Method for preparing biodegradable solid capsules and the resulting solid capsules

Abstract

The present invention relates to a method for preparing solid microcapsules, comprising the steps of: a) adding, under stirring, composition C1 to polymer composition C2, thus obtaining an emulsion (E1) comprising droplets of composition C1 dispersed in composition C2, wherein composition C2 comprises at least one aliphatic or aromatic ester or polyester, further comprising at least one functional group selected from the group consisting of acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, carboxylate functional groups, and mixtures thereof; b) adding, under stirring, emulsion (E1) to composition C3, thus obtaining a double emulsion (E2) comprising droplets dispersed in composition C3; c) applying shear forces to the emulsion (E2), thus obtaining a double emulsion (E3) comprising droplets of controlled size dispersed in a composition C3; and d) Polymerizing composition C2, thus obtaining solid microcapsules dispersed in composition C3.

Description

[Technical Field]

[0001] The subject of the present invention is a method for preparing biodegradable capsules. Further subject matter relates to the resulting capsules and compositions containing them. [Background technology]

[0002] Many compounds, called active ingredients, are added to formulated products to give the product beneficial application properties or to enhance its performance. However, in many cases, these materials react adversely with other ingredients in the formulated product, resulting in detrimental effects on stability and reduced performance. Encapsulation of an active ingredient provides a highly advantageous means for overcoming the limited performance or stability of a formulated product containing it, while benefiting from the effectiveness of the active ingredient upon use of the formulated product. Nevertheless, the future disposal of microcapsules remains a major concern, as they become waste that is likely to accumulate in the environment after releasing their contents. For this reason, the development of microcapsules that can be biodegradable is of great importance.

[0003] Numerous capsules have been developed to separate active ingredients in formulated products, which are obtained from a number of production processes, such as spray drying, interfacial polymerization, interfacial precipitation, or solvent evaporation, among others.

[0004] Some of these microcapsules have shells made of non-crosslinked materials, such as hydrogels or thermoplastic polymers. If the hydrogel or thermoplastic polymer is made of a material known to be biodegradable, the shell of the microcapsule made of this material is considered biodegradable. The primary biodegradable materials used in these types of capsules belong to the polyester family, particularly polyhydroxyalkanoates (e.g., polylactic acid or polyglycolic acid), or polysaccharides (e.g., alginate, starch, or dextran). However, diffusion across the shell of this type of capsule is relatively fast, limiting its performance. The encapsulated compound can quickly escape to the outside of the capsule, or, conversely, chemical species that degrade the encapsulated compound can quickly enter the capsule.

[0005] Other microcapsules have a shell resulting from the reaction of monomers that chemically interact with each other to form a cross-linked material, thereby making diffusion through them much slower and thus improving the performance of the capsules. In this category, we can mention capsules made with urea and formaldehyde, which are widely used but unfortunately are not biodegradable. Summary of the Invention [Problem to be solved by the invention]

[0006] Therefore, there is a need for a technology to form capsules formed from crosslinked shells that are biodegradable and have very good retention and protection properties for the active ingredients contained therein.

[0007] Therefore, an object of the present invention is to provide a method for encapsulating an active ingredient while avoiding the above-mentioned problem of leakage of the active ingredient, and to obtain capsules using this method. A further object of the present invention is to provide a capsule containing at least one active ingredient and having excellent biodegradable properties. [Means for solving the problem]

[0008] The present invention therefore relates to a method for preparing solid microcapsules comprising the steps of: a) adding, under stirring, a composition C1 containing at least one active ingredient to a polymer composition C2, wherein the compositions C1 and C2 are not miscible with each other; The viscosity of composition C2 is 500 mPa s to 100,000 mPa s at 25°C, and is preferably higher than the viscosity of composition C1; Composition C2 is - at least one monomer or polymer selected from the group consisting of aliphatic or aromatic esters or polyesters, anhydrides or polyanhydrides, sugars or polysaccharides, ethers or polyethers, amides or polyamides, and carbonates or polycarbonates, further comprising at least one functional group selected from the group consisting of acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, carboxylate functional groups, and mixtures thereof; at least one crosslinking agent, optionally at least one photoinitiator or crosslinking catalyst; Thereafter, an emulsion (E1) is obtained, which comprises droplets of composition C1 dispersed in composition C2; b) adding emulsion (E1) to composition C3 under stirring, compositions C2 and C3 being immiscible with each other; The viscosity of composition C3 is 500 mPa s to 100,000 mPa s at 25°C, and is preferably higher than the viscosity of emulsion (E1); Thereafter, a double emulsion (E2) is obtained, comprising droplets dispersed in a composition C3; c) applying shear force to the emulsion (E2); Thereafter, a double emulsion (E3) is obtained, which comprises droplets of controlled size dispersed in a composition C3; and d) Polymerizing composition C2, after which solid microcapsules dispersed in composition C3 are obtained. DETAILED DESCRIPTION OF THE INVENTION

[0009] In this application, the terms "microcapsules" and "capsules" are used interchangeably. Thus, using the method of the present invention, it is possible to prepare solid microcapsules having a core and a solid shell completely encapsulating the core around it, the core being composition C1 containing at least one active ingredient.

[0010] Preferably, the solid microcapsules obtained by the process of the present invention are formed from a core containing at least one active ingredient (composition C1) and a solid shell (obtained from composition C2) completely encapsulating said core.

[0011] In the search for microcapsules with good performance in terms of retention and protection, the present inventors have surprisingly and unexpectedly found that biodegradable microcapsules can be obtained from non-biodegradable materials under certain conditions. That is, the microcapsules obtained by the method of the present invention can be biodegradable by taking into account the selection of specific monomers and polymers in composition C2.

[0012] Biodegradability is defined herein as the ability to break down in natural media as defined by OECD standards: OECD 301 (ready biodegradability), i.e. OECD 301A (dissolved organic carbon (DOC) disappearance), OECD 301B (CO evolution), OECD 301C (modified MITI(I) test), OECD 301D (closed bottle test), OECD 301E (modified OECD screening), OECD 301F (manometric respirometry test), or also OECD 304A (intrinsic biodegradability in soil), OECD 306 (biodegradable in seawater), and OECD 310 (ready biodegradability - CO in closed containers).

[0013] The method of the present invention has the further advantage of not requiring the use of surfactants or emulsifiers, which may promote and lead to uncontrolled release of the active ingredient outside the capsule and / or may react with ingredients of the formulated product into which the capsule is to be incorporated.

[0014] In the present invention, a double emulsion is produced, consisting of droplets containing at least one active ingredient surrounded by a crosslinkable liquid phase. These double droplets are then made monodisperse in size before being converted into rigid capsules via crosslinking or polymerization. This preparation involves four steps, which are described in detail below.

[0015] Process a) In step a) of the process of the invention, a first emulsion (E1) is prepared. The first emulsion consists of a dispersion of droplets of composition C1 (comprising at least one active ingredient) in polymer composition C2, which is immiscible with C1, produced by adding C1 dropwise to C2 under stirring.

[0016] In step a), composition C1 is added to crosslinkable polymer composition C2, and this step is carried out under stirring, which means that while composition C1 is being added, composition C2 is typically kept under mechanical stirring to emulsify the mixture of compositions C1 and C2. The addition of composition C1 to composition C2 is typically carried out dropwise.

[0017] Throughout step a), composition C1 is at a temperature of 0°C to 100°C, preferably 10°C to 80°C, and more preferably 15°C to 60°C. Throughout step a), composition C2 is at a temperature of 0°C to 100°C, preferably 10°C to 80°C, and more preferably 15°C to 60°C.

