WO2021105637A1

WO2021105637A1 - Microgels and the stimulable photonic and interference applications thereof

Info

Publication number: WO2021105637A1
Application number: PCT/FR2020/052210
Authority: WO
Inventors: Nicolas BENOOT; Kamel CHOUGRANI; Valérie Alard; Laurent Billon
Original assignee: Lvmh Recherche; Universite De Pau Et Du Pays De L'adour; Centre National De La Recherche Scientifique
Priority date: 2019-11-27
Filing date: 2020-11-27
Publication date: 2021-06-03
Also published as: FR3103379B1; FR3103379A1

Abstract

The invention relates to microgels comprising a core coated with a shell: the core comprising a cross-linked organic polymer with a refractive index greater than 1.46, and the shell being obtainable through polymerisation by aqueous phase precipitation of monomers in the presence of a first cross-linking agent, said monomers comprising at least di(ethylene glycol) methyl ether methacrylate, an oligo(ethylene glycol) methyl ether methacrylate and a vinyl monomer comprising a carboxyl group.

Description

Title of the invention: Microgels and their stimulable photonic and interference applications

Technical area

The present invention relates to organic microgels having a core-shell structure, the shell being based on a heat-sensitive polymer of poly (oligo-ethylene glycol) methacrylate. The invention also relates to a process for the synthesis of these microgels, and their use in the cosmetics field.

[0002] The microgels of the invention create original color effects which can be alternative or complementary to those of conventional pigments and dyes. They form cohesive films with a multitude of colors depending on the deformations imposed on them and the angle from which they are observed. Microgels can therefore create dynamic color effects on a person's skin, both at rest and in motion.

Prior art

[0003] Microgels can be prepared from a wide variety of polymers, in organic solvents or in water. Depending on the intended applications, these spherical particles can be obtained from a single material or, on the contrary, have a core-shell architecture.

[0004] The core-shell spheres can be produced by self-assembly of block polymers, by grafting through coupling reactions, or else by seeded emulsion polymerization.

[0005] Thus, a first solution for producing core-shell structures is based on the self-assembly capacities of the polymers by hydrophilic / hydrophobic interactions or by electrostatic interactions. By exploiting the difference in solubility between a hydrophobic polymer and a hydrophilic polymer in water, it is thus possible to synthesize seeds of hydrophilic polymer in a first step, then to synthesize the hydrophobic polymer on the hydrophilic seeds in a second step. As both steps take place in water, a phase inversion takes place within the material at some point, resulting in a structure with a hydrophobic core and a hydrophilic shell.

Another strategy consists in producing these same structures in "one step". In this case, the method involves macro-monomers endowed with hydrophilic chains (PEG, PVP) and hydrophobic monomers (PMMA, PS).

[0008] A final approach consists in producing block copolymers in a controlled manner. The controlled radical polymerization process can be presented as a "living" polymerization in which termination reactions are inhibited in favor of chain propagation reactions. In this case, the block copolymers formed can spontaneously self-assemble into core-shell structures in the dispersed state. However, this synthetic process involves atom transfer radical polymerization (ATRP), which is not suitable for the manufacture of microgels for pharmaceutical or cosmetic applications: the latter require several purification steps to remove traces of complexes. metallic.

[0009] Electrostatic interactions can also be exploited to form multilayer core-shell structures. For example, poly (4-styrene sulfonic acid) is adsorbed onto a positively charged chitosan core. Successive layers are added by alternating addition of negatively charged polymer, such as polyallylamine, and positively charged polymer. The addition of each new layer is then preceded by a filtration and re-dispersion step.

A second method of manufacturing core-shell microgels uses a grafting mechanism through condensation reactions, generally by formation of ester or amide covalent bonds. This path allows you to link cores covalently with molecules exhibiting reactive functions. These molecules can be vinyl monomers as well as macromolecules. For example, PNIPAM cores are designed by controlled radical polymerization in a first step. In a second step, a polyethyleneimine (PEI) shell is grafted onto the cores by condensation of the acid functions of PNIPAM and amines of PEI to create amide bonds. An esterification reaction can also be used to graft double bonds to the surface of the hearts. This synthetic process can be combined with radical polymerization to improve grafting when the bark and the substrate are hydrophilic and hydrophobic, respectively.

Finally, a third process for preparing core / shell microgels is carried out by seeded emulsion polymerization. This process takes at least three stages: the synthesis of the hearts (seeds), their purification, and the grafting of the bark. Certain methods proposed in the prior art use a thermosensitive polymer, such as PNIPAM to synthesize the bark (CN 104759617 A). However, this method has drawbacks. The PNIPAM precursor monomer has the drawback of being toxic, and the seeds must systematically be purified before the grafting step in order to remove the residual amounts of surfactant which risk inhibiting the growth of PNIPAM on the heart.

The synthesis strategies of the prior art for producing core-shell structures can therefore prove to be expensive from an industrial point of view for several reasons: some require the use of macro-monomers, the price of which is relatively low. top, while others include purification steps to remove residual impurities related to the synthesis process. This is particularly the case of microgels with thermosensitive bark for which the purification step is essential to make the seeds operational.

[0013] The perception of color results from an interaction between light and the photoreceptor cells present in the fundus of the eye. In humans, three Cell types are distinguished and absorb visible light differently depending on their size. A distinction is thus made between “s”, “m” or “I” cells, having absorption maxima of 426, 530 and 555 nm respectively. The perception of colors thus results from the stimulation of these cells which varies according to the coloration of the incident light.

There are examples of so-called "physical" colorings in nature, such as the insignia hummingbird or natural mineral opals. These colors come from a specific interaction with light. The light is diffracted around a wavelength specific to the system and produces an iridescent coloration. In a bio-inspired approach, the present invention provides biocompatible organic compounds which generate colors according to this principle.

