EP3022214A1

EP3022214A1 - Polymerised cerium oxide nanoparticles in an active or bioactive network, protective topical treatments, methods for preparation thereof and uses thereof

Info

Publication number: EP3022214A1
Application number: EP14758589.7A
Authority: EP
Inventors: Sonia AMIGONI; Denis Josse; Thierry Devers; Arnaud ZENERINO; Frédéric GUITTARD; Elisabeth TAFFIN DE GIVENCHY; Cécile BIGNON
Original assignee: Centre National de la Recherche Scientifique CNRS; Universite dOrleans; Universite de Nice Sophia Antipolis UNSA
Current assignee: Centre National de la Recherche Scientifique CNRS; Universite dOrleans; Universite de Nice Sophia Antipolis UNSA
Priority date: 2013-07-18
Filing date: 2014-07-18
Publication date: 2016-05-25
Also published as: JP2016532678A; FR3008700B1; US10155869B2; US20160152832A1; FR3008700A1; WO2015007961A1

Abstract

The invention concerns a compound formed by functionalized micro- or nanoparticles associated covalently with rheology-modifying polymers. The invention is characterized in that the functionalized micro- or nanoparticles are functionalized micro- or nanoparticles of cerium oxide (CeO₂) having a nominal diameter of between 1 and 1500 nm. The rheology-adapting or -modifying polymers are selected from among non-associative or associative polymers. The invention is used in skin protection or decontamination.

Description

ACTIVE OR BIOACTIVE NETWORK POLYMERIZED CERAMIC NANOPARTICLES, TOPICAL PROTECTORS, PROCESSES FOR THEIR PREPARATION AND USES THEREOF

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.

Since chemical terrorism and bioterrorism have existed, many reflections to protect human beings have been initiated. During interventions, for example after an act of terrorism or during the use of poisons by soldiers, the wearing of protective clothing is mandatory. This type of outfit should also be used in agricultural and some industries. Indeed, the use of dangerous pesticides for example can contaminate the body and cause significant injury or death of the user. The major problem of protective clothing is that it involves a modification of the operational capabilities of the workers and a reduction of their sensory abilities (vision, hearing, manual dexterity ...). In others, they quickly have limits of use since they can be poorly adjusted or torn and thus expose the skin to toxic.

For all the above reasons, it is necessary to find new ways of protecting all or a large part of their abilities for their users. Before defining what these means of protection are, it is important to identify the agents of risk, as well as their properties and their mode of penetration into the skin.

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.

Today there is mainly an interest in the protection against vesicants and organophosphorus compounds which represent the main chemical threat. The vesicant agents are mainly represented by sulfur or nitrogen yperites and more modestly by lewisite and phosgene oxime. Organophosphorus compounds (COPs) include pesticides (POPs) and organophosphorus neurotoxins (NOPs). POPs are most often phosphates or phosphorothioates, containing O, O-dimethyl or O-diethyl substituents on the phosphorus atom. They are generally indirect inhibitors of cholinesterases that is to say that they become active only after metabolic transformation: S-oxidation of the P = S bond. This results in greater latency between exposure and the appearance of signs of intoxication. 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.

Thus, the best way to prevent the percutaneous toxicity of chemical agents is to never allow them to come into contact with the skin.

As previously stated, the prevention of skin contamination is mainly achieved by wearing protective gear such as coveralls, masks or gloves. However, there may remain areas of exposure to these agents, during movement of the human being or lack of protection, for example if the protective equipment is poorly adjusted or inappropriate.

Moreover, a transfer of contamination on the skin is also possible during the undressing phase.

There is therefore a need to develop other means of protection which are both well tolerated by their user, which are easy to use, resistant to the external environment and do not interfere with the wearer.

For this, the use of 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.

The majority of products sold under the term "protective topicals" (TP) includes both simply emollient cosmetic products and formulations that can potentially exert a barrier function against aggressive chemicals. These topics are intended for use in risky environments. Protective topics are related to home or professional use. They can thus be used:

- to prevent contact allergy to many metals including nickel, cobalt, chromium, palladium and gold;

- as sunscreens for UVZ and UVB filtration;

- as insect repellents;

- for chemical protection against acids, bases, surfactants and organic solvents.

Protective topicals based on perfluorinated compounds are good means of protecting the body and allow a certain ease of use. Such topics are, in particular, described in the document Zhang J.; Smith EW; Surber C.; Galenical principles in skin protection, Curr. Problem. Dermtol., 2007, 34, 11-18; as well as in US 5,607,979 and GB 2,314,020.

However, such topicals do not degrade the contaminants and their protective effect is limited especially in case of exposure to the vapors of chemical agents.

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).

Their protective efficacy is partially established and not optimized due in particular to the agglomeration of micro- and / or nanoparticles.

There is therefore a need to develop new protective topicals that are more effective, less or not toxic, easy to implement and that have a broad spectrum of action against biological and / or chemical risk agents. Preferably, such protective topical agents make it possible to destroy the biological and / or chemical risk agents. Thus, these agents do not penetrate the skin of the individual.

In addition, such topics should ideally be implemented by simple, fast and low cost methods and should have a homogeneous formulation.

In this context, 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.

Surprisingly, 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.

It also has for third object a compound or a protective topical according to the invention as a medicament.

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:

mixing a coupling agent with a catalyst;

adding the mixture obtained to a solution of modifying polymers or rheology adapters chosen from non-associative polymers or associative polymers, in water;

stirring the reaction mixture;

addition of functionalised micro- or nanoparticles of ceria ^* (CeO2) having a nominal diameter of between 5 and 1500 nm, previously dispersed in aqueous phase, to the reaction mixture;

purification of the reaction medium by dialysis; and

recovering the compound formed by one or more amino functionalized microparticles or nanoparticles covalently associated with one or more rheology modifying polymers.

