02 "); -CH 2 CH 2 -NH-C (CH 3) 3;
  • - R3 Represents [Q] di- ( ⁇ 3 ⁇ 4) ⁇ _ (3 ⁇ 4) ⁇ in which n is between 1 and 30, dl corresponds to 0 or 1, Q corresponds to -C (0) -0 or -C (0) - NH-, X is a fluorine atom F and p is between 1 and 12; and wherein the indices a and c are integers, identical or different, greater than 1 and b is greater than or equal to 0; or iii) among the associative polymers HASE with hydrocarbon chain macromers (HASE-H-RH or HASE-F-RH) or with fluorocarbon chain (HASE-F-RF) corresponding to the following general formula (III):
  • R2 and R6 represent a hydrogen atom or a methyl group
  • R5 represents [Q] di- (CH 2 ) n- (CX 2 ) pX wherein n is between 1 and 30, d1 is 0 or 1, and Q is -C (O) -0 or - C (O) -NH-;
  • p is between 1 and 12;
  • R5 represents [Q] d2-a, wherein:
  • R7 is - [Q '] d3 - (0CH 2 CH 2) q - [Q'] of 4- (CH 2) n (CX 2) pX wherein Q 'stands for CH 2, C (0) 0-C (0) or -NH-C (O), n is between 1 and 30, q is 1 to 150, d3 and d4 are 0 and / or 1, Q "is -OC (O) or -NH-C (O);
  • p is between 1 and 12;
  • indices a and c are integers, identical or different, greater than or equal to 1, and b is greater than or equal to 0.
  • the modifying polymers or rheology adapters are chosen from:
  • ASE-H polymers which comprise the following monomers:
  • hydrocarbon chain ASE polymers which comprise the following monomers:
  • MTFE 2,2,2-trifluoroethyl
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • the modifying polymers or rheology adapters are chosen from polymers: - ASE-H;
  • the molar percentage of macromers in the HASE polymers is between 1 and 85 mol%. More preferably, the molar percentage is between 3 and 50 mol% of macromers.
  • the molar percentage is 13.5 mol% of macromers.
  • the polymer according to the invention is the polymer HASE-F-RF8, preferably at 13.5 mol% of macromer.
  • the compound according to the invention is formed by the covalent association of one or more amino functionalized microparticles or nanoparticles as described above, with one or more rheology modifying polymers as described above.
  • the micro- or nanoparticles being powdery, they can cause inflammation of the lungs by attaching them (by inhalation) or passage into the blood (by skin penetration). Also, so to avoid this type of toxicity and in order to control the dispersion, the Applicant covalently grafted the micro- or nanoparticles to the polymers. This grafting can be performed by the so-called "grafting to" method.
  • the covalent association of microparticles or nanoparticles with polymers can be achieved by reacting amino functionalized microparticles or nanoparticles on polymers possessing carboxylic acid functional groups (amidation reaction) in the aqueous phase.
  • the grafting of the micro- or nanoparticles onto the polymers can be done via esterification or via amidation.
  • the grafting is carried out by amidation which is a reaction whose yield is greater than the esterification due to the greater nucleophilicity of the nitrogen compared to the alcohol.
  • Example 5 Examples of grafting of aminated functionalized microparticles or nanoparticles with associative or non-associative polymers are detailed in Example 5.
  • the ceria micro- or nanoparticles (CeO 2 ) were synthesized and then functionalized amine to react on the acid functions of the modifying polymers or rheology adapters.
  • the covalent bond has many advantages. It will make it possible, on the one hand, to prevent the penetration of micro- or nanoparticles by the respiratory route but also by the cutaneous route within the human or animal body, and on the other hand to control the dispersion of the micro- or nanoparticles within the matrix in which the micro- or nanoparticles are linked.
  • the polymer, or the polymer matrix contains compounds whose functions make it possible to react with the micro- or nanoparticles but also that can be used in a topical.
  • the micro- or nanoparticles are covalently bound to a rheology-modifying polymer containing fluorinated monomers for an increased film-forming property and an increase in hydrophobicity and oleophobia. to "repel" the toxics.
  • the objective is also to provide an optimum film-forming character for surface protection thanks to the various polymers, and to a more or less strong interaction between the micro- or nanoparticles.
  • micro- or nanoparticles of cerium dioxide allow photodegradation destruction of the toxins coming into contact with the film before they penetrate the skin or the support.
