Sunscreen formulation incorporating microcapsules, and method for manufacturing such microcapsules

Abstract

A core-shell type microcapsule comprising a core containing at least one active ingredient and a shell, the shell forming a wall around the core and representing a mass fraction of at least 20% of the total mass of the microcapsule, the microcapsule being characterized in that the shell comprises at least one cross-linked polymer, preferably obtained by interfacial polymerization. The size of the microcapsules is preferably less than 1 µm. The active ingredient may be a sunscreen.

Description

Title of the invention: Formulation of sun protection comprising microcapsules, and method for manufacturing such microcapsules. Technical field of the invention

[0001] The present invention relates to the field of cosmetology, and more particularly to that of sun protection formulations or formulations providing protection against photoaging of the skin or skin appendages, intended to be applied to the skin and comprising substances called sun filters. These formulations may be in particular in the form of liquid or paste emulsions, such as ointments, creams, lotions, mousses, or in the form of solid emulsions: sticks, bars, or in non-emulsified form, such as: oils, suspensions, gels, lotions, loose or pressed powders.

[0002] More specifically, the invention relates to a microencapsulated formulation in a thick shell formed by a cross-linked polymer. These microcapsules are submicron in size. State of the art

[0003] Sunscreen formulations or products claiming protection against photoaging of the skin and its appendages include specific molecules capable of attenuating ultraviolet (UV) rays from the solar spectrum. This attenuation is achieved through total or partial absorption or reflection of at least a portion of the near-ultraviolet spectrum by molecules referred to herein as ultraviolet filters. It has long been known that, in general, UV rays are harmful to the skin, and in particular UV rays belonging to two spectral regions designated by those skilled in the art as UV-A (approximately 320 nm to 400 nm) and UV-B (approximately 280 nm to 320 nm). UV rays with shorter wavelengths are the most aggressive, and UV rays with longer wavelengths penetrate deeper into the skin. They can cause immunosuppression and skin cancer.More specifically, UV-A rays induce immediate skin pigmentation, but also premature aging (photoaging). UV-B rays induce vitamin D synthesis in the skin and delayed skin pigmentation (tanning), but also sunburn.

[0004] The most effective UV filters protect against both UV-A and UV-B rays. Organic UV filters and mineral UV filters are known.

[0005] Organic UV filters (also called chemical UV filters) are organic molecules that absorb and dissipate UV rays through chemical reactions. The majority of these organic UV filters are lipophilic. Their maximum concentrations and combinations in sunscreen formulations or products claiming protection against photoaging of the skin and hair are regulated. Examples of organic UV filters include oxybenzone, octrocrylene, avobenzone, and roctyl methoxycinnamate. Organic UV filters have the advantage of being easily incorporated into sunscreen formulations that are pleasant for the user to apply.

[0006] However, some organic UV filters have drawbacks, including photostability (for example, avobenzone), allergenic potential (for example, alkyl para-aminobenzoates), and many possess a certain ability to penetrate the skin barrier (stratum comeum) (for example, ethylhexyl methoxycinnamate), and may exhibit endocrine-disrupting effects (for example, oxybenzone). For instance, in the United States, the Food and Drug Administration (FDA) now requires additional toxicological studies for organic sunscreens if these molecules are found in plasma at a concentration greater than 0.5 ng / mL.

[0007] And finally, all these molecules, despite their lipophilic nature, will eventually end up in the natural environment, where they represent chemical pollution that is becoming increasingly unacceptable. For example, two molecules commonly used as UV filters, namely benzophenone-3 and ethylhexyl methoxycinnamate, are considered toxic to aquatic environments, and some local authorities (such as the State of Hawaii) have banned or restricted the use of sunscreen formulations containing these molecules.

[0008] Mineral UV filters are typically made of insoluble inorganic powders, such as titanium dioxide, zinc oxide, cerium oxide, or iron oxides. These particles reflect UV-A and UV-B radiation. These powders must be dispersed. To facilitate their incorporation into sunscreen formulations, these inorganic particles are usually coated with a hydrophilic or hydrophobic coating (e.g., based on methoxysilane, dimethicone, silica, or alumina). This coating partially inhibits their photoreactivity, as these powders are metal oxides capable of releasing hydrogen peroxide (H₂O₂) into water through a photocatalytic reaction. This reaction is responsible for damage to biological material (planktonic animals).

[0009] Mineral UV filters have the advantages of being hypoallergenic and not penetrating the skin barrier. However, they are more difficult to formulate than organic UV filters, because sunscreen formulations or products claiming protection against photoaging of the skin and hair in which these UV filters are incorporated are often thicker and have They tend to leave unsightly white marks on the skin. To overcome this problem, the particle size of these mineral UV filters can be reduced to nanometric. This increases sun protection, but regulations then require specific labeling and prohibit dispensing in spray or aerosol form.

[0010] Sunscreen formulations or products claiming protection against photo-aging of the skin and hair are typically characterized by their sun protection factor (abbreviated SPF), defined according to the following formula:

[0011] SPF = (Minimum Erythematous Dose on protected skin) / (Minimum Erythematous Dose on unprotected skin)

[0012] Sunscreen formulations or products claiming protection against photoaging of the skin and hair containing UV filters must meet numerous requirements to ensure optimal photoprotection. In particular, these formulations must exhibit low penetration of active substances such as UV filters into the skin to limit toxicity or allergic reactions. Furthermore, the formulations must have good emollient properties to allow for pleasant and long-lasting application to the skin's surface. It is also desirable that they be film-forming and water-resistant, but not sticky, especially since frequent reapplication is recommended during sun exposure.

[0013] According to the prior art, sunscreen compositions or products for protecting against photoaging of the skin and its appendages can be presented in various types of formulations, including liquid or paste emulsions such as ointments, creams, lotions, and foams; solid emulsions such as sticks, bars, and tablets; and non-emulsified forms such as oils, suspensions, gels, lotions, and loose or pressed powders. The formulation of a sunscreen product depends on the physicochemical properties of the incorporated UV filters. When the photoprotection product is an emulsion, it comprises a lipid phase, an aqueous phase, and one or more surfactants. The UV filters are dispersed either in the lipid phase if they are lipophilic or in the aqueous phase if they are hydrophilic.It is known to add excipients to sunscreen formulations to ensure optimal distribution of UV filters on the skin's surface by forming a homogeneous protective film upon application.

[0014] Generally speaking, it is not desirable for UV filters to penetrate the skin, as they can be toxic or allergenic. Both of these phenomena can be caused or exacerbated by UV light which can make these filters phototoxic or photoallergenic; if these filters are photounstable, their decomposition products may also exhibit these undesirable effects.

[0015] The passage of UV filters through the skin can be facilitated, in particular, by poor overall skin condition, by the disruption of skin barrier lipids under the action of UV rays, by the presence of certain solvents such as ethanol, propylene glycol, surfactants, by the presence of certain emollients, alpha-hydroxy acids (commonly abbreviated AHAs), and by the molecular mass of the filters, given that molecules with a molecular mass below 500 Da are more likely to cross the skin barrier than molecules with a higher molecular mass

[0016] However, according to the prior art, organic UV filters are often lipophilic molecules with low molecular weight; they are therefore likely to penetrate the skin barrier and thus reach the nucleated cells of the skin, and then the systemic circulation. To limit this penetration through the skin barrier, the prior art offers formulations of sunscreens or products claiming protection against photoaging of the skin and its appendages in which the UV filter is encapsulated in a particle. In particular, numerous embodiments are known in which the UV filters are enclosed in microcapsules. These particles can also absorb and / or reflect UV radiation on their own.The outer wall of these particles can be chosen from a material that maintains the integrity of the solar filter mixture through sufficient sealing; it is desirable that this material be stable under solar irradiation to allow for prolonged application.

[0017] The prior art includes numerous particulate systems. For example, solid lipid nanoparticles (SLNs) are known. These are oily droplets of solid lipids at body temperature that are stabilized by surfactants. In other words, SLNs are nanoparticles consisting of a solid lipid core enveloped in one or more surfactants suspended in an aqueous phase; they thus possess occlusive properties that could make them usable for sun protection cosmetic products. Formulations containing SLNs in which liposoluble UV filters are encapsulated could be prepared; with these formulations, the penetration of the encapsulated UV filters into the skin would be reduced. Such compositions are described in US patent application 2003 / 0235540.

[0018] However, the use of SLNs has the following drawbacks: firstly, the quantities of encapsulable UV filters are limited, and secondly, these nano-encapsulated systems are not completely stable: the UV filters tend to be expelled from the nanoparticle during storage of the sun protection formulation. This latter problem is inherent to the solid lipids constituting the matrix of SLNs, which tend to form a perfect crystalline network whose interstices allow the ejection of UV filters from the nanoparticle.

[0019] Furthermore, SLNs can be more or less sensitive to heat depending on the melting point of the solid lipid matrix used. If the solid lipid matrix melts, this can disrupt the system, potentially leading to a decrease in the UV filtering capacity of the SLNs and also to the complete phase shift of the SLN suspension. Finally, the significant presence of solid lipids with a melting point higher than skin temperature (i.e., above approximately 32°C) makes SLN-based sunscreen formulations difficult to apply.

