Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/0241—Containing particulates characterized by their shape and/or structure
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/04—Dispersions; Emulsions
  • A61K8/042—Gels
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/04—Dispersions; Emulsions
  • A61K8/044—Suspensions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
  • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
  • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/10—Esters
  • C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
  • C08F220/28—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
  • C08F220/282—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing two or more oxygen atoms
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/10—General cosmetic use
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/41—Particular ingredients further characterized by their size
  • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F2810/00—Chemical modification of a polymer
  • C08F2810/20—Chemical modification of a polymer leading to a crosslinking, either explicitly or inherently

Definitions

• composition or medical device comprising polymers based on oligo (ethylene glycol)
• the present invention relates to a cosmetic, a pharmaceutical composition or a medical device for topical application or on mucous membranes, said composition comprising the combination of a polymer based on oligo (ethylene glycol) crosslinked in the form of an aqueous dispersion of colloidal particles of microgels and of a polymer based on oligo (ethylene glycol) soluble in water.
• the invention also relates to a process for the preparation of this composition.
• compositions based on poly (oligo- (ethylene glycol) methacrylate) microgels make it possible to achieve this objective.
• aqueous dispersions of such microgels has been described in the literature, in particular in patent applications WO 2016/110615 and WO 2019/077404, and the publications Boularas et al., Polymer Chem., 2016, 7 , 350-363; and Aguirre et al., Polymer Chem., 9, 1155-1159.
• a side product is formed which consists of a water soluble polymer (WSP), cited as a free polymer.
• the mixing of the purified microgels with the free polymer makes it possible to control and control the value of the viscoelastic modulus of the films without reducing the elongation at break.
• the free polymer makes it possible to increase the adhesion of a film of microgels without modifying its mechanical properties.
• the films obtained by drying the combination of the microgels and the free polymer exhibit particular mechanical properties of elasticity and tack.
• the inventors have surprisingly found that these properties can be modulated as a function of the microgel-polymer mass ratio.
• the inventors have discovered that the chemical composition of the free polymer is very comparable to that of microgels and allows good compatibility between the two components.
• the branched and crosslinked structure allows the preservation of the resistance to stretching of films obtained from their mixtures.
• the self-assembly of the microgel / polymer mixture forms a film with promising mechanical properties for skin applications: the elastic modulus is low, the deformability capacity is high and the elongation at break high. Reformulation with the free polymer potentially makes it possible to control and control the value of the viscoelastic modulus of the films without reducing the elongation at break.
• microgel films with adjustable mechanical properties have never been reported in the literature.
• the variation in the rheological properties of the films is directly obtained by virtue of a secondary synthesis product, the free polymer.
• This has the same chemical composition as the microgels and therefore has excellent compatibility with the latter. This has the advantage of not weakening the self-assembled network of the microgels, which results in the retention of resistance to stretching.
• the addition of the free polymer can induce a variation of the real part of the complex shear modulus (G) between lxlO 3 and lxlO 5 Pa. This makes it possible to obtain films having a very pronounced tack up to films not showing any tackiness at all.
• the elongation at break which reflects the cohesion of the microgel network at very large deformations, does not decrease with the addition of free polymer.
• the structural characterization of the free polymer by aqueous chromatography reveals a very branched polymer resembling nano-gels, whose structure explains the conservation of the resistance of the network which can thus follow the deformations of the skin or the mucous membranes without peeling off or breaking. .
• a first object of the invention is a composition, in particular a cosmetic composition, a pharmaceutical composition or a medical device, comprising a water-soluble polymer (WSP) and particles of microgels, in which the particles of microgels and the water-soluble polymer can be independently obtained, or are independently obtained, by aqueous phase precipitation polymerization of di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol) methyl ether methacrylate, and of a vinyl monomer bearing a carboxyl group, in which the ratio between the mass of the water-soluble polymer and the mass of the particles of microgels in the dry state is between 0% and 100%.
• WSP water-soluble polymer
• the medical device preferably includes a mixture consisting of the water-soluble polymer, the microgels and optionally water.
• the solid content of the cosmetic composition, the solid content of the pharmaceutical composition, or the solid content of said mixture is preferably from 1.5% to 100% by mass.
• the solid content may be greater than a percentage selected from the group consisting of 2%; 3%; 4%; 5%; 10%; 15%; 20%; 25%; 30 % ; 35%; 40%; 45% and 50% by mass.
• the solid content of the composition of the invention can be defined as the percentage by weight of the solid elements that it contains, in particular as equal to the sum of the percentage by weight of the microgels in the dry state, of the percentage by weight of the polymer soluble in water, and optionally a percentage of any other solid compound which would be present in the composition.
• the solid content can be the sum of the percentage of microgels in the dry state and the percentage of polymer which are contained in the mixture.