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.

The invention will be better understood on reading the nonlimiting description which follows, written with reference to the appended drawings, in which:

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

HASE;

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

(13.5 mol% macromer) / Ce and HASE-F-RF8 (13.5 mol% macromer) with respect to transmembrane penetration of paraoxon;

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;

- Figure 11 shows a possible general structure of compound according to the invention to obtain a new technology protection; and

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 <¾), having a nominal diameter of between 1 and 1500 nm;

According to the invention, 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.

Preferably, 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.

The 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.

According to one. preferred embodiment of the invention, the micro- or nanoparticles of ceria or cerium dioxide (Ce (½) 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:

Step 2: condensation:

• Oxidation: M '-OH + M' -OR '- M'-O-M' + R'OH

where 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.

Olation: M '-OH + HO-M' -> M '(ΟΗ) 2'

where M 'represents cerium.

The gel corresponds to the formation of a three-dimensional network of Van der Waals bonds.

The micro- or nanoparticles that can be used according to the invention preferably have a mean nominal diameter of between 1 and 1500 nm.

Advantageously, the ceria micro- or nanoparticles (CeCte) have a mean nominal diameter of between 1 and 300 nm. Preferably, their average nominal diameter is between 5 and 150 nm. More preferably, their mean nominal diameter is between 8 and 10 nm.

The micro- or nanoparticles may be functionalized for example by primary or secondary amine functional groups, epoxy functions, alcohol functional groups and thiol functions.

Preferably, ceria micro- or nanoparticles (CeCfe) are functionalized amine.

A general diagram of the amino functionalization of the micro- or nanoparticles is illustrated in FIG.

The detail of synthesis routes of ceria nanoparticles is described in Example 1.

Preferably, 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 Preferably, 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.

As has been described previously, the 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.

These are hydrocarbon or fluorocarbon polymers synthesized for example by emulsion polymerization.

They are then characterized by infrared (IR) by KBr pellet method, goniometry during dry deposition on glass surface, but also in nuclear magnetic resonance (NMR) solution and rheology. The polymers according to the invention also contribute to the stability of protective formulations or topicals.

The polymers that can be used belong to two different classes: non-associative polymers and associative polymers.

The 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.

They are generally synthesized by emulsion polymerization in acidic aqueous medium (pH less than 4) and are obtained in the form of a colloidal suspension of polymers (or synthetic latexes). The acid functions of the copolymer are ionized in a basic medium which causes the solubilization and swelling of the polymer (increase in hydrodynamic volume). The ethyl acrylate groups are sufficiently blocked to induce hydrophobic associations between polymer chains and to increase the viscosity. In addition, 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).

Preferably, the non-associative polymers ASE-H correspond to the following general formula (I):

(I)

in which :

- 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-;

or

R3 represents [Q] d2-oi, wherein:

• d2 is 0 or 1;

• 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 ;

-CM; -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, and wherein the indices a and b are integers, identical or different, greater than 1. Preferably, a is between 1 and 10,000 and b is between 1 and 20000.

Throughout the description, 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. Of course, the 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 Π / WV u I

11

More preferably, the ASE hydrocarbon chain polymers (ASE-H) include acrylic and / or methacrylic acid monomers and C 1 -C 4 alkyl acrylates.

Advantageously, the ASE hydrocarbon chain polymers (ASE-H) comprise:

from 5 to 50 mol% of acrylic and / or methacrylic acid;

from 50 to 95 mol% of C1-C4 alkyl acrylates.

More preferably, the ASE-H polymers comprise the following monomers:

from 10 to 20 mol% of methacrylic acid (AM);

from 80 to 90 mol% of ethyl acrylate (AE).

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.

As indicated above, the non-associative ASE polymers according to the invention may also comprise a fluorocarbon chain (ASE-F).

Preferably, the non-associative polymers ASE-F have the following general formula (II):

(II)

in which :

- 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-;

or

R3 represents [Q] d2-a, wherein:

• d2 is 0 or 1;

• Q is -C (O) -O or -C (O) -NH-; and

-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 - (C¾) 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.

These ASE-F polymers are preferably composed of monomers:

methacrylic acid (AM),

of 2,2,2-trifluoroethyl methacrylate (MTFE) or of trifluoroethyl acrylate or of 2-perfluorobutylethyl acrylate or of 2-perfluorohexylethyl acrylate or of 2-perfluorooctylethyl acrylate; and

from C1-C4 alkyl acrylate, preferentially ethyl acrylate

(AE).

The introduction of a fluorocarbon chain makes it possible, for a cosmetic or pharmaceutical use, to reduce the adsorption of toxic substances on the surface.

Preferably, the ASE fluorocarbon chain polymers (ASE-F) are composed of the following monomers:

from 20 to 75 mol% of acrylic and / or methacrylic acid;

from 0 to 30 mol% of C1-C4 alkyl acrylates; and

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.

More preferably, the fluorocarbon chain ASE polymers (ASE) include methacrylic acid (MA), ethyl acrylate (AE), and 2,2,2-trifluoroethyl methacrylate (MTFE) monomers.

Advantageously, the ASE hydrocarbon chain polymers (ASE-F) comprise:

from 50 to 60 mol% of methacrylic acid (AM);

from 5 to 15 mol% of ethyl acrylate (AE); and

from 30 to 40 mol% of 2,2,2-trifluoroethyl methacrylate (MTFE).