[0018] Under the conditions of addition in step a), compositions C1 and C2 are not miscible with each other, which means that the amount (by mass) of composition C1 that can be solubilized in C2 is 5% or less, preferably less than 1%, more preferably less than 0.5%, relative to the total mass of composition C2, and the amount (by mass) of composition C2 that can be solubilized in composition C1 is 5% or less, preferably less than 1%, more preferably less than 0.5%, relative to the total mass of composition C1. Thus, when composition C1 comes into contact with C2 under stirring, composition C1 disperses in the form of droplets called single droplets.

[0019] The immiscibility of compositions C1 and C2 also makes it possible to prevent the migration of the active ingredients of composition C1 towards composition C2.

[0020] Composition C2 is stirred to form an emulsion containing droplets of composition C1 dispersed throughout composition C2, also referred to as a "single emulsion" or a C1-in-C2 emulsion. To carry out step a), any type of mixer commonly used to form emulsions can be used, such as a mechanical blade mixer, a static emulsifier, an ultrasonic homogenizer, a membrane homogenizer, a high-pressure homogenizer, a colloid mixer, a high-shear disperser, or a high-speed homogenizer.

[0021] Composition C1 Composition C1 comprises at least one active ingredient A. This composition C1 acts as a carrier for active ingredient A in the process of the invention, both in the liquid droplets formed during the process and in the resulting solid capsules.

[0022] In a first embodiment of the method of the invention, composition C1 is monophasic, ie it is either the active ingredient A alone or a solution comprising the active ingredient A in solubilized form. In one embodiment, the active ingredient is solubilized in composition C1.

[0023] In this embodiment, Composition C1 typically comprises a solution of Active Ingredient A in an aqueous solution or organic solvent, or a mixture of organic solvents, with Active Ingredient A being present in an amount of 1% to 99% by weight, based on the total weight of Composition C1. Active Ingredient A may be present in an amount of 5% to 95%, 10% to 90%, 20% to 80%, 30% to 70%, or 40% to 60% by weight, based on the total weight of Composition C1. In one embodiment, composition C1 consists of active ingredient A.

[0024] In another embodiment of the present invention, composition C1 is a biphasic composition, which means that the active ingredient is dispersed in composition C1 in liquid or solid form and is not completely solubilized in composition C1. In one embodiment, the active ingredient is dispersed in the form of solid particles in composition C1. In this embodiment, composition C1 may consist of a dispersion of solid particles of the active ingredient in an organic solvent or a mixture of organic solvents. In this embodiment, composition C1 may consist of a dispersion of solid particles of the active ingredient in an aqueous phase comprising water and optionally a hydrophilic organic solvent.

[0025] For example, the active ingredients used are as follows: - Crosslinkers, curing agents, organic or metallic catalysts (e.g. organometallic or inorganic metal complexes of platinum, palladium, titanium, molybdenum, copper, zinc) used to polymerize polymer, elastomer, rubber, paint, adhesive, sealant, mortar, varnish or coating formulations; - Colorants or pigments for elastomer, paint, coating, adhesive, sealant, mortar or paper formulations;

[0026] - fragrances (within the meaning of the list of molecules drawn up by the International Fragrance Association (IFRA) and available on the website www.ifraorg.org) for cleaning agents, such as detergents and home cleaning products, cosmetics and personal hygiene products, textiles, paints and coatings; - Flavourings, vitamins, amino acids, proteins, lipids, probiotics, antioxidants, pH correctors, preservatives for food ingredients and animal feed; - fabric softeners, detergent conditioners, cleaning products, cosmetics, personal hygiene products. In this respect, active ingredients that can be used are listed, for example, in US Pat. No. 6,335,315 and US Pat. No. 5,877,145;

[0027] - Anti-fading agents (e.g. ammonium derivatives), anti-foaming agents (e.g. alcohol ethoxylates, alkylbenzenesulfonates, polyethylene ethoxylates, alkyl ethoxy sulfates or alkyl sulfates) for detergents, cleaning products and household cleaning products; - Optical brighteners, also called color activators, for detergents, cleaning products, cosmetics and personal hygiene products (for example stilbene derivatives, coumarin derivatives, pyrazoline derivatives, benzoxazole derivatives or naphthalimide derivatives);

[0028] - bioactive compounds such as enzymes, vitamins, proteins, plant extracts, emollients, disinfectants, antibacterial agents, UV protection agents, pharmaceuticals, etc. for cosmetics and personal hygiene products, textiles, including vitamins A, B, C, D and E, para-aminobenzoic acid, alpha-hydroxylated acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, or citric acid), camphor, ceramides, polyphenols (e.g., flavonoids, phenolic acids, ellagic acid, tocopherol, ubiquinol), hydroquinone, hyaluronic acid, isopropyl isostearate, isopropyl palmitate, oxybenzone, panthenol, proline, retinol, retinyl palmitate, salicylic acid, sorbic acid, sorbitol, triclosan, tyrosine;

[0029] - Bactericide, antibacterial and anti-UV agent for paints and coatings. - Fertilizers, herbicides, insecticides, pesticides, fungicides, insect repellents or fungicides for agricultural chemical products.

[0030] - Flame retardants for plastic materials, coatings, paints, and textiles (brominated polyols such as tetrabromobisphenol A, halogenated or non-halogenated organophosphorus compounds, chlorinated compounds, aluminum trihydrate, antimony oxide, zinc borate, red phosphorus, melamine, or magnesium dihydroxide); - Photonic crystals or optical chromophores for paints, coatings and polymer materials to form curved and flexible screens;

[0031] - Products intended for energy storage, known to those skilled in the art under the name of phase change materials (PCM), which are capable of absorbing or releasing heat when they undergo a phase change. Examples of PCMs and their applications are described in "A review on phase change energy storage: materials and applications", Farid et al., Energy Conversion and Management, 2004, 45(9-10), pp. 1597-1615. Examples of PCMs include molten aluminum phosphate, ammonium carbonate, ammonium chloride, cesium carbonate, cesium sulfate, calcium citrate, calcium chloride, calcium hydroxide, calcium oxide, calcium phosphate, calcium saccharinate, calcium sulfate, cerium phosphate, iron phosphate, lithium carbonate, lithium sulfate, magnesium chloride, magnesium sulfate, manganese chloride, manganese nitrate, manganese sulfate, potassium acetate, potassium carbonate, potassium chloride, potassium phosphate, rubidium carbonate, rubidium sulfate, disodium tetraborate, sodium acetate, sodium bicarbonate, sodium bisulfate, sodium citrate, sodium chloride, sodium hydroxide, sodium nitrate, sodium percarbonate, sodium persulfate, sodium phosphate, sodium propionate, sodium selenite, sodium silicate, sodium sulfate, sodium tellurite, sodium thiosulfate, strontium hydrogen phosphate, zinc acetate, zinc chloride, sodium thiosulfate, hydrocarbon paraffin wax, and polyethylene glycol.

[0032] Composition C2 Composition C2 is intended to form the future solid shell of the microcapsules. The volume fraction of C1 in C2 can be varied from 0.1 to 0.6 to control the shell thickness of the capsule obtained at the completion of the process. In one embodiment, the ratio between the volume of composition C1 and the volume of composition C2 varies between 1:10 and 10:1. Preferably, this ratio is between 1:3 and 5:1, more preferably between 1:3 and 3:1.

