Microcapsule manufacturing method and microcapsule

Abstract

A continuous process for preparing microcapsules having an active ingredient encapsulated in a cross-linked photopolymer shell, the process comprising: providing a double emulsion comprising droplets of at least one active ingredient (C1) dispersed in a photopolymerizable composition C2, the droplets dispersed in a composition C3, the droplets comprising at least one active ingredient (C1) dispersed in a cross-linked photopolymer shell, the cross-linked photopolymer shell comprising a cross-linked photopolymer shell and a cross-linked photopolymer shell, the cross-linked photopolymer shell comprising a cross-linked photopolymer shell, the cross-linked photopolymer shell comprising a cross-linked photopolymer shell, the cross-linked photopolymer shell comprising a cross-linked photopolymer shell, the compositions C2 and C3 are immiscible with each other; inducing a controlled shear rate in the double emulsion to provide a mixed double emulsion (C4); and irradiating the mixed double emulsion (C4) to produce the microcapsules.

Description

[0001] This application claims the priority of European patent application 22315247.1 filed on October 27, 2022, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The object of the present invention relates to a process for preparing capsules having improved retention and mechanical resistance properties, in particular an improved continuous process for preparing such capsules. The invention also relates to the capsules obtained and to the use of said capsules. Background Art

[0003] Many chemical compounds, known as active ingredients, are added to formulated products to impart to them beneficial application properties of interest or to enhance their performance. However, in many cases these substances react negatively with other components of the formulated product, with adverse consequences for stability and resulting in reduced performance levels.

[0004] Encapsulation of active ingredients represents a technology of great interest for overcoming limitations related to the performance or stability of formulated products containing them, while also obtaining the beneficial effects derived from the active ingredients when using the formulated products.

[0005] However, in order to completely isolate the active ingredients from the medium containing them, it is necessary to impart suitable retention properties to the capsules so that the active ingredients can be retained for a period of up to several years.

[0006] A large number of capsules have been developed to isolate active ingredients in formulated products. These capsules are usually obtained by manufacturing methods such as spray drying, interfacial polymerization, interfacial precipitation or solvent evaporation.

[0007] In particular, US-A-2020129948 and US-A-2021113984 in the name of the present applicant (the contents of which are incorporated by reference into the present patent application) provide capsules with very good retention properties. Summary of the invention

[0008] The present invention now provides a further improved method for preparing capsules, and improved capsules obtainable by said method.

[0009] The invention thus relates to a continuous process for preparing microcapsules having an active ingredient encapsulated in a crosslinked photopolymer shell, the process comprising: providing a double emulsion comprising droplets of at least one active ingredient C1 dispersed in a photopolymerizable composition C2, the droplets being dispersed in a composition C3, the compositions C2 and C3 being immiscible with one another;

[0010] applying a controlled shear rate to the double emulsion to provide a mixed double emulsion C4;

[0011] The mixed double emulsion C4 was irradiated to prepare the microcapsules.

[0012] Surprisingly, it has been found that the process of the present invention allows for the large-scale manufacture of capsules with excellent retention properties, and the uniformity of their properties (e.g. monodispersity and wall thickness) is still improved or at least comparable to known capsules. It has been found that by increasing the conversion of the reactive groups, the efficiency and uniformity of the photopolymerization step can be improved, thereby significantly improving the formation of the crosslinked shell of the capsules, while substantially avoiding degradation of the product capsules due to, for example, capsule rupture or coalescence of droplets in double emulsions. The retention properties of a capsule mean the ability of the capsule to retain the active ingredient until the desired external stimulus induces the release of the active ingredient.

[0013] Without wishing to be bound by any theory, it is believed that the improved retention and mechanical stability of the capsules results from improved cross-linking during continued processing.

[0014] For the purposes of the present invention, a "continuous process" is understood to mean a process carried out in a continuous mode, i.e. by continuously or possibly intermittently supplying starting materials to a reaction medium and continuously or possibly intermittently withdrawing products from said reaction medium. Preferably, said continuous process comprises continuously supplying starting materials to a reaction medium and continuously withdrawing products from said reaction medium.

[0015] For the purposes of the present invention, "monodisperse" for a series of droplets or a series of capsules is understood to mean that the standard deviation of the diameter distribution of the droplets or the capsules is less than 50%, in particular less than 25%, or less than 1 μm. For the purposes of the present invention, the diameter of the droplets or the capsules is determined by light scattering techniques using a Mastersizer 3000 (Malvern Instruments) equipped with a Hydro SV measuring cell.