More preferably still, the ASE fluorocarbon chain polymers (ASE-F) 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. Preferably, 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.

To date, three types of different associative polymers, usable according to the invention, are marketed, these are:

hydrophobic ethylene oxide-urethane-based urethanes (HEUR);

cellulose derivatives; and

- emulsions which can swell in an alkaline medium modified to make them hydrophobic or "hydrophobically modified alkaliswellable emulsions" (HASE).

These three types of polymers are classified into two categories of associative polymers according to their molecular architecture:

1. polymers called telechelic; or

2. comb-type polymers.

The schematic representation of telechelic and comb type compounds is illustrated in FIG. 1. Telechelic polymers (HEUR) are linear chains of polymers containing hydrophobic groups at the end of the chain. Comb type polymers (cellulose derivatives and HASE 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.

Like the ASE polymers, 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.

At basic pH, 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.

The use of a strong base (NaOH) for the neutralization of a HASE polymer causes the degradation thereof after a period of four weeks (pH = 9.5). The use of a weak organic base (1-amino-1- methylpropanol) induces stability of the rheological properties of the solution for six weeks (pH = 9.5).

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.

Finally, the addition of 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.

Preferably, 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:

(III)

in which :

- RI, 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-; and

When X is a hydrogen atom, then p is 0;

When X is a fluorine atom, then p is between 1 and 12;

or

R5 represents [Q] d2 ~ a, wherein:

• d2 is 0 or 1;

• Q is -C (O) -O or -C (O) -NH-; and

-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; 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

When X is a hydrogen atom, then p is 0;

When X is a fluorine atom, then p is between 1 and 12;

and wherein the 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 0 to 10000 and c is 1 to 5000.

Preferably, 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 ):

CH ₂ = CH (CH ₃ ) -C (O) (OC ₂ CH ₂ ) qOC (O) (CH ₂ ) --H

(IV)

in which q denotes a number between 5 and 10 and n is between 6 and 30 carbon atoms.

More preferably, 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):

(V)

in which :

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:

from 5 to 85 mol% of methacrylic acid (AM);

from 5 to 60 mol% of ethyl acrylate (AE); and

from 1 to 90 mol% of a macromer which is an ester of general formula (IV) defined above.

The particularly preferred HASE-H-RH polymers have the formula (V) above, and are such that:

q is equivalent to 7 and n is equal to 6 carbon atoms (hereinafter referred to as HASE-H-RH4 polymer);

q is equivalent to 7 and n is equal to 8 carbon atoms (hereinafter referred to as HASE-H-RH6 polymer);

q is 9 and n is 10 carbon atoms (hereinafter referred to as HASE-H-RH8 polymer).

Alternatively, according to the invention, 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):

(VI)

in which :

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.

More preferably, the HASE-F-RH polymers have the general formula (VI) above and include:

from 30 to 85 mol% of methacrylic acid (AM); from 0 to 50 mol% of 2,2,2-trifluoroethyl methacrylate (MTFE); and

from 1 to 90 mol% of a macromer which is an ester of general formula (IV).

The particularly preferred HASE-F-RH polymers have the formula (VI) above, and are such that:

q is equivalent to 7 and n is equal to 6 carbon atoms (hereinafter referred to as HASE-F-RH4 polymer);

q is equivalent to 7 and n is equal to 8 carbon atoms (hereinafter referred to as HASE-F-RH6 polymer);

q is equivalent to 9 and n is equal to 10 carbon atoms (hereinafter referred to as HASE-F-RH8 polymer).

Advantageously, 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.

By thus modifying its backbone with fluorocarbon macromers, 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.

The structure of such HASE fluorinated-chain polymers (HASE-F), also usable according to the invention, corresponds to the following general formula (VII):

(VII)

in which :

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-; and

When X is a hydrogen atom, then p is 0; When X is a fluorine atom, then p is between 1 and 12; ^{■ ■■} or R5 represents [Q] d2-a, in which:

• d2 is 0 or 1;

• 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; -CH ₂ CH ₂ -N (CH ₃₎ 2; pyrrolidinone, caprolactam;

q represents a number between 1 and 150;

n is an integer from 1 to 30;

p is an integer from 1 to 12;

and wherein the 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.

More preferably, the HASE-F polymers have the following general formula (VIII):

(VIII)

in which :

q denotes a number between 5 and 10;

n is an integer from 1 to 30;

p is an integer from 1 to 12;

More preferably still, the HASE-F polymers correspond to the general formula (VIII) above in which: - q equals 5, 7 or 9;

- n equals 2;

p is 4, 6 or 8; and

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:

from 5 to 85 mol% of methacrylic acid (AM);

from 1 to 70 mol% of 2,2,2-trifluoroethyl methacrylate (FE); and

from 1 to 50 mol% of a macromer which is an ester of general formula (IX):

CH ₂ = CH (C¾) -C (O) (OCH ₂ CH ₂ ) _q OC (O) (CH ₂ ) ₂ - (CF ₂ ) _P F

(IX)

in which :

- q equals 5, 7 or 9; and

- p equals 4, 6 or 8.

The particularly preferred HASE-F polymers have the formula (VIII) above, and are such that:

q equals 5 and p equals 4 (hereinafter referred to as HASE-F-RF4 polymer);

q equals 7 and p equals 6 (hereinafter referred to as HASE-F-RF6 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.