[0033] Preferably, the viscosity of composition C2 at 25°C is from 1,000 mPa·s to 50,000 mPa·s, more preferably from 2,000 mPa·s to 25,000 mPa·s, for example, from 3,000 mPa·s to 15,000 mPa·s. Preferably, the viscosity of composition C2 is higher than the viscosity of composition C1. Viscosity is measured using a Haake Rheostress™ 600 rheometer equipped with a 60 mm diameter cone with a 2 degree angle and a temperature controlled cell set at 25°C. Viscosity values ​​are reported in 10 s -1 The reading is taken at a shear rate of .

[0034] In this embodiment, the rate of destabilization of the droplets of emulsion (E1) is significantly slower, allowing the shells of the microcapsules to be polymerized in step d) before the emulsion becomes unstable. Once polymerization is complete, thermodynamic stabilization then occurs. Thus, the relatively high viscosity of composition C2 ensures the stability of emulsion (E1) obtained after step a).

[0035] Preferably, the interfacial tension between compositions C1 and C2 is low. Typically, these interfacial tensions vary from 0 mN / m to 50 mN / m, more preferably from 0 mN / m to 20 mN / m. The low interfacial tension between compositions C1 and C2 also advantageously allows a reliable stability of the emulsion (E1) obtained after step a).

[0036] Composition C2 comprises at least one monomer or polymer as defined below, at least one crosslinking agent, and optionally at least one photoinitiator or crosslinking catalyst, making the composition crosslinkable.

[0037] In one embodiment, composition C2 comprises 50% to 99% by weight of a monomer or polymer as defined below, or a mixture of monomers and polymers as defined below, relative to the total weight of composition C2. In one embodiment, composition C2 comprises 1% to 20% by weight of a crosslinking agent or a mixture of crosslinking agents, relative to the total weight of composition C2. In one embodiment, composition C2 comprises 0.1% to 5% by weight of a photoinitiator or a mixture of photoinitiators, based on the total weight of composition C2. In one embodiment, composition C2 contains 0.001% by mass to 20% by mass of a crosslinking agent relative to the mass of composition C2.

[0038] In the present invention, the term "monomer" or "polymer" refers to any basic unit adapted to form a solid material by polymerization, either alone or in combination with other monomers or polymers. The term "polymer" also includes oligomers.

[0039] These monomers are selected from monomers containing at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups.

[0040] The monomers or polymers used in composition C2 are chosen from among aliphatic or aromatic esters or polyesters, anhydrides or polyanhydrides, sugars or polysaccharides, ethers or polyethers, amides or polyamides, and carbonates or polycarbonates, said polymers further having at least one reactive functional group chosen from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups.

[0041] Preferably, the monomers or polymers used in composition C2 are selected from aliphatic or aromatic esters or polyesters, anhydrides or polyanhydrides, sugars or polysaccharides, ethers or polyethers, amides or polyamides, and carbonates or polycarbonates, said polymers further having at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups, said monomers or polymers not having any other reactive functional groups different from the acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups.

[0042] In one embodiment, the monomer or polymer used in composition C2 does not have a urethane functionality.

[0043] Preferably, the monomers or polymers used in composition C2 are selected from aliphatic or aromatic esters or polyesters, anhydrides or polyanhydrides, sugars or polysaccharides, ethers or polyethers, amides or polyamides, and carbonates or polycarbonates, said polymers further having at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups, said monomers or polymers having no urethane functional groups.

[0044] Preferably, the monomers or polymers used in composition C2 are selected from aliphatic or aromatic esters or polyesters, anhydrides or polyanhydrides, sugars or polysaccharides, ethers or polyethers, amides or polyamides, and carbonates or polycarbonates, said polymers further having a single reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups. Thus, in this embodiment, the monomers or polymers of composition C2 have no functional groups other than those listed above, and therefore in particular no urethane functional groups.

[0045] Examples of such monomers or polymers include, but are not limited to, the following compounds and mixtures thereof:

[0046] In particular polyglycolide (PGA), polylactide (PLA), poly(lactide-co-glycolide) (PLGA), poly(orthoesters), such as polycaprolactone (PCL), polydioxanone, poly(ethylene succinate), poly(butylene succinate) (PBS), poly(ethylene adipate), poly(butylene adipate), poly(ethylene sebacate), poly(butylene sebacate), poly(valerolactone) (PVL), poly(decalactone), polyhydroxyvaleric acid, poly(beta-malic acid), poly-3-hydroxybutyric acid (PH B), poly-3-hydroxybutyrate-co-3-hydroxyvalerate (P-3HB-3HV), poly-3-hydroxybutyrate-co-4-hydroxybutyrate (P-3HB-4HB), poly-3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate (P-3HB-3HV-4HB), poly(3-hydroxyvalerate), poly(3-hydroxypropionic acid), poly(3-hydroxycaproic acid), poly(3-hydroxyoctanoic acid), poly(3-hydroxydecanoic acid), poly(3-hydroxyundecanoic acid), poly(3-hydroxydodecanoic acid) , poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxydecanoate), poly(3-hydroxybutyrate-co-3-hydroxypropionic acid), poly(3-hydroxybutyrate-co-3-hydroxyoctanoic acid), poly(3-hydroxyheptanoic acid), poly(3-hydroxyhexanoic acid), poly(2-hydroxybutyrate), poly(3-hydroxybutyrate-co-4-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyhexanoic acid), poly(3-hydroxybutyrate-co-3-hydroxyhexanoic acid) , poly(4-hydroxybutyrate), poly(4-hydroxybutyrate-co-2-hydroxybutyrate), poly(4-hydroxypropionic acid), poly(4-hydroxyvaleric acid), poly(5-hydroxybutyrate), poly(5-hydroxyvaleric acid), poly(6-hydroxyhexanoic acid), poly(alkylene alkanoates), poly(alkylene dicarboxylates), poly(butylene adipate), poly(butylene adipate-co-terephthalic acid), poly(butylene carbonate), poly(butylene pimelate), poly(butylene succinate), poly(butylene succinate-co-adipic acid),Poly(butylene succinate-co-carbonate), poly(butylene sebacate), poly(butylene sebacate-co-terephthalic acid), poly(butylene succinate-co-terephthalic acid), poly(butylene succinate-co-lactic acid), poly(cyclohexene carbonate), polydiaxanone, poly(ethylene azelate), poly(ethylene carbonate), poly(ethylene decamethylate), poly(ethylene furanoate), Poly(ethylene oxalate), poly(ethylene succinate), poly(ethylene succinate-co-adipic acid), poly(ethylene sebacate), poly(ethylene succinate-co-terephthalic acid), poly(ethylene suberate), poly(hexamethylene sebacate), poly(glycolide-co-caprolactone), poly(lactide-co-epsilon-caprolactone), polymandelide, poly(B-malic acid) the group of aliphatic or aromatic esters and polyesters including poly(propylene succinate), poly(tetramethylene adipate-co-terephthalic acid), poly(tetramethylene carbonate), poly(trimethylene carbonate), poly(tetramethylene succinate)-co-(tetramethylene carbonate), poly(trimethylene adipate), poly(methylene adipate-co-terephthalic acid), poly(tetramethylene adipate), poly(tetramethyl glycolide), poly(butylene succinate), poly(valerolactone), further having at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups;

[0047] from the group of anhydrides or polyanhydrides, obtained for example from poly(sebacic acid), poly(adipic acid), polyterephthalic acid, poly(bis(p-carboxyphenoxy)alkanoic acid) or more generally from the polyanhydrides described, for example, in Advanced Drug Delivery Reviews 54 (2002) 889-910, and further comprising at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate and carboxylate functional groups;

[0048] the group of sugars and polysaccharides, including in particular carrageenans, dextrans, cyclodextrins, such as hyaluronic acid, agarose, chitosan, chitin, alginates, starch, cellulose and its derivatives, such as methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, ethylhydroxyethylcellulose, carboxymethylcellulose, hydroxypropylcellulose or methylhydroxypropylcellulose, and also having at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate and carboxylate functional groups;

[0049] - from the group of ethers and polyethers, including in particular polyethylene glycols, and also having at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate and carboxylate functional groups; and

[0050] - the group of amides and polyamides, including in particular poly(ester amides) or polyphthalamides, and further comprising at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate and carboxylate functional groups.