Several approaches are referenced in the literature for producing colored materials derived from microgels having a core-shell system. For example, in the work of Park et al. {Optical Materials Express 2017, 7 (1), 253), colored self-assemblies are produced from core-bark structures, the polystyrene core of which is coated with a layer of poly (N-isopropylacrylamide) (PNIPAM). The colloidal crystals obtained have the advantage of producing heat-sensitive colorations. However, these crystals are extremely fragile, and only form at the interface between the colloidal dispersion and the glass support. The thermosensitivity of crystals is only possible thanks to the existence of the fluid underlying the crystal which supports its stability. The fragility of the crystals is in particular due to the high glass transition temperature of the constituents of the core-shell system.

In the work of Viel et al. (Chemistry of Materials 2007, 19 (23), 5673-5679) self-assemblies are obtained from materials having a core, an interlayer and a shell. The objects are composed of cross-linked polystyrene coated with cross-linked polymethyl methacrylate (PMMA), covered with a poly (ethyl acrylate) (PEA) bark. While PEA provides flexibility to the final material via its low glass transition temperature, the very structure of the objects is not sufficient to ensure the stability of the colloidal crystals. Indeed, the crystal lattice requires photochemical crosslinking to maintain its stability. Otherwise, the coloring of the films would disappear irreversibly after deformation.

The formation of films from biocompatible and heat-sensitive materials has also been referenced in the literature. For example in the work of Hu et al. (US 2010/076105 A1), microgels based on poly (ethylene glycol methacrylate) (PEGMA) are used to form transparent and biocompatible films. However, the mechanical cohesion of the films is then again ensured by an additional step of photochemical crosslinking to maintain its stability.

The need remains to simplify and make profitable the methods for synthesizing microgels, in particular microgels comprising a heat-sensitive shell. It is desirable to reduce the number of steps and to use inexpensive starting materials. The need also remains to have biocompatible microgels devoid of toxicity which can be synthesized in water. Finally, it is desirable to provide microgel able to create self ^¬ assemblages whose cohesion and mechanical properties are improved.

The invention aims precisely to achieve at least one of these objectives.

General description of the invention

The invention therefore provides microgels comprising a core coated with a shell:

- the core comprising a crosslinked organic polymer whose refractive index is greater than 1.46, and

- the bark being capable of being obtained by polymerization by precipitation in aqueous phase of monomers in the presence of a first crosslinking agent, said monomers comprising at least di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol) methyl methacrylate ether and a vinyl monomer comprising a carboxyl group. The microgels of the invention have many advantages: they are biocompatible and form colored crystalline self-assemblies, cohesive, elastic and resistant to mechanical deformation.

They also have the particularity of forming self-assemblies resistant to mechanical deformation, without carrying out a preliminary step of photo-crosslinking of the material. The toughness of the material results from the entanglement capacities of the bark which allows to result in cohesive colloidal crystals.

The present invention makes it possible to produce films with iridescent colors, and which can be stimulated under the effect of mechanical stress. The colors obtained by diffraction of the film can be controlled according to the thickness of the bark, the size of the core and the difference in refractive index between the two. The accessible shades cover the entire visible spectrum. Moreover, the deformation of the colloidal crystal makes it possible to induce a displacement of the diffracted wavelength, so that the material changes color under deformation.

[0024] In addition, the microgels of the invention are biocompatible. The duration of the synthesis process makes it possible to achieve a complete conversion of the monomers constituting the core and the shell. Additionally, the bark is made from polymers similar to poly (ethylene glycol) (PEG) or poly (ethylene glycol methacrylate) (PEGMA), which are known to be biocompatibility.

The present invention therefore finds particular interest in pharmaceutical and cosmetic applications. Colored biocompatible films endowed with iridescent or opalescent effects can be considered as a new range of tinted cosmetics without pigments or dyes. In addition, the colors obtained change according to the deformations imposed on the film by the movements of the skin, which is itself elastic and deformable. The present invention provides access to a whole new range of “dynamic” cosmetic products.

The microgels of the invention thus have multiple advantages through their accessible synthesis protocol, their innovative optical and mechanical properties and their harmlessness. Description of Figures

Figures IA and IB are images obtained by AFM of microgel films according to the invention.

Figure 2 shows the diffraction curves of the microgels of the invention as a function of the proportion of the shell relative to the core which constitutes them.

FIG. 3 represents the variation of the dominant wavelength of three films of microgels as a function of the relative strain rate of the films.

FIG. 4 represents the absorption spectra of the photoreceptor cells of the eye.

Figures 5A and 5B are atomic force microscopy images taken on the wafer of a film of microgels of the invention. The contrast is expressed as a function of the relative stiffness of the material. A zoom of the microgels of Figure 5A where the "core-bark" structure is apparent with a rigid core (white) and a soft shell (darker) is shown in Figure 5B.

[0032] Figure 6 is a histogram of the values of the diameter of the contracted microgels measured by DLS, the values of the diameter of the dried microgels measured by AFM, and the measurements of the distances between microgels in dry films by AFM.

Figure 7 shows the diffraction curve of a film resulting from the drying of a cosmetic product of the invention.

Detailed description of the invention

Definitions

The expression "between" within the meaning of the invention excludes the digital terminals which succeed it. On the other hand, the expression "ranging from ... to" is intended to include the limits expressed.

By "microgel" is meant within the meaning of the invention particles or a set of spherical particles. The average size of these particles can vary depending on whether or not they contain water. For example, the size of microgels varies from 100 nm to 1000 nm in the dry state (i.e. when the particles contain less than 2% by weight of water). The size of the microgels is preferably from 200 nm to 300 nm. The microgels of the invention can be obtained by copolymerization of several monomers in the aqueous phase.

Microgels within the meaning of the present description can be in the form of an aqueous dispersion of particles or in the form of a film comprising particles. Microgels can encapsulate active organic cosmetic or pharmaceutical molecules. A film comprising microgel particles can have a thickness ranging from 10 microns to 500 microns or from 100 microns to 400 microns.

Microgels

In a particular embodiment, the microgels are preferably devoid of an inorganic material, and are called organic microgels.