[0016] For the purposes of the present invention, "viscosity" is understood to be the viscosity measured over a period of 10 s using a Haake RheostressTM 600 or Anton Paar MCR 92 rheometer equipped with a 60 mm diameter cone with a 2 degree angle and a temperature controlled cell set at 25°C. -1 The viscosity value is measured at a shear rate of .

[0017] For the purpose of this specification, the singular includes the plural and vice versa.

[0018] In the method according to the present invention, the double emulsion is preferably provided by the method according to US-A-2020129948 and US-A-2021113984 (the contents of both are incorporated into the present application by reference).

[0019] In one aspect, the double emulsion can be provided by a method comprising the steps of:

[0020] a) adding, under stirring, a composition C1 comprising at least one active ingredient to a polymeric composition C2, said compositions C1 and C2 being immiscible with one another, the volume fraction of C1 in C2 being between 0.1 and 0.5;

[0021] The composition C2 comprises at least one -1 Monomers or polymers, at least one of which has an average molecular weight of less than 5000 g.mol -1 A crosslinking agent and optionally at least one having an average molecular weight of less than 5000 g.mol -1 Photoinitiator with average molecular weight less than 5000 g.mol -1 A cross-linking catalyst;

[0022] The viscosity of the composition C2 at 25° C. is between 500 mPa·s and 100,000 mPa·s;

[0023] wherein an emulsion (E1) is obtained, comprising droplets of said composition C1 dispersed in said composition C2;

[0024] b) adding the emulsion (E1) to the composition C3 under stirring, the compositions C2 and C3 being immiscible with each other;

[0025] The viscosity of the composition C3 at 25° C. is between 500 mPa·s and 100,000 mPa·s; wherein a double emulsion (E2) is obtained, which comprises droplets dispersed in the composition C3;

[0026] c) applying shear to the emulsion (E2);

[0027] Therein a double emulsion (E3) is obtained comprising droplets of controlled size dispersed in said composition C3.

[0028] In the method according to the invention, the droplets of the double emulsion are preferably monodisperse.

[0029] In the method according to the invention, the induced shear rate is usually less than 200 s -1 The shear rate is usually equal to or lower than 50s -1In the method according to the invention, the induced shear rate is usually higher than 10 s -1 The shear rate is usually equal to or higher than 20 s -1 The induced shear rate is typically selected to prevent droplet coalescence.

[0030] Although the induced shear rate may undergo adaptive changes, for example due to the viscosity of the double emulsion, it will be suitably selected to ensure good photopolymerization of the shell.

[0031] In another aspect, the shear rate induced in step (b) is such that the proportion of broken droplets in step (b) is less than 0.1%, preferably less than 0.01%.

[0032] For the purposes of the present invention, the ratio of droplets is determined by optical microscopy of the droplets in the double emulsion, as detailed below: Determination of breakup of droplets is performed in situ using a CSS450 optical rheology system from Linkam Systems. The shear rate is controlled by an Ares-G2 system from TA Instruments using the two-dimensional small amplitude oscillatory shear (2D-SAOS) function.

[0033] In another aspect, the shear rate induced in step (b) is such that the droplets of the mixed double emulsion remain monodisperse.

[0034] In a specific aspect, the shear is induced before and / or during the irradiation. For example, an initial means for inducing the shear rate can be selected that is sufficient to maintain the desired shear rate throughout the reactor. In another aspect, the shear rate is induced by a combination of an initial means for inducing the shear rate and at least one subsequent means for inducing an additional shear rate.

[0035] In the method according to the invention, the shear may be induced in the double emulsion, for example using one or more devices selected from stirrers, vortex mixers, static mixers, rotary mixers, rotor-stator mixers and interfacial surface generator mixers.

[0036] Examples of agitators include, for example, overhead mixers equipped with blades, including but not limited to spiral, sawtooth, cross blade, straight blade, pitched blade, annular blade, anchor, propeller, radial flow, cross, paddle, centrifugal, half-moon, coil, beater, chain paddle overhead mixers, and any combination thereof.

[0037] Examples of vortex mixer devices include, for example, tube rack vortex mixers of orbital, vertical, or horizontal geometry.

