Microcapsules comprising a UV filter

Abstract

The invention relates to a microcapsule having a core surrounded by a gelled shell, the core further comprising at least one active agent, and the shell comprising dispersed UV filter colloidal particles, a method for producing said microcapsule, and uses thereof in various fields of applications.

Description

[0001] DESCRIPTION

[0002] TITLE: Microcapsules containing a UV filter

[0003] The present invention relates to a microcapsule with an aqueous, oily or H / W and W / O emulsion liquid core, surrounded by a gelled shell, in which the core further comprises at least one active agent, and the shell comprises dispersed colloidal UV filter particles, a method for producing said microcapsule, its uses in various fields of application such as crop and / or seed treatment, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater decontamination.

[0004] Exposure of active compounds, particularly organic compounds, to ultraviolet (UV) radiation causes the formation of free radicals through oxidation reactions. Among organic molecules, the DNA bases that make up the genome undergo mutations that can be harmful to microorganisms.

[0005] The energy emitted by the sun and reaching the Earth's surface can be divided as follows: 5% UV radiation, 45% visible radiation, and 50% infrared radiation. Ultraviolet rays are the most destructive due to their higher energy.

[0006] The invention relates to the implementation of a concentrated suspension of colloidal UV filter particles within the shell of a capsule to protect the active agent at the heart of the latter. In the case of microorganisms, the inventors have discovered that this incorporation improves their viability following their exposure to ultraviolet radiation.

[0007] UV filters are molecules or particles that absorb, reflect, and / or scatter ultraviolet rays. They are often used in cosmetics, in the form of nanoparticles, to protect against the harmful effects of ultraviolet rays on the skin.

[0008] The effectiveness of a UV filter depends on its ability to absorb, reflect, and / or diffuse light. Several physicochemical parameters influence these physical phenomena, such as particle size, refractive index, and concentration.

[0009] Thus the invention relates to a microcapsule with a liquid core surrounded by a gelled shell in which the microcapsule has an average diameter of between 50 and 4000 pm when in hydrated form, and in which: a. the core further comprises at least one active agent, and b. the shell comprises dispersed colloidal UV filter particles, in which the UV filter is not a soluble antioxidant compound.

[0010] The invention also relates to a method for producing microcapsules comprising the following steps: a. separate conveyance in a double envelope of a first liquid solution comprising at least one active agent and a second liquid solution comprising a biopolymer having gelling properties and dispersed colloidal UV filter particles; b. formation at the outlet of the double envelope, of a series of drops, each drop comprising a central core formed from the first solution and a peripheral film formed from the second solution and completely covering the central core; c. immersion of each drop in a gelling solution capable of reacting with the biopolymer having gelling properties to make it pass from a liquid state to a gelled state and form the gelled envelope, the central core forming the liquid core; d. recovery of the capsules formed.

[0011] The invention also relates to the microcapsule obtainable by this method.

[0012] The invention relates to the use of microcapsules for any purpose aimed at protecting the active agent from the harmful effects of UV radiation. For example, when storing the capsules in extreme sunlight conditions, during a process that would involve a step using UV exposure or during its use / application in various fields such as agriculture, agri-food, cosmetics or pharmaceuticals.

[0013] The subject of the invention is the use of microcapsules for the treatment of plant crops and / or their seeds, for animal nutrition and / or feed, for human nutrition and / or feed, for the formulation of cosmetics and / or pharmaceutical compositions and for the decontamination of soils and wastewater. The invention also relates to pharmaceutical compositions comprising a microcapsule according to the invention.

[0014] The invention also relates to a method of treating crops and / or their seeds comprising spreading, foliar spraying or coating seeds with a suspension of microcapsules according to the invention.

[0015] Detailed description of the invention

[0016] Microcapsule

[0017] By "microcapsule" is meant here a capsule with an average diameter of less than 10 mm and comprising at least a core and a shell. Such capsules preferably comprise a liquid core encapsulated by a substantially solid gelled envelope. This type of capsule has applications in numerous technical fields. The shell encompasses one or more concentric or non-concentric compartments. Preferably, the microcapsules according to the invention comprise only a single core coated by the shell.

[0018] These microcapsules are therefore very different from microbeads, because microbeads are mainly made up of a solid or gelled matrix comprising multiple small inclusions.

[0019] The use of microcapsules rather than microbeads also makes it possible to confine microorganisms without immobilizing them.

[0020] According to a preferred embodiment of the invention, the microcapsules have a core volume to total microcapsule volume ratio greater than 20%. These microcapsules thus make it possible to protect a large volume of core and therefore of active agent, for a given shell volume.

[0021] Microcapsules are well known to those skilled in the art and can be formed by different techniques and have different shell compositions.

[0022] Typically, the microcapsules used in the context of the invention are produced according to the manufacturing process described in French patent no. 2939012.