According to a first aspect, the invention relates to microgels comprising a core coated with a shell:

- the bark being capable of being obtained by polymerization by precipitation in aqueous phase of monomers in the presence of a first crosslinking agent,

Said monomers comprising at least di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol) methyl ether methacrylate and a vinyl monomer comprising a carboxyl group.

The invention also relates to a composition comprising the microgels, for example a cosmetic product intended to be applied to a part of the body of a person.

Finally, the subject of the invention is a process for synthesizing microgels.

The microgels of the invention comprise particles of core-shell structure each comprising a core consisting of a crosslinked organic polymer coated with a shell.

Heart chemistry The crosslinked organic polymer, the refractive index of which is greater than 1.46, is preferably obtained from at least one vinyl monomer and a second crosslinking agent. The value of the refractive index can be determined by any method known to those skilled in the art.

The vinyl monomer is preferably chosen from vinyl monomers leading to the formation of a polymer whose refractive index is greater than 1.46 and which can be synthesized by free radical emulsion polymerization in which the solvent is water. . This vinyl monomer can be chosen from isobutyl methacrylate, hexyl methacrylate, 3-methoxypropyl acrylate, butyl methacrylate, propyl methacrylate, methyl methacrylate, cyclohexyl methacrylate, 2-chloroethyl methacrylate, 2-bromoethyl methacrylate , 2-phenylethyl methacrylate, chloroprene, phenyl methacrylate, vinyl benzoate, 4-methylstyrene, 2-methylstyrene, benzyl methacrylate, styrene, 4-bromophenyl methacrylate, 2-chlorostyrene, N-benzyl methacrylamide, 2-6-dichlorostyrene. Preferably styrene is used.

The organic polymer is crosslinked using a crosslinking agent called in the remainder of the present description "second crosslinking agent".

In a particular embodiment, a second crosslinking agent is chosen of a chemical nature similar to the first crosslinking agent used to prepare the bark, in particular from oligo (ethylene glycol) di methacrylate comprising from 1 to 10 ethylene units glycol.

According to one embodiment, the crosslinked organic polymer is capable of being obtained by radical emulsion polymerization of the vinyl monomer in the presence of a second crosslinking agent chosen from the group of oligo (ethylene glycol) dimethacrylates of average molecular mass in number ranging from 180 g / mol to 650 g / mol or oligo (ethylene glycol) diacrylate with average molecular mass in number ranging from 200 g / mol to 600 g / mol, the second crosslinking agent possibly being identical or different from the first agent crosslinking.

The second crosslinking agent is preferably ethylene glycol di-methacrylate (EGDMA). The second crosslinking agent can also correspond to one of the following compounds: 1,3-butanediol diacrylate, 1,4-butanediol diacrylate, 1,6-hexanediol diacrylate, pentaerythritol diacrylate monostearate, glycerol 1,3-diglycerolate diacrylate , neopentyl glycol diacrylate, poly (propylene glycol) diacrylate, 1,6-hexanediol ethoxylate diacrylate, trimethylolpropane benzoate diacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol dimethacrylate, 1,6-hexanediol di methacrylate, or glycerol dimethacrylate.

Bark chemistry

The bark is obtainable by polymerization by precipitation in aqueous phase of monomers in the presence of a first crosslinking agent, said monomers comprising at least di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol ) methyl ether methacrylate and a vinyl monomer comprising a carboxyl group.

In a particular embodiment, the bark is capable of being obtained by polymerization by precipitation in aqueous phase of di (ethylene glycol) methyl ether methacrylate, of an oligo (ethylene glycol) methyl ether methacrylate of molecular mass number average ranging from 200 g / mol to 650 g / mol, of (meth) acrylic acid. In this embodiment, the first crosslinking agent can be chosen from oligo (ethylene glycol) diacrylates with a number average molecular weight ranging from 200 g / mol to 600 g / mol.

The vinyl monomer comprising a carboxyl group can be a monomer of formula CR1R2 = CR3R4 in which RI, R2, R3 and R4 represents a hydrogen, a halogen or a hydrocarbon group, at least one of the four groups comprising a -COOH group or -COO-M +, such that M + represents a cation.

The di (ethylene glycol) methyl ether methacrylate represents for example 50 to 90% by moles of the total number of moles of the three monomers, the oligo (ethylene glycol) methyl ether methacrylate preferably represents 10% to 50% by moles of the total number of moles of the three monomers, and the vinyl monomer preferably represents 0.1% to 20% by moles of the total number of moles of the three monomers, the sum of these three contents being equal to 100%. The molar ratio between the di (ethylene glycol) methyl ether methacrylate and the oligo (ethylene glycol) methyl ether methacrylate is preferably between 1: 1 and 20: 1, preferably between 5: 1 to 10: 1 .

The number of moles of vinyl monomer comprising a carboxyl group can be between 0 mol% and 20 mol%, for example ranging from 0.1 mol% to 5 mol% of the total number of moles of the three monomers.

According to one embodiment, the di (ethylene glycol) methyl ether methacrylate represents for example 80% to 90% by moles of the total number of moles of the three monomers, the oligo (ethylene glycol) methyl ether methacrylate preferably represents 5% to 15% by moles of the total number of moles of the monomers and (meth) acrylic acid preferably represents 0.1% to 10% by moles of the total number of moles of the monomers, the sum of these three contents being equal 100%.

The monomer of formula CR1R2 = CR3R4 is preferably such that RI and R2, each represent a hydrogen, R3 represents a hydrogen atom or an alkyl group, preferably C1-C6, optionally substituted by a hydroxyl group - OH or carboxyl -COOH, and R4 represents independently of R3 the carboxyl group -COOH or an alkyl group, preferably C1-C6, substituted by a hydroxyl group -OH or a carboxyl group -COOH, provided that at least one of the four groups comprises a -COOH or -COOM + group, such that M + represents a cation. The alkyl group can be methyl, ethyl or n-butyl. According to a particular embodiment, R1 and R2 each represent a hydrogen and R3 and R4 independently represent -H, -COOH, or -CH2-COOH. The vinyl monomer comprising a carboxyl group may for example be chosen from methacrylic, methyl acrylic, methyl methacrylic, ethyl acrylic, ethyl methacrylic, n-butyl acrylic, n-butyl methacrylic, or itaconic acids.