• a second object of the invention is a process for the preparation of the cosmetic composition, the pharmaceutical composition or the medical device, said process comprising a step of preparing a mixture of microgel particles and a soluble polymer. in water, said step comprising:
• a third object of the invention is a method for the cosmetic treatment or pharmaceutical treatment via a topical route of the skin, nails, lips, mucous membranes or hair of a person, said method comprising a first step application of the cosmetic composition, of the pharmaceutical composition or of the medical device as defined above.
• Figure 1 is a graph of conformation of radius of gyration as a function of molar mass for MBA-WSP (red), OEGDA-WSP (blue), PEG35K (black). WSP comes from a synthesis with 2 mol% of crosslinking agent. The dotted line is representative of a power law with an exponent of 0.6. The solid black line fits the MBA-WSP curve according to a power law of exponent 0.27.
• FIG. 2 In Figure 2, the number and mass molecular weights, and the polydispersity index for different WSPs are shown.
• FIG. 3 represents the curve of the conversion modulus G ′ and of the loss modulus G ′′ as a function of the frequency of an unpurified MBA film and of an OEGDA film with different levels of crosslinking agent: 2% in mole and 8 mole%.
• Figure 4 is a table providing the mass composition of unpurified films, after synthesis.
• FIG. 5A represents the expansion viscosity as a function of time of unpurified MBA films and OEGDA films with different levels of crosslinking agent: 2% by mole and 8% by mole.
• Figure 5B is the elongation at break for MBA film and OEGDA film for different crosslink densities at 2 mole% and 8 mole%.
• Figure 6A shows the modulus of conservation G ′ and the modulus of loss G ′′ as a function of the frequency of a 2.0 mole% OEGDA-MG film with different levels of MG.
• Figure 6B is the modulus of conservation G "and the modulus of loss G" as a function of the frequency of a 2.0 mole% MBA-MG film with different levels of MG.
• Solid symbols correspond to OEGDA, hollow symbols correspond to MBA.
• Figure 8A is the expansion viscosity versus time curve for OEGDA-MG films at different MG contents.
• Figure 8B is the extensional viscosity versus time curve of OEGDA-MG films for different MG contents.
• Fig. 9 is a bar graph showing the elongation at break for an MBA film and an OEGDA film for different MG contents.
• Figure 10A shows the extension viscosity versus time curve for pure OEGDA-MG films at different film forming temperatures.
• Figure 10B is a bar graph showing the elongation at break values for pure OEGDA-MG films at different film forming temperatures.
• FIG. 11 shows two images obtained by AFM atomic force microscopy of the upper surface of films of OEGDA-MG (left image) and of MBA-MG (right image).
• Figure 12 shows two AFM images of a cross section of films of OEGDA-MG (left image) and MBA-MG (right image).
• FIG. 13 shows two images obtained by AFM atomic force microscopy of the upper surface of films of OEGDA-MG (left image) and of MBA-MG (right image) subjected to an elongation of 30%.
• Figure 14 shows AFMs in topographic contrast and images of the LogDMT module: (a) AFM in topographic contrast and (b) LogDMT module for 2 mol% MBA-MG films containing 25% MG, (c) AFM in topographic contrast and (d) LogDMT modulus for 2 mol% MBA-MG films containing 50% MG; (e) AFM in topographic contrast and (f) LogDMT modulus for 2 mol% MBA-MG films containing 75% MG. Definitions
• microgel particles are a crosslinked polymer in the form of spherical particles having an average size which can vary from 100 nm to 1000 nm in the dry state (c ' that is to say containing less than 2% by mass of water), preferably between 100 nm and 500 nm, from 350 to 450 nm, even better still 400 nm.
• the hydrodynamic radial distribution function of the microgels measured at an angle of 60 ° and at a temperature of 20 ° C may be less than 1.1.
• the microgel of the invention can be obtained by copolymerization in aqueous phase of several monomers.
• the average size of the microgel particles can vary depending on whether they contain water or not.
• Microgel in the sense of the present description, can be in the form of an aqueous dispersion of "particles of microgels” or in the form of a film comprising particles of microgels as defined above.
• Microgels can trap cosmetic or pharmaceutical active organic molecules.
• a film comprising microgel particles can have a thickness of 1 micron to 10 millimeters, for example 10 microns to 500 microns, 100 microns to 400 microns or 500 microns to 1000 microns.
• the microgel particles preferably do not include any inorganic material.
• microgel particles consist of organic compounds.
• the microgel particles do not, for example, contain silica, in particular silica as a support for the crosslinked polymer.
• crosslink is a group (part of a molecule) which binds the copolymer chains together. This crosslink originates from a “crosslinker” molecule which is mixed with the monomers during the polymerization process of the crosslinked polymer.