[0020] Thus, in the current state of knowledge on the properties of SLN, sun protection formulations comprising UV filters encapsulated with this system do not prove to be fully satisfactory.

[0021] UV filter entrapment systems consisting of nanoparticles made up of a solid and liquid lipid core enveloped in one or more surfactants, resulting from the mixing of solid lipids with liquid lipids, are also known. These particles, which can be suspended in an aqueous phase, are known as nanostructured lipid carriers (NLCs). Compared to SLNs, NLCs have a heterogeneous structure that gives their matrix an imperfect structure with spaces in which UV filters can be embedded. This overcomes the UV filter ejection problems encountered with SLNs. However, due to the presence of solid lipids, NLCs exhibit the same type of spreading and heat sensitivity defects as SLNs.

[0022] Although their greater capacity to encapsulate UV filters and their better stability make NLCs more suitable than SLNs in the field of sun protection product formulation, their stability during storage and after spreading on the skin is still not totally satisfactory.

[0023] Another approach is represented by nanocapsules comprising an oily core and UV filters surrounded by a polymeric shell (also called a bark); this approach is described in numerous documents, such as FR 3 009 682 (Polaar SAS and Université Claude Bernard). These polymeric barks can be of different types.

[0024] By way of example, document WO 2009 / 091726 (Dow Global Technologies) describes the encapsulation of hydrophobic sunscreen molecules in polyurea shells obtained by interfacial polymerization of an isocyanate with an amine. The optimal shell thickness depends on the diameter of the microcapsules: for a diameter up to 4 pm, the bark must have a thickness greater than 10 nm, while for a size greater than 10 pm the bark must have a thickness of at least 100 nm.

[0025] Document WO 2013 / 059166 (Dow Global Technologies) describes a microencapsulated sunscreen in which the UV filter is encapsulated in polymeric microcapsules resulting from the reaction between an isocyanate prepolymer and water to form a polyurea shell. These microcapsules can be smaller than 1 µm, and with respect to their thickness, the teaching in this document is similar to that in the previous document.

[0026] Document WO 2014 / 132261 (Tagra Biotechnologies) describes microcapsules formed from a polyacrylate, a polymethacrylate, a cellulosic ether, a cellulosic ester, or a mixture of these polymers, containing UV filters. Document WO 2012 / 004461 (Biosynthis) describes microcapsules formed by polymerization of methyltrimethoxysilane or methyltriethoxysilane, containing UV filters.

[0027] There is a need for UV filter encapsulation systems and sun product formulations with improved sun protection performance, while reconciling several other parameters, such as: the proper distribution of sun filters between UVA and UVB with a minimum UVA / UVB intensity ratio of 33% for UVA protection on the skin and a critical wavelength greater than 370 nm, the prevention of transcutaneous passage of UV filters, improved aesthetic properties such as the reduction of white marks left on the skin, particularly by mineral UV filters after application.

[0028] It is also desirable to have formulations of sun products using as little as possible of the substances called sun filters to present a given sun protection factor.

[0029] The present invention aims to provide cosmetic formulations comprising micro-encapsulated UV filters, said formulations offering protection in the UVA and UVB spectra which meet all these requirements. Objects of the invention

[0030] The present invention aims to fulfill these aforementioned requirements by means of a selection of core-shell type microcapsules, comprising a shell encapsulating at least one active substance, which are very small in size, i.e., whose Ds50 value does not exceed 1 µm, is preferably less than 1.0 µm and preferably remains less than 0.80 µm, but which penetrate only as far as the stratum corneum (namely the upper layer of the epidermis). These microcapsules are also water-resistant and mechanically strong against crushing and friction, while not giving a sticky appearance to cosmetic compositions including said microcapsules. This Strength is achieved through the use of a cross-linked polymer for the shell, and through a sufficient thickness of the shell which represents at least 20% of the total mass of the microcapsule.

[0031] The microcapsules of the present invention are capable of being obtained by interfacial polymerization (and in particular by interfacial polymerization of a precursor of a polyurea-type polymer compound), so as to enclose an active substance such as a sunscreen.

[0032] The invention relates to cosmetic and / or dermo-cosmetic and / or pharmaceutical compositions comprising the microcapsules according to the invention, and in particular to sun protection compositions or compositions claiming protection against photo-aging of the skin or hair, preferably water-resistant. These formulations may be emulsions; in particular, they may be "oil-in-water emulsion" or "water-in-oil emulsion" type formulations.Within the framework of the present invention, compositions comprising the microcapsules according to the invention, preferably sun protection cosmetics or cosmetics claiming protection against photo-aging of the skin or skin appendages, can be formulated in particular in the form of liquid or paste emulsions: ointments, creams, milks, mousses, or in the form of solid emulsions: sticks, bars, or in non-emulsified form: oils, suspensions, gels, lotions, loose or compact powders and more generally, with other active ingredients, in the form of shower gel, shampoo etc.

[0033] A first object of the invention is a core-shell type microcapsule, comprising a core containing at least one active ingredient, and comprising a shell, said shell forming a wall around said core and representing a mass fraction of at least 20%, preferably at least 25%, more preferably at least 28%, even more preferably at least 30%, and even more preferably at least 32% (or even at least 35%), of the total mass of the microcapsule, said microcapsule being characterized in that the shell comprises at least one cross-linked polymer. Said microcapsule is preferably prepared by interfacial polymerization.

[0034] Said cross-linked polymer is advantageously selected from polyurethane and / or polyurea. The shell may further comprise an anionic surfactant, preferably alkyl ether sulfate, and / or at least one non-ionic surfactant, such as polyethylene glycol esters or ethers, polyglycerol esters, esters of sorbitol derivatives such as sorbitan stearate, sucrose esters, or a polysorbate, for example polysorbate 20, polysorbate 40, or polysorbate 60. Said core is advantageously liquid.

[0035] A second object is the use of core-shell microcapsules according to the invention for the preparation of a sun protection formulation or a formulation providing protection against photo-aging of the skin and hair, usable in the form of liquid or paste emulsions: ointments, creams, milks, mousses, or in the form of solid emulsions: sticks, bars, or in non-emulsified form: oils, suspensions, gels, lotions, loose or compact powders.

[0036] A third object of the invention is a sun protection formulation, particularly in the form of liquid or paste emulsions: ointments, creams, lotions, foams, or in the form of solid emulsions: sticks, bars, or in non-emulsified form: oils, suspensions, gels, lotions, loose or pressed powders, comprising a plurality of microcapsules according to the invention. Advantageously, said sun protection formulation comprises at least 20% by mass, preferably at least 30% by mass, and even more preferably at least 35% by mass of core-shell microcapsules relative to the total weight of said formulation.

[0037] Yet another object of the invention is a process for manufacturing by interfacial polymerization of core-shell microcapsules comprising a core containing at least one active ingredient and a shell, said shell constituting a wall around said core, representing a mass fraction of at least 20%, preferably at least 25%, even more preferably at least 30% and even more preferably at least 35% of the total mass of the microcapsule, and comprising at least one cross-linked polymer obtained from at least two precursor compounds A and B,

[0038] said process comprising the steps of:

[0039] (a) mix said at least one active ingredient, a solvent and at least one compound A comprising more than two functional groups A', to obtain a lipophilic phase;

[0040] (b) introduce, under stirring, the lipophilic phase obtained in step (a) into a phase continuous aqueous, which preferably includes NaCl, to form an emulsion;

[0041] (c) maintain, under agitation, said emulsion at a temperature between about 35 °C and about 90 °C, preferably between about 40 °C and about 70 °C, and even more preferably between about 55 °C and about 65 °C, and introduce, under stirring, an aqueous solution comprising at least one compound B comprising more than two functional groups B' into the emulsion obtained at the end of step (b) so as to react the functional groups A' of said compound A comprising more than two functional groups A' with the functional groups B' of compound B comprising more than two functional groups B', to form the cross-linked polymer shell constituting a wall around said core and thus to obtain core-shell microcapsules.

[0042] In an advantageous embodiment, the agitation during step (b) is carried out with a greater tangential velocity than the agitation during the introduction of said aqueous solution comprising at least one compound B in step (c), and preferably with a tangential velocity of at least 10 m / s, and even more preferably between 10 m / s and 30 m / s.

[0043] Another object of the invention is a method for manufacturing core-shell microcapsules by interfacial polymerization, comprising a core containing at least one sunscreen and a shell forming a wall around said core, said shell comprising a cross-linked polymer and at least one alkyl ether sulfate,

[0044] the method comprising the steps of:

[0045] (a) mixing said at least one sunscreen, a solvent and a compound A comprising more than two functional groups A', precursor of the cross-linked polymer bark constituting a wall around said core, to obtain a lipophilic phase;

[0046] (b) introduce, under stirring, the lipophilic phase obtained in step (a) into a phase continuous aqueous solution comprising NaCl and at least one alkyl ether sulfate, to form an emulsion;

[0047] (c) maintain, under agitation, said emulsion at a temperature between about 35 °C and about 90 °C, preferably between about 40 °C and about 70 °C, and even more preferably between about 55 °C and about 65 °C, and introduce, under stirring, an aqueous solution comprising a compound B comprising more than two functional groups B' into the emulsion obtained at the end of step (b) so as to react the functional groups A' of compound A comprising more than two functional groups A' with the functional groups B' of compound B comprising more than two functional groups B', to form the cross-linked polymer shell constituting a wall around said core, and thus to obtain core-shell microcapsules. Figures

[0048] Figures 1 to 12 relate to the invention and illustrate different aspects of it.