Acrylic acid can be excluded from the definition of the monomer of formula CR1R2 = CR3R4 in certain cases. According to one embodiment, the vinyl monomer bearing a carboxyl is methacrylic acid or itaconic acid. The first crosslinking agent is preferably chosen from the group consisting of oligo (ethylene glycol) diacrylate with a number average molecular weight ranging from 200 to 600 g / mol or from the group of oligo (ethylene glycol) di methacrylates of number average molecular weight ranging from 180 to 650 g / mol. It is for example chosen from the compounds 1,3-butanediol diacrylate, 1,4-butanediol diacrylate, 1,6-hexanediol diacrylate, pentaerythritol diacrylate monostearate, glycerol 1,3-diglycerolate diacrylate, neopentyl glycol diacrylate, poly (propylene glycol) diacrylate, 1,6-hexanediol ethoxylate diacrylate, trimethylolpropane benzoate diacrylate, ethylene glycol di methacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol di methacrylate, 1,6- hexanediol di methacrylate, glycerol dimethacrylate, N, N divinylbenzene N, N- methylenebisacrylamide, N, N- (1,2-Dihydroxyethylene) bisacrylamide, poly (ethylene glycol) diacrylamide, allyl disulfide, bis (2-methacryloyl) oxyethyl disulfide and N, N- bis (acryloyl) cystamine.

The first crosslinking agent represents, for example, from 1% to 10% by moles of the total number of moles of the three monomers.

In a particular embodiment, the monomers used are preferably oligo (ethylene glycol) methyl ether methacrylate of Mn equal to 475 g.mol-1 and methacrylic acid (MAA). The first crosslinking agent is, for example, oligo (ethylene glycol) diacrylate comprising 4 to 5 ethylene oxide (OEGDA) units with Mn equal to 250 g.mol-1.

Size - Bark thickness - nature of the core polymer

The microgels preferably have an average diameter of between 1 and 1000 nanometers (nm), preferably between 200 nm and 600 nm.

Once the self-assembled microgels in a composition comprising 0 to 50% by weight of water, different colors can be obtained depending on the thickness of the shell and the difference in refractive index between the core and bark. Those skilled in the art will know how to choose the nature of the polymer constituting the core and adjust the thickness of the shell based on poly (oligo-ethylene glycol) methacrylate according to the color and the desired effect. In a particular embodiment, the thickness of the shell is between 10 nm and 200 nm, and more preferably between 25 nm and 80 nm, when the core has an average diameter ranging from 25 nm to 300 nm , preferably from 150 nm to 250 nm.

Process for the synthesis of microgels and dispersions

A second object of the invention relates to a synthesis process used to form core-shell objects whose heat-sensitive properties derive from the biocompatible heat-sensitive material forming the shell. By studying the size of microgels in solution by dynamic light scattering, it is possible to assess the impact of the temperature of the medium on the ability of the microgels to swell or contract in water. The microgels change from a swollen state to a contracted state depending on the temperature. The contraction temperature is noted VPTT (Volume Phase Transition Temperature).

The synthesis of the microgels is preferably carried out entirely in water, in two successive steps. The synthesis protocol is advantageously reduced to two steps in comparison with the methods of the prior art by comprising at least three. The method of the invention comprises the synthesis of the core (seed) then the synthesis of the bark, without an intermediate purification step necessary in the syntheses of microgels of the prior art.

The method has the advantage of being simple to implement and allows obtaining homogeneous core-shell structures while minimizing the formation of poly (oligo-ethylene glycol) methacrylate which is not grafted onto the heart.

The quality of the grafting of the bark on the polymeric core can be optimized by several routes.

For example, a significant improvement in the grafting rate is achieved by controlling the chemical nature of the hearts, and by the synthesis process. Obtaining a high degree of grafting close to 80% by mass can thus be obtained in a very surprising manner in the context of the invention. We hear by grafting rate within the meaning of the invention, the mass of bark actually grafted onto the core relative to the mass of the microgel.

The process for synthesizing microgels comprises two steps. In a first step, we carry out the synthesis of the heart (also called seed), then in a second step, the bark is grafted on the heart.

The process of the invention is preferably a seed polymerization process comprising two successive emulsion polymerization stages. The objects formed during the first polymerization serve as seed on which the bark of the second polymerization grows. The emulsion polymerizations are advantageously carried out in water in the presence of surfactant. Those skilled in the art will know how to adjust the temperature, the stirring speed, the initiator concentration and the surfactant concentration of these two polymerization steps.

The method of the invention makes it possible to produce microgels of different sizes all exhibiting the same degree of grafting. The process of the invention also makes it possible, for the same core, to obtain barks of different thicknesses. This thickness can be modulated by adjusting the relative amount of seed and precursor monomers of the bark. Varying the thickness of the bark thus makes it possible to control the optical properties of the microgels, once they are organized in a colloidal network.

First step: Synthesis of the heart (seed)

In the first polymerization step, the core of the microgels can be prepared by free radical polymerization in emulsion in water of a vinyl monomer, in the presence of a crosslinking agent.

The heart is synthesized by emulsion polymerization, with an ionic surfactant, an initiator, an ethylenically unsaturated monomer, and a second crosslinking agent.

According to a particular embodiment, a dispersion of at least one vinyl monomer and of at least one crosslinking agent is prepared in water in the presence of a surfactant. According to a particular embodiment, the dispersion is prepared by adding the monomer and the crosslinking agent to an aqueous solution of the surfactant, with stirring.

A solution comprising the radical initiator and water is prepared separately, then poured into the preceding dispersion, the reaction temperature preferably being between 40 ° C and 80 ° C, and more preferably between 65 ° C. and 75 ° C.

The surfactant can be sodium dodecyl sulfate (also called sodium lauryl sulfate), sodium docusate or sodium laureth sulfate.