• a "water-soluble polymer” is a polymer having a radius of gyration at 20 ° C which is from 5 nm to 80 nm, for example from 10 nm to 30 nm.
• the water soluble polymer can have an average molecular mass of 1 x 10 5 g. mol 1 to 1 x 10 6 g. mol 1 .
• the radius of gyration and the molecular mass can be measured by any method known to those skilled in the art, for example by size exclusion chromatography.
• a water soluble polymer is distinguished from microgel particles: for example microgel particles can be identified by atomic force microscopy (AFM) observation of a film made by drying an aqueous dispersion of microgel particles. On the contrary, no particle can be detected by AFM observation of films which are made by drying a solution of the water soluble polymer.
• AFM atomic force microscopy
• a first object of the invention is a composition, in particular a cosmetic composition, a pharmaceutical composition, or a medical device, comprising a polymer soluble in water and particles of microgels, said particles of microgels having an average diameter from 100 nm to 1000 nm in the dry state, wherein the microgel particles and the water soluble polymer can be independently obtained, or are independently obtained, by aqueous phase precipitation polymerization of at least the three following monomers, in the presence of a crosslinking agent:
• an oligo (ethylene glycol) methyl ether methacrylate having a number average molar mass between 400 g / mole and 600 g / mole
• a vinyl monomer comprising a carboxyl group provided that when the microgel particles and the water-soluble polymer are prepared from 83 mol% to 84 mol% of di (ethylene glycol) methyl ether methacrylate, from 9.0 mol% to 9.5 mol% of an oligo (ethylene glycol) methyl ether methacrylate having a number average molar mass of 475 g / mol, from 4.9 mol% to 5, 1 mole% of methacrylic acid as a vinyl monomer comprising a carboxyl group, and 1.9 mole% to 2.0 mole% of a crosslinking agent, the sum of the four mole fractions being 100% in mole, then if the crosslinking agent is an oligo (ethylene glycol) diacrylate, the ratio between the mass of the water soluble polymer and the mass of the microgel particles is not equal to 34%, if the crosslinking agent is N, N'-methylenebisacrylamide, the ratio between the mass of the water soluble poly(ethylene
• the microgel particles and the water-soluble polymer comprise, according to one embodiment, chains having monomer units of diethylene glycol methacrylate, monomer units of oligoethylene glycol methacrylate comprising from 6 to 10 ethylene glycol units, monomeric units of methacrylic acid, and crosslinks.
• the oligo (ethylene glycol) methyl ether methacrylate preferably comprises from 7 to 8 ethylene glycol units.
• the oligo (ethylene glycol) methyl ether methacrylate may have a number-average molar mass (Mn) between 400 g / mole and 600 g / mole, preferably between 450 and 500 g / mole.
• the vinyl monomer is preferably a (meth) acrylic acid monomer.
• the microgel particles and the water-soluble polymer can be independently obtained by polymerization by aqueous phase precipitation of three monomers in the presence of a crosslinking agent.
• the precipitation polymerization step comprises contacting, in an aqueous phase, the three monomers described above and the crosslinking agent, at a temperature between 40 ° C and 90 ° C, preferably of the order 70 ° C.
• a surfactant such as SDS (sodium dodecyl sulfate)
• the polymerization can be initiated by the addition of a water-soluble free radical initiator, for example potassium persulfate ( KPS).
• KPS potassium persulfate
• the mole fraction of di (ethylene glycol) methyl ether methacrylate is 80 mole% to 90 mole%
• the mole fraction of oligo (ethylene glycol) methyl ether methacrylate is 5% by mole to 15% by mole
• the mole fraction of the vinyl monomer bearing a carboxyl group is from 2% by mole to 8% by mole
• the mole fraction of the crosslinking agent is from 0.5 to 10% by mole , the sum of the four mole fractions being equal to 100 mole%.
• the mole fractions can be defined as the mole fractions of the monomers which are used to prepare the microgel or the water soluble polymers.
• mole fractions can be defined as the mole fractions of the monomer units in the microgel or in the water soluble polymer which have been obtained from the reaction between the monomers.
• the mole fraction of the crosslinking agent can be from 0.5 mole% to 10 mole%, from 0.5 mole% to 8 mole%, from 1 mole% to 7 mole% or from 1.5 mole% to 6 mole%.
• the molar ratio (a: b) between the di (ethylene glycol) methyl ether methacrylate (a) and the oligo (ethylene glycol) methyl ether methacrylate (b) is preferably between 1: 1 and 20: 1, for example between 5: 1 and 10: 1.
• the (meth) acrylic acid monomer can be selected from the group consisting of methyl acrylic, methyl methacrylic, ethyl acrylic, ethyl methacrylic, n-butyl acrylic, and n-butyl methacrylic, methacrylic, itaconic or acrylic acids. Methacrylic acid is preferred.