[0049] [Fig. 1] relates to Example 1 and shows the particle size distribution of a batch of reference microcapsules 108, expressed in number (curve (a)), in surface area (curve (b)) and in volume (curve (c)).

[0050] [Fig.2] relates to example 1 and shows the particle size distribution of a batch of reference microcapsules 110, expressed in number (curve (a)), in surface area (curve (b)) and in volume (curve (c)).

[0051] [Fig.3] refers to example 1 and compares the surface particle size distribution between sample 108 (curve (a)) and sample 110 (curve (b)).

[0052] [Fig. 4] relates to Example 3 and shows the SPF (Solar Protection Factor) as a function of the microcapsule diameter (expressed in Ds50) according to a surface-weighted distribution according to the invention, all all other things being equal.

[0053] [Fig.5] relates to example 4 and shows the volume-weighted Dv50 particle size distribution of microcapsules in a slurry.

[0054] [Fig.6] relates to example 4 and shows the surface weighted Ds50 particle size distribution of microcapsules in the same slurry that generated [Fig.5].

[0055] [Fig.7] relates to Example 4 and shows the zeta potential which expresses the state of electrical charge of the surface of a particle within a colloid.

[0056] [Fig.8] relates to example 5 and shows the photostability as a function of the number of irradiations (in 30-minute increments) of a composition according to the invention comprising about 25% UV filter (curves c and d) and of a non-micro-encapsulated composition according to the prior art (curves a and b) comprising the same concentration of the same active ingredient.

[0057] [Fig.9] relates to example 5 and shows the photostability as a function of the number of irradiations (in 30-minute increments) of a composition according to the invention comprising about 35% UV filter (curves c and d) and of a non-micro-encapsulated composition according to the prior art (curves a and b) comprising the same concentration of the same active ingredient.

[0058] [Fig. 10] relates to example 5 and shows the SPF factor as a function of the UV filter concentration for a microencapsulated composition according to the invention (curve a) and a non-microencapsulated composition (curve b) comprising the same concentration of the same active ingredient.

[0059] [Fig. 11] relates to Example 6 and shows fluorescence micrographs (magnification factor: 20) of human skin explant samples prepared using a cryomicrorotome. On the left, a sample taken from untreated skin; in the middle, a sample taken from skin treated with a non-microencapsulated formulation; and on the right, a sample taken from skin treated with a microencapsulated formulation according to the invention.

[0060] [Fig. 12] refers to [Fig. 11] and shows the total intensity of the images, for a magnification factor of 20 (right) and a magnification factor of 10 (left). Detailed description

[0061] Unless otherwise stated, all percentage values ​​refer to mass. Unless otherwise stated, all D50 values ​​are Ds50 values: the median or Ds50 size is the size for which the cumulative function is equal to 50%; it is area-weighted. The choice of area weighting is most relevant when studying the activity of a certain dispersed component, as in the present context.

[0062] The microcapsules according to the invention have a liquid core, which represents the active substance to be encapsulated, and a shell made of a cross-linked polymeric material. This cross-linked polymer is selected from polyurea and / or polyurethane. Said active substance comprises at least one active substance selected from UV filters.

[0063] We first describe the manufacture of the microcapsules.

[0064] According to the invention, these microcapsules are prepared by an interfacial polymerization process.

[0065] In a first step (also referred to herein as "step (a)"), the active ingredient to be encapsulated, intended to form the liquid core of the microcapsule, is mixed with a solvent if necessary and a compound A comprising more than two functional groups A', which is one of the precursors of the cross-linked polymer shell constituting a wall around the core. This yields a lipophilic phase, that is to say, a phase immiscible with water.

[0066] In a second step (also referred to here as "step (b)"), the lipophilic phase obtained at the end of the first step is introduced, under agitation, into a continuous aqueous phase, to form an emulsion.

[0067] This continuous aqueous phase preferably comprises NaCl.

[0068] In a third step (also referred to herein as "step (c)"), under After stirring, the emulsion is heated to a temperature between approximately 35 °C and approximately 90 °C, preferably between approximately 40 °C and approximately 70 °C, and even more preferably between approximately 55 °C and approximately 65 °C. An aqueous solution comprising a compound B containing more than two functional groups B' is then introduced, under stirring, into the emulsion obtained at the end of step (b) of compound B in such a way as to react the functional groups A' of compound A containing more than two functional groups A' with the functional groups B' of compound B containing more than two functional groups B'. The product of this reaction is a cross-linked polymer. It forms the shell or wall of the microcapsule. Core-shell microcapsules are thus obtained, comprising a shell of cross-linked polymer forming a wall around the liquid core.Typically, the reaction mixture is left to stir until all the monomers, and in particular the isocyanate, have been consumed.

[0069] The execution of this process requires a certain degree of temperature control of the reaction mixture. The temperature depends on the reactivity of the monomers or prepolymers used, and on the degree of agitation.

[0070] In a highly advantageous embodiment of the invention, the agitation during step (b) is carried out with a greater tangential velocity than the agitation during step (c), and preferably with a tangential velocity of at least 10 m / s, and preferably between 10 m / s and 30 m / s. It should be noted that, generally speaking, the The number of rotor revolutions per unit of time is not a suitable parameter for characterizing the shear stress experienced by the liquid phase agitated by that rotor. The tangential velocity at an extreme point of the rotor provides a better and simpler description of the shear stress in an emulsion chamber.

[0071] According to the invention, step b requires strong agitation, ensuring high shear. This agitation is achieved, in a known manner, by using a rotor, and is simply characterized by the tangential speed of the rotor. This high shear is advantageously obtained with a tangential speed of at least approximately 10 m / s, and which is advantageously between approximately 10 m / s and approximately 30 m / s. Below approximately 10 m / s, the microcapsules obtained have a diameter that is too large, which prevents the benefits associated with a small diameter from being realized. Above approximately 30 m / s, controlling the temperature of the emulsion becomes difficult due to excessive local heating from the rotor-stator shear.Preferably, the tangential velocity is between approximately 10 m / s and approximately 28 m / s, more preferably between approximately 15 m / s and approximately 25 m / s, and even more preferably between approximately 15 m / s and approximately 23 m / s.

[0072] The third step typically begins with a period during which the temperature of the mixture is regulated to a desired value, preferably by maintaining the reaction mixture under vigorous stirring, that is, at least initially within the same limits as during the second step. The addition of the aqueous solution containing at least one compound B in step (c) is carried out with stirring characterized by a lower tangential velocity than the stirring during step (b). Thus, a tangential velocity during the addition of compound B of between approximately 1 m / s and approximately 6 m / s is suitable; preferably, it is between approximately 2 m / s and approximately 5 m / s. The duration of the third step must be sufficient for the emulsion formed to have the desired fineness and homogeneity, given that during polymerization, the microcapsules that form have a size comparable to that of the emulsion droplets.

[0073] In order for the addition of said aqueous solution during step (c) to occur within the target temperature range, it is typically necessary to regulate this temperature. In particular, it is possible to preheat said dispersed phase and / or said continuous aqueous phase during step (b), and / or it is also possible to heat the emulsion at the beginning of step (b). Since shearing of the emulsion releases thermal energy, in some cases it may be necessary to cool the emulsion. The exothermic nature of this reaction must be taken into account when managing the temperature during the polymerization reaction in step (b).

[0074] It is advantageous for the emulsion at the end of step (b) to be transferred to a different reactor, which is, on the one hand, equipped with different stirring means than those of the reactor in which step (b) took place, and which is, on the other hand, equipped with specific heat exchange means.

[0075] This process can be carried out according to different embodiments.

[0076] According to one embodiment, in the second step, said lipophilic phase is brought to a temperature between about 35 °C and about 90 °C, preferably between about 40 °C and about 70 °C, and even more preferably between about 55 °C and about 65 °C; in the third step, said continuous aqueous phase is at a temperature between about 35 °C and about 90 °C, preferably between about 40 °C and about 70 °C, and even more preferably between about 55 °C and about 65 °C.

[0077] Advantageously, in the third step, the temperature of said aqueous solution is similar to the temperature of said emulsion. Preferably, their temperatures should not differ by more than 15 °C, preferably not by more than 10 °C, and even more preferably not by more than 5 °C.

[0078] The core of the microcapsules is advantageously liquid. Said aqueous continuous phase may comprise at least one anionic surfactant and / or at least one non-ionic surfactant. An advantageous anionic surfactant may be selected from the group consisting of: sodium lauryl sulfate, sodium C14-C16 olefin sulfonate, sodium laureth sulfate, disodium laureth sulfosuccinate, sodium methyl cocoyl taurate, sodium cocoyl isethionate, sodium lauryl sarcosinate, sodium lauroyl glycinate, sodium lauroyl lactate, magnesium laureth sulfate, TEA lauryl sulfate, sodium lauroyl glutamate, sodium laureth carboxylate, sodium laureth phosphate, sodium laureth sulfoacetate, hydrogenated lecithin; knowing that these names are those of the INCI (International Nomenclature of Cosmetic Ingredients).