The size of the cores is preferably between 10 nm and 500 nm, and can be controlled according to the concentration of surfactant and of initiator.

The surfactant, the initiator, the monomer and the second crosslinking agent used are respectively preferably sodium dodecylsulphate (SDS), potassium peroxodisulphate (KPS), EGDMA, and styrene (St ). In the context of this protocol, the EGDMA / styrene molar proportion is preferably between 0 mol% and 15 mol%, the SDS concentration is preferably less than 7 mmol.L ¹ and the final solid content of the aqueous dispersion of microgels obtained is preferably between 1% by mass and 15% by mass. The respective concentrations of KPS and SDS are preferably respectively between 0 and 10 mmol.L ¹ and between 0.5 and 1.5 mmol.L ¹ .

The water-soluble radical initiator is chosen from initiators known to those skilled in the art. Potassium peroxodisulfate can be used.

Second step: Synthesis of the bark

In a second polymerization step, the bark is grafted onto the heart prepared in the first step. The bark is preferably synthesized by seeded precipitation polymerization. The seed used is advantageously the dispersion synthesized previously in the first polymerization step, without any treatment. This synthesis step involves an initiator and all the monomers leading to the formation of the biocompatible shell. This second step may consist of i) the preparation of an initial mixture comprising the seed prepared in the first step to which water is optionally added, ii) the preparation of an initiator solution.

According to one embodiment, the adequate mass of seed and of monomers is poured into the reactor. The contents of the reactor are then supplemented with the necessary quantity of water. The oxygen is then removed from the reaction medium, for example by bubbling gaseous nitrogen through the mixture contained in the reactor. The mixture must imperatively be at a temperature between 40 ° C and 90 ° C, preferably at 70 ° C, before the injection of the initiator.

The second polymerization step preferably comprises the injection of the dispersion of monomers and the injection of the reaction initiator solution into a reactor containing the seed. The method of the invention preferably comprises a simultaneous and separate injection of the solution containing the initiator and of the dispersion containing all of the monomers, into the suspension containing the seed, in order to optimize the grafting rate of the. bark on seeds. The injection speed is preferably sufficiently high to optimize the value of the rate of grafting of the bark on the heart.

The level of solid of the final dispersion of the microgels in water is preferably between 1% by mass and 10% by mass.

The proportion of all the monomers used for the shell relative to the final solid content is preferably between 25% by mass and 95% by mass. When the diameter of the core ranges from 150 nm to 250 nm, it is preferred that the proportion of all the monomers used for the shell relative to the level of final solid is preferably between 65% and 90% by weight. Below 65% by mass, the microgel films do not systematically exhibit iridescent colors, and above 90% by mass, the intensity of the colors tends to decrease. Movies

The use of aqueous dispersions of microgels of the core-shell type makes it possible to produce materials, in particular in the form of films, which are endowed with very advantageous properties, both in terms of color and mechanically. This is the first time that dry films have been obtained with physical colors and capable of spontaneously resisting mechanical deformations. The colloidal network of microgels advantageously adapts to mechanical stress without breaking.

The films obtained from the aqueous dispersions of the microgels described above spontaneously generate iridescent colors. These films are mechanically stimulable in the sense that their colors can be modified according to their rate of deformation in elongation.

The invention provides cosmetic or pharmaceutical compositions capable of creating biocompatible microgel films exhibiting different colors without the necessary addition of pigments or dyes.

The perception of the coloring of the films can be increased when they are applied to a dark support. This perception can also be reinforced by adding a black additive. These additives must absorb light from the entire visible spectrum. These additives can be, for example, carbon black or oxides of black irons such as black powders of iron (III) oxide or of iron (II, III) oxide. The black iron oxides have for example an average particle size ranging from 50 nm to 250 nm.

The color of the films of the invention can change according to the thickness of the shell of the microgels, according to their angle of observation but also according to the deformation of the films.

On a microscopic scale, the microgels form colloidal crystals spontaneously exhibiting a high cohesive force. The self-assembly further has the peculiarity of not breaking when the film is stretched, but it deforms. This results in a change in the diffracted wavelength depending on the rate of deformation of the films. The films produced are thus also capable of reversibly changing color under elongation.

The microgel suspensions of the invention make it possible to produce iridescent colored films. These colored films are spontaneously tenacious to mechanical deformations. In addition, the modification of the inter-object distances induced by the deformation of the films causes a modification of the perceived colors, without requiring the crystalline lattice to be fixed by photo-crosslinking for example, as has been proposed in the prior art. The change in color of the films of the invention is obtained by means of a modification of the crystal lattice as a function of the degree of elongation. There is a color change associated with a diffracted wavelength change when the film is deformed. The difference between the frequency of the wave diffracted at an elongation rate equal to 0% and the frequency of the wave diffracted by the film at an elongation rate of 50% can range from 0 to 150 nm. In the film, the inter ^¬ distance object corresponds to the diameter of the objects and ranges from 200 nm to 600 nm.

The strong cohesion of the films obtained is very surprising and opens up new fields of application. Indeed, colloidal crystals are known for the fragility of their assemblies. However, the films of the invention are not only capable of withstanding deformations.

We prefer to use microgels having a grafting rate greater than 60% in order to increase the self-assembly capacities of the core-shell objects. Indeed, the microgel products with a high degree of grafting form self ^¬ regular assemblies as those products at reduced rate of grafting.

They are able to self-assemble into colloidal crystals in the form of films. The films obtained have the particularity of presenting iridescent and mechano-stimulable colors: the films are capable of reversibly changing colors according to their deformation. The colors obtained can be checked according to the synthesis protocol.

Compositions A subject of the invention is also a composition comprising the microgels described above and optionally a black additive. A black additive makes it possible to reinforce the changes of color which one perceives by looking at the composition.

The composition can comprise from 1% to 100% by mass of the microgels. According to one embodiment, the composition comprises from 1% to 50% by mass of microgels relative to the mass of the composition, and from 0.9% to 100% by mass of water relative to the mass of the composition .