• the oligo (ethylene glycol) methyl ether methacrylate can have a molecular mass between 200 g / mole and 600 g / mole, or between 300 g / mole and 550 g / mole or between 450 g / mole and 500 g / mole.
• the mole fraction of monomer units of di (ethylene glycol) methacrylate is 80 mole% to 90 mole%, preferably 82 mole% to 86 mole%
• the mole fraction of oligo (ethylene glycol) methyl ether methacrylate monomer units is 5 mole% to 15 mole%, preferably 7 mole% to 11 mole%
• the mole fraction of monomer units of (meth) acrylic acid is 2 mole% to 8 mole%, preferably 3 mole% to 7 mole%
• the mole fraction of the crosslink is 1 mole% to 6 mole% or 1 mol% to 3 mol%.
• the crosslinked polymer comprises copolymer chains having monomer units of diethylene glycol methacrylate, monomer units of oligoethylene glycol methacrylate comprising from 4 to 10 ethylene glycol units, and acid monomer units.
• methacrylic The monomer units are preferably: oligo (ethylene glycol) methyl ether methacrylate having 7 or 8 ethylene glycol units; and methacrylic acid.
• the monomer units of oligo (ethylene glycol) methyl ether methacrylate can also have 8 to 9 ethylene glycol units.
• the microgel is obtained by polymerization of at least three monomers, in the presence of a first crosslinking agent, and the water-soluble polymer is obtained from a polymerization of at least three monomers, in presence of a second crosslinking agent.
• the first crosslinking agent and the second crosslinking agent can be independently selected from the group consisting of oligo (ethylene glycol) diacrylate comprising from 1 to 10 ethylene glycol, 1,3-butanediol diacrylate units, 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, trimethylacrylate benzo glycol di methacrylate,
• the crosslinking agent has di (meth) acrylate end groups and a unit chosen from the group consisting of - (CH 2 -CH2-0) m-CH2-CH 2 - where n is 0 to 6.
• the number m is preferably 3 to 6.
• the crosslinking agent is for example (ethylene glycol) dimethacrylate or oligo (ethylene glycol) diacrylate.
• a particular microgel comprises monomer units of diethylene glycol methacrylate, monomer units of oligoethylene glycol methacrylate comprising from 7 to 8 ethylene glycol units, and a crosslinking agent comprising terminal di (meth) acrylate groups and a unit chosen from the following group: group consisting of -CH 2 -CH 2 - and - (CH 2 -CH2-0) m-CH2-CH 2 - where m is 4 to 5.
• microgel particles can depend on the crosslinking agent used.
• Three different microstructures were obtained according to several embodiments: microgels crosslinked in a homogeneous manner using an oligo (ethylene glycol) diacrylate (OEGDA), microgels with a slightly crosslinked core and highly crosslinked shell using N, N'-methylenebisacrylamide (MBA), and slightly crosslinked bark and highly crosslinked core microgels using (ethylene glycol) dimethacrylate (EGDMA).
• OEGDA oligo (ethylene glycol) diacrylate
• MSA N, N'-methylenebisacrylamide
• EGDMA ethylene glycol dimethacrylate
• the cosmetic composition, the pharmaceutical composition or the mixture which is included in the medical device are in a particular embodiment in the form of a film which has a thickness of 500 microns to 1000 microns.
• the ratio between the mass of the water-soluble polymer and the mass of the microgel particles is greater than 0% and less than 100%.
• the ratio may have a lower value which is chosen from the group consisting of 5%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65% , 70%, 75%, 80%, 85%, 90% and 95%.
• the ratio may have a higher value which is chosen from the group consisting of 5%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65% , 70%, 75%, 80%, 85%, 90% and 95%.
• the ratio between the mass of the water-soluble polymer and the mass of the microgel particles can be between 0% and 34% or between 34% and 100%.
• the ratio between the mass of the water-soluble polymer and the mass of the microgel particles can be between 0% and 20% or between 20% and 100%.
• the cosmetic composition and the pharmaceutical composition can be a liquid, a gel or a solid.
• the cosmetic composition, the pharmaceutical composition or the mixture consisting of the polymer soluble in water, the microgels and optionally water which is included in the medical device may contain from 50% to 100% by mass of a mixture consisting of particles of microgels and polymer soluble in water, and from 0% to 50% by mass of water, the percentages being relative to the mass of the composition and the mass of the particles of microgels being the mass of the particles in the dry state.
• the solid content of the cosmetic composition, the solid content of the pharmaceutical composition, and the solid content of the mixture consisting of the water soluble polymer, the microgels and optionally water which is included in the medical device can be from 50% to 100% by mass.