  • the nanoparticles are preferred to the microparticles. Indeed, the choice of nanoparticles is oriented by their very large surface area relative to microparticles in order to increase the adsorption efficiency.
  • This micro- or nanoparticulate network is dispersible in a basic aqueous medium thanks to the presence of carboxylic acid in the copolymer and can therefore easily be integrated into a topic.
  • cerine (CeO 2 ) equivalents in the compounds according to the invention, that is to say the number of equivalent functions of amines carried by the ceria micro- or nanoparticles ( This functionalized amine (2) is based on the number of equivalent acid functions carried by the polymer. A number of ceria equivalents of less than or equal to 1 would then make it possible to obtain compounds with improved properties, for example dispersion and oleophobicity.
  • the polymer / micro- or nanoparticle ratio was calculated by the number of equivalents of acid functions carried by the polymer as a function of the number of amino function equivalents carried by the micro- or nanoparticles (for 1 equivalent of acid functions contained in the polymer, 1 equivalent of amino functions has been introduced) (where for 1 eq of acid functions, 0.3 eq of introduced amino functions).
  • the number of cerine equivalents (Ce (3 ⁇ 4)) in the compounds according to the invention is between 0.05 and 1. More preferably, it is between 0.3 and 0.8. the number of equivalents is 0.13.
  • the invention has for object a protective second topical composition comprising a compound according to the invention in a pharmaceutically 'and / or cosmetically acceptable medium.
  • the protective topical additionally comprises one or more detoxifying agents and / or one or more complementary polymers.
  • the detoxifying agents are non-toxic and dermatologically acceptable.
  • detoxifying agents mention may be made of benzoyl peroxide, zinc peroxide, magnesium monoperoxyphthalate, sodium perborate, sodium percarbonate, potassium permanganate and peroxide carbamide (peroxide). urea), calcium peroxide, titanium dioxide, and sulfur compounds such as N-acetyl such as zinc oxide, complexing agents such as etidronic acid and sodium propionate, magnesium hydroxy carbonate, potassium nitrate or thioglycolic acid.
  • the weight percentage of these detoxifying agents is preferably between 0.001 and 60% of the total weight of the composition.
  • the protective topic according to the invention may also comprise one or more complementary polymers chosen from polyperfluoromethyl-isopropyl ether, the copolymer of dimethicone and vinyldimethicone, the copolymer of diethylene glycol, adipic acid and glycerine, polysilicon And polyglycerides of oleic / linoleic / linolenic acids whose role is to make the compositions more fluid or more pleasant to apply.
  • Polyperfluoromethylisopropyl ether is especially marketed under the trademark Fomblin TM HC.
  • the dimethicone and vinyldrmethicone polymer is especially marketed under the trademark Silicone Elastomer Blend DC9041 TM.
  • the copolymer of diethylene glycol, adipic acid and glycerin is in particular marketed under the trademark Lexorez 100 TM.
  • Polysilicone-8 is especially marketed under the trademark Silicones Plus Polymer VS80Dry TM.
  • These complementary polymers are introduced as a mass percentage ranging, for example, from 0.005% to 10% of the total weight of the composition.
  • the dermatological and / or cosmetic composition according to the invention may furthermore contain emollient agents, softening agents, preservatives or even perfumes.
  • the topic according to the invention further comprises glycerine.
  • the topic according to the invention comprises between 5 and
  • the protective topicals can be in the form of gel, lotion, oil emulsion in water or water in oil, dispersion, milk, cream, ointment, mousse, stick, spray, aerosol or any other form suitable for topical application.
  • the protective topicals according to the invention are intended to be applied to the skin, in prevention and in anticipation of a possible contact with toxic chemical agents. They are applied in a sufficient layer on the face and on all parts of the body likely to be exposed to toxic chemical agents.
  • the protective topicals therefore preferably also contain a protective barrier base and one or more detoxifying agents, in order, on the one hand, to delay the skin penetration of the toxic chemical agents and / or, on the other hand, to neutralize them before they can reach their sites of action in a living organism.
  • the compounds which are the subject of the invention are introduced into the BariedermTech TM cream marketed by the company Uriage TM, which contains in particular water, the Poly-2p® complex consisting of pyrrolidone polymer and polymer of biomimetic phosphorylcholine (Poly-2F M), glycerin and alcohol.
  • Uriage TM which contains in particular water
  • Poly-2p® complex consisting of pyrrolidone polymer and polymer of biomimetic phosphorylcholine (Poly-2F M), glycerin and alcohol.