[0079] In particular, the anionic surfactant may include an alkyl ether sulfate. A particularly advantageous surfactant includes disodium-2-sulfolaurate; such a product is known under the brand name Texapon™.

[0080] A nonionic surfactant is preferred, which may be an ester or ether of polyethylene glycol, a polyglycerol ester, an ester of sorbitol derivatives such as sorbitan stearate, a sucrose ester, or an alkyl ether sulfate or polysorbate, for example polysorbate 20 (polyoxyethylene sorbitan monolaureate), also known as Tween™20, polysorbate 40, or polysorbate 60. Advantageously, a nonionic surfactant may be selected from the group consisting of: Poloxamer 407, poloxamer 188, oleth-10, oleth-20, laureth-23, laureth-4, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, polysorbate-20, polysorbate-40, poysorbate-60, polysorbate-80, sorbitan oleate, sorbitan stearate, sorbitan palmitate, sorbitan myristate, sorbitan laurate, gluceth-20, PEG-7 glyceryl cocoate, PEG-6 caprylic capric glycerides, PPG-l-PEG-9 lauryl glycol ether, hepthyl glucoside, polyglyceryl-10 laurate, glyceryl oleate, polyglyceryl-4-oleate, PEG / PPG 20 / 23 dimethicone, PEG / PPG-23 / 6 dimethicone, PEG-8 dimethycone, di-methicone PEG-10 phosphate, sucrose laurate, sucrose palmitate; knowing that these names are those of INCI.

[0081] These surfactants are found after polymerization in the bark.

[0082] According to an advantageous embodiment, the aqueous continuous phase used in this third step comprises at least one alkyl ether sulfate. Magnesium lauryl ether sulfate and sodium lauryl ether sulfate are preferred for this purpose.

[0083] According to another advantageous aspect of the invention, the NaCl content in said aqueous continuous phase used in step (b) is chosen such that the emulsion obtained at the end of this step (b) has a NaCl content of between 0.10% and 1% by mass, and preferably between 0.15% and 0.90% by mass. The addition of NaCl makes it possible to obtain more concentrated suspensions without aggregates.

[0084] According to an essential feature of the invention, said shell comprises at least one cross-linked polymer. This yields microcapsules exhibiting good mechanical strength. It is therefore necessary to select suitable monomers or oligomers that allow for the production of a cross-linked polymer. The functional groups A' of compound A, comprising more than two functional groups A', are selected from isocyanate groups, in particular from polyisocyanates, which are molecules containing two or more isocyanate groups, such as diisocyanates. Diisocyanates and triisocyanates are preferred, in which the isocyanate groups can be linked to an aliphatic or aromatic skeleton. Aliphatic polyisocyanates can be selected from aliphatic polyisocyanates containing two, three, or more than three isocyanate functions, or mixtures of such polyisocyanates.Preferably, aliphatic polyisocyanate comprises one or more cyclokyl skeletons.

[0085] By way of example, compound A may be selected from the group consisting of: - dicyclohexylmethane 4,4'-diisocyanate, hexamethylene 1,6-diisocyanate, isophorone diisocyanate, trimethylhexamethylene diisocyanate, hexamethylene 1,6-diisocyanate trimer, isophorone diisocyanate trimer, 1,4-cyclohexane diisocyanate, 1,4-(dimethylisocyanato)cyclohexane, hexamethylene diisocyanate biuret, hexamethylene diisocyanate biuret (CAS No. 4035-89-6), trimethylene diisocyanate, propylene-1,2-diisocyanate, butylene-1,2-diisocyanate, tetramethylene diisocyanate, pentamethylene diisocyanate, hexamethylene diisocyanate, 4-(isocyanatomethyl)-1,8-octyl diisocyanate; - mixtures of aliphatic diisocyanates and aliphatic triisocyanates phatic, - aromatic polyisocyanates such as 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, naphthalene diisocyanate, diphenylmethane diisocyanate, triphenylmethane-p,p',p”-trityl triisocyanate, - aromatic isocyanates such as toluene diisocyanate, polymethylene polyphenylisocyanate, 2,4,4'-diphenyl ether triisocyanate, polymethylene polyphenylisocyanate, 2,4,4'-diphenyl ether triisocyanate, 3,3'-dimethyl-4,4'-diphenyl diisocyanate, 3,3-dimethoxy-4,4' diphenyl diisocyanate, 1,5-naphthalene diisocyanate, 4,4',4”-triphenylmethane triisocyanate, isophoron diisocyanate.

[0086] The functional groups B' of compound B comprising more than two functional groups B' are chosen so that compound B is an amine (such as diamines or polyamines). As an example, one or more of the following amines can be used: ethylenediamine, diethylenetriamine, propylenediamine, tetraethylenepentaamine, pentamethylenehexamine, alpha-omegadiamine, propylene-1,3-diamine, tetramethylenediamine, pentamethylenediamine, 1,6-hexamethylenediamine, triethylenetriamine, pentaethylenehexamine, 1,3-phenylenediamine, 2,4-toluynediamine, 4,4'-diaminodiphenylmethane, 1,5-diaminonaphthalene, 1,3,5-triaminobenzene, 2,4,6-triaminotoluene, 1,3,6-triaminonaphthalene, 2,4,4'-triaminodiphenyl ether, 3,4,5-triamino-1,2,4-triazole, bis(hexamethylene triamide), 1,4,5,8-tetraamino anthraquinone.

[0087] A preferred amine is guanidine carbonate.

[0088] According to an advantageous embodiment, the interfacial polymerization process uses an amount of prepolymer in the oily phase which is greater than 25% by volume.

[0089] According to an essential feature of the invention, said bark forming a wall around said core represents a mass fraction of at least 20%. Advantageously, this fraction is between approximately 20% and approximately 45%, and more preferably between approximately 25% and approximately 35%.

[0090] With certain isocyanates leading to a relatively hard shell, the mass fraction of the wall around the core advantageously represents between about 28% and about 32% of the total mass of the microcapsule.

[0091] According to an advantageous aspect of the invention, the microcapsules have a size Ds50 less than or equal to 0.80 pm. This makes it possible to benefit from an effect that the inventors unexpectedly discovered: for a sun protection formulation comprising a given content of sunscreen, the SPF factor increases when the size Ds50 of the microcapsules containing this formulation is less than or equal to 0.80 pm. This allows for either a higher SPF with a given concentration of sunscreen formulation, or a given SPF with a lower concentration of sunscreen formulation. A Ds50 size of 0.75 pm or less is preferred, even more preferably 0.70 pm or less, and even more preferably 0.65 pm or less, or even 0.60 pm or less, because below a Ds50 size of approximately 0.8 pm, the SPF increases as the size of the microcapsules decreases.

[0092] At the end of the third step, a suspension is obtained comprising a dispersed phase (referred to as "slurry" by those skilled in the art) containing the microcapsules, and a liquid phase containing solvents, a surfactant, unreacted reagents, and various secondary reaction products. In a typical embodiment, the slurry contains approximately 20% microcapsules by mass. The microcapsules are washed and concentrated using methods known to those skilled in the art. After removal of the continuous phase, a suspension can be obtained containing more than 50% microcapsules by mass, preferably between approximately 50% and approximately 70%, and even more preferably between approximately 60% and approximately 70%, the remainder being water (as well as various residues).This suspension can be used directly for the preparation of sun protection formulations incorporating the microcapsules according to the invention; this can be done using known methods, as will be illustrated in the examples. It is also possible to continue drying to obtain a microcapsule powder.

[0093] In order to avoid softening of the microcapsules and their rupture, the microcapsules must be introduced under moderate agitation, and preferably at a temperature not exceeding that at which the emulsion was prepared (third step of the process described above), and even more preferably at a temperature below 60°C.

[0094] Generally speaking, basic ingredients, active ingredients, and known cosmetic excipients and additives can be used. The nature and quantities of sunscreens used must comply with the legislation in force regarding compositions containing sunscreens in the countries of marketing. For example, for marketing the sun protection formulation in the USA, the concentration of avobenzone must not exceed 3%.

[0095] The microcapsules according to the invention can contain all types of active substances (also called "active ingredients"). We provide here, by way of example, a list of active ingredients capable of acting as sunscreens, which are preferred for the implementation of the present invention. These active ingredients are identified here by their INCI (International Nomenclature of Cosmetic Ingredients) name and by their CAS number:

[0096] Glyceryl PABA (CAS No. 136-44-7), Menthyl antranilate (CAS No. 134-09-8), Die- thylamino hydroxybenzoyl hexylbenzoate (N° CAS 302776-68-7), Polysilicone-15 (N° CAS 207574-74-1), Bis-ethylhexyloxyphenol methoxyphenyl triazine (N° CAS 187393-00-9-6), Ethylhexyl dimethyl PABA (N° CAS 21245-02-3), Ethylhexyl sa-licylate (N° CAS 118-60-5), 3-Benzylidene camphor (N° CAS 15087-24-8), Die-thylhexyl butamimido triazone (N° CAS 154702-15-5), 4-Methylbenzylidene camphor (N° CAS 38102-62-4 / 36861-47-9), PABA (N° CAS 150-13-0), Homosalate (N° CAS 118-56-9), Benzophenone-3 (N° CAS 131-57-7), Butyl methoxydibenzoylmethane (N° CAS 70356-09-1), Octocrylene (N° CAS 6197-30-4), Ethylhexyl methoxycinnamate (N° CAS 5466-77-3), Isoamyl p-methoxycinnamate (N° CAS 71617-10-2), Ethylhexyl triazone (N° CAS 88122-99-0).