[0051] Preferably, the monomers or polymers used in composition C2 are chosen from aliphatic or aromatic esters or polyesters, further having at least one reactive functional group selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate and carboxylate functional groups, said monomers or polymers having no urethane functional groups. Preferably, the monomer or polymer used in composition C2 is not an aliphatic or aromatic ester or polyester having at least one urethane functional group.

[0052] By "crosslinker" is meant a compound having at least two reactive functional groups that is capable of crosslinking a monomer or polymer, or a mixture of monomers or polymers, upon polymerization. The crosslinker can be selected from among molecules having at least two identical or different functional groups selected from the group formed by acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, and carboxylate functional groups.

[0053] Crosslinking agents that may be mentioned in particular are: diacrylates, such as 1,6-hexanediol diacrylate, 1,6-hexanediol dimethacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, 1,9-nonanediol dimethacrylate, 1,4-butanediol dimethacrylate, 1,3-butanediol dimethacrylate, 1,10-decanediol dimethacrylate, bis(2-methacryloxyethyl) N,N'-1,9-nonylenebiscarbamate, 1,4-butanediol diacrylate ol, 1,5-pentanediol dimethacrylate, allyl methacrylate, N,N'-methylenebisacrylamide, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane, tetraethylene glycol diacrylate, diethylene glycol diacrylate, triethylene glycol diacrylate, triethylene glycol dimethacrylate, polyethylene glycol diglycidyl ether, N,N-diallylacrylamide, or glycidyl methacrylate;

[0054] polyfunctional acrylates, such as dipentaerythritol pentaacrylate, 1,1,1-trimethylolpropane triacrylate, 1,1,1-trimethylolpropane trimethacrylate, ethylenediamine tetramethacrylate, pentaerythritol triacrylate, or pentaerythritol tetraacrylate; and

[0055] - acrylates which also carry other reactive functional groups, such as propargyl methacrylate, N-acryloxysuccinimide, N-(2-hydroxypropyl)methacrylamide, N-(t-BOC-aminopropyl)methacrylamide, monoacryloxyethyl phosphate, acrylic anhydride, 2-(tert-butylamino)ethyl methacrylate, N,N-diallylacrylamide, or glycidyl methacrylate.

[0056] In one embodiment, composition C2 comprises 0.001 to 20% by weight of the crosslinker, based on the total weight of the composition.

[0057] "Photoinitiator" means a compound capable of decomposing under the influence of light irradiation. Photoinitiators that can be used in the present invention are known in the art and are described, for example, in "Photoinitiators in the Crosslinking of Coatings" (Photoinitiators in the Crosslinking of Coatings), G. Li Bassi, Double Liaison-Chimie des Peintures, No. 361, November 1985, pp. 34-41; "Industrial Applications of Photoinduced Polymerization" (Industrial Applications of Photoinduced Polymerization), Henri Strub, L'Actualite Chimique, February 2000, pp. 5-13; and "Photopolymeres: Theoretical Considerations and Reaction of the Prise" (Photopolymers: Theoretical Considerations and Curing Reactions), Marc, J.M. Abadie, Double Liaison-Chimie des Peintures, No. 435-436, 1992, pp. 28-34.

[0058] These photoinitiators include: α-hydroxyketones, such as 2-hydroxy-2-methyl-1-phenyl-1-propanone, sold under the trade names DAROCUR® 1173 and 4265, IRGACURE® 184, 2959 and 500 by BASF and ADDITOL® CPK by CYTEC;

[0059] α-aminoketones, in particular 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butanone-1, sold for example under the trade names IRGACURE® 907 and 369 by BASF;

[0060] aromatic ketones, such as those sold under the trade name ESACURE® TZT by LAMBERTI; or thioxanthones and quinones, such as those sold under the trade name ESACURE® ITX by LAMBERTI. These aromatic ketones often require the presence of a hydrogen donor compound, such as a tertiary amine or an alkanolamine. Mention may be made in particular of the tertiary amine ESACURE® EDB sold by LAMBERTI.

[0061] - α-dicarbonyl derivatives, most frequently represented by benzyl dimethyl ketal sold by BASF under the trade name IRGACURE® 651. Another commercially available product is sold by LAMBERTI under the trade name ESACURE® KB1; and

[0062] Acylphosphine oxides, for example the bisacylphosphine oxides (BAPO) sold by BASF under the trade names IRGACURE® 819, 1700 and 1800, DAROCUR® 4265, LUCIRIN® TPO and LUCIRIN® TPO-L.

[0063] Photoinitiators can include aromatic ketones such as benzophenone, phenylglyoxylates such as the methyl ester of phenylglyoxylic acid, oxime esters such as [1-(4-phenylsulfanylbenzoyl)heptylideneamino]benzoate, sulfonium salts, iodonium salts, and oxime sulfonates.

[0064] In one embodiment, composition C2 may also comprise further monomers or polymers that can improve the properties of the shell of the microcapsules and / or impart new properties to the shell of the microcapsules. These additional monomers or polymers may include monomers or polymers with pH-sensitive groups, or groups that are sensitive to temperature, UV, or IR. These further monomers or polymers can trigger the rupture of the solid microcapsules and subsequent release of their contents after stimulation by, for example, pH, temperature, UV, or IR.

[0065] These further monomers or polymers may be chosen from monomers or polymers bearing at least one of the following groups:

[0066] pH-sensitive groups such as primary, secondary, or tertiary amines, carboxylic acids, phosphates, sulfates, nitrates, or carbonate groups; UV-sensitive or UV-cleavable groups (photochromic groups), such as azobenzene, spiropyran, 2-diazo-1,2-naphthoquinone, o-nitrobenzyl, thiol groups, or 6-nitro-veratroyloxycarbonyl, such as poly(ethylene oxide)-block-poly(2-nitrobenzyl methacrylate) and other block copolymers, as described, in particular, in Liu et al., Polymer Chemistry 2013, 4, 3431-3443; - IR-sensitive or IR-cleavable groups, such as o-nitrobenzyl or 2-diazo-1,2-naphthoquinone, for example in the polymers described in Liu et al., Polymer Chemistry 2013, 4, 3431-3443; - hydrolysis-sensitive groups, such as poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), polycaprolactone, polyhydroxybutyric acid, chitosan, dextran, agarose, cellulose, and derivatives of these compounds; and - Temperature sensitive groups, such as poly(N-isopropylacrylamide).

[0067] Step b) In step b) of the process of the invention, a second emulsion (E2) is prepared. The second emulsion consists of a dispersion of droplets of the first emulsion in a composition C3 immiscible with C2, produced by adding emulsion (E1) dropwise to C3 under stirring. Throughout step b), emulsion (E1) is at a temperature of 15°C to 60°C. Throughout step b), composition C3 is at a temperature of 15°C to 60°C.