[0023] As described below, the microcapsules according to the invention can be dehydrated. However, when they are in hydrated form, such as for example in suspension in an aqueous solution, the microcapsules according to the invention have an average diameter of between 50 and 4000 μm, preferably between 100 and 2000 μm, more particularly between 200 and 1000 μm, advantageously between 200 and 600 μm. This average diameter can be measured by various techniques well known to those skilled in the art, such as particle size analysis based on laser light diffraction, sieve fractionation or optical microscopy imaging.

[0024] In one embodiment, the microcapsules according to the invention additionally comprise an intermediate layer between the core and the shell. Preferably, this layer is composed of at least one biopolymer in the form of a solution or hydrogel. It would, among other things, limit possible interactions between the UV filter and the active agent.

[0025] Preferably, the microcapsules according to the invention are free, that is to say that they are not included in another structure such as a film, a bead, a gel or encapsulated a second time, but that they are in direct contact with the medium which surrounds them, typically a liquid (if they are in suspension for example) or a gas.

[0026] The heart

[0027] The core of the microcapsules according to the invention is a liquid core comprising at least one active agent. Preferably the viscosity of the core is less than 2000 mPa.s.

[0028] The core of the microcapsules according to the invention can be aqueous, oily or in the form of an oil-in-water (O / W) or water-in-oil (W / O) emulsion.

[0029] By "aqueous core" we mean a core based on a predominantly aqueous phase in which the active agent is dispersed or solubilized.

[0030] By "oily core" we mean a core based on a predominantly oily phase where the active agent is dispersed or solubilized.

[0031] In the case where the core is an O / W emulsion, the hydrophobic active agent would be dispersed in the oil droplets. This type of emulsion would also allow the encapsulation of both a hydrophobic and a hydrophilic active agent.

[0032] By "active agent" is meant an active substance, an active principle or active ingredient that is known and / or used for a particular purpose. Preferably the active agent is UV-sensitive, i.e. exposure to UV can cause irreversible changes to the active agent, which may reduce its activity.

[0033] Advantageously, the active agent is chosen from microorganisms, natural extracts, semiochemical compounds and their mixtures.

[0034] By "microorganisms" we mean a living organism, invisible to the naked eye, which can only be observed using a microscope, and in particular bacteria, fungi, microalgae, and viruses. By "natural extracts" we mean extracts of animal, plant or mineral origin and for example, extracts of plants, algae, minerals and microorganisms, such as essential oils, etc.

[0035] For example, in one embodiment, the active agent is a biocontrol agent, a biofertilizer and / or a biostimulant.

[0036] A "biocontrol agent" means an agent intended to protect crops and / or their seeds from diseases or pests, based on the use of natural mechanisms. These agents include macro-organisms (insects and nematodes), plant protection products that are composed of microorganisms (viruses, bacteria and fungi), chemical mediators (pheromones and kairomones) and natural substances of plant, animal or mineral origin.

[0037] The term "biofertilizer" means a non-pathogenic living substance or microorganism capable of increasing the availability of nutrients to plants.

[0038] “Biostimulant” means a non-pathogenic living substance or microorganism capable of stimulating natural processes to improve / benefit nutrient absorption, nutrient efficiency, tolerance to abiotic stresses, and / or crop quality, regardless of the nutrient content of the biostimulant.

[0039] In another embodiment, the active agent may be a macronutrient (carbohydrates, lipids and proteins) or a micronutrient (vitamins, minerals, trace elements or amino acids), preferably aimed at providing organoleptic or nutritional properties. Thus the active agent may be a food supplement, an agent facilitating the digestion and / or absorption of certain compounds. For example, the active agent in the microcapsule according to the invention may be: a vitamin, an amino acid, a fatty acid.

[0040] In another embodiment, the active agent may be a cosmetic product. A cosmetic product is understood to mean any substance or mixture intended to be placed in contact with the superficial parts of the human body (epidermis, hair and capillary system, nails, lips and external genital organs) or with the teeth and oral mucous membranes with a view, exclusively or mainly, to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odors.

[0041] In another embodiment, the agent may be an active ingredient in a drug composition that has a therapeutic or preventative effect.

[0042] In another embodiment, the agent may be an active ingredient used for the decontamination of water or soil, for example in water treatment plants. Preferably, the core of the capsule according to the invention does not comprise UV filter particles.

[0043] The hull

[0044] The microcapsules according to the invention preferably comprise at least one liquid core encapsulated by a substantially solid gelled envelope called the shell.

[0045] Preferably, the shell of the microcapsules according to the invention is mainly composed of a biopolymer having gelling properties, this biopolymer in the majority proportion in the shell is hereinafter called the main biopolymer. Such biopolymers having gelling properties are for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.

[0046] The materials that make up the shell are preferably biodegradable and bio-sourced. The shell is preferably semi-permeable to gases and low molecular weight molecules.

[0047] The gels forming the shell can be physical or chemical, i.e. formed by coacervation or by polymerization.

[0048] The gelation of these biopolymers can be achieved by a variation in temperature (gellan gum), a variation in pH (chitosan, pectin) or ionic (alginate, carrageenan).