[0038] Examples of static mixers include, but are not limited to, helical static mixers, plate static mixers, low pressure drop static mixers, and interfacial surface generator mixers.

[0039] Examples of rotating mixers include, for example, planetary mixers, orbital mixers including tank mixers for industrial scale production, and Couette mixers as described in FR9604736.

[0040] Examples of rotor-stator mixers include commercially available devices such as the Ross TM High shear mixers, which are used in e.g. A., Rotor-Stator Mixers: From Batch to Continuous Mode of Operation—A Review, Processes 2018, 6, 32. https: / / doi.org / 10.3390 / pr6040032.

[0041] The process according to the present invention may advantageously be carried out using in-line mixers, including but not limited to static in-line mixers and dynamic in-line mixers.

[0042] The device may include at least one component in direct contact with the double emulsion. Such components may be suitably selected to provide reduced chemical reactivity and mechanical stability during the irradiation step. Therefore, such components are preferably made of chemically and mechanically resistant materials, such as stainless steel, PTFE or non-reactive metals such as platinum, gold and diamond coatings.

[0043] In another aspect, the device is preferably made of a material that allows for maximum dispersion of UV radiation in the double emulsion by limiting the absorption of UV light in the device. Such materials include, but are not limited to, UV transparent materials such as quartz glass or synthetic silica, borosilicates (such as those disclosed in US5547904A), and SCHOTT 8337B, 8347 and 8347 optimized for UV transmission. D 99 glass.

[0044] The shear rate is generally further determined by taking into account other reaction parameters, such as flow rate and reactor geometry if appropriate.

[0045] In the process according to the invention, the irradiation is suitably carried out in one or more continuous stirred tank reactors and / or continuous flow reactors.

[0046] In a first specific aspect, the irradiation is performed in a continuous stirred tank reactor, wherein the double emulsion is continuously fed into the continuous stirred tank reactor and a product stream comprising microcapsules is continuously withdrawn from the continuous stirred tank reactor.

[0047] In one embodiment of the first specific aspect, a portion of the product stream is recycled to the continuous stirred tank reactor. In another embodiment of the first specific aspect, the product stream comprising microcapsules is continuously introduced into at least one further irradiation step in one or more continuously stirred tank reactors. In another embodiment of the first specific aspect, the product stream comprising microcapsules is continuously introduced into at least one further irradiation step in one or more continuously stirred tank reactors.

[0048] In another aspect, the irradiation is carried out in one or more continuous flow reactors. Where appropriate, the continuous flow reactor is equipped with at least one device for applying a shear rate, such as, in particular, the above-mentioned device. Preferably, the continuous flow reactor is equipped with at least one vortex mixer and / or at least one static mixer. When using a plurality of continuous flow reactors, the reactors can be arranged in parallel and / or in series.

[0049] When the irradiation is performed in a fluid, a Reynolds number of less than 1 is typically maintained in the fluid. The Reynolds number is typically equal to or less than 0.01. Typically, the Reynolds number is greater than 0.00001.

[0050] In the method according to the present invention, the irradiation may suitably be carried out in a cylindrical, flat cylindrical, prismatic, cuboid chamber or a combination thereof.

[0051] In the process according to the invention, in particular with the aim of achieving a desired conversion of the photopolymerizable groups, particular regard is given to the components of the photopolymerizable composition C2 and to the arrangement of the reactor.

[0052] Suitably, the photopolymerizable composition C2 comprises at least one monomer that can be polymerized by free radical induction. Particularly suitable are monomers comprising acrylates and / or methacrylates. Preferably, such monomers comprise at least 2, 3, 4, 5 or 6 acrylate and / or methacrylate groups. Alternatively, the monomer comprises another polymerizable group, such as mercapto ester, thioene, siloxane, epoxide, oxetane, carbamate, isocyanate and peroxide groups. The typical content of the monomer is 50 to 99% by weight relative to the total weight of the composition C2, preferably 60 to 95% by weight relative to the total weight of the composition C2.

[0053] In a preferred embodiment, the photopolymerizable composition C2 additionally comprises a crosslinker. The crosslinker may suitably be selected from molecules carrying at least two functional groups selected from acrylate, methacrylate, vinyl ether, N-vinyl ether, mercapto ester, thiol, siloxane, epoxide, oxetane, urethane, isocyanate and peroxide functional groups.