  • the third object of the invention is a compound or topical protective agent according to the invention as a medicament.
  • the compound or the protective topical according to the invention has preventive properties with respect to human or animal diseases.
  • the compound or the protective topic according to the invention can also be used as a substance or composition that can be used in humans or animals, with a view to correcting or modifying their physiological functions by exerting a pharmacological, immunological or metabolic action.
  • the compound or the protective topical according to the invention find applications in human medicine, especially in dermatology, for the prevention of cutaneous irritations or allergies.
  • the fourth subject of the invention is therefore a protective compound or topic according to the invention for its use in the prevention of irritations or allergies.
  • Irritations can be, for example, skin irritations or allergies related to unsafe work practices or DIY activities.
  • Occupational risk practices include the use of chemical or biological risk agents, for example in hospital or military settings.
  • DIY activities include the use of chemicals for example in painting, mechanics, gardening or furniture renovation.
  • the fifth subject of the invention is the use of a compound or topical protective agent according to the invention, for the protection or the skin decontamination, in particular due to biological or chemical risk agents.
  • the compound or topical protector can also be used for non-therapeutic applications, for example cosmetic, that is to say that it finds an application as epidermal barrier protection against external aggression.
  • the invention also relates to the cosmetic use of the compound or topical protective according to the invention, for the cutaneous protection against toxic agents of the family of organophosphorus compounds (COP) that include pesticides (POPs) and organophosphorus neurotoxins (NOP), or against vesicants such as sulfur or nitrogen yperites, or lewisite and phosgene oxime.
  • COP organophosphorus compounds
  • POPs pesticides
  • NOP organophosphorus neurotoxins
  • vesicants such as sulfur or nitrogen yperites, or lewisite and phosgene oxime.
  • the invention also relates to the cosmetic use of the protective compound or topic according to the invention, for protection against UVA and / or UVB ultraviolet rays originating from a natural or artificial source.
  • the compounds according to the invention can also find applications such as:
  • Oxygen buffers because they store, release and carry oxygen.
  • the subject of the invention is also processes for synthesizing the compounds according to the invention. Such synthetic methods are described in the examples below.
  • the preferred method of preparation of a compound according to the invention comprises the steps of:
  • the coupling agent is N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride (EDC) and the catalyst is N-hydroxysuccinimide (NHS).
  • EDC N-(2-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride
  • NHS N-hydroxysuccinimide
  • the ceria nanoparticles can be synthesized by different methods. Two methods are listed below.
  • a solution of cerium nitrate (Ce (N (3 ⁇ 4) 3 .63 ⁇ 40) at 1.15 mol.L- 1 is mixed with a solution of sodium hydroxide of 5 mol.l -1 at room temperature.
  • cerium hydroxide (III) obtained is recovered by centrifugation by washing it three times with deionized water. A solution of 27% hydrogen peroxide (by mass) is then added at a temperature of 50 ° C.
  • the oxidized precipitate is centrifuged and washed with deionized water before filtration on filter paper and calcination at 500 ° C. in air for 6 hours in a porcelain crucible.
  • the precursor is converted into cerine according to the reaction:
  • a beige powder is obtained at the end of the experimental procedure.
  • the nanoparticle size measured by X-ray diffraction and transmission electron microscopy is 9.3 nm and 8.3 nm ⁇ 2.3, respectively.
  • Crystallization and crystallite size can be increased by carrying out a heat treatment of 400 to 700 ° C for 4 hours in air.
  • the crystallites obtained are between 5 and 30 nm in size.
  • the ceria nanoparticles are then functionalized with (3-aminopropyl) triethoxysilane in anhydrous toluene with a cerine / amino-silane ratio of 10/1 (FIG. 2).
  • the amino silane will react by condensation reaction with ceria functionalized with -OH groups. It is important to work in an anhydrous medium so that the amino-silane is not hydrolysed which would cause condensation between the hydrolyzed Ce-OH groups and nanoparticles of different sizes would be obtained. After removal of toluene by centrifugation and washing with ethanol, the nanoparticles are stored in aqueous solution in order to avoid any contamination by the respiratory route.
  • the ASE polymers may for example be constituted of methacrylic acid (AM), of ethyl acrylate (AE) and / or 2,2,2-trifluoroethyl methacrylate (MTFE).