[0049] Preferably, the shell of the microcapsules according to the invention is mainly composed of a biopolymer having gelling properties by ionic or temperature variation.

[0050] Preferably, the shell of the microcapsules according to the invention is mainly composed of alginate.

[0051] The shell may further comprise one or more other biopolymers than the main biopolymer such as starch (in its various forms, for example amylose, pregelatinized starch), potato protein, or another biopolymer than the main biopolymer having gelling properties, such as for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.

[0052] Preferably, the shell of the microcapsules according to the invention comprises a gel containing water, one or more biopolymers having gelling properties, and optionally a surfactant resulting from its manufacturing process. Preferably, the shell of the microcapsules according to the invention comprises a gel containing water, alkaline alginate, and optionally a surfactant resulting from its manufacturing process.

[0053] Preferably, the alkaline alginate is a sodium alginate or a potassium alginate. Alginates are produced from brown algae called laminaria, known by the English term "sea weed". Such alginates advantageously have an aL-guluronate content greater than approximately 50%, preferably greater than 55%, or even greater than 60%.

[0054] The surfactant is advantageously an anionic surfactant, a non-ionic surfactant, a cationic surfactant or a mixture thereof. The molecular weight of the surfactant is between 150 g / mol and 10000 g / mol, advantageously between 250 g / mol and 1500 g / mol.

[0055] In the case where the surfactant is an anionic surfactant, it is for example chosen from an alkyl sulfate, an alkyl sulfonate, an alkylarylsulfonate, an alkali metal alkylphosphate, a dialkylsulfosuccinate, an alkaline earth metal salt of saturated or unsaturated fatty acids. These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic anionic group, such as a sulfate, a sulfonate or a carboxylate linked to one end of the hydrophobic chain. In the case where the surfactant is a cationic surfactant, it is for example chosen from an alkylpyridium or alkylammonium halide salt such as n-ethyldodecylammonium chloride or bromide, cetylammonium chloride or bromide (CTAB).These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic cationic group, such as a quaternary ammonium cation. In the case where the surfactant is a non-ionic surfactant, it is for example chosen from polyoxyethylenated and / or polyoxypropylenated derivatives of fatty alcohols, fatty acids, or alkylphenols, arylphenols, or from alkyl glucosides, polysorbates, cocamides.

[0056] In one embodiment, the surfactant is sodium lauryl sulfate (LSS) also called sodium dodecyl sulfate and / or polyoxyethylene sorbitan monooleate (Polysorbate 80).

[0057] Preferably, the surfactant is polyoxyethylene sorbitan monooleate (Polysorbate 80).

[0058] In one embodiment, the mass content of surfactant in the shell is greater than 0.001% and is advantageously greater than 0.1%. Advantageously, the mass concentration of surfactant is approximately 0.03%. The shell of the microcapsule preferably has a thickness of between 0.1% and 30%, advantageously between 1% and 20%, and more particularly between 10% and 20% of the diameter of the capsule.

[0059] The shell of the microcapsule further comprises dispersed colloidal UV filter particles. Indeed, preferably, the UV filter particles are in the shell of the microcapsule, and advantageously, are not in the core thereof. This makes it possible to use less filter for equivalent anti-UV activity, but also to limit the interactions between the anti-UV filter and the active agent.

[0060] By "colloidal UV filter particles" we mean particles with an average size between 10 nm and 10 pm and more preferably between 100 nm and 5 pm. In general, the smaller the particles, the more effective they will be against UV rays. These filters can also make microcapsules opacified.

[0061] Preferably, the UV filter is not a soluble antioxidant compound. Indeed, these compounds tend to degrade more quickly once exposed to UV.

[0062] The UV filter according to the invention can be organic or inorganic, or a mixture of organic and inorganic filters.

[0063] Preferably, the UV filter is chosen from titanium oxide, carbon black, biochar, charcoal, latex, silica, clays, and mixtures thereof.

[0064] Biochar is the product of biomass pyrolysis and is used as an amendment to agricultural soils.

[0065] Clays used as UV filters include, for example, talc or kaolin and their mixtures.

[0066] Kaolin is a type of clay used to filter ultraviolet rays. It is also used to protect certain crops from pests in agriculture.

[0067] Preferably, the UV filter according to the invention is biodegradable and / or edible and / or cosmetically acceptable and / or pharmaceutically acceptable.

[0068] By "cosmetically acceptable" is meant here compositions and molecular entities that do not produce side, allergic or otherwise unwanted reactions when administered to a subject. Thus, a cosmetically acceptable UV filter is compatible with the skin, integuments and / or mucous membranes, it does not induce feelings of discomfort, or more generally disorders likely to lead the user to suspend or stop the administration of the cosmetic composition comprising it. By "pharmaceutically acceptable" is meant here compositions and molecular entities that do not produce, or produce few side, allergic or otherwise unwanted reactions when administered to a subject. Thus, a pharmaceutically acceptable UV filter does not induce disorders likely to lead the user to suspend or stop the administration of the pharmaceutical composition comprising it.