[0054] As examples of crosslinking agents, mention may in particular be made of diacrylates, for example 1,6-hexanediol diacrylate, 1,6-hexanol dimethacrylate, polyethylene glycol dimethacrylate, 1,4-nonanediol dimethacrylate, 1,4-butanediol dimethacrylate, 2,2-bis(4-methacryloxyphenyl)propane, 1,3-butanediol dimethacrylate, 1,10-decanediol dimethacrylate, bis(2-methacryloxyethyl) N,N′-1,9-nonanediol dicarbamate, 1,4-butanediol dimethacrylate. acrylate, ethylene glycol diacrylate, 1,5-pentanediol dimethacrylate, 1,4-phenylene diacrylate, allyl methacrylate, N,N'-methylenebisacrylamide, 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane, tetraethylene glycol diacrylate, ethylene glycol dimethacrylate, diethylene glycol diacrylate, triethylene glycol diacrylate, triethylene glycol dimethacrylate, polyethylene glycol diglycidyl ether, N,N-diallylacrylamide, 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane

[0063] 1,2-dimethylolpropane, 1,1,1-trimethylolpropane triacrylate, 1,1,1-trimethylolpropane trimethacrylate, ethylenediamine tetramethacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate; acrylates having other reactive functional groups, such as propargyl methacrylate, 2-cyanoethyl acrylate, tricyclodecane dimethanol diacrylate, hydroxypropyl methacrylate, N-acryloyloxysuccinimide, N-( 2-hydroxypropyl)methacrylamide, N-(3-aminopropyl)methacrylamide hydrochloride, N-(t-BOC-aminopropyl)methacrylamide, 2-aminoethyl methacrylate hydrochloride, monoacryloxyethyl phosphate, o-nitrobenzyl methacrylate, acrylic anhydride, 2-(tert-butylamino)ethyl methacrylate, N,N-diallylacrylamide, glycidyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxybenzophenone, N-(phthalimidomethyl)acrylamide, cinnamyl methacrylate. Typical contents of crosslinkers are, if appropriate, 1 to 49% by weight, relative to the total weight of the composition C2, preferably 10 to 30% by weight, relative to the total weight of the composition C2.

[0055] The photopolymerizable composition C2 generally comprises a photoinitiator. If appropriate, the photoinitiator is generally active in the wavelength range of 250 to 500 nm. The photoinitiator is generally capable of forming free radicals, which allow the induction of free radical polymerization of the monomers. The typical content of the photoinitiator is 1 to 5% by weight, preferably about 3% by weight, relative to the total weight of the composition C2.

[0056] In a particular aspect, the photopolymerizable composition C2 consists of the above-mentioned monomers, the above-mentioned crosslinking agent and the above-mentioned photoinitiator, preferably in the contents indicated above.

[0057] In a particular embodiment of the method according to the invention, the average residence time in the irradiation step is generally equal to or greater than 20 s, preferably equal to or greater than 90 s. In the method according to the invention, the average residence time in the irradiation step is generally equal to or less than 600 s, preferably equal to or less than 300 s.

[0058] In a particular aspect of the method according to the invention, the irradiation is carried out in a fluid under conditions providing a Bodenstein number of at least 50. A preferred range of the Bodenstein number is greater than 50, preferably equal to or greater than 100, more preferably equal to or greater than 200. Preferably, the Bodenstein number is maintained above the above values ​​throughout the irradiation process.

[0059] The Bodenstein number is a dimensionless number that describes axial mixing in the axial dispersion model of a flow reactor. It represents the ratio between convective transport and axial diffusive transport.

[0060] It has been found that a narrow distribution of residence times in the irradiation step, as reflected by the above-mentioned Bodenstein numbers applied in the above-mentioned particular aspects of the process according to the invention, allows to ensure a particularly uniform polymerization, which is evident in the uniformity of the final microcapsule properties.

[0061] In the method according to the invention, the viscosity of the composition C3 at 25°C is generally equal to or greater than 2000 mPa*s. Preferably, at 25°C, the viscosity is equal to or greater than 10000 mPa*s. In the method according to the invention, the viscosity of the composition C3 at 25°C is generally equal to or lower than 100000 mPa*s. Preferably, at 25°C, the viscosity is equal to or lower than 50000 mPa*s.