[0097] On peut ajouter des agents stabilisants, qui peuvent être de type connu.

[0098] Formulations containing Butyl methoxydibenzoylmethane gain photostability if at least one of the following ingredients is added to the formulation of the microencapsulated phase: butyloctyl salicylate, C12-15 alkyl benzoate, diethylhexyl 2,6-naphthalate, polyester-8, ethylhexyl methoxycrylene, octocrylene, diethylhexyl sy-ringylidene malonate, tocopherol, triethylcitrate.

[0099] This results in sun protection formulations that offer numerous advantages. These formulations are highly resistant to spreading on the skin because the microcapsules withstand significant shear forces in an aqueous environment when applied to the skin. These formulations minimize the penetration of the sunscreen filter into the skin, as the microcapsules containing it are mechanically very stable. For a given concentration of sunscreen filter, these formulations offer a higher sun protection factor. These formulations can be produced with an SPF that varies within fairly wide limits. It is preferable that the SPF be at least 10, preferably at least 15, more preferably at least 30, and even more preferably at least 40. Formulations with an SPF greater than 50 are possible. Examples

[0100] Example 1: Preparation of microcapsules

[0101] We describe here eight examples of implementation of the process according to the invention.

[0102] Example 1-1

[0103] Monomer A was an aliphatic polyisocyanate. Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of butyl methoxydibenzoylmethane (15%), octocrylene (15%) and homosalate (70%).

[0104] A lipophilic phase was prepared containing 69.7% of the active ingredient mixture (sunscreens) to be encapsulated with 30% of monomer A and 0.3% of a non-ionic surfactant SPAN™ 60. A continuous aqueous phase was prepared with 6500 mL of demineralized water, 1% of the surfactant Texapon™, and 0.3% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomer B.

[0105] The lipophilic phase and the aqueous continuous phase were heated to 60°C. At this temperature, the lipophilic phase to be dispersed was added to the hot continuous phase in a circuit containing a stator rotor with very high shear, for 6 min, at a ratio of 20% lipophilic phase to the aqueous continuous phase containing the surfactant. The dispersion from the circuit was then emptied into a tank thermostatically controlled at 60°C under constant, low-level stirring. The monomer B solution was slowly added, and the temperature was maintained at 60°C for at least 6 hours.

[0106] The Dx50(SurfaCe) value of the microcapsules was 680 nm.

[0107] Example 1-2

[0108] Monomer A was a mixture of an aliphatic polyisocyanate (80%) and a polyphenyl-polymethylene polyisocyanate (20%). Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of butyl methoxydiben-zoylmethane (13%), ethylene salicylate (22%), homosalate (55%), and propylene carbonate (10%).

[0109] A lipophilic phase was prepared containing 69.7% of the active ingredient mixture (sunscreens) to be encapsulated with 30% of monomer A and 0.3% of the non-ionic surfactant SPAN™ 60. A continuous aqueous phase was prepared with 6500 mL of demineralized water, 0.5% of the surfactant Texapon™, 1% of the surfactant Tween™ 80, and 0.1% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomer B.

[0110] The remaining steps of the process were carried out as described in relation to Example 1-1: The lipophilic phase and the aqueous continuous phase were heated to 60°C. At this temperature, the lipophilic phase to be dispersed was added to the hot continuous phase in a circuit containing a stator rotor with very high shear, for 6 min, at a ratio of 20% lipophilic phase to the aqueous continuous phase containing the surfactant. The dispersion from the circuit was then emptied into a tank thermostatically controlled at 60°C under constant, low stirring. The monomer B solution was added slowly, and the temperature was maintained at 60°C for at least 6 hours.

[0111] The Dx50(SurfaCe) value of the microcapsules was 840 nm.

[0112] Example 1-3

[0113] Monomer A was a mixture of an aliphatic polyisocyanate (60%) and a polyphenyl-polymethylene polyisocyanate (40%). Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of butyl methoxydiben-zoylmethane (15%), ethylhexyl dimethyl PABA (15%), and homosalate (70%).

[0114] A lipophilic phase was prepared containing 69.8% of the mixture of active ingredient (sunscreen filters) to be encapsulated with 30% of monomers A and 0.2% of a ten- Non-ionic surfactant SPAN™ 60. A continuous aqueous phase was prepared with 6500 mL of demineralized water, 1% of surfactant T ween™20, and 0.1% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomer B.

[0115] The other steps of the process were carried out as described in relation to example 1-1.

[0116] The Dx50(SurfaCe) value of the microcapsules was 720 nm.

[0117] Example 1-4

[0118] Monomer A was a mixture of an aliphatic polyisocyanate (90%) and a polyphenyl-polymethylene polyisocyanate (10%). Monomer B was a mixture of guanidine carbonate (90%) and glycerol (10%). The active ingredient to be encapsulated was a mixture of butyl methoxydibenzoylmethane (13%), ethylhexyl salicylate (18%), homosalate (65%), and tocopheryl acetate (4%).

[0119] A lipophilic phase was prepared containing 69.7% of the active ingredient mixture (sunscreens) to be encapsulated with 30% of monomers A and 0.3% of the non-ionic surfactant SPAN™ 60. A continuous aqueous phase was prepared with 6500 mL of demineralized water, 1% of the surfactant Texapon™, and 0.3% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomers B.

[0120] The other steps of the process were carried out as described in relation to example 1-1.

[0121] The value Dx5o(SUrface) of the microcapsules was 750 nm.

[0122] Example 1-5

[0123] Example 1-1 was repeated with the following changes: Monomer A was an aliphatic polyisocyanate. Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of butyl methoxydibenzoylmethane (15%), ethylhexyl triazone (8%), bibutyl adipate (69%), tocopheryl acetate (8%).

[0124] The Dx50(SurfaCe) value of the microcapsules was 450 nm.

[0125] Example 1-6

[0126] Example 1-1 was repeated with the following changes: Monomer A was a mixture of an aliphatic polyisocyanate (90%) and a polyphenyl-polymethylene-polyisocyanate (10%). Monomer B was a mixture of guanidine carbonate (90%) and lysine (10%). The active ingredient to be encapsulated was a mixture of butyl methoxydibenzoylmethane (15%), ethylhexyl triazone (7%), dibutyl adipate (55%), ethylhexyl methoxycinnamate (15%), and polyester-8 (8%).

[0127] The value Dx5o(SUrface) of the microcapsules was 560 nm.

[0128] Example 1-7

[0129] Monomer A was a mixture of an aliphatic polyisocyanate (50%) and a polyphenyl-polymethylene polyisocyanate (50%). Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of butyl methoxydiben- zoylmethane (13%), ethylhexyl triazone (7%), dibutyl adipate (55%), ethylhexyl methoxycinnamate (15%) and triethyl citrate (10%).

[0130] A lipophilic phase was prepared containing 69.7% of the active ingredient mixture (sunscreen filters) to be encapsulated with 30% monomers A, 1% of the surfactant SPAN™ and 1% of the surfactant Tween™20. A continuous aqueous phase was prepared with 6500 mL of demineralized water and 0.1% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomers B.

[0131] The other steps of the process were carried out as described in relation to example 1-1.

[0132] The Dx50(SurfaCe) value of the microcapsules was 510 nm.

[0133] Example 1-8

[0134] Monomer A was a mixture of an aliphatic polyisocyanate (64%) and a polyphenyl-polymethylene polyisocyanate. Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of diethylamino hydroxybenzoyl hexylbenzoate (13%), ethylhexyl triazone (7%), bis-ethylhexyl-oxyphenol methoxyphenyl triazine (20%), and dibutyl adipate (60%).

[0135] A lipophilic phase was prepared containing 69.7% of the active ingredient mixture (sunscreen filters) to be encapsulated with 30% of monomer A and 0.3% of the surfactant SPAN™60. A continuous aqueous phase was prepared with 6500 mL of demineralized water containing 0.1% of the surfactant Texapon™, 1% of the surfactant Tween™80, and 0.3% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomer B.

[0136] The other steps of the process were carried out as described in relation to example 1-1.

[0137] The Dx50(SurfaCe) value of the microcapsules was 670 nm.

[0138] Example 1-9

[0139] Monomer A was a mixture of an aliphatic polyisocyanate (85%) and a polyphenyl-polymethylene polyisocyanate (15%). Monomer B was guanidine carbonate. The active ingredient to be encapsulated was a mixture of benzophenone-3 (12%), ethylhexyl triazone (8%), ethylhexyl dimethyl PABA (20%), 4-methylbenzylidene camphor (20%), and etisopropyl palmitate (40%).