Advantageously, 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)

in which :

- 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-;

or

R3 is [Q] d2 ^_ a wherein:

• d2 is 0 or 1;

• Q is -C (O) -O or -C (O) -NH-; and

-VS ; -CH ₂ CH ₂ -N + (CH ₃₎ ₂ (CH ₂ C0 ₂ ^~); -CH ₂ C¾-NH-C (CH ₃ ) ₃ ; -CH ₂ CH ₂ - N (CH ₃ ) ₂ ; pyrrolidinone; caprolactam;

and wherein the indices a and b are integers, identical or different, greater than 1; or ii) among non-associative polymers ASE-F of general formula (II)

(II)

in which :

- 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-;

or

R3 is [Q] d2 ^_ a wherein:

• d2 is 0 or 1;

• 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;

CH ₂ CH ₂ -N (CH ₃ ) ₂ ; pyrrolidinone; caprolactam;

- R3 'represents [Q] di- (<¾) _η ^_ (¾) ρΧ 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):

(III)

in which :

- RI, 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-; and

When X is a hydrogen atom, then p is 0;

When X is a fluorine atom, then p is between 1 and 12;

or

R5 represents [Q] d2-a, wherein:

• d2 is 0 or 1;

• Q is -C (O) -O or -C (O) -NH-; and

• at. 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 C0 ₂ ^~); -CH ₂ CH ₂ -NH-C (CH ₃ ) ₃ ; -CH ₂ CH ₂ -N (CH ₃ ) ₂ ; pyrrolidinone; caprolactam;

- 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);

When X is a hydrogen atom, then p is 0;

When X is a fluorine atom, then p is between 1 and 12;

In a particularly advantageous manner, the modifying polymers or rheology adapters are chosen from:

the ASE-H polymers which comprise the following monomers:

from 10 to 20 mol% of methacrylic acid (AM);

from 80 to 90 mol% of ethyl acrylate (AE);

or

hydrocarbon chain ASE polymers (ASE-F) which comprise the following monomers:

from 50 to 60 mol% of methacrylic acid (AM);

from 5 to 15 mol% of ethyl acrylate (AE); and

from 30 to 40 mol% of methacrylate, 2,2,2-trifluoroethyl (MTFE);

or

the HASE-H-RH polymers which correspond to the general formula (V) and which comprise:

from 5 to 85 mol% of methacrylic acid (AM);

from 5 to 60 mol% of ethyl acrylate (AE); and

from 1 to 90 mol% of a macromer which is an ester of general formula (IV) defined above;

or

the HASE-F-RH polymers which correspond to the general formula (VI) and which comprise:

from 30 to 85 mol% of methacrylic acid (AM);

from 0 to 50 mol% of 2,2,2-trifluoroethyl methacrylate (MTFE); and

from 1 to 90 mol% of a macromer which is an ester of general formula (IV).

Even more advantageously, the modifying polymers or rheology adapters are chosen from polymers: - ASE-H;

- ASE-F;

- HASE-H-RH4;

- HASE-H-RH6;

- HASE-H-RH8;

- HASE-F-RH4;

- HASE-F-RH6; ^'

- HASE-F-RH8;

- HASE-F-RF4;

- HASE-F-RF6;

- HASE-F-RF8.

By. Moreover, the Applicant has been able to demonstrate, as described in Example 4, that increasing the molar level of hydrocarbon or fluorinated macromers in the HASE polymers makes it possible to increase the viscosity of the polymers.

Also, preferably, 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.

More preferably still, the molar percentage is 13.5 mol% of macromers.

The characterization of all the polymers in rheology and direction finding has made it possible to demonstrate that the HASE-F-RF8 polymers at 3.3%; 13.5% and 45.9 mol% of macromers were particularly preferred in particular for their oleophobia and the viscosity of their solutions.

In a particularly advantageous manner, 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.

In order to obtain an optimal protective effect against toxic agents, it is preferable to obtain a homogeneous dispersion of the micro- or nanoparticles within the polymer matrix, eliminating any aggregation.

In addition, 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.

Preferably, 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.

Examples of grafting of aminated functionalized microparticles or nanoparticles with associative or non-associative polymers are detailed in Example 5.

As described above, prior to the grafting step, 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. To allow this, 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.

According to the invention, 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.

The 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. Advantageously, according to the invention, 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.

It is possible to vary the number of 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).

Preferably, the number of cerine equivalents (Ce (¾)) 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.

According to a particular embodiment of the invention, 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.

As non-limiting examples of 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.

In addition, 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 ™ HC.

The dimethicone and vinyldrmethicone polymer is especially marketed under the trademark Silicone Elastomer Blend DC9041 ™. The copolymer of diethylene glycol, adipic acid and glycerin is in particular marketed under the trademark Lexorez 100 ™. Polysilicone-8 is especially marketed under the trademark Silicones Plus Polymer VS80Dry ™. 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.

Preferably, the topic according to the invention further comprises glycerine.

More preferably, the topic according to the invention comprises between 5 and

20% of a compound according to the invention, preferably 13%; and between Γ and 5% of glycerine, preferably 3.7%, by weight of the total weight of the topical.

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.

According to one particular embodiment, the compounds which are the subject of the invention are introduced into the BariedermTech ™ cream marketed by the company Uriage ™, which contains in particular water, the 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.

Indeed, by acting on the skin barrier, the compound or the protective topical according to the invention has preventive properties with respect to human or animal diseases. Thus, 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.

Indeed, 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.

Thus, 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.

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.

Alternatively, the compounds according to the invention can also find applications such as:

- catalyst;

polishing agent;

- agent for ultraviolet filtration;

- paintings;

- glasses;

- ceramics;

- luminescent materials;

- electronic;

- gas detectors;

- photovoltaic cells;

Oxygen buffers (because they store, release and carry oxygen).