[0068] Under the conditions of addition in step b), compositions C2 and C3 are not miscible with each other, which means that the amount (by mass) of composition C2 that can be solubilized in composition C3 is 5% or less, preferably less than 1%, more preferably less than 0.5%, relative to the total mass of composition C3, and the amount (by mass) of composition C3 that can be solubilized in composition C2 is 5% or less, preferably less than 1%, more preferably less than 0.5%, relative to the total mass of composition C2.

[0069] Thus, when emulsion (E1) comes into contact with composition C3 under stirring, it is dispersed in the form of droplets called double droplets, and the dispersion of these droplets of emulsion (E1) in the C3 continuous phase is called emulsion (E2).

[0070] Typically, the double droplets formed in step b) correspond to a single droplet of composition C1 as described above, surrounded by a shell of composition C2 that completely encapsulates the single droplet. The double droplets formed in step b) may also comprise at least two single droplets of composition C1, which are surrounded by a shell of composition C2 that completely encapsulates the single droplets.

[0071] Said double droplets therefore comprise a core made up of one or more single droplets of composition C1 and a layer of composition C2 surrounding said core. The resulting emulsion (E2) is generally a polydisperse double emulsion (C1-in C2-in C3 emulsion, or C1 / C2 / C3 emulsion), which means that the double droplets in emulsion (E2) do not have a distinct size distribution.

[0072] The immiscibility between compositions C2 and C3 prevents mixing between the layers of composition C2 and composition C3, thereby ensuring the stability of the emulsion (E2). Also, the immiscibility between compositions C2 and C3 can prevent the migration of water-soluble substances of C1 from the core of the droplet towards composition C3.

[0073] To carry out step b), any type of mixer commonly used to form emulsions can be used, such as a mechanical blade mixer, a static emulsifier, an ultrasonic homogenizer, a membrane homogenizer, a high-pressure homogenizer, a colloid mixer, a high-shear disperser, or a high-speed homogenizer.

[0074] Composition C3 In one embodiment, the viscosity of composition C3 at 25°C is higher than the viscosity of emulsion (E1) at 25°C. In the present invention, the viscosity of composition C3 at 25°C is 500 mPa·s to 100,000 mPa·s. Preferably, the viscosity of composition C3 at 25°C is from 3,000 mPa·s to 100,000 mPa·s, more preferably from 5,000 mPa·s to 80,000 mPa·s, for example from 7,000 mPa·s to 70,000 mPa·s.

[0075] In this embodiment, given the very high viscosity of the continuous phase formed by composition C3, the rate of destabilization of the double droplets of emulsion (E2) is significantly slow compared to the duration of the method of the present invention, thus resulting in kinetic stabilization of emulsion (E2) and then (E3) until polymerization of the capsule shell is complete. Once polymerized, the capsules are thermodynamically stable. The very high viscosity of composition C3 therefore ensures the stability of the emulsion (E2) obtained after step b).

[0076] The low surface tension between C3 and the primary emulsion and the high viscosity of this system advantageously ensure the kinetic stability of the double emulsion (E2) and prevent dephaser throughout the production time. Preferably, the interfacial tension between compositions C2 and C3 is low. This low interfacial tension between compositions C2 and C3 also advantageously makes it possible to ensure the stability of the emulsion (E2) obtained after step b).

[0077] The volume fraction of the first emulsion in C3 can be varied between 0.05 and 0.5 to first improve the production yield and then change the average capsule diameter. After this process is completed, the size distribution of the second emulsion becomes relatively broad. In one embodiment, the ratio of the volume of emulsion (E1) to the volume of composition C3 varies between 1:10 and 10:1. Preferably, this ratio is between 1:9 and 3:1, more preferably between 1:9 and 1:1.

[0078] In one embodiment, composition C3 also preferably contains 5,000 g.mol -1 At least one branched polymer having a molecular weight higher than 5,000 g.mol -1 It contains at least one polymer with a higher molecular weight and / or solid particles such as silicates. In one embodiment, composition C3 preferably has a molecular weight of 5,000 g.mol -1 Higher, more preferably with a molecular weight of 10,000 g.mol -1 ~500,000 g.mol -1 , e.g. 50,000 g.mol -1 ~300,000 g.mol -1 The branched polymer comprises at least one of the following:

[0079] By "branched polymer" is meant a polymer having at least one branch point between its two end groups, a branch point being a point on the chain to which a side chain, also called a branched chain or pendant chain, is attached. Branched polymers can include grafted polymers, comb or star polymers, or dendrimers.

[0080] In one embodiment, composition C3 is 5,000 g.mol -1Higher, preferably 10,000 g.mol -1 ~500,000 g.mol -1 , e.g. 50,000 g.mol -1 ~300,000 g.mol -1 The polymer comprises at least one polymer having a molecular weight of

[0081] Polymers that can be used in composition C3 include the following compounds, used alone or mixed together:

[0082] cellulose derivatives, such as cellulose ethers: methylcellulose, ethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, ethylhydroxyethylcellulose, carboxymethylcellulose, hydroxypropylcellulose or methylhydroxypropylcellulose;

[0083] - polyacrylates (also called carbomers), such as polyacrylic acid (PAA), polymethacrylic acid (PMAA), poly(hydroxyethyl methacrylate) (pHEMA), poly(N-2-hydroxypropyl methacrylate) (pHPMA); - polyacrylamides, such as poly(N-isopropylacrylamide) (PNIPAM);

[0084] - Polyvinylpyrrolidone (PVP) and its derivatives; - Polyvinyl alcohol (PVA) and its derivatives; - poly(ethylene glycol), poly(propylene glycol) and their derivatives, such as poly(ethylene glycol) acrylate / methacrylate, poly(ethylene glycol) diacrylate / dimethacrylate, polypropylene carbonate;

[0085] - polysaccharides, such as carrageenan, locust bean gum or tara gum, dextran, xanthan gum, chitosan, agarose, hyaluronic acid, gellan gum, guar gum, gum arabica, gum tragacanth, diutan gum, oat gum, karaya gum, ghatti gum, curdlan, pectin, konjac gum, starch; - protein derivatives, such as gelatin, collagen, fibrin, polylysine, albumin, casein;

[0086] - silicone derivatives, such as polydimethylsiloxane (also known as dimethicone), alkyl silicones, aryl silicones, alkylaryl silicones, polyethylene glycol dimethicone, polypropylene glycol dimethicone;

[0087] waxes, such as diester waxes (diesters of alkanediols, diesters of hydroxyl acids), triester waxes (triacylglycerols, triesters of alkane-1,2-diols, triesters of ω-hydroxy acids and fatty acids, esters of hydroxymalonic acid, esters of fatty acids and alcohols, triesters of hydroxyl acids, triesters of fatty acids and fatty alcohols, triesters of fatty acids, triesters of hydroxyl acids and diols) and polyester waxes (polyesters of fatty acids). For example, esters of fatty acids that can be used as waxes in the present invention are cetyl palmitate, cetyl octanoate, cetyl laurate, cetyl lactate, cetyl isononanoate, cetyl stearate, stearyl stearate, myristyl stearate, cetyl myristate, isocetyl stearate, glyceryl trimyristate, glyceryl tripalmitate, glyceryl monostearate, or glyceryl palmitate and cetyl palmitate;

[0088] fatty acids which can be used as waxes, such as cerotic acid, palmitic acid, stearic acid, dihydroxystearic acid, behenic acid, lignoceric acid, arachidic acid, myristic acid, lauric acid, tridecylic acid, pentadecylic acid, margaric acid, nonadecylic acid, heneicosylic acid, tricosylic acid, pentacosylic acid, heptacosylic acid, montanic acid or nonacosylic acid;

[0089] salts of fatty acids, in particular aluminium salts of fatty acids, such as aluminium stearate, hydroxyaluminium bis(2-ethylhexanoate);

[0090] - isomerized jojoba oil; - Hydrogenated sunflower seed oil; - Hydrogenated copra oil; - Hydrogenated lanolin oil; castor oil and its derivatives, in particular modified hydrogenated castor oil or compounds obtained by esterification of castor oil with fatty alcohols; - polyurethanes and their derivatives; - styrene polymers, such as styrene butadiene; and - Polyolefins, for example polyisobutene.