[0069] By "dispersed UV filter particles" we mean particles dispersed in the shell of the microcapsule, in order to allow a homogeneous anti-UV effect on the surface of the microcapsule.

[0070] The microcapsule according to the invention may be in dehydrated form. Preferably, the dehydration is partial, and the microcapsules according to the invention have a humidity level of less than 10%, measured by a humidity analyzer after dehydration.

[0071] In dehydrated form, the average diameter of the microcapsule tends to decrease. Preferably, the microcapsule according to the invention has an average diameter of between 10 μm and 4 mm in dehydrated form.

[0072] Production process

[0073] The invention also relates to a method for producing microcapsules comprising the following steps: a. separate conveyance in a double envelope of a first liquid solution comprising at least one active agent and a second liquid solution containing biopolymer having gelling properties and dispersed colloidal UV filter particles; b. formation, at the outlet of the double envelope, of a series of drops, each drop comprising a central core formed from the first solution and a peripheral film formed from the second solution and completely covering the central core; c. immersion of each drop in a gelling solution capable of reacting with the biopolymer having gelling properties to make it pass from a liquid state to a gelled state and form the gelled envelope, the central core forming the liquid core; d. recovery of the capsules formed.Preferably, the invention relates to a method for producing microcapsules comprising the following steps: a. separate conveyance in a double envelope of a first liquid solution comprising at least one active agent and a second liquid solution containing an alkali alginate and dispersed UV filter particles; b. formation, at the outlet of the double envelope, of a series of drops, each drop comprising a central core formed from the first solution and a peripheral film formed from the second solution and completely covering the central core; c. immersion of each drop in a gelling solution containing a reagent capable of reacting with the alkali alginate to make it pass from a liquid state to a gelled state and form the gelled envelope, the central core forming the liquid core; d. recovery of the capsules formed.

[0074] The definitions defined in the microcapsule section apply here as well.

[0075] In one embodiment of the methods according to the invention, the second solution contains at least one surfactant before its contact with the first solution.

[0076] The surfactant is preferably selected from an anionic surfactant, a cationic surfactant, a non-ionic surfactant or mixtures thereof.

[0077] For example, said surfactant is an alkyl sulfate, an alkyl sulfonate, an alkylarylsulfonate, an alkali metal alkylphosphate, a dialkylsulfosuccinate, an alkaline earth metal salt of saturated or unsaturated fatty acids, an alkylpyridium or alkylammonium halide salt such as methyldodecylammonium chloride or bromide, cetylamonium chloride or bromide, polyoxyethylenated and / or polyoxypropylenated derivatives of fatty alcohols, fatty acids or alkylphenols, or among arylphenols, alkyl glucosides, polysorbates, cocamides or mixtures thereof.

[0078] In one embodiment, the surfactant is sodium lauryl sulfate (LSS) also called sodium dodecyl sulfate and / or polyoxyethylene sorbitan monooleate (Polysorbate 80).

[0079] Preferably, the surfactant is polyoxyethylene sorbitan monooleate (Polysorbate

[0080] 80). The total mass percentage of surfactant in the second solution is preferably greater than 0.01% and is advantageously between 0.01% and 0.5% by mass.

[0081] The mass content of biopolymer having gelling properties in the second solution is advantageously less than 5% by mass and is preferably between 0.5 and 3% by mass.

[0082] Preferably, in the case of the production of a microcapsule with a shell comprising mainly alginate, the mass content of alkali alginate in the second solution is advantageously less than 5% by mass and is preferably between 0.5 and 3% by mass.

[0083] Preferably, the alkali alginate of the second solution has an aL-guluronate block content greater than 50%, especially greater than 55%.

[0084] Preferably, the second liquid solution comprises from 0.1 to 20% v / v of UV filter.

[0085] The ratio of the flow rate of the first solution to the flow rate of the second solution at the outlet of the double jacket is between 0.01 and 100, advantageously between 0.05 and 50 and more particularly between 0.1 and 10, the gelled jacket having a thickness between 0.1% and 30%, advantageously between 1% and 20%, and more particularly between 10% and 20% of the diameter of the capsule, after recovery of the capsules formed.

[0086] By "gelling solution capable of reacting with the biopolymer" is meant a solution at a particular temperature, or a particular pH, or comprising a particular reagent making it possible to change the biopolymer from the second liquid solution from a liquid state to a gelled state.

[0087] In the case of the production of a microcapsule with a shell comprising mainly alginate, the gelling solution is for example an aqueous solution of a type X reagent n L mwhere X is advantageously a halide ion such as a chloride ion, a bromide ion, an iodide ion or a fluoride ion, and I is advantageously a multivalent cation of an alkaline earth such as calcium, magnesium, or barium, and n and m are greater than or equal to 1. Preferably, the gelling solution further comprises a surfactant such as polysorbate 20 or polysorbate 80.