Finally, 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:

mixing a coupling agent with a catalyst; adding the mixture obtained to a solution of modifying polymers or rheology adapters chosen from non-associative polymers or associative polymers, in water;

stirring the reaction mixture;

addition of functionalized micro- or nanoparticles of ceria (Ce ⁽ ¾) having a nominal diameter of between 5 and 1500 nm, previously dispersed in aqueous phase to the reaction mixture;

purification of the reaction medium by dialysis; and recovering the compound formed by one or more amino functionalized micro- or nanoparticles covalently associated with one or more rheology-modifying polymers.

Preferably, the coupling agent is N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride (EDC) and the catalyst is N-hydroxysuccinimide (NHS).

Example 1 Synthesis of Ceria Nanoparticles

The ceria nanoparticles can be synthesized by different methods. Two methods are listed below.

i. Synthesis by the co-precipitation method:

A solution of cerium nitrate (Ce (N (¾) ₃ .6¾0) at 1.15 mol.L- ¹ is mixed with a solution of sodium hydroxide of 5 mol.l ^-1 at room temperature.

A precipitate of cerium (III) hydroxide is then formed instantly according to the reaction:

This (N0 3) 3 + 3NaOH - »Ce (OH) ₃ + 3NaNO ₃

The precipitate of 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.

Thus, the Ce ³⁺ ions are oxidized with hydrogen peroxide according to the reaction:

2Ce (OH) ₃ + H2O2 → 2Ce (OH) ₄

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:

This (OH) -> CeÛ2 + 2Ώ.0

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.

ii. Microwave synthesis

100 ml of a solution of (H ₄ ) 2 Ce (NO ₃ ) 6 at 0.5 mol.L ^-1 are mixed with 100 ml of a solution of sodium hydroxide at 2 mol.l ^-1 and then the mixture is treated with microwaves (Multiwave 3000 Anton Paar). The treatment is summarized in Table 1 below. The setting parameters are: rate at 0.5 bar / s, power of 1200w and maximum pressure of 10 bar.

Table 1: Program for microwave treatment

After centrifugation of the precipitate, ca.

1.5 to 3 nm poorly crystallized. 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.

Example 2 Synthesis of ASE Polymers

As illustrated in FIG. 3, the ASE polymers (ASE-H or ASE-F) may for example be constituted of methacrylic acid (AM), of ethyl acrylate (AE) and / or 2,2,2-trifluoroethyl methacrylate (MTFE).

These polymers can be synthesized by emulsion polymerization with sodium dodecyl sulfate (SDS) as surfactant and acetone as co-solvent. 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.

The introduction of a fluorinated monomer has a consequence on the stability of the emulsion during the polymerization and an increase of the coagulation phenomenon has been observed when the length and the amount of fluorinated monomers increases, inducing a decrease in the conversion efficiencies. . In order to stabilize the system, 1% by weight of acetone is used as a co-solvent. This solvent is known to solubilize fluorinated monomers in emulsions. Yields of 88 and 51% for the ASE-H and ASE-F polymers were obtained after purification by dialysis (4000-6000 Da).

From Table 2 below, it appears that the amount of methacrylic acid (AM) increases significantly upon addition of the fluorinated monomer. This is probably due to the poorer integration of MTFE during the emulsion process. This can be confirmed by the decrease in the yield of the copolymer (51%).

TABLE 2 Composition of polymers ASE-H and ASE-F determined by

In Table 2 above, 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 and 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.

Example 3 Synthesis of HASE Polymers

As illustrated in FIG. 4, 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.

According to Figure 4, 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).

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.

Table 3: Summary of the chains used, the reference of the macromers and the yields of reactions:

String Reference of Number m in Yield (%) macromere macromer

(MXn) (determined by

NMR ¹ !!)

C4H9 MH4 7 11

C6H13 MH6 7 23

C8H17 MH8 9 24

C4F9 MF4 5 27

C6F13 MF6 7 63

C8F17 MF8 7 55

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 composition of the _medium: the polymerization is given in Table 4. The macromer was introduced at 0, 5% by mass.

Table 4: Mass Composition of Olmers

At the end of the polymerization, the polymers obtained, in yields ranging from 52 to 81%, are purified by dialysis (4000-6000 Da) and then characterized by IR, NMR¾ and 19F. The synthesized polymers as well as the molar composition calculated by R ^ H are listed in Table 5 below:

Table 5: Summary of the main polymers synthesized and their molar composition determined by R ^ H:

No. of protons

Resonance Intensity Comp (% mol.)

(nominal)

HASE-H-RH4 m 1 1000 8.5

7AE 2,1071.9 9.1

MH4 24 9694.9 82.4

Resonance Proton No. Comp Intensity (% mol.)

HASE-H-RH6

M 1 1000 64.7

ΑΕ 2,492 31.9

ΜΗ6 24 52.9 3.4

Resonance Proton No. Comp Intensity (% mol.)

HASE-H-RH8

m 1 1000 51.4 m 2 921.4 47.3

MH8 32 24.6 1.3

Resonance Proton No. Comp Intensity (% mol.)

HASE-F-RH4

m 1 1000 78.9

MTFE 2 0 0

MH4 24 266.7 21.1

Resonance Proton No. Comp Intensity (% mol.)

HASE-F-RH6

m 1 1000 63.1

MTFE 2,482.5 30.5

MH6 24 100.9 6.4

Resonance Proton No. Comp Intensity (% mol.)

HASE-F-RH8.