  • AM methacrylic acid
  • AE ethyl acrylate
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • polymers can be synthesized by emulsion polymerization with sodium dodecyl sulfate (SDS) as surfactant and acetone as co-solvent.
  • SDS sodium dodecyl sulfate
  • Two polymers have been synthesized: ASE-H and ASE-F.
  • the synthesis of a polymer before the grafting of the micro- or nanoparticles makes it possible to change the polymer chain according to the application or properties desired for the micro- or nanocomposite.
  • AM relates to the resonance of the proton of the carboxylic acid
  • AE relates to the resonance assigned to the methylene proton of the ethyl ester
  • MTFE relates to the resonance of the methylene proton of the trifluoroethylene ester.
  • the intensity of the AM resonance is normalized to 1000 in each case and the intensities are normalized according to the nominal proton number provided by the resonance.
  • the HASE polymers are synthesized by the same method as for the ASE polymers. They consist of methacrylic acid (AM), ethyl acrylate (AE) and / or 2,2,2-trifluoroethyl methacrylate (MTFE) and a hydrocarbon or fluorinated macromer.
  • AM methacrylic acid
  • AE ethyl acrylate
  • MTFE 2,2,2-trifluoroethyl methacrylate
  • hydrocarbon or fluorinated macromer hydrocarbon or fluorinated macromer.
  • HASE-X-RXn is the reference name of the synthesized polymer.
  • X is the letter H if the ethyl acrylate monomer is used. X corresponds to the letter F (HASE-F-RXn) if the fluorinated monomer is used.
  • RXn varies according to the type of hydrocarbon chain (HASE-X-RHn) or fluorocarbon (HASE-X-RFn) and n varies according to the number of carbon within the macromer.
  • the macromers (MHn or MFn) are not commercial products, they were synthesized by esterification reaction of a polyethylene glycol monomethyl methacrylate on a hydrocarbon carboxylic acid compound or fluorocarbon, as shown in Figure 5.
  • the reaction was catalyzed by the use of a coupling agent, N, N '-dicyclohexylcarbodiiird.de (DCC) in the presence of N, N'-dimethylamino pyridine (DMAP).
  • DCC N, N '-dicyclohexylcarbodiiird.de
  • DMAP N, N'-dimethylamino pyridine
  • the synthesized compounds are obtained with different yields and are characterized by infrared and MR.
  • the synthesized compounds are listed in Table 3 below.
  • the number of PEG monomers, denoted m in FIG. 5, is determined by the integration of the signals in 1 H NMR in the chemical shift domains of 4.39-4.21 ppm (multiplet) and 3.76-3, 64 ppm (multiplet).
  • the starting polyethylene glycol monomethyl methacrylate used being commercial and polydisperse, the chromatographic column made it possible to separate the various monomers.
  • the yields of the monomers that were used in the synthesis of the polymers are given in Table 3.
  • the HASE polymers were then synthesized according to the same emulsion polymerization process as the ASE polymers. These polymers are therefore synthesized by emulsion polymerization with sodium dodecyl sulfate (SDS) as surfactant and acetone as co-solvent. Two polymers were synthesized: HASE-H and HASE-F.
  • the polymers obtained are purified by dialysis (4000-6000 Da) and then characterized by IR, NMR3 ⁇ 4 and 19F.
  • the synthesized polymers as well as the molar composition calculated by R ⁇ H are listed in Table 5 below:
  • AM relates to the resonance of the proton of the carboxylic acid
  • AE relates to the resonance assigned to the methylene proton of the ethyl ester
  • MTFE relates to the methylene proton resonance of the trifluoroethylene ester
  • MHn relates to the proton resonance of the ethoxylated units except the four alpha protons of the two esters.
  • the intensity of the AM resonance is normalized to 1000 in each case and the intensities are normalized according to the nominal proton number provided by the resonance.
  • the various polymers synthesized underwent different analyzes (rheological, by dynamic scattering of the light, %) as well as goniometry analyzes.
  • FIG. 6 illustrates the contact angles with olive oil on the polymers previously deposited on a glass plate.
  • the most viscous polymer in the initial state is the one that has the best contact angle with olive oil, that is to say the HASE-F-RF8 polymer.
  • this last feature is very important because the toxic does not adhere, or very little, to the surface of the topical.
  • the HASE-F-RF8 polymer was chosen as the preferred polymer for further experiments.
  • the polymer HASE-H-RH8 has also been studied in order to carry out certain analyzes and for a comparison with its fluorocarbon counterpart HASE-F-RF8.