[0140] A lipophilic phase was prepared containing 69.7% of the active ingredient mixture (sunscreen filters) to be encapsulated with 30% of monomer A and 0.1% of the surfactant SPAN™60. A continuous aqueous phase was prepared with 6500 mL of demineralized water with 1% of the surfactant Texapon™ and 0.5% NaCl. A 500 mL solution was prepared with a stoichiometric amount of monomer B.

[0141] The other steps of the process were carried out as described in relation to example 1-1.

[0142] Example 2: Particle size distribution of reference microcapsules 110 and 108

[0143] The water suspension and surfactant containing the microcapsules according to the invention were diluted with demineralized water and analyzed using a Masterizer™ 3000 particle size analyzer (Malvern). The results for the reference 108 microcapsules are shown in [Fig. 1], with the different representations provided by the instrument (Volume; Surface Area; Number). All distributions are unimodal. This indicates that the dispersion of the microcapsules is rather homogeneous, even though the difference between "number" and "volume" suggests a significant degree of polydispersity in microcapsule size. In all cases, the average size of the microcapsules is between 200 nm and 800 nm.

[0144] The results for the reference sample 110 are reported in [Fig. 2]. In this case, the distributions have a quasi-bimodal tendency (shoulder at 500 nm in the volume distribution; overlapping distribution of two Gaussians in the surface area distribution), which suggests a greater polydispersity in size compared to sample 110, with the distinction of two families of microcapsules with markedly different sizes. This is evident from the surface area distribution, with the two peaks coinciding with the median of the number (smaller size) and volume (larger size) distributions.

[0145] To better see the differences in the finely dispersed fraction between samples 110 and 108, the surface distributions were compared and the results reported in [Fig. 3]. It can clearly be seen that the average surface area of ​​the reference microcapsules 108 is significantly smaller compared to the reference microcapsules 110, with a more homogeneous distribution as well.

[0146] Laser particle size analysis results on samples 110 and 108 show that both types of microcapsules have a very fine size distribution (above one micron). Reference microcapsules 108 exhibit a more uniform and finer size distribution compared to reference 110, which could result in greater UV protection efficacy when used in a cosmetic formulation.

[0147] These results also show that laser granulometry can be used to determine the average size of microcapsules in colloidal dispersion. It is a fast and inexpensive method compared to electron microscopy.

[0148] A laser particle size analyzer is capable of measuring the particle size distribution in a colloidal dispersion using laser diffraction. Particle size can be described in several ways: by its maximum length, minimum length, volume, and surface area. Thus, the size distribution of a colloidal dispersion can also be represented in different modes, depending on the analytical technique used: 1. Number (D[l,0]): weighted at the smallest sizes (used rather in mid- (croscopy) ([Fig.1]) 2. Volume (D[4,3]): weighted at the largest sizes (used more in laser diffraction) ([Fig.1]) 3. Surface area (D[3,2]): median between number and volume.

[0149] Volume representation is often used to observe differences between two colloidal dispersions when focusing on the coarse fraction of the dispersion. Surface representation, on the other hand, is more commonly used when determining differences in the finely dispersed fraction, which is particularly useful in applications where the surface area of ​​the dispersed particles is significant (pharmaceuticals; cosmetics; paints).

[0150] Typically, in a laser particle size analyzer, the sample passes continuously under suction through the laser analysis chamber. The laser light scattered by the sample is intercepted by detectors located at different angles around the sample. This type of configuration allows for the discrimination of different particle size families in a colloidal dispersion, because smaller particles scatter the laser light at greater angles than larger particles. To avoid detector saturation, the sample must have an appropriate degree of dilution.

[0151] Example 3: Relationship between particle size and SPF factor of reference microcapsules 110

[0152] The samples analyzed are slurries of reference 110 microcapsules containing 20% ​​by mass of a mixture of UV filters compliant with US FDA requirements. The microcapsules are synthesized from different emulsions produced by a stator rotor at different shear speeds. These emulsions are then transformed into microcapsules by an interfacial polymerization process. This process yields different slurries of microcapsules, which are characterized by a particle size measurement that can be weighted by number, surface area, volume, or mass.

[0153] Diameter measurements are performed using a Mas-tersizer™ 3000 particle size analyzer (Malvern). Before each measurement, the initial sample is diluted with demineralized water until optimal saturation of the optical detectors is reached. Three measurement iterations are performed per sample reference. The resulting particle size distribution can be processed in three different ways: by volume, by number, and by surface area.

[0154] For this study, the results of the Ds50 of the surface weighted particle size distribution are retained.

[0155] The median or Ds50 size is the size for which the cumulative function is equal to 50%; it is area-weighted. The choice of area weighting is the most relevant when studying the activity of a certain dispersed component (paint; catalysis; pharma).

[0156] SPF measurements were carried out on these same samples, using the in vitro method on PMMA plate in order to relate Ds50 with SPF.

[0157] The results are reported in [Fig.4] and in Table 1.

[0158] [Tables 1] Surface-weighted microcapsule diameters of Ds 50 [pm] 1.37 1.28 0.98 0.86 0.81 0.69 SPF 1.5 1.8 6.7 12.6 15.0 25.1

[0159] Fig. 4 represents the curve of the measured SPF as a function of the median diameter (Ds 50) of the slurries of the microcapsules.

[0160] The results clearly show that when the Ds50 of the microcapsules decreases, the SPF of the suspension increases. This effect, as shown by the interpolation curve (red line), is exponential and gives good SPF (relative to the amount of encapsulated filter) when the surface-weighted median diameter (Ds50) is less than 800 nm.

[0161] These results suggest that when suspensions contain finely dispersed microcapsules, they are able, for the same application surface, to absorb UV rays more effectively and consequently to better protect against the harmful effects of these same rays. This property is therefore essential for obtaining a high-performance product in terms of efficacy (SPF) for products containing microcapsules of sunscreen filters.

[0162] Example 4: Characterization of the zeta potential of a colloidal suspension

[0163] In this study, the four samples analyzed are micro-suspensions Reference capsules (MCs) 110 with 20%. Each sample was made with a different amount of NaCl: 0% (110A); 0.35% (110B), 0.7% (HOC) and 1.4% (110D).

[0164] For Zeta Potential measurements, the suspensions containing type 110 microcapsules were pre-diluted with demineralized water by a factor of 1000 to obtain a clear and transparent dispersion suitable for analysis. Three measurement iterations were performed for each sample using a Malvern Zetasizer Nano (Malvem Instruments).

[0165] Diameter measurements are performed using a Mastersizer 3000 particle size analyzer (Malvern). Before each measurement, the initial sample is diluted with demineralized water until an optimal level of optical detector saturation is reached. The resulting particle size distribution can be weighted according to three different methods: in volume, number and surface area. For this study, the results of the surface-weighted particle size distribution parameter Ds50 (see [Fig. 6]) and the volume-weighted particle size distribution parameter Dv50 (see [Fig. 5]) are used. In Figures 5, 6 and 7, curve (a) corresponds to sample 110A, curve (b) to sample 110B, curve (c) to sample 110C and curve (d) to sample 110D.

[0166] The Zeta Potential results in [Fig. 7] clearly show a net increase in the charge on the surface of the microcapsules, which increases from -40 mV to -66 mV with the presence of salt during synthesis. This increase is, however, only slightly dependent on the NaCl concentration; that is, the charge varies very little with salt concentration (0.35%; -67 mV; sample 110B) and the largest (1.4%; -74 mV; sample 110D).

[0167] The particle size distribution results presented in Figures 5 and 6 clearly show that the increase in surface charge is due to the presence of salt; however, the size dispersion of the microcapsules is independent or almost independent of the presence of salt. Both the surface and volume distributions exhibit a bimodal pattern, suggesting the presence of two families of microcapsules with average sizes centered around 0.6 µm and 1.3 µm. The more finely dispersed family of microcapsules becomes predominant when the NaCl concentration reaches 1.4%.

[0168] This example shows that the presence of NaCl increases the negative zeta potential at the surface of the microcapsules independently of the concentration of the salt tested.

[0169] Consequently, the stability of the microcapsule suspensions is directly impacted by the presence of salt during synthesis. The higher surface charges stabilize the microcapsule dispersions by promoting electrostatic repulsion and minimizing aggregation effects. This effect can be achieved with a low salt concentration (0.35%). This explains why, during the synthesis of the suspensions, more concentrated and aggregate-free suspensions can be obtained when salt is added.

[0170] Example 5: Study of the photostability of UV filter compositions according to the invention

[0171] The results were obtained with specific in vitro methods for determining the sun protection factor SPF, UV-A protection and calculating the Critical Wavelength (abbreviated LOC) on Sunplate type polymethyl methacrylate (PMMA) support.

[0172] Four measurements were performed with a Kontron™ 933 spectrophotometer equipped with an integrating sphere to determine the sun protection factors. The HelioTest® methods No. 1, HelioTest® No. 2, HelioTest® No. 3, and HelioTest® No. 5 were used to determine the SPF, UVA, LOC, and to assess photostability.

[0173] The solar irradiation test was carried out with a Suntest Atlas CPS+ simulator at 550 W / m2 in 30-minute increments; the correspondence with the DEM (minimum erythematous dose) unit is: 30 min = 4 DEM, 60 min = 8 DEM, 120 min = 16 DEM. As is known to those skilled in the art, the DEM unit expresses the smallest quantity of light capable of triggering, after 24 hours, a sunburn at the site of exposure.