M 1 1000 69.0

MTFE 2,400.1 27.6

MH8 32 49.4 3.4

HASE-F-RF4

m 1 1000 61.4

MTFE 2 41.6 2.6

MF4 16,586.5 36.0

HASE-F-RF6

m 1 1 000 16.0

MTFE 2 4227.6 67.4

MF6 24 1041.5 16.6 HASE-F-RF8

m 1 1000 78.2

MTFE 2,236.8 18.5

MF8 ^■ 24 42.5 3.3

In Table 5 above, 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 and 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.

Also, Table 5 above suggests that the MH4 macromer is incorporated in the polymer more significantly than the others.

The comparison of the different families of polymers, HASE-H-RHn, HASE-F-RHn and HASE-F-RFn, makes it possible to observe that, when the length of the hydrocarbon or fluorocarbon chain constituting the macromer increases, the level of incorporation of the macromer into the polymer decreases.

For AM, AE and MTFE monomers no linear variation in incorporation rate as a function of macromer type and chain length is observed. The DSC analysis made it possible to determine the glass transition temperature (s) of the polymers and the analysis by CES of the polymer mass as well as their polydispersity index. Two HASE polymers were characterized by CES and the results are shown in Table 6 below with polymerization yields.

Table 6:

Polymer Mw (g.mol-i) Tg (° C) Yield (%)

HASE-H-RH8

1,162,632 4.48 54 64

HASE-F-RF8

593 115 1.75 63 70 The differences in the molar mass between the hydrocarbon and fluorocarbon polymers can be explained by the fact that the introduction of fluorinated chains causes the destabilization of the medium during the polymerization process which brings about the creation of shorter polymer chains.

Example 4 Selection of the Preferred Polymer and Modification of the Polymer for Optimization

at. Selection of the preferred polymer:

The various polymers synthesized underwent different analyzes (rheological, by dynamic scattering of the light, ...) as well as goniometry analyzes.

For the realization of. Directional analysis, polymer solutions were spread on a model surface. 2.5 mg of each of the polymers was deposited on a glass plate on about 2-3 cm ² and then the water was evaporated in the open air. Olive oil drops were deposited on the surfaces, which made it possible to determine the oleophilic / oleophobic properties of each polymer.

Three drops of liquid probe of 3 μL were deposited to make an average. The results of this analysis are shown in FIG. 6 which illustrates the contact angles with olive oil on the polymers previously deposited on a glass plate.

Olive oil was chosen because this liquid has a surface tension close to the toxic agents used for the study (γ = 32 m / m at 20 ° C). The water was not used because the polymer being soluble in water, the film would be solubilized and the contact angle obtained would be insignificant.

As shown in Figure 6, except for HASE-H-RH6, upon insertion of a fluorocarbon monomer or chain, the value of the contact angle increases. This is especially noticeable with the polymer HASE-F-RF8 and its hydrocarbon counterpart which has a contact angle of 66 ° against 25 °, respectively. This value is also dependent on the length of the fluorocarbon chain as it can be evidenced by an increase of 10 to 15 ° C when the chain ₈ is introduced compared Fn channels C ₄ F ₈ and C ₆ F _i3. Also, compared to the glass alone, a very small amount of polymer increases the contact angle with olive oil. It can thus be deduced that the HASE-F-RF8 polymer has the best contact angle (Θ = 66 °) compared to other polymers. Taking into account the various analyzes carried out, by grouping rheological and goniometric studies, it has been demonstrated that 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. For an application as topical protector, this last feature is very important because the toxic does not adhere, or very little, to the surface of the topical. As a result, 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.

b. Modification of the preferred polymer:

Since the HASE-F-RF8 polymer with a 3.3% macromeric molar level showed interesting surface (deposition) and rheological properties, the amount of MF8 macromers was increased to increase the amount of fluorinated chain in the medium. . For this purpose two other polymers have been synthesized: one at 13.5% and the other at 45.9% molar macromers. The synthetic route is emulsion polymerization; the quantity of monomers introduced is given in Table 7 below:

Table 7: Mass Composition of the Monomers Introduced During Polymerization

The molar composition of the monomers constituting the polymers, deduced by RM ¹ , is given in Table 8 below:

Table 8:

No. of protons

Resonance Intensity Comp (% mol.)

(nominal)

HASE-F-RF8 (13.5%)

AM 1 1000 41.9 MTFE 2,1061 44.5

MF8 24 322.5 13.5

Resonance No. of protons Intensity Coup (% mol.)

HASE-F-RF8 (45.9%)

m 1 1000 33.8

MTFE 2,600.6 20.3

MF8 24 1361.8 45.9

The direction finding analyzes carried out for these polymers HASE-F-RF8 (13.5 mol% of macromers) and HASE-F-RF8 (45.9 mol% of macromers), which are illustrated in FIG. 7, show that the Increasing the level of macromers does not change the contact angle for 2.5 mg of deposited polymers.

On the other hand, increasing the macromer level from 3.3% to 13.5% molar, increases the viscosity over the entire speed gradient range, as illustrated in Figure 8 which shows the flow curves. for polymers HASE-F-RF8 (3.3%), (13.5%) and (45.9%).

However, the behavior of the copolymer with 45.9 mol% of macromers shows that there is a threshold value from which the amount of macromers no longer improves the rheological properties.

Example 5 Coupling of the ceria nanoparticles with the polymer

N- (3-Dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride

(EDC) (0.15 equivalents relative to the amount of acid functions contained in the polymer) and N-hydroxysuccinimide (NHS) (1/15 equivalents relative to EDC) are mixed and then added to a solution of polymer (1 equivalent of acid functions contained in the polymer) in water. The reaction mixture is stirred for 1 hour at room temperature.

Then, 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.