[0062] In the method according to the invention, the photopolymerizable composition C2 is typically photopolymerizable in the wavelength range of 100-500 nm, typically 200-450 nm, preferably 300-450 nm. In another embodiment, the photopolymerizable composition C2 is typically photopolymerizable in the wavelength range of 100-400 nm, preferably 300-400 nm.

[0063] In the method according to the present invention, the composition C3 generally has an absorbance of 0.5% to 30% in the wavelength range of 100-400 nm.

[0064] In the method according to the invention, the irradiation is usually carried out using at least one irradiation source emitting irradiation in the wavelength range of 100-500 nm, typically 200-450 nm, preferably 300-400 nm, which irradiates the mixed double emulsion through a barrier showing transmittance at the emission wavelength. In this case, the irradiation source preferably emits perpendicularly to the barrier placed closest to the irradiation source. However, the irradiation source can also be positioned to emit in other directions, as long as sufficient irradiation is provided to the mixed double emulsion. For example, such a direction can be between perpendicular and parallel orientations between the irradiation source and the barrier.

[0065] In the method according to the present invention, the thickness of the mixed double emulsion in the direction of propagation of the radiation is generally from 1 mm to 20 cm, preferably from 5 mm to 5 cm.

[0066] The radiation source can be placed inside the reactor, for example in the center of the radiation chamber or at the edge of the radiation chamber. The radiation source can also be placed outside the reactor. In some aspects, multiple radiation sources can be placed inside and / or outside the reactor.

[0067] The barrier material may be composed of a material that allows maximum transmission of UV radiation to the emulsion by limiting the absorption of UV light in the mixer. Such materials include, but are not limited to, UV transparent materials such as quartz glass or synthetic silica, borosilicates (such as those disclosed in US5547904A), and SCHOTT 8337B, 8347 and 8347 optimized for UV transmission. D99 glass.

[0068] In the method according to the invention, the active ingredient may be suitably selected from, for example:

[0069] Crosslinkers, hardeners, organic or metallic catalysts (e.g. organometallic or inorganic metal complexes of platinum, palladium, titanium, molybdenum, copper, zinc) for polymerizing polymers, elastomers, rubbers, paints, adhesives, sealants, mortars, varnishes or coating preparations;

[0070] Dyes or pigments intended for use in elastomers, paints, coatings, adhesives, sealants, mortars or paper preparations;

[0071] Fragrances intended for use in detergent products such as cleaning / laundry products, household care products, cosmetics and personal care products, textiles, paints, coatings (based on the list of molecules developed by the International Fragrance Association (IFRA), available on the website www.ifraorg.org);

[0072] Aromas / flavorings, vitamins, amino acids, proteins, lipids, probiotics, antioxidants, pH adjusters, preservatives for food compounds and animal feed;

[0073] Softeners and conditioners for decontamination products, cleaning / washing products, cosmetics and personal care products. In this regard, active agents that can be used are, for example, those listed in U.S. Pat. No. 6,335,315 and U.S. Pat. No. 5,877,145;

[0074] Anti-spotting or anti-fading agents (e.g. ammonium derivatives), defoamers (e.g. alcohol ethoxylates, alkylbenzene sulfonates, polyethylene ethoxylates, alkyl ethoxy sulfates or alkyl sulfates) intended for use in stain removal products, cleaning / laundering products and household care products;

[0075] Brighteners, also known as color activators (e.g., stilbene derivatives, coumarin derivatives, pyrazoline derivatives, benzoxazole derivatives, or naphthimide derivatives) intended for use in stain removal products, cleaning / washing products, cosmetics, and personal care products;

[0076] Biologically active compounds intended for use in cosmetics and personal care products and textiles, such as enzymes, vitamins, proteins, plant extracts, emollients, disinfectants, antibacterial agents, anti-UV agents, drugs. Among these biologically active compounds, the following may be mentioned: vitamins A, B, C, D and E, para-aminobenzoic acid, alpha-hydroxy acids (such as glycolic acid, lactic acid, malic acid, tartaric acid or citric acid), camphor, ceramides, polyphenols (such as flavonoids, phenolic acids, ellagic acid, tocopherol, panthenol), hydroquinone, hyaluronic acid, isopropyl isostearate, isopropyl palmitate, oxybenzone, panthenol, proline, retinol, retinyl palmitate, salicylic acid, sorbic acid, sorbitol, triclosan, tyrosine;