The composition can be in the form of a dispersion of the microgels in water.

The composition can also be in the form of a film with a thickness ranging from 1 micron to 10 millimeters comprising from 50% to 100% by mass of microgels, and from 0% to 50% by mass of water. , the percentages being expressed relative to the total mass of the composition. The films can be produced from the dispersion described above by evaporation of the solvent, here water. Deposits on rigid or flexible supports are made at a temperature between 20 ° C and 60 ° C, more preferably at a temperature ranging from 30 ° C to 40 ° C, more preferably equal to 35 ° C.

The composition can be a cosmetic product and comprise at least one compound chosen from the group consisting of preservatives, perfumes, emollients, surfactants, oils, biologically active products, pigments and dyes.

In this case, the black additive can be a black pigment such as carbon black or a black iron oxide such as iron (III) or iron (II, III) oxide. The black iron oxides have for example an average particle size ranging from 50 nm to 250 nm.

It is preferred to use a pigment or a black dye to highlight the changes in color that the microgels may undergo when the cosmetic composition is handled or worn on the body. The skin of the individual to which the cosmetic composition is applied, preferably a makeup composition, may be light or dark. It is advantageously dark.

The core / shell microgel can be integrated into a cosmetic product comprising, for example, a preservative, a perfume and an emollient with a respective proportion of between 0% and 25%, 0% and 25%, and 0% and 50. % relative to the mass of dry extract. The total sum of the additives preferably does not exceed 50% by mass relative to the mass of dry extract.

A particular cosmetic product comprises, for example, comprising a preservative such as phenoxyethanol, a perfume and an emollient such as glycerol with a respective proportion of between 0% and 1%, 0% and 1%, and 0% and 50%. relative to the mass of dry extract.

Another cosmetic product according to the invention contains a dispersion of microgels having an initial solid content of between 2% and 10%, for example between 2% and 6% by mass, preferably between 3% and 5% by weight. mass, the percentages being expressed relative to the mass of the composition.

It is also preferred that the cosmetic compound (s) added to the microgels are liquid at 20 ° C. and atmospheric pressure. In the case where one or more cosmetic compounds are present and are solid at 20 ° C and atmospheric pressure, it is preferred that the total mass of solid cosmetic compounds in the composition is less than 0.1% by mass relative to the dry extract of the composition.

The invention is illustrated in more detail by the examples which follow.

We prepared several heart / bark microgels by playing on several variables:

- the rate of injection of the precursor monomers of the bark into the seed suspension,

- the mass proportion between the heart and the bark, and

- the nature of the crosslinking agent used to prepare the heart.

Examples G01111 Example 1: Core / shell microqels according to the invention with an ethylene qlvcol di-methacrylate (EGDMA) crosslinking agent

1. Preparation of microqels

1.1 Materials used

[0112] Di (ethylene glycol) methyl ether methacrylate (ME02MA, 95%), oligo (ethylene glycol) methyl ether methacrylate (OEGMA Mn = 475g.mol-l), methacrylic acid (MAA), poly (ethylene glycol) diacrylate ( OEGDA, Mn = 250 g.mol- 1), ethylene glycol di-methacrylate (EGDMA), sodium dodecylsulfate (SDS), potassium persulfate (KPS).

1.2 Synthesis of the heart (seed):

Preparation of the initial mixture (water, surfactant, monomer and crosslinking agent) ·.

An aqueous solution of surfactant (SDS) (0.427 g / 5 ml_) is added to 650 ml_ of distilled water in a 1 L reactor. After 5 minutes of stirring, styrene (42.636 g) and a crosslinking agent ( EGDMA) (4.057 g) are added to the surfactant solution. The mixture is stirred at 300 rpm and nitrogen is bubbled through. Then the mixture is heated to 70 ° C. When the temperature is reached, and after at least 45 minutes of degassing, the nitrogen flow has risen to the surface of the mixture.

Preparation of the initiator solution (water, initiator):

A solution of water-soluble radical initiator of KPS (0.193 g / 5 mL) is left under stirring, under an inert atmosphere for 20 minutes. A flow of nitrogen gas is maintained in the mixture throughout the stirring.

Injection of the initiator solution into the initial mixture:

The degassed initiator solution is then injected into the reactor at a rate of 120 mL / h. The reaction is left for 3 hours with stirring at 70 ° C., then the temperature is raised to 80 ° C. for an additional 1 hour. The reaction is finally stopped by cooling the mixture to room temperature and opening the reactor to air. The cores obtained have an average diameter measured by dynamic light scattering (DLS) of 190 nm.

1.3 Synthesis of the bark:

[0115] Preparation of the initial mixture (seed, water):

The suspension of the hearts obtained previously (319.974 g - 49.6 g.L-1) is poured into a 1 L reactor. Then distilled water (428.248 g) is added to the reactor. The whole is heated to 70 ° C., with stirring at 300 rpm and nitrogen is bubbled through for 45 minutes.

Preparation of the dispersion of monomers (ME02MA, OEGMA, OEGDA, MAA):

A dispersion composed of ME02MA (12,000 g), OEGMA (3.031 g), OEGDA (0.366 g) and MAA (0.299 g) mixed with water (7.484 g) is prepared. The dispersion containing all of the monomers is produced by successively adding MAA, distilled water, then the remaining monomers. MAA is first dissolved in the appropriate volume of water, then all the monomers are introduced. This mixture is left with stirring. At the same time, the oxygen is removed from the mixture, by bubbling gaseous nitrogen with stirring for 20 minutes.

[0117] Preparation of the initiator dispersion (water, KPS):

The adequate mass of KPS (0.1749 g) is dissolved with the necessary quantity of distilled water (23.180 g), with stirring. The oxygen is then removed by bubbling nitrogen gas through the mixture, with stirring for 20 minutes.

The dispersion of monomers and the initiator solution are then injected simultaneously and in parallel at a speed of 120 ml / h into the reactor containing the suspension of hearts. The whole is left with stirring and under a flow of nitrogen for 6 hours. The reaction is finally stopped by cooling the mixture to room temperature and opening the reactor to air.