^'25

Example 6 Introduction of Polymer / Nanoparticle Compounds in Cosmetic Cream and Gel Formulations

at. Formulation in a cream:

The compounds were introduced into the BariedermTech ™ cream sold by Uriage ™. The products were concentrated and then introduced into the cold cream at 10% by weight and at pH = 9. The pH chosen is relatively high compared to the pH of the skin (pH * 5) and it is important not to attack by a basic cream (risk of damage to the skin) but the selected compounds have the best properties towards pH = 9. The 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).

b. Formulation in a gel:

Two types of gels were synthesized, a hydrophilic gel and a hydrophobic gel.

The formulations of the gels are detailed in Table 10 below:

Table 10:

Fomblin ™ 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

- HASE-F-RF8 (13.5%) / Si (0.3 eq).

The Applicant was therefore interested in the influence of the polymer / nanoparticle and Fomblin® compounds in the hydrophobic gel.

For this, a gel without these two compounds (white gel), a gel with the compound HASE-F-RF8 (13.5 mol% of macromers) / Ce (0.13 eq) (gel 2) and a gel with Fomblin ™ and the compound HASE-F-RF8 (13.5 mol% macromers) / Ce (0.13 eq) (gel 3) were formulated. The formulas are shown in Table 11 below:

Table 11:

In order to better compare the effects of the products, 50 mg (~ 5 mg / cm ² ) of each of the gels (gels 1, 2 and 3) was deposited on a 9-10 cm ² silicone membrane with a Parafilm thimble ™. The deposit of the olive oil was made 20 minutes after the spreading of the topical and the measurements were made after one minute of the deposit of the drop. The white gel and the gel 2 spread out with difficulty because they have an elastic behavior. This is not the case for gel 3, which highlights the fluidifying properties of Fomblin ™.

From these experiments, it appears that the white gel is oleophilic and has a contact angle less than that of the membrane alone. Compared to 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. Finally, the addition of Fomblin ™ almost makes it possible to obtain an oleophobic gel and shows its influence on oleophobia but also its protective effect.

Example 7 Efficiency Test of the Pure Product

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).

Synthetic membrane tests:

The synthetic membrane used is a silicone membrane (polydirrtethylsiloxane) with a thickness of 400 + 100 μm 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).

Table 12: Distribution of membranes with respect to products

Treatment :

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 ™ 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 . When the cell is closed, it 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. Finally 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.

Determination of the amount of POX in the receiving media:

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). 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.

The results are shown in Figure 9 where appears the evaluation of the product vis-à-vis the transmembrane penetration of paraoxon. QO represents the percentage of absorbed dose of paraoxon.

It is found that the transmembrane penetration of paraoxon is slowed down and slightly decreased when the membrane is pretreated with the polymer HASE-F-RF8 (13.5 mol% of macromers) and more with the compound HASE-F-RF8 (13.5%). mol% of macromers) / Ce.

To compare the different products with each other, a non-parametric Kruskal-Wallis statistical test that compares the variances of more than two independent samples at t = 6h, followed by a Dunn test that allows the comparison of a sample with a sample. other, made the conclusions about the protective effect of the compounds. The polymer does not have a significant protective effect, whereas the polymer / ceria compound has a significant protective effect on the membrane and the polymer alone.

This highlights the protective effect of the fluorocarbon polymer compound / micro- or nanoparticles synthesized on the transmembrane penetration of POX.

As compared with the polymer / silica nanoparticle compound (FIG. 10), it appears that the compounds HASE-F-RF8 (13.5%) / Ce and HASE-F-RF8 (13.5%) / Si do not show significant difference in their protective effect (non-parametric Kruskal-Wallis statistical test followed by a Dunn test). This is despite the fact that the compound HASE-F-RF8 (13.5%) / Ce has a slightly higher efficiency than the compound with HASE-F-RF8 (13.5%) / Si. By replacing the silica nanoparticles with ceria nanoparticles, the compound has the same protective efficacy but with the toxicity of the silica nanoparticles less.

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. In the diagram of this figure 11:

the groups ¾ 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;

- a, a ', a ", a'", b, b ', b ", c, c' and c", identical or different, are integers, greater than 1; and

the balls or circles represent micro- or nanoparticles of ceria (CeCfe), having a nominal diameter of between 1 and 1500 nm.

Example 9 Introduction of Polymer / Nanoparticle Compounds in Cosmetic Formulations and Efficacy Test of the said Formulations:

The percentages below are expressed by weight of the total weight of the formulation.

at. Formulation:

(I). Active subtances :

The active principles are the compounds according to the invention, that is to say ceria graft polymers, integrated at least 9% in the formulation.

(ii) Ingredients:

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.

After formulation, the film-forming effect and the homogeneity of the formulas is verified.

20Qmg of formulas are spread on glass plate (10cm ² ) and silicone membrane (7.3cm ² ) and the plates are left to dry between 4h and 1 night (about 12h).

Then a visual observation and under the microscope allows to observe the film-forming effect of the ingredients (non-cracking of the formulas) and the homogeneity.

The filmogene and homogeneous formulas are then tested for effectiveness.

Table 13 below shows the major preparation steps and the various components of a formulation according to the invention called "CM14":

Not sure (g)

Mix 1 5.1193 -

P-Ce 16.2% 0 ^ 288 13.0

Water 48.5% 2,4853 39.1

Soda IN 35.3% 13051 28.4

Distilled water 10067 153

Glycerine 0 52 3.7

TOTAL 63612 100

The formulation "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. b. Efficiency tests:

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 μl of paraoxon is applied to the center. Each hour, 400 μl 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 (λ).

The formulas (tests) are compared to the control membranes (without protection) of the experiment (for each test, a control is carried out). The number of replicas is fixed at n = 3 for the first tests, an effective cream will have to be validated on n = 6.