  • EDC EDC
  • NHS N-hydroxysuccinimide
  • the nanoparticles (0.13 equivalents of amino functions with respect to the acid functions of the polymer) previously dispersed in the aqueous phase are added and the reaction is continued for 5 days at room temperature.
  • the reaction medium is then purified by dialysis (MWCO: 4000-6000 Da).
  • the product obtained is denoted HASE-F-RF8 (13.5%) / Ce.
  • the compounds were introduced into the BariedermTech TM cream sold by Uriage TM.
  • test compounds formulated in these creams were HASE-F-RF8 (3.3 mol% of macromers) / If (0.3 eq); HASE-F-RF8 (13.5 mol% macromers) / Si (0.3 eq); HASE-F-RF8 (3.3 mol% macromers) / TiO2 (0.3 eq); HASE-F-RF8 (3.3 mol% macromers) / CeO2 (0.02 eq).
  • Fomblin TM is a perfluoropolyether (perfluorinated oil) that plays two roles. The first is to increase the hydrophobicity and oleophobia of the medium and the second is to thin the gel. This second property has been very useful because at high polymer content, the gel has an elastic appearance and can not be properly spread.
  • the formula presented in Table 10 above is that which makes it possible to obtain a viscous gel with good spreading on the skin and a pH of between 7.30 and 7.50.
  • the gels showing the most interest and the best spreading properties are those containing the compounds: HASE-F-RF8 (13.5 mol% of macromers) / Ce (0.13 eq), and
  • the Applicant was therefore interested in the influence of the polymer / nanoparticle and Fomblin® compounds in the hydrophobic gel.
  • the white gel is oleophilic and has a contact angle less than that of the membrane alone.
  • gel 2 where the polymer / nanoparticle compound has been introduced, a increase of the contact angle.
  • the polymer / nanoparticle compound therefore has a positive influence because it reduces the oleophilicity of the gel.
  • Fomblin TM almost makes it possible to obtain an oleophobic gel and shows its influence on oleophobia but also its protective effect.
  • the purpose of this experiment is to determine the protective potential of a topical protector according to the invention by kinetics of penetration on semipermeable membranes, vis-à-vis organophosphorus compounds such as O-ethyl-O- ( ethyl nitro-4-phenyl) phosphonate (paraoxon or POX).
  • organophosphorus compounds such as O-ethyl-O- ( ethyl nitro-4-phenyl) phosphonate (paraoxon or POX).
  • the synthetic membrane used is a silicone membrane (polydirrtethylsiloxane) with a thickness of 400 + 100 ⁇ m marketed by Samco Silicone Products (Nuneaton, UK).
  • the membrane is cut into discs of about 10 cm 2 .
  • the penetration test was carried out on glass type Franz static diffusion cells (cells manufactured by a glassmaker: Laboratoires VERRE LABO-MULA, Corbas, France).
  • the receiving medium is filled with Hank's Balance Solution Solution (HBSS).
  • HBSS Hank's Balance Solution Solution
  • the topical protector according to the invention is applied at a rate of 5 mg / cm 2 , distributed using a flexible silicone spatula.
  • the membrane is then deposited on the receiving compartment.
  • a Teflon TM seal is added on.
  • the membrane and the cell is closed by the donor compartment leaving an exposure area of the membrane of 1, 13 cm 2 .
  • the cell is placed on a cell holder disposed in a water bath, then a screw is added to allow good contact between the membrane and the receiving medium.
  • the membrane and the gel are equilibrated at temperature for 20 min.
  • the water bath is set at 38 ° C to obtain a temperature of 32 ° C ⁇ 1 ° C on the surface of the membranes.
  • the toxic is deposited in the center of the membrane as a drop.
  • the amount of paraoxon (POX) deposited is 5 mg / cm 2 or 4.9uL.
  • Samples of 400 are made in the sampling elbow every 1:30 min for the POX. Once the samples have been taken, an identical volume of HBSS is added in order to keep the amount of receiving medium constant. All samples are kept in the freezer at -20 ° C.
  • the method used is an enzymatic determination of the toxic.
  • This assay method is an indirect method for assaying the activity of an enzyme in the presence of paraoxon (POX).
  • POX paraoxon
  • the concentration of paraoxon in the sample is determined according to a well-defined concentration range and is proportional to the degree of inhibition of the enzyme (butyrylcholinesterase) which has been added in known amount in each sample.