[0088] The multivalent ions present in the gelling solution thus formed are capable of reacting with the alginate to form bonds between the different alginate chains present in the second solution, when the second solution comes into contact with the gelling solution. In the case where the alginate is sodium alginate (NaAlg), and where the reactant is calcium chloride, the reaction which occurs is as follows:

[0089] 2NaAlg + CaCI2Ca(Alg)2+ 2NaCI

[0090] In the methods according to the invention, the concentration of reagent in the gelling solution is advantageously between 5% and 20% by mass.

[0091] Preferably, the gelling solution is arranged below and away from the outlet of the double jacket, so that the drops formed by coextrusion in the double jacket fall spontaneously by gravity through a volume of air into the gelling solution where they are immersed.

[0092] In one embodiment, the formed microcapsules may follow an additional rinsing step by passing through a rinsing and storage solution consisting essentially of water.

[0093] The method according to the invention may further comprise a step (step e.) of dehydrating the microcapsules. This step may be carried out by techniques well known to those skilled in the art, for example by hot drying techniques or cold drying techniques. Preferably, this step is carried out by steaming, freeze-drying or osmotic dehydration. In a particular embodiment, the dehydration is carried out by drying on a fluidized air bed and / or by freeze-drying. Preferably, the dehydration step makes it possible to remove at least 90% of water (by weight) from the microcapsules.

[0094] The invention also relates to the microcapsules capable of being obtained by the process according to the invention.

[0095] Uses and methods

[0096] The definitions defined in the microcapsule section apply here as well.

[0097] Preferably, in the methods and uses according to the invention, the microcapsules are used as such, that is to say that they are not included in another structure (such as a film, a bead, a gel or encapsulated a second time), but that they are used directly, possibly in suspension in a liquid.

[0098] The invention relates to the use of microcapsules according to the invention for the treatment of plant crops and / or their seeds. By "treatment of plant crops and / or their seeds" is meant biocontrol, biofertilization and / or biostimulation treatments which can take place before, during or after cultivation.

[0099] Indeed, the active agent of the microcapsules according to the invention may be an agent with effects on plant crops and / or their seeds. In particular, the active agent may allow the protection of crops and / or their seeds against diseases or pests but also serve as a fertilizer and / or promote the growth of plant crops and / or their seeds.

[0100] The invention therefore relates in particular to the use of microcapsules for the treatment of plant crops and / or their seeds, in which the active agent is a biocontrol agent, a biofertilizer and / or a biostimulant. The microcapsules can be used in suspension in a liquid or in dehydrated and solid form.

[0101] The invention comprises a method for treating crops and / or seeds comprising the application of microcapsules according to the invention. The invention therefore also relates to a method for treating crops and / or seeds comprising spreading, foliar spraying or coating seeds with microcapsules according to the invention, preferably microcapsules according to the invention in which the active agent is a biocontrol agent, a biofertilizer and / or a biostimulant. In this method, the microcapsules can be used in suspension in a liquid or in dehydrated and solid form.

[0102] In another embodiment, the invention relates to the use, preferably non-therapeutic, of microcapsules according to the invention for animal and / or human nutrition and / or food. In this embodiment, the active agents used are preferably not therapeutic active agents, that is to say they have an interest from a nutritional or dietary point of view but they do not make it possible to prevent or treat diseases of the subject consuming them. Preferably, the active agents used are edible agents, preferably with organoleptic or nutritional properties. Thus, in this use, the active agents preferably have an interest from a nutritional or dietary point of view but do not make it possible to prevent or treat diseases of the subject consuming them.

[0103] By "diet" we mean the habitual or frequent intake of food. Indeed, the microcapsules can contain various active agents that improve the properties of a food product, such as its organoleptic properties, its shelf life or its bioavailability. By "nutrition" we mean the intake, often more occasional or during a course of treatment, of a food supplement typically to avoid or compensate for a deficiency. Indeed, the microcapsules according to the invention can contain various active agents that improve nutrient intake by improving their bioavailability or modifying the intestinal flora.

[0104] By "animal" is meant a wild or domesticated animal. Preferably the animal is a domesticated, farmed or companion animal. In particular, the animals according to the invention are chosen from companion animals such as dogs, cats, fish, rabbits, horses, turtles, livestock species such as: cattle (cow, ox), sheep (mutton), goats, rabbits, pigs (pig), camels, and birds raised in poultry farming (chicken, quail, etc.).

[0105] The invention also relates to the use of microcapsules according to the invention for the formulation of cosmetics. In this embodiment, the active agents used are preferably not therapeutic active agents, that is to say they have an interest from a cosmetic point of view but they do not make it possible to prevent or treat diseases of the subject using them.

[0106] The invention also relates to the use of microcapsules according to the invention for the formulation of pharmaceutical compositions. In this embodiment, the active agents used are preferably therapeutic active agents, that is to say they make it possible to prevent or treat diseases of the subject consuming them.

[0107] Indeed, the use of microcapsules according to the invention makes it possible to facilitate the storage, packaging or preparation of cosmetic or pharmaceutical formulations while maintaining good quality of the active agent.