Ideally, a barrier cream is considered effective if the penetration time of the toxin through the skin is extended (latency λ greater) and if its penetration rate is decreased (Jmax lower).

As illustrated in FIG. 12, 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.

Table 14:

In particular, it emerges from these experiences that:

(1) The maximum flow is decreased more than 26 times;

(2) The latency is not measurable for CM14 (point <3 for the trend line); and

(3) The quantity at T = 6h is significantly decreased (9.09% Q0 vs <0.01% Q0)

Thus, the 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.

Claims

A compound formed by functionalized microparticles or nanoparticles covalently associated with rheology modifying polymers, characterized in that:

functionalized microparticles or nanoparticles are functionalised micro- or nanoparticles of ceria (0β (¾), having a nominal diameter of between 1 and 1500 nm;

2. Compound according to claim 1, characterized in that the micro- or nanoparticles are functionalized amine.

3. Compound according to one of the preceding claims, characterized in that the modifying polymers or rheology adapters are chosen:

among non-associative polymers ASE-H of general formula (I) below:

(I)

in which :

- Ri and R2 represent a hydrogen atom or a methyl group -CH ₃ ;

- R3 represents [Q] _d i ~ (CH ₂ ) rrH in which n is between 1 and 30, dl corresponds to 0 or 1, and Q corresponds to -C (O) -O or -C (0) - NH-;

or

R3 represents [0.] & -α, wherein:

• d2 is 0 or 1;

• 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 CO ₂ ^" ); -CH ₂ CH ₂ -NH-C (CH ₃ ) ₃ ; -CH ₂ CH ₂ -N (CH ₃ ) ₂ ; pyrrolidinone; caprolactam; and wherein the indices a and b are integers, identical or different, greater than 1; or

among non-associative polymers ASE-F of general formula (II) below:

(II)

in which :

- R1, R2 and R4 represent a hydrogen atom or a methyl group -CH ₃ ;

- R3 is [Q] _d i ^_ (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-;

or

R3 represents [Q] d2 ^_ o (in which:

• d2 is 0 or 1;

• Q is -C (O) -O or -C (O) -NH-; and

-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;

R 3 'represents [Q] di- (CH ₂ ) _n - (CX ₂ ) _p X wherein n is between 1 and 30, d1 is 0 or 1, Q is -C (O) -O or -C (O) - 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

- Among associative HASE polymers with hydrocarbon chain (HASE-H-RH or HASE-F-RH) or fluorocarbon chain (HASE-F-RF) macromers having the following general formula (III):

(III)

in which :

- RI, R2 and R6 represent a hydrogen atom or a methyl group;

- R5 represents [Q] - (<¾) _η ^_ (CX2) p in which n is between 1 and 30, dl corresponds to 0 or 1, and Q corresponds to -C (O) -O or - C (0) -NH-; and

When X is a hydrogen atom, then p is 0; When X is a fluorine atom, then p is between 1 and 12;

or

R5 represents [Q] d2 ~ oi, wherein:

• d2 is 0 or 1;

· 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; - -VS ; . -CH ₂ CH 2 N + (CH ₃₎ 2 (CH ₂ C02 ^"); -CH ₂ CH ₂ -NH-C (CH ₃₎ _3;

-0¾ <¾-Ν ((Ή ₃ ) 2; pyrrolidinone; caprolactam;

- R7 is - [Q '] CB (OCH ₂ CH ₂₎ _q - [Q'] D4 (CH ₂₎ n (CX ₂₎ pX wherein Q 'corresponds to -C¾, 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 -O-C (0) or -NH-C (O); and

When X is a hydrogen atom, then p is 0;

When X is a fluorine atom, then p is between 1 and 12;

4. Compound according to claim 3, characterized in that the modifying polymers or rheology adapters are chosen from:

- ASE-H;

- ASE-F;

- HASE-H-RH4; HASE-H-RH6

HASE-H-RH8

HASE-F-RH4

H7ASE-F-RH6

HASE-F-RH8

HASE-F-RF4

HZSE-F-RF6 or

HASE-F-RF8.

5. Topical protector comprising a compound according to one of claims 1 to 4, in a pharmaceutically and / or cosmetically acceptable medium.

6. Topical according to claim 5, further comprising one or more detoxifying agents and / or one or more complementary polymers.

7. Topical according to one of claims 5 or 6, characterized in that it further comprises glycerin.

8. Topical according to claim 7, characterized in that it comprises between 5 and 20% of a compound according to one of claims 1 to 4, and between 1 and 5% of glycerin, by weight of the total weight of the topical .

9. Topical according to claim 8, characterized in that it comprises 13% of a compound according to one of claims 1 to 4 and 3.7% glycerin, by weight of the total weight of the topical.

10. Compound according to one of claims 1 to 4 or protective topical according to one of claims 5 to 9, as a drug.

11. Compound or protective topical according to claim 10, for its use in the prevention of cutaneous irritations or allergies.

12. Compound according to one of claims 1 to 4 or topical protective according to one of claims 5 to 9 for its use in the protection or skin decontamination due to biological or chemical hazard agents.

13. Process for synthesizing a compound according to one of claims 1 to 4 comprising the steps of:

stirring of the reaction mixture;

addition of functionalized micro- or nanoparticles of ceria (CeO ₂ ) having a nominal diameter of between 5 and 1500 nm, previously dispersed in aqueous phase to the reaction mixture;

purification of the reaction medium by dialysis; and recovering the compound formed by one or more amino functionalized microparticles or nanoparticles covalently associated with one or more rheology-modifying polymers.