[0091] In one embodiment, composition C3 comprises solid particles such as clays, silica, and silicates.

[0092] Solid particles that can be used in Composition C3 include clays and silicates, particularly those belonging to the category of phyllosilicates (also known as sheet silica). Examples of silicates that can be used in the present invention include bentonite, hectorite, attapulgite, sepiolite, montmorillonite, saponite, sauconite, nontronite, kaolinite, talc, sepiolite, and chalk. Pyrogenic synthetic silica can also be used. The aforementioned clays, silicates, and silicas can be advantageously modified with organic molecules such as polyethers, ethoxylated amides, quaternary ammonium salts, long-chain diamines, long-chain esters, polyethylene glycols, and polypropylene glycols. These particles can be used alone or in mixtures.

[0093] In one embodiment, composition C3 is 5,000 g.mol -1 at least one polymer having a higher molecular weight, and solid particles. Mixtures of any of the foregoing compounds may be used.

[0094] Process c) In step c) of the method of the invention, the size of the droplets of the second emulsion (E2) is refined. In this process, a controlled uniform shear force can be applied to the emulsion (E2), and the applied shear rate is 10 s -1 ~100,000s -1 is.

[0095] In one embodiment, the polydisperse double droplets obtained in step b) are subjected to size refinement, whereby they are subjected to shear capable of fragmenting them into new double droplets of controlled and uniform diameter. Preferably, this fragmentation step is carried out using a Couette-type high-shear cell, according to the method described in European Patent Application No. 15306428.2.

[0096] In one embodiment, the second emulsion (E2) obtained after step b), consisting of polydisperse double droplets dispersed in a continuous phase, is subjected to shear forces in a mixer that applies controlled uniform shear in step c). Thus, in this embodiment, in step c), a controlled uniform shear force is applied to the emulsion (E2), and the applied shear rate is 1,000 s -1 ~100,000s -1 is.

[0097] In this embodiment, the shear rate in the mixer is considered to be controlled and uniform if it reaches a maximum value at a given moment, which may vary from point to point in the emulsion, and is the same for all parts of the emulsion, regardless of the length of time.The exact configuration of the mixer is not essential to the present invention, as long as the entire emulsion is subjected to the same maximum shear force when it leaves the device.Mixers suitable for carrying out step c) are particularly described in US Patent No. 5,938,581.

[0098] The second emulsion is - Two concentric rotating cylinders (also called Couette type mixers); - two parallel rotating discs; or - Two parallel diaphragms As the particles circulate through the cells formed by the process, they are subjected to a controlled and uniform shear force.

[0099] In this embodiment, the shear rate applied to the second emulsion is 1,000 s -1 ~100,000s -1 , preferably 1,000s -1 ~50,000s -1 , preferably 2,000s -1 ~20,000s -1 is.

[0100] In this embodiment, in step c), the second emulsion is placed in a mixer and subjected to shear force to form a third emulsion. The third emulsion (E3) is chemically the same as the second emulsion (E2), except that emulsion (E3) is composed of monodisperse double droplets, whereas emulsion (E2) is composed of polydisperse double droplets. The third emulsion (E3) typically consists of a dispersion of double droplets comprising a core formed from one or more droplets of composition C1 and a layer of composition C2 encapsulating the core, the double droplets being dispersed in composition C3.

[0101] The difference between the second and third emulsions is the diversity of the size of the double droplets: the droplets of the second emulsion are polydisperse in size, whereas the droplets of the third emulsion are monodisperse due to the fragmentation mechanism mentioned above. Preferably, in this embodiment, the second emulsion is added continuously to the mixer, which means that the amount of double emulsion (E2) fed to the mixer is the same as the amount of third emulsion (E3) leaving the mixer.

[0102] Since the droplet size of emulsion (E3) essentially corresponds to the droplet size of the solid microcapsules after polymerization, the strong correlation between a decrease in droplet size and an increase in shear rate allows the size and shell thickness of the microcapsules to be adjusted by adjusting the shear rate in step c). This allows the resulting dimensions of the microcapsules to be adjusted by changing the shear rate applied in step c).

[0103] In one preferred embodiment, the mixer used in step c) has an inner radius R o outer cylinder and outer radius R i The couette-type mixer contains two concentric cylinders, the outer cylinder being fixed and the inner cylinder rotating at an angular velocity ω.

[0104] The couette type mixer applied in the process of the present invention can be supplied by TSR France. In one embodiment, the angular velocity ω of the rotating inner cylinder of the Couette mixer is 30 rad.s -1 That's all. For example, the angular velocity ω of the inner rotating cylinder of a Couette mixer is approximately 70 rad.s -1 is. The dimensions of the outer fixed cylinder of a Couette mixer are the space between the inner rotating cylinder and the outer fixed cylinder (d = R o -R i ) can be selected to adjust the

[0105] In one embodiment, the space between two concentric cylinders of a Couette-type mixer (d=R o -R i ) is 50 μm to 1,000 μm, preferably 100 μm to 500 μm, for example, 200 μm to 400 μm. For example, the distance d between two concentric cylinders is 100 μm.

[0106] In this embodiment, in step c), the second emulsion is typically fed to a mixer via a pump and directed into the space between two concentric cylinders, the outer cylinder being fixed and the inner cylinder rotating at an angular velocity ω.

[0107] When the double emulsion reaches the space between the two cylinders, the shear rate applied to the emulsion is given by:

number

[0108] In another embodiment, if the viscosity of composition C3 is greater than 2,000 mPa s at 25° C., in step c), -1 A shear rate of less than 1000 rpm is applied to the emulsion (E2). In this embodiment, the fragmentation step c) is typically performed for 1,000 s -1 This can be carried out using any type of mixer used to form emulsions at shear rates below 2,000 mPa.s, in which case the viscosity of composition C3 is higher than 2,000 mPa.s, i.e. under the conditions described in French Patent Application No. 1 661 787. The geometrical properties of the double droplets formed at the completion of this process determine the geometrical properties of the future capsules.

[0109] In this embodiment, the emulsion (E2) formed of polydisperse droplets dispersed in a continuous phase is subjected in step c) to a low shear rate, i.e., 1,000 s , for example in a mixer. -1 Shear force is applied at less than In this embodiment, the shear rate applied in step c) is, for example, 10 s -1 ~1,000s -1 is. Preferably, the shear rate applied in step c) is exactly 1,000 s -1 is smaller than.

[0110] In this embodiment, the droplets of emulsion (E2) can only be efficiently fragmented into fine monodisperse droplets of emulsion (E3) when large shear forces are applied. The shear stress σ exerted on the droplets of emulsion (E2) is defined as the tangential force per unit surface area of ​​the droplet resulting from the macroscopic shear exerted on the emulsion when mixed in step d).