• the composition of the invention in the case where the composition of the invention is liquid, it can be spread on the skin or on the mucous membranes, and can form a transparent film adhering to the skin or to the mucous membranes by simple evaporation of the water.
• the skin has a low elastic modulus and that the product applied must have a modulus comparable to that of the skin so as not to be felt by the user.
• the free polymer is a lever for adjusting the modulus according to the intended application.
• the addition of components such as gelling agents or bioactants, can increase the modulus: it is then possible to add the proportion of free polymer agreed to reduce it to a target value.
• the films have a high elongation at break whatever the level of free polymer, which is essential for application to the face for example.
• the composition can comprise from 1% to 100% by mass of the microgels.
• the composition comprises according to one embodiment 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 microgels in water.
• the aqueous dispersion may comprise from 1% to 50% by mass of a mixture consisting of microgels and water soluble polymer based on the mass of the composition, and from 50% to 99% by mass of water, based on the mass of the composition.
• the composition can be in the form of a film having a thickness of 1 micron to 10 millimeters comprising from 50% to 100% by mass of a mixture consisting of microgels and water-soluble polymer, and 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 an aqueous dispersion comprising the microgel and the water soluble polymer by evaporation of the water.
• the aqueous dispersion is for example spread on a rigid or flexible substrate, where the substrate has a temperature between 20 ° C and 60 ° C, even better a temperature of 30 ° C to 40 ° C, much better still a temperature equal to 35 ° C. ° C.
• the films can be formed by a step consisting in placing in a mold a dispersion of particles of microgels in water and the water-soluble polymer, and by a step of drying the dispersion. Drying can be achieved by placing the mold at a temperature above room temperature, for example a temperature of 30 ° C to 60 ° C.
• the cosmetic composition can comprise at least one component chosen from the group consisting of preservatives, perfumes, emollients, surfactants, oils, biologically active products, pigments and dyes.
• the method for the preparation of a composition comprises a first step of preparing microgels, a second step of preparing the water-soluble polymer and a third step of mixing the two .
• the process for the preparation of a cosmetic composition, of a pharmaceutical composition or of a medical device as described above can comprise a stage of preparation of a mixture of particles of microgels and of a soluble polymer. in water, said step comprising a first step and a second step which may be successive in any order, or simultaneous:
• said first step being a step of preparing microgel particles, and comprising a step (i) of polymerization by precipitation in aqueous phase of at least the following three monomers, in the presence of a first crosslinking agent: di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol) methyl ether methacrylate, a vinyl monomer bearing a carboxyl group, and a purification step (ii) to recover microgel particles which were obtained at the end of the step (i),
• a third step which follows said first step and said second step, said third step being a step of mixing a mass of particles of purified microgels which have been obtained at the end of said first step, and a mass of water-soluble polymer which is obtained at the end of said second step, where the ratio between the mass of the water-soluble polymer and the dry mass of the microgel particles is between 0% and 100%.
• Step (ii) can comprise at least one centrifugation / redispersion cycle to separate the precipitate and the supernatant, and a step of recovering the microgel particles from the precipitate.
• Step (b) can comprise at least one centrifugation / redispersion cycle to separate the precipitate and the supernatant, and a step of recovering the water-soluble polymer from the supernatant.
• the first step and the second step are a single step, so that particles of microgels and a water-soluble polymer are produced at the same time from the same monomers, in which the 'single step comprises at least one centrifugation / redispersion cycle to separate the precipitate and the supernatant which have been obtained from the aqueous phase precipitation polymerization of the monomers, said microgel particles being recovered in the precipitate, and said polymer soluble in water being recovered in the supernatant.
• the ratio between the mass of the water-soluble polymer in the supernatant, and the mass of the microgel particles in the precipitate is a first ratio and - in the third step - the ratio between the mass of the water-soluble polymer and the mass of the microgel particles is a second ratio which is between 0% and 100% and which is different from the first ratio.
• the first crosslinking agent and the second crosslinking agent can be as described above in the present description.
• a third subject of the invention also relates to a process for topical cosmetic or pharmaceutical treatment of the skin, nails, lips, mucous membranes or hair of a person, said process comprising a first step of application to the person of a composition or a medical device as described above.
• the cosmetic composition, pharmaceutical composition or medical device may comprise a water soluble polymer (WSP) and microgel particles, wherein the microgel particles and the water soluble polymer.
• WSP water soluble polymer
• Water can be independently obtained, or are independently obtained, by aqueous phase precipitation polymerization of di (ethylene glycol) methyl ether methacrylate, an oligo (ethylene glycol) methyl ether methacrylate, and a vinyl monomer bearing a group carboxyl, in which the ratio between the mass of the water soluble polymer and the mass of the particles of microgels in the dry state is between 0% and 100%.