[0108] Pharmaceutical compositions and therapeutic application

[0109] The invention also relates to a pharmaceutical composition comprising a microcapsule according to the invention. The application also relates to a microcapsule according to the invention for its use as a medicament.

[0110] The present invention also relates to a method of treating a subject, comprising administering a therapeutically effective amount of microcapsules according to the invention to a subject in need thereof. In this embodiment, the microcapsule according to the invention advantageously comprises a therapeutic active agent.

[0111] By "therapeutic active agent" is meant an active agent as defined in the microcapsule section above which is further known and / or used for a particular therapeutic purpose, i.e. it is known and / or used in the treatment or prevention of diseases.

[0112] The term "pharmaceutical composition" as defined herein means a mixture or solution comprising at least one therapeutic agent to be administered to a subject in order to prevent or treat a particular disease affecting the subject.

[0113] The pharmaceutical compositions as defined herein therefore preferably further comprise pharmaceutically acceptable excipients.

[0114] By "pharmaceutically acceptable" is meant herein compositions and molecular entities which do not produce adverse, allergic or otherwise unwanted reactions when administered to a subject.

[0115] By "subject" we mean here a living being, preferably a mammal, and more particularly a human.

[0116] The term "therapeutically effective amount" herein means an amount effective, at doses and for periods of time necessary, to achieve the desired therapeutic result. This amount may vary depending on factors such as the disease, the extent of the disease, the age, sex, and weight of the subject, and the ability of the microcapsules to cause a desired therapeutic result. A therapeutically effective amount encompasses an amount in which any toxic or detrimental effects are outweighed by the therapeutically beneficial effects. A therapeutically effective amount also encompasses an amount sufficient to confer a benefit, for example, a clinical benefit.

[0117] Such pharmaceutical compositions are preferably adapted to the route of administration.

[0118] In a particular embodiment, the pharmaceutical compositions are suitable for oral, sublingual, buccal, intranasal or topical administration.

[0119] The invention also relates to the use of microcapsules according to the invention for the manufacture of a medicament. The invention also relates to the use of microcapsules according to the invention for the formulation of pharmaceutical compositions.

[0120] For these uses, the microcapsule according to the invention advantageously comprises a therapeutic active agent. Indeed, the use of microcapsules according to the invention makes it possible to facilitate the storage, packaging or preparation of pharmaceutical compositions while preserving the active agents.

[0121] By "treatment" or "treat" is meant herein the achievement, partially or substantially, of one or more of the following results: partially or totally reducing the extent of the disease, improving a clinical symptom or indicator associated with the disease, delaying, inhibiting or preventing the progression of the disease.

[0122] By "prevention" or "prevent" is meant here achieving, partially or substantially, one or more of the following results: preventing or delaying the onset of the disease or at least one of its symptoms, preventing or delaying the deterioration of an indicator associated with the onset of the disease.

[0123] The invention also relates to the use of microcapsules according to the invention for the decontamination of soils or wastewater. Indeed, such compositions make it possible to protect the active agent enabling decontamination from UV rays, for example when used in a treatment plant or on the surface of the soil.

[0124] In the following description and examples, unless otherwise indicated, percentages are percentages by weight and ranges of values ​​expressed as "between ... and ...", "from ... to ...", or "greater than ..." include the limits specified.

[0125] Throughout the application, the wording "comprising a" or "comprising a" means "comprising at least one" or "comprising at least" one unless otherwise specified.

[0126] The following examples are presented for illustrative purposes and are not intended to limit the scope of the invention.

[0127] Figures:

[0128] [Fig 1] Figure 1: Evolution of the percentage of viability of the bacterium Bacillus sp. encapsulated with carbon black as a function of the time of exposure to artificial ultraviolet rays.

[0129] [Fig 2] Figure 2: Survival of bacteria exposed to UV. These curves represent the survival of the bacterium Paraburkholderia phytofirmans PsJN in suspension (dotted curve) and the survival of bacteria encapsulated in microcapsules according to the invention with biochar as a UV filter.

[0130] [Fig 3] Figure 3: Comparison of the survival rate of bacteriophages encapsulated with biochar in the shell to that of bacteriophages encapsulated without biochar, and to that of bacteriophages in suspension exposed to artificial ultraviolet radiation.

[0131] Examples:

[0132] Example 1

[0133] Laboratory tests on bacterial samples were subjected to an accelerated aging test. A comparison was made of the survival of suspended (unencapsulated) and encapsulated Bacillus sp. bacteria when exposed to artificial ultraviolet rays. The encapsulation of these bacteria was done in a shell formed of alginate and carbon black, which is known to be an ultraviolet filter. The source of UV rays used was an oven containing a mercury vapor lamp whose power is approximately 18 times greater than that of solar radiation (on a summer day at noon in the United States). This means that approximately one minute in the oven is equivalent to 18 minutes in the open field. Two exposure times were tested: 3 minutes and 5 minutes.