2. Grafting rate and size of microqels The rate of grafting of the bark, measured by Fourier transform infrared spectroscopy in attenuated total reflectance (FTIR-ATR) was equal to 83% by mass. The hydrodynamic diameter of the microgels measured at 60 ° C by Dynamic Light Scattering (DLS) was equal to 246 nm, so that the radial thickness of the bark, extrapolated by subtracting the diameter of the microgels and the diameter of the hearts, was equal to 25 nm

[0119] Example 2: Heart / bark microuels according to the invention (variation of the heart / bark ratio

2.1 Preparation of the Microgels [0120] The synthesis of Example 1 was reproduced by varying the proportion by mass of the shell and of the heart. The degree of grafting of the microgels and their diameter at 60 ° C. were measured.

2.2 Preparation of films and measurement of diffraction peaks of films

The films are prepared by evaporation of the water contained in the microgel suspensions, on a silicon substrate having a temperature between 15 and 65 ° C, preferably at 35 ° C. The suspensions deposited on their supports are left to dry under atmospheric conditions of pressure and temperature.

The positions of the maximums of the experimental diffraction peaks of the microgels were determined as a function of the proportion of the crust relative to the core.

The results are shown in Table 1 and Figure 2.

[0122] [Table 1]

Table 1

Suspensions of core-shell microgels with a relatively constant grafting rate, around 81 ± 5% by mass, are obtained. The size of the core-bark objects is controlled according to the bark mass proportion as shown by the evolution of the hydrodynamic diameters.

The optical properties of the film are in particular due to a crystalline surface self-assembly. This self-assembly selectively diffracts light over a range of wavelengths. According to Snell-Bragg theory, the diffraction peak is shifted according to the distance between the cores. Here this distance is set by the thickness of the shell, itself controlled by the proportion of biocompatible material in the final solid.

It is observed that the distance between the objects and the color of the films varies as a function of the thickness of the bark.

[0125] The coloration perceived macroscopically is also due to a diffusion phenomenon which occurs in the core of the film. This phenomenon induces the appearance of transparent and sometimes slightly bluish fringes on the film.

The addition of an absorbent pigment, such as carbon black, in the initial dispersions makes it possible to greatly reduce this diffusion phenomenon. The diffraction phenomenon, localized on the surface of the films, is significantly less affected. This results in an increased perception of the iridescent coloration of the films produced. The deposition of the dispersions obtained on a dark support also makes it possible to obtain a comparable effect extrinsically to the film.

3. Absorption spectrum of films under stress [0127] The absorption properties of three films were studied when they are stretched by a tensile machine, at a controlled deformation rate.

The films are prepared from dispersions of microgels exhibiting core / shell proportions of 67% by mass, 75% by mass and 80% by mass. The dispersions were enriched with 1% by mass of a black pigment (carbon black).

[0129] The self-assemblies obtained at the surface have the particularity of diffracting light to produce colored surfaces. These self-assemblies also have the advantage of being spontaneously tenacious at relative strain rates of up to 50%.

[0130] FIG. 3 represents the variation in the dominant wavelength of each of the three films as a function of the relative strain rate of the films. FIG. 4 represents the absorption spectra of the photo-receptor cells which make it possible to see the shades of hues. The comparison between Figures 3 and 4 highlights the perceived color change according to the relative deformation rate of the films.

Some values in Figure 3 are shown in Table 2.

[0131] [Table 2]

Table 2

The crystal structure is deformed under stress and leads to a change in the diffracted wavelength. The film changes color and tends towards tints corresponding to lower dominant wavelengths when the film is stretched. 3.1 Assembly of microgels in the whole film

[0132] In FIG. 5, atomic force microscopy images taken on the wafer of a film obtained from a dispersion of microgels according to Example 1 are shown. The contrast is expressed as a function of the relative rigidity of the material. .

[0133] Observations by atomic force microscopy of surfaces taken from the edges of the films make it possible to visualize the quality of the self-assembly in depth. It appears that close to the surface, the objects tend to line up, forming self-assembled structures capable of inducing a physical coloring. In the heart of the film, the objects appear more and more disorganized the closer you get to the medium. The iridescent color obtained previously is due to a self-assembly of the surface. The underlying, disorganized, amorphous region contributes to the optical spectrum through diffusive behavior. This diffusion phenomenon interferes with the perception of physical color and can be limited by the addition of an additive which absorbs visible light, such as carbon black, or black iron oxides. Note also the possibility of using a support absorbing visible light to make it possible to exacerbate the perception of the diffracted signal, such as for example in application on dark skin.

3.2 Cohesion of films

The tenacity of the film under deformation is due to the properties of the biocompatible shell. The weakly crosslinked biocompatible material consists of long, flexible polymer chains that can become entangled with each other. In the case of two spheres with a core-bark morphology, the biocompatible bark allows the spheres to become entangled with each other. Indeed, if we compare the sizes of the spheres to the inter-object distances of a self-assembled surface, the inter-object distance is systematically lower. In other words, the spheres interpenetrate. This makes it possible to increase the force of inter-object cohesion, and to increase the toughness of the material under deformation.

FIG. 6 shows the diameter measurements obtained by DLS on the microgels in which the bark is contracted, the measurements obtained by AFM on the microgels. dried microgels, and measurements of distances between microgels in dry films in AFM.

G01361 Example 3: Microqels according to the invention (variation of the injection speed)

The synthesis of Example 1 was reproduced identically except that the dispersion of monomers and the initiator solution used to synthesize the bark were injected into the reactor containing the suspension of hearts at a speed of 1 mL / h (not 120 mL / h). The degree of grafting was in this case equal to 55% by mass.

The microgels of each of the two syntheses are purified by 5 successive cycles of centrifugation / re-dispersion in water at 10,000 rpm for 30 min.