• Oligo (ethylene glycol) methyl ether methacrylate can have a number average molar mass between 400 g / mole and 600 g / mole,
• the microgel particles and the water-soluble polymer are prepared from 83 mol% to 84 mol% of di (ethylene glycol) methyl ether methacrylate, from 9.0 mole% to 9.5 mole% of an oligo (ethylene glycol) methyl ether methacrylate having a number average molar mass of 475 g / mole, from 4.9 mole% to 5.1% by mole of methacrylic acid as a vinyl monomer comprising a carboxyl group, and from 1.9% by mole to 2.0% by mole of a crosslinking agent, the sum of the four mole fractions being equal to 100% by mole, then if the crosslinking agent is an oligo (ethylene glycol) diacrylate, the ratio between the mass of the water soluble polymer and the mass of the microgel particles is not equal to 34%, if the crosslinking agent is N, N'-methylenebisacrylamide, the ratio between the mass of the water-soluble polymer
• the cosmetic or pharmaceutical treatment process can comprise a second step of drying the composition or the device which has been applied to the person to obtain a flexible, cohesive and adhesive film.
• Poly (oligo- (ethylene glycol) methacrylate) microgels, water-soluble polymers, and films comprising the mixture of these microgels and water-soluble polymers were prepared according to the following protocol. Their rheology (linear and non-linear) was studied and their structure observed by atomic force microscopy (AFM). ration of microaels (MG), water-soluble polymers t films comprising these
• ME02MA (92.6 mmol), OEGMA (10.3 mmol) and a crosslinker (OEGDA or MBA) were dissolved in 930 g of water.
• the ratios of crosslinking agents are set either at 2.0% by mole or at 8.0% by mole depending on the total of the vinyl molecules, corresponding respectively to 2.12 mmol and 9.42 mmol.
• the mixture is introduced into the 2 L reactor and the stirring is set at 150 rpm.
• the reactor is purged with nitrogen for 45 min to remove oxygen at room temperature.
• MAA (5.41 mmol) is dissolved in 30 g of water and added to the reactor.
• the mixture is then heated to 70 ° C.
• KPS (0.958 mmol) is dissolved in 40 g of water and inserted into the reactor to start the reaction.
• the reaction is finally maintained at 70 ° C for 6 hours.
• a first part of the aqueous suspension comprising MG and WSP is obtained and the films (F6, F6 ', F7 and F7') are formed.
• a second part of the aqueous suspension is separated by 3 cycles of centrifugation (20,000 rev / m, 20 min), where WSP is maintained in the aqueous supernatant while MG is found in the precipitate.
• Films with WSP alone (F5 and F5 ') and films with MG alone (Fl and Fl') are formed as comparative films.
• Films comprising a mixture of WSP and MG in a predetermined ratio are also prepared (F2, F2 ', F3, F3', F4 and F4 ').
• Films were formed by the direct evaporation of water from solutions of microgels in a glass bell oven heated to 37 ° C. It has been shown that the formation temperature does not influence the properties of the film. Silicone molds were used as containers for easy removal of the films after drying. For the rheological experiments, the final film thicknesses are between 500 ⁇ m and 1000 ⁇ m. All thicknesses less than and greater than these values are nevertheless technically feasible, for example as low as 500 nm.
• the steric exclusion chromatography (SEC) apparatus consists of a set of aqueous columns from Shodex and an Agilent 1260 Iso pump from Agilent technologies.
• the device is coupled with a Multi Angle Light Scattering (MALS) and a differential refractometer (RI) detector.
• MALS detector used is a Dawn Heleos detector from WYATT Technology.
• RI detector is an Optilab T-rEX from WYATT Technology operating at a laser wavelength of 664 nm.
• the flow rate is fixed during the experiment at 0.5 mL / min and the column temperature is set at 30 ° C.
• the mobile phase consists of a solution of NaN0 3 at 0.1 g / mole (8.2 g / L), and sodium azide NaN 3 (0.1 mol / L) as eluent, stabilized with a buffer at pH 8
• the mobile phase is filtered at 0.1 ⁇ m before use.
• the water-soluble polymer solutions are prepared at a concentration of 200 ppm in a buffer of pH 8, of which a volume of 100 ⁇ L is injected.
• the solutions are filtered before use at 250 nm to remove any impurities and possible microgels.
• the value of the refractive index increment (dn / dc) is experimentally measured on an Optilab T-rEX refractometer from WYATT Technology with a laser wavelength of 532 nm.
• Five WSP solutions are prepared with Milli-Q water at different concentrations (0.97 gL 1 ; 0.75 gL 1 ; 0.51 gL 1 and 0.11 gL 1 ).
• the size exclusion chromatography makes it possible to determine the molar mass of WSP from a synthesis of 2 mol% OEGDA and a synthesis of 2 mol% MBA. This technique has the advantage of measuring both molecular mass and radius of gyration. It thus provides more information about the structure of WSP.