[0134] The results are shown in Figure 1. The inventors observed that the percentage of viability is higher for encapsulated bacteria compared to those in suspension. After 5 minutes of exposure, which is equivalent to 1.5 hours in the field, the survival of suspended bacteria is 1% while the survival of encapsulated bacteria is 57%.

[0135] Example 2

[0136] Encapsulation operating conditions:

[0137] Heart solution (or heart fluid): bacterial suspension in TSB medium (tryptone soy broth) diluted 1 / 10 e to limit bacterial proliferation during UV exposure).

[0138] Shell solution (or shell fluid): 1.8% by mass alginate solution, 0.5 mM SDS surfactant, 1.5% v / v biochar. The flow rate ratio between the core and shell suspension is set at 0.5. Thus, the inventors want to maximize the thickness of the shell.

[0139] The total fluid flow rate is 340 mL / h.

[0140] Under these conditions, the capsules formed have an average diameter of 516 pm with a coefficient of variation (CV) of 17%.

[0141] Two UV filters were selected for testing: biochar and kaolin.

[0142] The characterization of these two candidates was carried out in order to verify their compatibility with the microencapsulation process. Thus, the distribution of the particle sizes that compose them was studied. In addition, the absorbance of ultraviolet rays by these compounds was studied by spectrophotometry. The inventors observed that for the same volume fraction (0.01%), the absorbance of ultraviolet rays by kaolin is slightly higher than that of biochar.

[0143] The effectiveness of UV protection with biochar was evaluated by determining the survival rate of bacteria encapsulated with biochar in the shell compared to that of bacteria in suspension, and to that of bacteria encapsulated without biochar, exposed to artificial ultraviolet radiation. The bacteria used for these tests belong to the species Paraburkholderia phytofirmans of the PsJN strain. These are bacteria that stimulate plant growth and help protect them from certain biotic and abiotic stresses.

[0144] The results obtained from these tests are presented in Figure 2. The survival rate of bacteria encapsulated with 1.5% v / v biochar is higher than that of bacteria in suspension or bacteria encapsulated without biochar. Indeed, the survival rate of bacteria in suspension after 10 minutes of exposure is 8% compared to 46% for bacteria encapsulated with biochar.

[0145] Encapsulation with biochar in the shell therefore represents a very interesting solution for the protection of microorganisms from ultraviolet rays.

[0146] The performance of biochar in terms of protection against ultraviolet radiation was also evaluated on bacteriophages of the M13K07 strain. Two prototype capsules were produced and their performance was evaluated. Prototypes 1 and 2 correspond to wet alginate capsules without biochar and with biochar, respectively.

[0147] The encapsulation operating conditions are as follows: The injector nozzle diameter is 200 pm. The total flow rate of the core and shell fluid, named Qtot, is 500 mL / h, the flow rate ratio between the core and shell fluid, named Rq, is 0.8 and gives a membrane thickness of at least 30 pm.

[0148] Heart solution (or heart fluid): suspension of bacteriophages in physiological medium diluted 1 / 200 e (to limit bacterial proliferation during UV exposure).

[0149] Shell solution (or shell fluid): 1.8% by mass alginate solution, 0.5 mM SDS surfactant, 2.9%v / v biochar.

[0150] Under these conditions, the capsules of prototype 1 have an average diameter of 462 pm with a coefficient of variation (CV) of 17%.

[0151] The capsules of prototype 2 have an average diameter of 542 pm with a coefficient of variation (CV) of 18%.

[0152] The survival rate of bacteriophages encapsulated with biochar in the shell compared to that of bacteriophages encapsulated without biochar, and to that of bacteriophages in suspension exposed to artificial ultraviolet radiation were estimated. The results obtained from these tests are presented in Figure 3 and Table 1 below.

[0153] [Tab 1] Table 1

[0154] The survival rate of bacteriophages in suspension after 30 minutes is 0.00005% (i.e. an approximate loss of 6 log) compared to 30% (i.e. a loss of 0.5 log) for bacteriophages in capsule form in the presence of biochar in the shell and a survival rate of 0.002% (i.e. an approximate loss of 4 log).

[0155] These results confirm that microorganisms, in this case bacteriophages, are effectively protected against ultraviolet rays when they are in capsule form with biochar in the shell. Furthermore, a slightly higher survival rate is observed when the bacteriophages are encapsulated than when they are in suspension.

[0156] Example 3:

[0157] Encapsulation operating conditions:

[0158] Core solution (or core fluid): inverse emulsion (W / O - water in oil) containing phenylalanine solubilized in the aqueous phase. This emulsion is prepared as follows:

[0159] Preparation of the aqueous phase by solubilizing phenylalanine (960 mg) in 120 mL of ultrapure water while stirring with a magnetic bar for 30 minutes. 1.37 g of surfactant Polyglycerol polyricinoleate (PGPR 90) is introduced into MCT oil. PGPR 90 is dispersed in the oil phase using a rotor-stator at 12,000 rpm for 2 minutes. The emulsion is then formed by introducing the aqueous phase into the oil phase while the rotor-stator is stirring. The rotor-stator is operated at 18,000 rpm during the introduction of the aqueous phase into the oil phase.