[0111] The shear stress σ (expressed in Pa) applied to the emulsion (E2) when mixed in step d), the viscosity η (expressed in Pas) of composition C3, and the shear rate γ (s -1 ) are related by the following formula: σ=ηγ Thus, in this embodiment, the high viscosity of composition C3 allows for the application of very high shear stresses to the droplets of emulsion (E2) in the mixer, even at low shear rates and when the shear is non-uniform.

[0112] To carry out step c) in this embodiment, any type of mixer commonly used to form emulsions can be used, such as a mechanical blade mixer, a static emulsifier, an ultrasonic homogenizer, a membrane homogenizer, a high-pressure homogenizer, a colloid mixer, a high-shear disperser, or a high-speed homogenizer. In one preferred embodiment, a simple emulsifier such as a mechanical paddle blade mixer or static emulsifier is used to carry out step c). This embodiment uses controlled shear or 1,000 s -1 This is possible because it does not require any higher shear forces.

[0113] Step d) In step d) of the process of the present invention, the shell of the solid microcapsules of the present invention is crosslinked and thus formed. This step makes it possible to reach the expected performance levels both in terms of capsule retention and in terms of its thermodynamic stability by ensuring that destabilizing mechanisms such as fusion and maturation are prevented.

[0114] In one embodiment, when composition C2 comprises a photoinitiator, step d) is a photopolymerization step, whereby emulsion (E3) is exposed to a light source capable of initiating the photopolymerization of composition C2, in particular a UV light source emitting preferably in the wavelength range from 100 nm to 400 nm, in particular for a time of less than 15 minutes.

[0115] In this embodiment, in step d), emulsion (E3) is subjected to photopolymerization, which allows for the photopolymerization of composition C2, which allows for the production of microcapsules encapsulating water-soluble substances as defined above. In one embodiment, in step d), emulsion (E3) is exposed to a light source capable of initiating photopolymerization of composition C2. Preferably, the light source is a UV light source. In one embodiment, the UV light source emits light in the wavelength range of 100 nm to 400 nm.

[0116] In one embodiment, the emulsion (E3) is exposed to the light source for a period of less than 15 minutes, preferably 5 to 10 minutes. In step d), the shells of the above double droplets consisting of photocrosslinkable composition C2 are crosslinked, thereby converting them into viscoelastic polymer shells that encapsulate the water-soluble substance and protect it from release, in the absence of a mechanical trigger.

[0117] In another embodiment, when composition C2 does not contain a photoinitiator, step d) is a polymerization step without exposure to a light source, the duration of this polymerization step d) is preferably between 8 hours and 100 hours, and / or this step d) is carried out at a temperature between 20°C and 80°C. In this embodiment, polymerization is initiated, for example, by exposure to heat (thermal initiation) or by simply contacting the monomer, polymer, and crosslinker together or with a catalyst, in which case the polymerization time is generally longer than several hours. Preferably, step d) of polymerizing composition C2 is carried out at a temperature between 20°C and 80°C for a period between 8 hours and 100 hours.

[0118] The composition obtained after step d) comprising solid microcapsules dispersed in composition C3 is ready to use and can be used without the need for an additional post-treatment step of the capsules. The shell thickness of the microcapsules thus obtained is typically 0.1 μm to 20 μm, preferably 0.2 μm to 8 μm, and more preferably 0.2 μm to 5 μm.

[0119] In one embodiment, the solid microcapsules obtained after step d) are surfactant-free. The method of the present invention has the advantage that it does not require surfactants in any of the steps described, thus making it possible to reduce the presence of additives that may alter the properties of the final product obtained after release of the active ingredient.

[0120] The present invention also relates to a series (or set) of solid microcapsules obtainable by the method as defined above, each microcapsule comprising: a core comprising a composition C1 as defined above, a solid shell completely encapsulating the core therearound; Here, the average diameter of the microcapsules is 1 μm to 30 μm, the thickness of the rigid shell is 0.1 μm to 20 μm, preferably 0.2 μm to 8 μm, more preferably 0.2 μm to 5 μm, and the standard deviation of the microcapsule diameter distribution is less than 50%, particularly less than 25%, or less than 1 μm.

[0121] Preferably, the solid microcapsules obtained by the process of the present invention are formed from a core (composition C1) containing at least one active ingredient and a solid shell (obtained from composition C2) completely encapsulating the core around it.

[0122] As mentioned above, the method of the present invention makes it possible to obtain monodisperse particles, i.e., the series of solid microcapsules described above are formed from a population of particles of a monodisperse size, for example, the standard deviation of the diameter distribution of the microcapsules is less than 50%, in particular less than 25%, or even less than 1 μm. The size distribution of the solid microcapsules can be measured by light scattering using a Mastersizer 3000 instrument (Malvern Instruments) equipped with a Hydro SV measuring cell.

[0123] In one embodiment, the solid microcapsules described above comprise a solid shell composed entirely of crosslinked polymer (obtained from composition C2).

[0124] As mentioned above, the method of the present invention makes it possible to obtain solid microcapsules, i.e. the present invention also relates to solid microcapsules comprising a core and a solid shell completely encapsulating the core around it, wherein the core is composition C1 as defined above and the solid shell is made of a crosslinked polymer. The diameter of the microcapsules is 1 μm to 30 μm, and the thickness of the rigid shell is 0.1 μm to 20 μm, preferably 0.2 μm to 8 μm, and more preferably 0.2 μm to 5 μm.

[0125] The present invention also relates to a composition comprising a series of solid microcapsules as defined above. The expressions "between... and...", "from... to..." and "ranging from... to..." should be construed as inclusive of the limits unless otherwise specified.

[0126] The following examples illustrate the invention without limiting its scope. [Example]

[0127] Example 1 Preparation of solid biodegradable capsules according to the present invention A mechanical stirrer (Ika Eurostar 20) equipped with a dispersing blade type impeller was used for all mixing steps.

[0128] Step a): Preparation of the first emulsion (E1) [Table 1]

[0129] Composition C1 was stirred at 1,000 rpm until completely homogenized, and then left at ambient temperature for 1 hour. Composition C1 was then added dropwise to composition C2 in a ratio of 3:7 while stirring at 2,000 rpm. This resulted in a first emulsion (E1).

[0130] Step b): Preparation of the second emulsion (E2) [Table 2]

[0131] Composition C3 was stirred at 1,000 rpm until completely homogenized, and then left at ambient temperature for 1 hour. Then, the first emulsion (E1) was added dropwise to composition C3 while stirring at 1,000 rpm. This resulted in a second emulsion (E2).

[0132] Step c): Size refinement of the second emulsion The polydisperse secondary emulsion (E2) obtained in the previous step was stirred at 1,000 rpm for 10 minutes, resulting in a monodisperse emulsion (E3).

[0133] Step d): Crosslinking of capsule shell The monodisperse second emulsion (E3) obtained in the previous step was exposed to a maximum light intensity of 0.1 W / cm. 2 The film was irradiated for 10 minutes at a wavelength of 365 nm using a UV light source (Dymax LightBox ECE 2000) having a wavelength of 365 nm. The microcapsules obtained showed a good size distribution, ie an average size of 15 μm, with a standard deviation of the size distribution of 6.1 μm, ie 41%.