• OEGDA-WSP and MBA-WSP are compared to linear PEG with an average molecular weight of 35,000 g. mol 1 . Molar mass and radius of gyration are related by Flory's theory.
• FIG. 1 represents the conformity graphite that is to say the radius of gyration as a function of the molecular mass for OEGDA-WSP, MBA-WSP and PEG 35K.
• Figure 2 summarizes the molecular weights and polydispersity index of OEGDA-WSP, MBA-WSP and PEG 35K.
• PEG 35K exhibits an average Mw at 34,000 g. mol 1 which validates the reliability of the method used.
• As the polymer has a very narrow mass distribution, it is not possible to observe the change in the radius of gyration as a function of molecular weight.
• OEGDA-WSP and MBA-WSP share a similar population of molecular weights between 1 x 10 4 and 1 x 10 5 g. mol 1 .
• Some films are formed from the aqueous suspension comprising MG and WSP which is obtained from the aqueous precipitation polymerization process, before any centrifugation step.
• F3 - 2% by mole OEDGA 50% by mass WSP - 50% by mass MG
• F3 '- 2% by mole MBA 50% by mass WSP - 50% by mass MG
• the films are characterized by linear oscillatory rheology and non-linear extensional rheology on an MCR 302 rheometer from Anton Paar.
• Oscillatory rheology is carried out on films approximately 1 mm thick with parallel 8 mm plates at controlled temperature. Frequency sweeps are performed at 20 ° C from 0.01 to 600 rad / s at constant 1% elongation which ensures linear speed.
• Extension rheology is performed using SER (Sentmanat Extension Rheometer) geometry which consists of paired winding drums moving in equal but opposite rotation. The tests are carried out at 20 ° C. The film dimensions are in the following range: 0.5-1mm x 1-2mm x 15-20mm. The thickness and the width are before the test respectively measured by optical microscopy and compass. The films are extended until break with a constant elongation rate, also cited as the Hencky eH elongation rate. A minimum of fifty samples are tested for each type of film. The extensional viscosity hE is measured as a function of time.
• the logarithmic elongation in the sample is a function of e, of the constant rate of elongation; t, time; L of the sample length at time t and LO of the initial sample length.
• the constant elongation rate is multiplied by the time at break.
• the impact of the formation temperature was evaluated by forming films purified at 20 ° C, 32 ° C, 37 ° C and 60 ° C.
• the object was to evaluate whether the state of the microgels, that is to say collapsed or swollen, impacts the quality of the assembly during the formation of the film. Indeed, during the liquid-to-solid transition, one can imagine that the state of the microgel can play an important role, that is to say that the microgels inflated under the VPTT would create more intra-tangles than microgels collapsed above the VPTT.
• the extensional viscosity was measured at 20 ° C with a constant elongation rate of 0.5 s 1 .
• Figure 10 shows the average expansion viscosity for four different formation temperatures. It is clearly observed that the formation temperature does not impact the extensional viscosity or the elongation at break. It is not a parameter controlling the mechanical properties of films. If the microgels are under the VPTT (20 ° C), in the range (32 ° C, 37 ° C) or above (60 ° C), the elongation at break remains equal to 133 plus or minus 2 %. The microgel bark appears to retain some mobility at 60 ° C which allows the microgels to interpenetrate each other in their collapsed state. In addition, the microgel films, once formed, are maintained at 20 ° C and tested at 20 ° C. The chains thus have time to relax and reach a similar state of interpenetration regardless of the formation temperature.
• An 8 mol% OEGDA film surprisingly demonstrates moduli very similar to 2 mol% films. This particular behavior could be explained by a higher quantity of water in the film at the time of the test, due to the environment of uncontrolled hygrometry or to incomplete drying of the film.
• Extensional rheology consists of the elongation of materials in the non-linear domain of deformations, at a constant rate of elongation. Uniaxial extension can produce a much higher degree of molecular orientation and stretching than a simple tear. Therefore, extension rheology is more sensitive to polymer long chain branching and may be more descriptive than other types of bulk rheology tests. The Extensional rheology makes it possible to establish a relationship with adhesive behavior.
• FIG. 5 shows the mean extensional viscosity as a function of time of MBA and OEGDA for the two levels of crosslinking agent.
• the extensional viscosity increases permanently following the linear viscoelastic envelope defined by the slope of 3 times the complex viscosity: 3.rf.
• the extensional viscosity begins to deviate upwards from the shear viscosity at zero speed.
• This upward deflection is referred to as elongation-cure and conventionally occurs in chemically crosslinked or physically well-entangled polymers.
• This is an indicative aspect of the branching chain architecture. Chain tangles begin to resist stretching whenever the chain stretch limit is approached and cause the network to stiffen. Therefore, the extensional viscosity follows an upward deviation.