  • Example 8 Example of compounds according to the invention
  • FIG. 11 represents a general diagram of compounds according to the invention making it possible to obtain a new technology protection.
  • FIG. 11 represents a general diagram of compounds according to the invention making it possible to obtain a new technology protection.
  • FIG. 11 represents a general diagram of compounds according to the invention making it possible to obtain a new technology protection.
  • FIG. 11 represents a general diagram of compounds according to the invention making it possible to obtain a new technology protection.
  • FIG. 11 represents a general diagram of compounds according to the invention making it possible to obtain a new technology protection.
  • the groups 3 ⁇ 4 correspond, for example, to hydrogen atoms or to alkyl groups having from 1 to 4 carbon atoms;
  • the groups R 2 correspond to groups CnX n + 1 where X represents a hydrogen or fluorine atom and n is between 1 and 9;
  • the groups R 3 correspond to a hydrocarbon or fluorocarbon chain C n X n + 1 in which X represents a hydrogen or fluorine atom and n is between 4 and 8;
  • the balls or circles represent micro- or nanoparticles of ceria (CeCfe), having a nominal diameter of between 1 and 1500 nm.
  • the active principles are the compounds according to the invention, that is to say ceria graft polymers, integrated at least 9% in the formulation.
  • the ingredients include film-forming agents and deters. They are selected after studying their compatibility with the polymer, their oleophobic / oleophilic potential and their use protocol (% and integration).
  • the active ingredients are embedded in distilled water (aqueous phase) and are stirred overnight using a magnetic bar and a stirring plate. The following day the formulas are neutralized to pH 7 using IN sodium hydroxide. The ingredients are then added by squeezing by hand with a spatula.
  • CM14 finally contains 13% of polymer-cerine, 3.7% glycerin, 28.4% of IN sodium hydroxide and the remainder of distilled water (54.9%).
  • the deposits are homogeneous and film-forming.
  • Tests are performed on silicone membranes (7.3cm 2 ) mounted in Franz cells. About 200 mg of formulas are applied (27 mg / cm 2 ) and dried (about 1 to 3 hours). After complete drying, the membranes are mounted in Franz cells (HBSS receptor medium) and 4.9 ⁇ l of paraoxon is applied to the center. Each hour, 400 ⁇ l of receiving medium is taken for six hours. In addition, after 6 hours (fina T i) amounts remained on the surface and in the formula are also recovered.
  • the cumulative amount of recovered toxin is expressed as a percentage of the initial dose applied (% Q0) and its evolution is graphed as a function of time.
  • the maximum absorption rate or maximum flux (Jmax) is given by the slope of the curve (trend line) obtained when the penetration speed becomes constant and maximum. The intersection of this slope with the abscissa axis corresponds to the latency time ( ⁇ ).
  • tests are compared to the control membranes (without protection) of the experiment (for each test, a control is carried out).
  • a barrier cream is considered effective if the penetration time of the toxin through the skin is extended (latency ⁇ greater) and if its penetration rate is decreased (Jmax lower).
  • the Applicant has been able to demonstrate that the CM14 formulation significantly reduces the penetration of the paraoxon.
  • the main penetration parameters are shown in the table below.
  • CM14 formulation comprising 13% of the polymer-ceria compound according to the invention, combined with 3.7% glycerin makes it possible to obtain a formulation having a homogeneous and film-forming deposit and preserving the protective properties of the polymer-ceria active ingredients.