[0174] The results are summarized in Table 2 below, as well as in Figures 8 and 9.

[0175] [Tables2] Reference sample IR [min] SPF measured SPF displayed UVA LOC CM [nm] Photo stability [%] 8S0F1-1021 Fatty phase FDA Ref. 5421_15L (23%) 0 23.8 20 18.2 378 - 30 6.0 6 4.1 380 25 60 3.1 * 1.8 378 13 120 1.6 * 1.3 378 6 22SOF1-1021 Slurry pCaps US Dry extract 23% (23%) 0 31.2 30 21.7 382 - 30 21.7 20 13.0 380 69 60 12.7 10 6.9 380 40 120 6.4 6 3.1 380 20 22SOF2-1021 Fatty phase FDA Ref. 5421_15L (35%) 0 28.4 25 16.7 378 - 30 7.5 6 4.9 380 26 60 3.8 * 2.4 378 13 120 1.6 * 1.3 382 5 8SOF2-1021 Slury pCaps US Dry extract (35%) 0 63.6 50+ 56.7 382 - 30 48.6 30 37.4 382 77 60 34.6 30 22.0 381 55 120 13.9 10 4.7 378 22 IR = solar irradiation at 550 W / m2 with Suntest Atlas CPS+ simulator

[0176] Figure 8 shows the evolution of the SPF factor as a function of the UV filter concentration in the core of the microcapsule, and compares an encapsulated sample, with a sunscreen content of 23% relative to the total mass of the microcapsule (curve (c); UV-A; curve (d); UV-B), according to the invention, with the same non-active substance encapsulated (curve (a): UV-A; curve (b): UV-B) contained in an oily phase according to the prior art without microcapsules. The vertical axis represents the SPF value (100% being the initial value), the horizontal axis represents the number of 30-minute irradiation periods.

[0177] It is noted that the oil phase is not stable under UV irradiation: this instability is total after two hours of irradiation at 550 W / m² (16 DEM). The suspension is stable during the first irradiations, and then develops an instability that becomes very significant after two hours of irradiation at 550 W / m² (16 DEM). Encapsulating the UV filter improves the photostability of the formulation for both the SPF factor and UV-A protection.

[0178] Figure 9 shows the same type of curve for a microcapsule representing a sunscreen content of 35%. The curves refer to a microencapsulated formulation according to the invention (curve (c): UV-A; curve (d): UV-B) and to an oil-based formulation according to the prior art without microcapsules (curve (a): UV-A; curve (b): UV-B).

[0179] The observations regarding the photostability of the oil phase and the suspension are the same as for the previous figure. The oil phase is not stable under UV irradiation: this instability is total after two hours of irradiation at 550 W / m² (16 DEM). The suspension is stable during the first irradiations, and then develops instability that becomes very significant after two hours of irradiation at 550 W / m² (16 DEM). Encapsulating the UV filter improves the photostability of the formulation for both the SPF factor and the protection against UV-A.

[0180] Figure 10 shows the evolution of the SPF factor measured for microencapsulated suspension compositions according to the invention (curve (a)) and for non-microencapsulated suspension compositions not of the invention (curve (b)), for compositions containing different concentrations of the UV filter. It can be seen that above a concentration of approximately 21% to 22%, the microencapsulated suspension shows significantly higher protective activity than the non-encapsulated suspension, whereas at lower concentrations, no difference is observed.

[0181] Example 6: Comparison of in vitro skin absorption of encapsulated and non-encapsulated sunscreens

[0182] A suspension of microcapsules concentrated at 33% in water and comprising 23% of encapsulated sunscreens, according to the invention, and a control of unencapsulated sunscreens diluted at 23% in a product sold under the trade name Cétiol Ultimate (undecane / tridecane mixture) were used.

[0183] Human skin expiants mounted on Transwell inserts in a 6-well plate were used. The treatment area was 1 cm². The receiving fluid was PBS (1 mL). The treatment volume was 10 pL / cm², and the treatment duration was 24 hours. 37 °C.

[0184] Three different treatments were used: a control treatment (without active ingredient), an encapsulated formulation according to the invention, a non-encapsulated formulation outside the invention.

[0185] At the end of the treatment, excess formulation was removed with cotton swabs. A biopsy was taken from the treated area using a 100 mm diameter punch. The biopsy was cut in half with a scalpel, mounted in a cryomatrix, and placed on the cryobar at -50 °C before being mounted on the sectioning support. Slices 5 µm thick were cut from each sample using the cryomicrotome.

[0186] The slices were observed under a fluorescence microscope using a DAPI filter, at magnifications of 10 and 20. The exposure time for image acquisition was 20 ms. Image analysis was performed using ImageJ software, which allows semi-quantitative analysis of fluorescence intensity.

[0187] Fig. 11 shows fluorescence micrographs obtained for the three samples (two different areas for each of the treated samples) with a magnification of 20.

[0188] Figure 12 shows the fluorescence signal, in arbitrary units, obtained by image analysis, for magnifications of 10 and 20, of the three samples. More specifically, Figure 12 shows the total intensity of the images in Figure 11, for a magnification factor of 20 (right) and a magnification factor of 10 (left).

[0189] Regarding the untreated control sample, a diffuse fluorescent signal is observed which corresponds to the auto-fluorescence of the skin.

[0190] Regarding the sample treated with the non-encapsulated formulation, image analysis shows that the fluorescence intensity (diffuse signal) is slightly higher compared to the control sample.

[0191] Regarding the sample treated with the encapsulated formulation according to the invention, the signal is localized to the stratum corneum. The fluorescence intensity is much higher compared to the untreated control sample and the sample treated with the unencapsulated formulation; this signal is therefore specific to the formulation according to the invention.

[0192] Examples 7: Examples of carrier formulations for sunscreens

[0193] Example 7-1:

[0194] The formulation was based on the following ingredients: Phase Ingredient according to INCI name % mass A Microcapsule suspension according to the invention, at 50% 66 A Citric acid 0.5 B Xanthan gum 0,1 B Hydroxypropyl guar 0,1 C Aqua 2,5 C Disodium EDTA 0,05 D Sodium stearoyl glutamate 1 D Cetyl alcohol 1 D Cetearyl alcohol, Coco-glucoside, Aqua, Glucose 2 D Dicaprylyl carbonate, Tocopherol 8 D Squalane 7 D Tricontanyl PVP 2 E Undecane, Tridecane, Tocopherol 8 F Tocopherol, Helianthus Annuus Seed Oil 0,5 G Phenoxyethanol, Ethylhexylglycerin 1 H Citric acid 0,25

[0195] For this test, a planetary mixer was used, but no homogenizer. The components of phase A were mixed cold without using a homogenizer. Next, the components of phase B were dispersed in phase A, again without using a homogenizer, and then the ingredients of phase C, previously thoroughly dissolved, were added. Phase D was heated to 80 °C to thoroughly mix its components, and then unheated phase E was added to phase D. This mixture of phases D and E was then introduced, again without using a homogenizer, into the mixture being prepared, which consisted mainly of phase A. Phases F and G were then introduced, again without using a homogenizer. Phase H was added to adjust the pH to a value of approximately 6.

[0196] Example 7-2:

[0197] The formulation was based on the following ingredients: Phase Ingrédient selon dénomination INCI % massiques A Suspension de microcapsules selon l’invention, à 60 % 55 A Citric acid 0,1 B Xanthan gum 0,1 B Hydroxypropyl guar 0,15 C Aqua 8,85 C Disodium EDTA 0,05 D Sodium stearoyl glutamate 1 E Cetyl alcohol 1 E Sucrose polystearate, Cetyl palmitate 3 E Dicaprylyl carbonate, Tocopherol 12 E Squalane 5 E Butyrospermum Parkii Butter 2 E Tricontanyl PVP 2 F Undecane, Tridecane, Tocopherol 8 G Tocopherol, Helianthus Annuus Seed Oil 0,5 H Phenoxyethanol, Ethylhexylglycerin 1 I Citric acid 0,25

[0198] For this test, a planetary mixer was used, but no homogenizer. The components of phase A were mixed cold without using a homogenizer. The components of phase B were then dispersed in phase A, again without using a homogenizer. Next, the ingredients of phase C, previously thoroughly dissolved, were added, followed by phase D. Phase E was heated to 80 °C to thoroughly mix its components, and then added to unheated phase F. This mixture of phases E and F was then introduced, again without using a homogenizer, into the mixture being prepared, which consisted mainly of phase A. Phases G and H were then introduced, again without using a homogenizer. Phase I was added to adjust the pH to approximately 6.