[0077] Disinfectants, antibacterial agents, anti-UV agents intended for use in paints and coatings;

[0078] Fertilizers, herbicides, insecticides, pesticides, fungicides, repellents or disinfectants intended for use as agricultural chemicals;

[0079] Fire retardants, also known as flame retardants, intended for use in plastic materials, coatings, paints and textiles (for example brominated polyols such as tetrabromobisphenol A, halogenated or non-halogenated organophosphorus compounds, chlorinated compounds, aluminium trihydrate, antimony oxide, zinc borate, red phosphorus, melamine or magnesium dihydroxide);

[0080] Photonic crystals or photochromophores intended for use in paints, coatings, and polymeric materials for forming curved flexible screens;

[0081] Products known to those skilled in the art under the generally accepted term phase change materials (PCMs) are materials capable of absorbing or releasing so-called "latent" heat when undergoing a phase change and are intended for use in storing energy. Examples of PCMs and their applications are described in Farid et al., "A review on phase change energy storage: materials and applications", Energy Conversion and Management, 2004, 45 (9-10), 1597-1615. As examples of PCMs, mention may be made of aluminum phosphate, ammonium carbonate, ammonium chloride, cesium carbonate, cesium sulfate, calcium citrate, calcium chloride, calcium hydroxide, calcium oxide, calcium phosphate, calcium sucrose, 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, silicates, sodium sulfate, sodium tellurate, sodium thiosulfate, strontium hydrogen phosphate, zinc acetate, zinc chloride, sodium thiosulfate, paraffin wax, molten salts of polyethylene glycol.

[0082] In the method according to the present invention, the photopolymer forming the microcapsule shell is generally selected from polyethers, polyesters, polyurethanes, polyureas, polyethylene glycols, polypropylene glycols, polyamides, polyacetals, polyimides, polyolefins, polysulfides and polydimethylsiloxanes, and the polymer has at least one reactive functional group selected from acrylates, methacrylates, vinyl ethers, N-vinyl ethers, mercapto esters, thioenes, siloxanes, epoxides, oxetanes, urethanes, isocyanates and peroxides.

[0083] In the method according to the invention, the average diameter of the produced microcapsules is usually between 1 μm and 30 μm.

[0084] In the method according to the invention, the microcapsules produced generally have a solid encapsulating shell. The thickness of the shell is preferably between 0.2 μm and 8 μm.

[0085] The present invention also relates to a series of solid microcapsules, wherein each microcapsule comprises:

[0086] a core comprising a composition C1 as defined in claim 1; and

[0087] a solid encapsulating shell that completely encapsulates the core at its periphery, the solid encapsulating shell comprising pores having a size less than 1 nm;

[0088] The average diameter of the microcapsules is between 1 μm and 30 μm, the thickness of the solid encapsulating shell is between 0.2 μm and 8 μm, the standard deviation of the distribution of the microcapsules diameter is less than 50% or less than 1 μm, and the conversion of the reactive groups of the photopolymerizable composition C2 is at least 80%, preferably at least 90%. Preferably, in a series of microcapsules according to the invention, the distribution of the conversion has a standard deviation of not more than 5%.

[0089] It has been found that a series of microcapsules according to the invention having a high and uniform conversion of the reactive groups allows to achieve particularly interesting mechanical stability and release properties of the microcapsules.

[0090] Therefore, in a particular aspect, the present invention relates to a series of microcapsules, each microcapsule having a core, the core comprising a solid encapsulating shell of the active ingredient obtained by conversion of reactive groups, the thickness of the shell being between 0.2 μm and 8 μm, the average diameter of the microcapsules being between 1 μm and 30 μm, and the standard deviation of the microcapsule diameter distribution being less than 50% or less than 1 μm, wherein the conversion rate of the reactive groups is at least 80%, preferably at least 90%, and the conversion rate distribution has a standard deviation of not more than 5%.

[0091] The conversion of the reactive groups can be determined by monitoring the disappearance of a band representing the functional group under FTIR, the absorption of the IR band is proportional to the amount of the functional group, so a decrease in the peak height corresponds to a decrease in the amount of the functional group, further indicating successful polymerization. A standard method for doing this is to compare the FTIR absorption of the emulsion before and after photopolymerization. For the purposes of the present invention, this can be accomplished using the method disclosed in Barszczewska-Rybarek, Materials 2019, 12(24), 4057.