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EP14758589.7A 2013-07-18 2014-07-18 Polymerisierte ceriumoxidnanopartikel in einem aktiven oder bioaktiven netzwerk, schützende topische behandlungen, verfahren zur herstellung und verwendungen davon Withdrawn EP3022214A1 (de)

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FR1301712A FR3008700B1 (fr) 2013-07-18 2013-07-18 Nanoparticules de cerine polymerisees en reseau actif ou bioactif, topiques projecteurs, leurs procedes de preparation et leurs utilisations
PCT/FR2014/000167 WO2015007961A1 (fr) 2013-07-18 2014-07-18 Nanoparticules de cerine polymerisees en reseau actif ou bioactif, topiques protecteurs, leurs procedes de preparation et leurs utilisations

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Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0299974A (ja) 1988-10-06 1990-04-11 Daikin Ind Ltd 静電荷現像用キャリアー
JPH05323678A (ja) 1992-05-25 1993-12-07 Daikin Ind Ltd 静電像現像用キャリアー
US5607979A (en) 1995-05-30 1997-03-04 The United States Of America As Represented By The Secretary Of The Army Topical skin protectants
GB2314020B (en) 1996-06-13 2000-12-20 Secr Defence Use of perfluoro compounds in a topical barrier cream
US6599631B2 (en) 2001-01-26 2003-07-29 Nanogram Corporation Polymer-inorganic particle composites
US7226966B2 (en) 2001-08-03 2007-06-05 Nanogram Corporation Structures incorporating polymer-inorganic particle blends
FR2780275B1 (fr) * 1998-06-25 2000-08-04 Oreal Produit de maquillage associant un pigment photochrome et un filtre u.v, ses utilisations
US7282470B2 (en) 2002-07-19 2007-10-16 Sandia Corporation Decontamination formulation with sorbent additive
JP2004331883A (ja) 2003-05-09 2004-11-25 Nissan Motor Co Ltd 複合樹脂組成物中間体、複合樹脂組成物、複合樹脂組成物中間体の製造方法、及び複合樹脂組成物の製造方法
FR2885367B1 (fr) 2005-05-03 2007-07-27 Rhodia Chimie Sa Organosol stabilise par des polymeres sequences amphiphiles
US8333993B1 (en) * 2006-12-29 2012-12-18 University Of Central Florida Research Foundation, Inc. Synthesis of polymer coated ceria nanoparticles for biomedical applications
JP5159246B2 (ja) * 2007-10-25 2013-03-06 富士フイルム株式会社 インク組成物、これを用いた画像形成方法および画像記録物
JP4701409B2 (ja) * 2008-12-26 2011-06-15 独立行政法人産業技術総合研究所 コアシェル型酸化セリウムポリマーハイブリッドナノ粒子及びその分散液の製造方法
JP4682368B2 (ja) 2009-08-11 2011-05-11 独立行政法人産業技術総合研究所 球状コアシェル型酸化セリウム／高分子ハイブリッドナノ粒子の集積体及びその製造方法
US20120213854A1 (en) 2010-09-30 2012-08-23 Fetzer Oliver S Methods of treating a subject and related particles, polymers and compositions
EP2694015B1 (de) * 2011-04-05 2017-07-19 Akzo Nobel Chemicals International B.V. Gepfropfte partikel zur verwendung in hautpflegeanwendungen
KR101239262B1 (ko) * 2011-04-27 2013-03-06 고려대학교 산학협력단 마이크로에멀젼을 이용하는 이산화규소-이산화세륨 코어-쉘 나노입자의 제조방법
US20140147726A1 (en) 2011-07-06 2014-05-29 Zeon Corporation Porous membrane for secondary battery, separator for secondary battery, and secondary battery

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
A ZENERINO: "Nanoparticules polymerisées en réseau actif ou bioactif pour la protection ou la décontamination", DOCTEUR EN SCIENCES DE L'UNIVERISTÉ DE NICE-SOPHIA ANTIPOLIS, 1 October 2012 (2012-10-01), pages 1 - 195, XP055578281 *
C BIGNON: "Nanoparticules en reseau pour la protection cutanee", THESE, 10 November 2015 (2015-11-10), pages 1 - 2, XP055499896, Retrieved from the Internet <URL:www> [retrieved on 20180815] *
CLÉMENT LAURA ET AL: "Toxicity assessment of silica nanoparticles, functionalised silica nanoparticles, and HASE-grafted silica nanoparticles", SCIENCE OF THE TOTAL ENVIRONMENT, vol. 450, 5 March 2013 (2013-03-05), pages 120 - 128, XP028596457, ISSN: 0048-9697, DOI: 10.1016/J.SCITOTENV.2013.01.042 *
See also references of WO2015007961A1 *
ZENERINO ARNAUD ET AL: "Homogeneous dispersion of SiO2nanoparticles in an hydrosoluble polymeric network", REACTIVE AND FUNCTIONAL POLYMERS, ELSEVIER, AMSTERDAM, NL, vol. 73, no. 8, 20 April 2013 (2013-04-20), pages 1065 - 1071, XP028574648, ISSN: 1381-5148, DOI: 10.1016/J.REACTFUNCTPOLYM.2013.04.004 *

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US20160152832A1 (en) 2016-06-02
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JP2016532678A (ja) 2016-10-20
FR3008700B1 (fr) 2015-08-14

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