Microgel films are then prepared by a method of drying the colloidal dispersion of microgels obtained. A constant volume of solution is poured onto a silicon surface and allowed to dry until the water has completely evaporated. FIG. 1 shows the images obtained by AFM of the films of microgels 150 μm in thickness from a dispersion concentrated at 4% by mass of dry matter. The top image and the bottom image correspond respectively to the microgel films of the first and the second synthesis.

Microgels having a high grafting rate form more regular self-assemblies than microgels having a lower grafting rate. The difference in the rate of injection of the precursor monomers of the shell therefore has an impact on the self-assembly of the microgels obtained.

The significant improvement in the grafting rate is obtained when the monomers are injected in parallel and simultaneously into the diluted seed. The speed of injection has a significant impact on the grafting rate. With the EGDMA crosslinking agent, the grafting rate is approximately 50% by mass with a slow injection speed (1 mL / h), whereas it reaches 80% by mass in the case of a rapid injection (120 mL / h). G01411 Example 4: Core / shell microqels according to the invention with a divinylbenzvne (DVB) crosslinking agent

The first synthesis of Example 1 was reproduced by replacing EGDMA with divinylbenzene (DVB) to crosslink the core. Using DVB, the degree of grafting of the biocompatible material is equal to 53% by mass.

Using DVB, the grafting rate of the biocompatible material does not exceed 50% by mass, while it reaches values around 80% by mass with EGDMA. This crosslinker exhibits dipole moments which allow the heart to develop a greater affinity with the biocompatible material of the shell. Its precipitation on the seeds is then facilitated.

G0142Ί Example 5: Cosmetic composition containing microqels

A cosmetic product was prepared composed, for a total mass of 100 g, of 0.200 g of phenoxyethanol, 0.200 g of perfume, 0.043 g of vegetable glycerol, 3.982 g of dry heart-bark microgel prepared in Example 1. The additional mass to reach 100 g being done with water.

The total mass of additives relative to the mass of dry extract is 10% in this product. The proportions of glycerol, phenoxyethanol, perfume and microgels are respectively 0.1%, 4.5%, 4.5% and 90% relative to the mass of dry extract. Drying such a product under the conditions described above in the description makes it possible to obtain a film colored with iridescent colors according to the spectrum given in FIG. 7.

Claims

[Claim 1] Microgels comprising a core coated with a shell:

- the bark being capable of being obtained by polymerization by precipitation in aqueous phase of monomers in the presence of a first crosslinking agent, said monomers comprising at least di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol) methyl methacrylate ether and a vinyl monomer comprising a carboxyl group.

[Claim 2] Microgels according to claim 1, characterized in that the oligo (ethylene glycol) methyl ether methacrylate has a number molecular mass ranging from 400 g / mol to 500 g / mol, and in that the ethylenic monomer is methacrylic acid.

[Claim 3] Microgels according to claim 1 or 2, characterized in that the crosslinked organic polymer is obtainable by radical emulsion polymerization of at least one vinyl monomer in the presence of a second crosslinking agent.

[Claim 4] Microgels according to claim 3, characterized in that the vinyl monomer is styrene.

[Claim 5] Microgels according to claim 3, characterized in that the first crosslinking agent and the second crosslinking agent are chosen from ethylene glycol di (meth) acrylate and oligo (ethylene glycol) di (meth) acrylates of molecular mass number average less than 800 g / mol.

[Claim 6] Microgels according to claim 3, characterized in that the first crosslinking agent and the second crosslinking agent are chosen independently of one another from oligo (ethylene glycol) diacrylates with a number average molecular weight ranging from 200 g / mol to 600 g / mol and oligo (ethylene glycol) di methacrylates with a number average molecular mass ranging from 180 g / mol to 650 g / mol.

[Claim 7] Microgels according to one of claims 1 to 5, characterized in that the first crosslinking agent is an oligo (ethylene glycol) diacrylate, the number average molecular mass of which ranges from 200 g / mol to 300 g / mol.

[Claim 8] Microgels according to one of claims 3 to 7, characterized in that the second crosslinking agent is ethylene glycol di methacrylate.

[Claim 9] Process for preparing microgels according to one of claims 1 to 8, characterized in that it comprises two successive stages of polymerization in aqueous phase, a first stage of polymerization leading to an aqueous suspension of hearts and a second polymerization step in which a bark grows on each of the hearts.

[Claim 10] A method according to claim 9, characterized in that the second polymerization step comprises a first injection and a second injection into the aqueous suspension comprising the cores obtained at the end of the first polymerization step,

- said first injection being an injection of a dispersion comprising di (ethylene glycol) methyl ether methacrylate, oligo (ethylene glycol) methyl ether methacrylate, ethylenic monomer, and the first crosslinking agent,

- said second injection being an injection of a solution containing a polymerization initiator,

- Said first injection and said second injection being carried out simultaneously and separately.

[Claim 11] A composition comprising from 1% to 100% by mass of the microgels according to one of claims 1 to 8.

[Claim 12] Composition according to Claim 11, characterized in that it comprises from 1% to 50% by mass of microgels relative to the mass of the composition, and from 0.9% to 100% by mass of water relative to the mass of the composition.

[Claim 13] Composition according to one of claims 11 and 12, characterized in that it is in the form of a dispersion of microgels in water.

[Claim 14] A composition according to claim 11, characterized in that it is in the form of a film with a thickness ranging from 1 micron to 10 millimeters comprising from 50% to 100% by mass of microgels, and of 0 % to 50% by mass of water, the percentages being expressed relative to the total mass of the composition.

[Claim 15] Composition according to one of claims 11 and 14, characterized in that it contains a black additive.

[Claim 16] Composition according to one of claims 11 to 14, characterized in that it is in the form of a cosmetic product comprising at least one cosmetic compound chosen from the group consisting of preservatives, perfumes, emollients , surfactants, oils, biologically active products, pigments and dyes.

[Claim 17] A composition according to claim 15 and 16, characterized in that the black additive is a pigment, such as an iron oxide.

[Claim 18] Cosmetic process comprising a step of applying to at least part of the body a cosmetic composition according to one of claims 11 to 17.