• the appearance of elongation-cure was expected since the films contained 2 mole% and 8 mole% crosslinker, respectively.
• Elongation-cure has been considered a desirable property for better adhesive performance. It fulfills the typical requirement for an adhesive that fails without leaving a sticky residue on the surface by providing cohesion to the network at high strain.
• OEGDA and MBA films exhibit similar behavior in the linear region.
• the elongation at break is however significantly higher for MBA than OEGDA regardless of the crosslinker density, FIG. 5 (image on the left).
• FIG. 5 image on the left.
• the increase in the crosslink density leads to a lower elongation at break for the two crosslinking agents. Indeed, a more reticulated network cannot stretch as much to adapt to the stress, and break at a less advanced stage. More dense and more crosslinked particles also tend to interpenetrate less with each other, thus creating a weaker lattice.
• FIG. 8 shows the mean extensional viscosity as a function of time of MBA and OEGDA for different MG contents.
• microgel content has no impact on either elongation-hardening or elongation at break.
• this result is extremely positive since it indicates that the proportion of water-soluble polymer can be modified to adjust the desired modulus according to the application but without losing in all cases the capacity of stretching of the film.
• Method Topographic images were captured by AFM (Bruker Multi mode 8 apparatus) in order to analyze the assembly of microgels on the film surface. Peak Force QNM Air mode and ScanAsyst Air probes (mean spring constant k of 0.4 Nm 1 ) were used for all scans. Clean cross sections of microgel films were also prepared to visualize the assembly within the film, with a Leica EM UC7 ultra cryo-microtome apparatus, using a Leica EM-FC7 cryo-chamber, cooled to -80 ° C. Finally, the films were manually subjected to unidirectional stretching and images were formed in the stretched state. The elongation corresponded to 30%.
• Atomic force microscopy was performed on the upper surface of films made with 100% microgels (no water soluble polymer).
• the microgel particles self-assemble in a perfect close-to-hexagonal settlement as seen on the topographic contrast images in Figure 11 (image on the right) for 2 mol% OEGDA-crosslinked and microgels (image at left) for 2 mol% MBA-crosslinked microgels.
• the particles do not coalesce but maintain their spherical shape with some interpenetration with each other.
• AFM topographic contrast images showed the slightly larger size of the MBA-crosslinked microgels.
• the cross sections of films were surface treated by ultra cryomicrotomy and observed by AFM.
• the topographic contrast images in Figure 12 show the settlement of spherical particles with localized hexagonal settlement.
• the several MG stack layers during solvent evaporation did not flatten and remain spherical.
• a contrast difference of about 15 nm between core and bark is observed for most microgels in both types of crosslinkers.
• the microgel films contain and absorb water from their surroundings. As a result, it can be suggested that the bark, which is much more swollen, is loosely reticulated and the core, which is more hollow, is more reticulate than the bark.
• Microgel films were stretched to obtain 30% elongation and their upper surfaces were observed by AFM.
• Figure 13 shows a 5mm topographic contrast image of OEGDA-crosslinked and MBA-crosslinked microgel films.
• the direction of stretching is parallel to the X axis. Stretching causes the loss of the hexagonal compact settlement and the deformation of the particle network. Gaps appear between the microgels in the direction of deformation. However, it seems that the microgels are not significantly deformed and maintain their spherical shape. It is suggested that at this elongation most tangled chains of the microgel bark stretch to accommodate the strain and the dense core is not yet deformed.
• Figure 14 shows the 2 micron topographic contrast image (a) and logDMT modulus (b) of 2 mol% MBA-MG to 25 mass% MG films.
• the logDMT module channel has the steepest regions in lighter color and the softer regions in darker color.
• the microgels are much denser than the water soluble polymer and look like fillers dispersed in a flexible composite matrix. They do not form aggregates but are not perfectly dispersed evenly.
• Figure 14 shows the 2 micron topographic contrast image (c) and logDMT modulus (d) of 2 mol% MBA-MG to 50 mass% MG films. The microgels begin to come into contact with each other but no structured arrangement is observed.
• microgel depletion is observed.
• Figure 14 is shown the topographic contrast image of 500 nm (e) and the logDMT modulus (f) of MBA-MG films for 75% by mass of MG. Similar conclusions can be expressed, the microgels are closer but no hexagonal packing arrangement is observed.
• the core / shell structure is well observed with a clear modulus gradient between the core relative to the WSP matrix.
• the denser and less swollen hearts are characterized by hollows, the rinds are more swollen than the hearts but slightly denser than the water soluble polymer which is characterized by the lower modulus.
• a very gradual transition is observed between the microgel shell and the water soluble polymer, suggesting a similar structure as well as some interpenetration between the two phases.

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