[0160] Shell solution (or shell fluid): 1.8% by mass alginate solution, 0.5 mM SDS surfactant, 4% by mass of E-153 food grade charcoal.

[0161] The flow rate ratio between the core emulsion and the shell solution is set at 0.5.

[0162] The total fluid flow rate is 350 mL / h.

[0163] The diameter of the injector nozzle is 145 pm.

[0164] UV exposure is achieved using a lamp emitting at 254 nm with an irradiance of 0.76 mW / cm 2 The samples were placed 10 cm from the source. The effectiveness of UV protection with activated carbon was evaluated spectrophotometrically by measuring the absorbance at 280 nm of the aqueous phase of the emulsion at exposure times t0, t20 min and t1 h of the emulsion alone, the encapsulated emulsion without food carbon and the encapsulated emulsion with food carbon.

[0165] The aqueous phase of the emulsion is extracted by introducing between 500 mg and 1 g of sample in 8 mL of PBS with 25 mM EDTA into a 15 mL tube placed for 20 minutes on a shaker. The tubes are then placed for 8 minutes in an ultrasonic bath. Finally, the tubes are placed in a centrifuge at 4700 rpm for 15 minutes. The aqueous phase is then collected in each tube below the oil phase and filtered using a 0.2 μm porosity filter.

[0166] Result :

[0167] Phenylalanine exposed to this UV source is modified, its absorbance measured at 280 nm increases as exposure progresses. The lower the increase in this absorbance, the more effective the UV protection has been.

[0168] The absorbance at 280 nm of the emulsion sample alone increased by more than 300 times after one hour. In the case of the encapsulated emulsion without the edible charcoal, this absorbance increased by 13 times, while for the capsules containing the edible charcoal, this increase was limited to a multiplication by less than 2.

[0169] Table 2: Absorbance at 280 nm of the aqueous phase of the emulsion at exposure times t0, t20 min and t1 h

[0170] Table 3: Increase in absorbance at 280 nm of the aqueous phase of the emulsion after UV exposure for 20 min and for 1 h

Claims

CLAIMS 1. A microcapsule with a liquid core surrounded by a gelled shell wherein the microcapsule has an average diameter of between 50 and 4000 pm when in hydrated form, and wherein: a. the core further comprises at least one active agent, and b. the shell comprises dispersed colloidal UV filter particles, wherein the UV filter is not a soluble antioxidant compound.

2. Microcapsule according to claim 1, in which the core does not comprise UV filter particles.

3. Microcapsule according to claim 1 or 2 comprising an intermediate layer between the core and the shell.

4. Microcapsule according to any one of claims 1 to 3 in which the UV filter is organic or inorganic.

5. Microcapsule according to any one of claims 1 to 4 in which the UV filter is chosen from titanium oxide, carbon black, biochar, charcoal, latex, silica, clays, and mixtures thereof.

6. Microcapsule according to any one of claims 1 to 5 in which the at least one active agent is chosen from a microorganism, a natural extract, a semiochemical and their mixtures.

7. Microcapsule according to any one of claims 1 to 6 in dehydrated form.

8. A method for producing microcapsules comprising the following steps: a. separate conveying in a double envelope of a first liquid solution comprising at least one active agent and a second liquid solution comprising a biopolymer having gelling properties and dispersed colloidal UV filter particles; b. formation, at the outlet of the double envelope, of a series of drops, each drop comprising a central core formed from the first solution and a peripheral film formed from the second solution and completely covering the central core; c. immersion of each drop in a gelling solution capable of reacting with the biopolymer having gelling properties to make it pass from a liquid state to a gelled state and form the gelled envelope, the central core forming the liquid core; d. recovery of the capsules formed.

9. A method of producing microcapsules according to claim 8 wherein the second liquid solution comprises from 0.1 to 20% v / v of UV filter.

10. Process for producing microcapsules according to claim 8 or 9 comprising a step e. of dehydrating the microcapsules.

11. Microcapsule obtainable by the method according to any one of claims 8 to 10.

12. Use of microcapsules according to any one of claims 1 to 7 and 11 for the treatment of plant crops and / or their seeds.

13. A method of treating crops and / or seeds comprising spreading, foliar spraying or coating seeds with a suspension of microcapsules according to any one of claims 1 to 7 and 11.

14. Use of microcapsules according to any one of claims 1 to 7 and 11 for animal nutrition and / or feed.

15. Use of microcapsules according to any one of claims 1 to 7 and 11 for human nutrition and / or food.

16. Use of microcapsules according to any one of claims 1 to 7 and 1 1 for the formulation of cosmetics Use of microcapsules according to any one of claims 1 to 7 and 11 for the formulation of pharmaceutical compositions. Pharmaceutical composition comprising a microcapsule according to any one of claims 1 to 7 and 11. Use of microcapsules according to any one of claims 1 to 7 and 11 for the decontamination of soil or wastewater.

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