[0134] For biodegradation testing, the microcapsules were washed by several centrifugation-redispersion steps to completely remove the alginate. Soil samples were collected and purified, and bacterial contents were extracted from them and placed in a liquid medium containing the microcapsules of the present invention as the sole carbon source. After 5 days of incubation at ambient temperature, the microcapsules were imaged under an optical microscope and a scanning electron microscope. A biofilm was observed on the microcapsules, indicating bacterial growth from the carbon source indicated by the shell. Erosion and destruction were observed on the microcapsule shells, confirming bacterial degradation of the microcapsules.

[0135] Example 2 Preparation of biodegradable solid polyester capsules according to the present invention A mechanical stirrer (Ika Eurostar 20) equipped with a dispersing blade type impeller was used for all mixing steps.

[0136] Step a): Preparation of the first emulsion (E1) [Table 3]

[0137] Compositions C1 and C2 were stirred at 2,000 rpm until completely homogenized. Then, composition C1 was added dropwise to composition C2 in a 5:5 ratio while stirring at 2,000 rpm. This resulted in a first emulsion (E1).

[0138] Step b): Preparation of the second emulsion (E2) [Table 4]

[0139] Composition C3 was stirred at 3,500 rpm until completely homogenized, and then left at ambient temperature for 1 hour. Then, the first emulsion (E1) was added to composition C3 and stirred at 2,000 rpm. This resulted in a second emulsion (E2).

[0140] Step c): Size refinement of the second emulsion The second polydisperse emulsion (E2) obtained after the previous step was stirred at 2,000 rpm for 3 minutes, resulting in a monodisperse emulsion (E3).

[0141] Step d): Crosslinking of capsule shell The second monodisperse emulsion (E3) obtained in the previous step was exposed to a maximum light intensity of 0.1 W / cm. 2 The film was irradiated for 10 minutes at a wavelength of 365 nm using a UV light source (Dymax LightBox ECE 2000) having a wavelength of 365 nm. The microcapsules obtained showed a good size distribution, ie an average size of 5 μm, with a standard deviation of the size distribution of 1 μm, ie 20%.

[0142] For biodegradability testing, the microcapsules were washed by several centrifugation-redispersion steps to completely remove the alginate.

[0143] BioDScreen™ analysis was performed to determine the aerobic biodegradability of the microcapsules. The BioDScreen™ (Scanae) method is a screening method in a microplate format that uses fluorescence detection. BioDScreen™ is based on the use of a resazurin-derived bioreagent that is sensitive to bacterial metabolic activity and is reduced to a fluorescent form in proportion to the degradation of the sample by the bacteria. The biodegradation rates correspond to the analysis of biodegradability by the BioDScreen™-A method using an inoculum from a wastewater treatment station, incubated at 30°C for 10 days.

[0144] In Example 2, the biodegradation rate after 10 days of incubation was 45% with a standard deviation of 3%, reaching a plateau after 4 hours.

[0145] Example 3 Preparation of biodegradable solid polyepoxy capsules according to the present invention A mechanical stirrer (Ika Eurostar 20) equipped with a dispersing blade type impeller was used for all mixing steps.

[0146] Step a): Preparation of the first emulsion (E1) [Table 5]

[0147] Compositions C1 and C2 were stirred at 2,000 rpm until completely homogenized. Then, composition C1 was added dropwise to composition C2 in a 5:5 ratio while stirring at 2,000 rpm. This resulted in a first emulsion (E1).

[0148] Step b): Preparation of the second emulsion (E2) [Table 6]

[0149] Composition C3 was stirred at 3,500 rpm until completely homogenized, and then left at ambient temperature for 1 hour. The first emulsion (E1) was then added to composition C3 and stirred at 2,000 rpm. This resulted in a second emulsion (E2).

[0150] Step c): Size refinement of the second emulsion The second polydisperse emulsion (E2) obtained in the previous step was stirred at 2,000 rpm for 3 minutes, resulting in a monodisperse emulsion (E3).

[0151] Step d): Crosslinking of capsule shell The second monodisperse emulsion (E3) obtained in the previous step was exposed to a maximum light intensity of 0.1 W / cm. 2 The film was irradiated for 10 minutes at a wavelength of 365 nm using a UV light source (Dymax LightBox ECE 2000) having a wavelength of 365 nm. The microcapsules obtained showed a good size distribution, ie an average size of 8 μm, with a size distribution of 1.4 μm, ie a standard deviation of 18%.

[0152] For biodegradability testing, the microcapsules were washed by several centrifugation-redispersion steps to completely remove the alginate. BioDScreen™ (Scanae) analysis was performed according to the instructions in Example 2 above to determine the aerobic biodegradability of the microcapsules. After 10 days of incubation, the biodegradation rate was 31% with a standard deviation of 3%.

Claims

1. A method for preparing solid microcapsules having biodegradability as defined by OECD standards, comprising the steps of: a) adding, under stirring, a composition C1 comprising at least one active ingredient to a polymer composition C2, wherein the compositions C1 and C2 are not miscible with each other; The viscosity of composition C2 is 500 mPa.s to 100,000 mPa.s at 25°C; Composition C2 is at least one monomer or polymer selected from the group consisting of aliphatic or aromatic esters or polyesters, anhydrides or polyanhydrides, sugars or polysaccharides, ethers or polyethers, amides or polyamides, and carbonates or polycarbonates, further comprising at least one functional group selected from the group consisting of acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, carboxylate functional groups, and mixtures thereof, with the proviso that said monomer or polymer does not have a urethane functional group; at least one crosslinking agent, optionally comprising at least one photoinitiator or crosslinking catalyst, thereafter obtaining an emulsion (E1) comprising droplets of composition C1 dispersed in composition C2; b) adding emulsion (E1) to composition C3 under stirring, compositions C2 and C3 being immiscible with each other; Composition C3 has a viscosity of 3000 mPa.s to 100,000 mPa.s at 25°C; Thereafter, obtaining a double emulsion (E2) comprising droplets dispersed in composition C3; c) Emulsion (E2) for 1000 s －１ applying a shear force at a shear rate of less than Thereafter, obtaining a double emulsion (E3) comprising droplets of controlled size dispersed in a composition C3; and d) polymerizing composition C2, after which solid microcapsules dispersed in composition C3 are obtained; Said composition C3 comprises at least one polymer with a molecular weight higher than 5,000 g.mol −1 .

2. 10. The method of claim 1, wherein composition C2 comprises a monomer or polymer having at least one functional group selected from the group consisting of aliphatic or aromatic esters or polyesters, and further comprising acrylate, methacrylate, vinyl ether, N-vinyl ether, epoxy, siloxane, amine, lactone, phosphate, carboxylate functional groups, and mixtures thereof.

3. 3. The method of claim 1, wherein composition C2 comprises 0.001% to 20% by weight of a crosslinker relative to the total weight of the composition.

4. 4. The method according to claim 1, wherein, if composition C2 comprises a photoinitiator, step d) is a photopolymerization step, and thus emulsion (E3) is exposed to a light source capable of initiating photopolymerization of composition C2.

5. Composition C3 also contains at least one branched polymer, and / or 5,000 g.mol －１ The method of any one of claims 1 to 4, comprising at least one polymer with a higher molecular weight and / or solid particles.

6. A set of solid microcapsules, each microcapsule comprising: a core comprising a composition C1 according to claim 1, a solid shell completely encapsulating the core therearound, said shell being obtained from composition C2 according to claim 1, wherein the microcapsules have an average diameter of 1 μm to 30 μm, a rigid shell thickness of 0.1 μm to 20 μm, and a standard deviation of the microcapsule diameter distribution is less than 50% or less than 1 μm.

7. A composition comprising a set of solid microcapsules according to claim 6.

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