[0199] Example 7-3:

[0200] The formulation was based on the following ingredients: Phase Ingredient according to INCI name % by mass A Aqua 53.65 A Disodium EDTA 0.1 A Glycerin 5 B Polyacrylate Crosspolymer-6 1.5 C Aqua, Acrylate copolymer 2 D Microcapsule suspension according to the invention, 99% 33 E Phenoxyethanol, Ethylhexylglycerin 1 E Tocopherol, Helianthus Annuus Seed Oil 0.5 F Dimethicone 3 G Citric acid 0.25

[0201] For this test, a planetary mixer was used, but no homogenizer. The components of phase A were mixed cold, then the components of phase B were dispersed in phase A under vigorous stirring, and then phase C was added. Phase D was added to this mixture without using a homogenizer. Next, the ingredients of phase E were mixed, and phase E was introduced into the mixture being prepared, which consisted mainly of phase A, without using a homogenizer. Phase E was then slowly introduced under vigorous planetary stirring, again without using a homogenizer. Phase I was added to adjust the pH to a value of approximately 6.

[0202] Example 7-4:

[0203] The formulation was based on the following ingredients: Phase Ingredient according to INCI name % by mass A Aqua 22.65 A Disodium EDTA 0.1 B Polyacrylate Crosspolymer-6 1.5 C Aqua, Acrylate copolymer 2 D Microcapsule suspension according to the invention, at 50% 66 E Phenoxyethanol, Ethylhexylglycerin 1 E Tocopherol, Helianthus Annuus Seed Oil 0.5 F Undecane, Tridecane, Tocopherol 3 F Dimethicone 3 G Citric acid 0.25

[0204] The components of phase A were mixed cold, and then the components of phase B were dispersed in phase A under vigorous stirring; for this purpose, the use of a homogenizer is advantageous. Under the same conditions, phase C was then added. The remainder of the process was carried out without a homogenizer and under planetary stirring. Phase D was thus introduced. The ingredients of phase E were then mixed, and phase E was introduced into the mixture being prepared under planetary stirring, but without the use of a homogenizer. Next, the ingredients of phase E were mixed, and phase E was introduced into the mixture being prepared, consisting mainly of phase D, without the use of a homogenizer. homogenizer. Phase F was then slowly introduced under vigorous planetary stirring, but still without the use of a homogenizer. Phase G was added to adjust the pH to a value of approximately 6.

Claims

Demands

1. Core-shell type microcapsule, comprising a core containing at least one active ingredient, and comprising a shell, said shell constituting a wall around said core and representing a mass fraction of at least 20%, preferably at least 25%, more preferably at least 30%, and even more preferably at least 35% of the total mass of the microcapsule, said microcapsule being characterized in that - the shell comprises at least one cross-linked polymer, preferably obtained by interfacial polymerization, and - said core-shell microcapsule has an average DS50 size of less than 1.0 pm, preferably less than 0.80 pm, more preferably less than 0.70 pm and even more preferably less than 0.60 pm.

2. Core-shell microcapsule according to claim 1 characterized in that at least one crosslinked polymer is selected from polyurethane and / or polyurea.

3. Core-shell microcapsule according to claim 1 or 2, characterized in that said shell comprises at least one anionic surfactant, preferably an alkyl ether sulfate, and / or at least one nonionic surfactant, whereas said at least one nonionic surfactant is preferably selected from the group formed by: polyethylene glycol esters, polyethylene glycol ethers, polyglycerol esters, sorbitol derivative esters such as sorbian stearate, sucrose esters, polysorbates such as polysorbate 20, polysorbate 40 or polysorbate 60, whereas polysorbate-20 is the preferred nonionic surfactant.

4. Core-shell microcapsule according to any one of claims 1 to 3, characterized in that the active ingredient is selected from sunscreens.

5. Sunscreen formulation comprising a plurality of core-shell microcapsules according to any one of claims 1 to 4.

6. Sun protection formulation according to claim 5 characterized in that it comprises at least 20% by mass, preferably at least 30% by mass, even more preferably at least 35% by mass of core-shell microcapsules relative to the total weight of said formulation.

7. Sun protection formulation according to claim 5 or claim 6, characterized in that it has an SPF factor of at least 10, preferably of at least 15, more preferably of at least 30, and even more preferably of at least 40, and optimally of at least 50.

8. Use of core-shell microcapsules according to any one of claims 1 to 4 for the preparation of a sun protection formulation or a product exhibiting protection against photoaging of the skin or skin appendages usable in the form of liquid or paste emulsions, such as ointments, creams, milks, mousses, or in the form of solid emulsions such as sticks, bars, or in non-emulsified form such as oils, suspensions, gels, lotions, loose or compact powders.

9. A process for manufacturing core-shell microcapsules by interfacial polymerization comprising a core containing at least one active ingredient and a shell, said shell forming a wall around said core, representing a mass fraction of at least 20%, preferably at least 30%, even more preferably at least 35% of the total mass of the microcapsule, and comprising at least one cross-linked polymer obtained from at least two precursor compounds A and B, said process comprising the steps of: (a) mixing said at least one active ingredient, a solvent and at least one compound A comprising more than two functional groups A' to obtain a lipophilic phase; (b) introducing, under stirring, the lipophilic phase obtained in step (a) into a continuous aqueous phase, preferably comprising NaCl, to form an emulsion;(c) maintain, under stirring, said emulsion at a temperature between about 35 °C and about 90 °C, preferably between about 40 °C and about 70 °C, and even more preferably between about 55 °C and about 65 °C, and introduce, under stirring, an aqueous solution comprising at least one compound B comprising more than two functional groups B' into the emulsion obtained at the end of step (b) so as to react the functional groups A' of compound A comprising more than two functional groups A' with the functional groups B' of compound B comprising more than two functional groups B', to form the cross-linked polymer shell constituting a wall around said core and; thus to obtain core-shell microcapsules.

10. A process for manufacturing core-shell microcapsules according to claim 9 by interfacial polymerization, characterized in that the agitation during step (b) is carried out with a tangential velocity greater than the agitation during the introduction of said aqueous solution comprising at least one compound B in step (c), and preferably with a tangential velocity of at least 10 m / s, and preferably between 10 m / s and 30 m / s.

11. A process for manufacturing core-shell microcapsules according to claim 10 by interfacial polymerization, characterized in that the aqueous continuous phase comprises at least one anionic surfactant and / or a non-ionic surfactant, said anionic surfactant being preferably selected from alkyl ether sulfates, and even more preferably selected from magnesium lauryl ether sulfate and sodium lauryl ether sulfate.

12. A process for manufacturing core-shell microcapsules by interfacial polymerization according to any one of claims 9 to 11, characterized in that the NaCl content in the emulsion obtained in step b) is between 0.10% and 1% by mass, and preferably between 0.15% and 0.90% by mass.

13. A process for manufacturing core-shell microcapsules by interfacial polymerization according to any one of claims 9 to 12, characterized in that: - the functional groups A' of compound A comprising more than two functional groups A' are selected from isocyanate groups, and compound A is preferably selected from the group formed by: • dicyclohexylmethane 4,4'-diisocyanate, hexamethylene 1,6-diisocyanate, isophorone dii-socyanate, trimethylhexamethylene diisocyanate, hexamethylene 1,6-diisocyanate trimer, isophorone diisocyanate trimer, 1,4-cyclohexane diisocyanate, 1,4-(dimethylisocyanato)cyclohexane, hexamethylene diisocyanate biuret, hexamethylene diisocyanate biuret (CAS No. 4035-89-6), tri-methylene diisocyanate, propylene- 1,2-diisocyanate, butylene-1,2-düsocyanate, te-tramethylene diisocyanate, pentamethylene dii-socyanate, hexamethylene diisocyanate, 4-(isocyanatomethyl)-1,8-octyl diisocyanate; • mixtures of aliphatic diisocyanates and aliphatic triisocyanates, • aromatic polyisocyanates such as 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, naphthalene diisocyanate, diphenylmethane diisocyanate, triphenylmethane-p,p',p”-trityl triisocyanate, • aromatic isocyanates such as toluene diisocyanate, polymethylene polyphenylisocyanate, 2,4,4'-diphenyl ether triisocyanate, polymethylene polyphenylisocyanate, 2,4,4'-diphenyl ether triisocyanate, 3,3'-dimethyl-4,4'-diphenyl diisocyanate, 3,3-dimethoxy-4,4' diphenyl diisocyanate, 1,5-naphthalene diisocyanate, 4,4',4”-triphenylmethane triisocyanate, isophoron diisocyanate; - The B' functional groups of compound B, comprising more than two B' functional groups, are chosen so that compound B is an amine, and are preferably selected from the group formed by: ethylenediamine, diethylenetriamine, propylenediamine, tetraethylenepentaamine, pentamethylenehexamine, an alpha omega dimaine, propylene-1,3-diamine, tetramethylenediamine, pentamethylenediamine, 1,6-hexamethylenediamine, triethylenetriamine, pentaethylenehexamine, 1,3-phenylenediamine, 2,4-toluynediamine, 4,4'-diaminodiphenylmethane, 1,5-diaminonaphthalene, 1,3,5-triaminobenzene, 2,4,6-triaminotoluene, 1,3,6-triaminonaphthalene, 2,4,4'-triaminodiphenyl ether, 3,4,5-triamino-l,2,4-triazole, bis(hexamethylene triamide), 1,4,5,8-tetraamino anthraquinone.

14. A method for manufacturing core-shell microcapsules by interfacial polymerization according to any one of claims 9 to 13, ca characterized in that the cross-linked polymer is chosen from polyurea or polyurethane.

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