[0092] Different series of microcapsules according to the invention can be obtained by the process according to the invention.

[0093] The invention also relates to the use of the microcapsules according to the invention for delivering active ingredients.

[0094] If there is any inconsistency between any document incorporated by reference and this specification, the present specification shall control.

[0095] The following examples are intended to illustrate the present invention but not to limit the present invention. Example

[0096] Example 1

[0097] Preparation of double emulsion according to US2021113984

[0098] Step a): Formation of capsule core (dispersion of particles - composition C1b)

[0099] [Table 1]

[0100] weight (g) ％ Composition C1a Solvesso200ND 14 40 Saturated triglyceride wax (SuppocireDM wax, Gattefosse) 6 17.1 Composition B Dispersant (Tween 80, SigmaAldrich) 2 5.7 Deionized water 13 37.2 total 35 100

[0101] Composition C1a is placed in a bath thermostated at 35°C and stirred at 500 rpm until the wax is completely dissolved. Composition B is placed in a bath thermostated at 35°C and stirred at 200 rpm until complete homogenization. Composition C1a is then added dropwise to composition B, still at 35°C and stirring at 2000 rpm. The mixture is stirred at 2000 rpm for 5 minutes and then ultrasonically treated (Vibra-cell 75042, Sonics) for 20 minutes at an amplitude of 30% (pulse 5s / 2s). If the temperature exceeds 35°C during the ultrasonic treatment, the mixture is cooled with ice. After cooling, 1.05 g of modified polyethylene glycol gelling agent (Aculyn 44N, Dow) is added to the mixture under stirring at 500 rpm until gelation. Composition C1b is thus obtained.

[0102] Step b): Preparation of the first emulsion (E1)

[0103] [Table 2]

[0104]

[0105] At room temperature T and stirring at 2000 rpm, composition C1 was added dropwise to composition C2.

[0106] Step c): Preparation of the second emulsion (E2)

[0107] [Table 3]

[0108]

[0109] The composition C3 was stirred at 1000 rpm until completely homogenized.The first emulsion (E1) was then added dropwise to the composition C3 at room temperature T and stirring at 1200 rpm.

[0110] Step d): Refine the size of the second emulsion

[0111] The second polydisperse emulsion obtained in the previous step was stirred at 1200 rpm for 10 minutes at a temperature Td = 20° C. Thus a monodisperse emulsion (E3) was obtained.

[0112] Example 2 - Photopolymerization according to the present invention

[0113] As described in Example 1 above, a double emulsion E3 with a volume of 3000 mL was prepared. -1 A quartz flask with a useful volume of 1000 mL and a stirring device with a shear rate of 1000 mL was charged with the double emulsion E3 obtained as described above, wherein the transmittance of the double emulsion E3 was 0.9 and the viscosity was 5000 mPa*s. Stirring was started to provide a mixed double emulsion E4, and a light source arranged perpendicular to the flask wall, emitting at 365 nm and having a maximum light intensity of 1 W / cm 2 The mixed polymerized double emulsion was continuously taken out through the take-out line at a flow rate of 300 mL / min, while fresh double emulsion was fed through the feed line at the same rate.

[0114] The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0115] Example 2a

[0116] The method of Example 2 was followed, except that the withdrawn mixed double emulsion was allowed to flow through a quartz tube having a diameter of 5 cm and provided with a light source emitting at 365 nm and having a maximum intensity of 1 W / cm 2 The obtained microcapsules are monodisperse. Essentially no coalescence of droplets is observed. The conversion rate of reactive groups is at least 90%.

[0117] Example 2b

[0118] The process of Example 2 was carried out, but in addition the flask was equipped with a recirculation line, through which 50% of the withdrawn stream was recirculated. The feed rate of the double emulsion E3 was adjusted accordingly. The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0119] Example 2c

[0120] Double emulsion E3 was continuously introduced into a flask equipped with a static mixer (which provided 70 s -1The mixed double emulsion was then fed into the feed line of the flask at a rate of 300 ml / min and irradiated as described in Example 2. The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0121] Example 2d

[0122] The process of Example 2c was carried out, but the mixed double emulsion was irradiated in a quartz tube according to Example 2a instead of a flask. The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0123] Comparative Example 1

[0124] 200 ml of the double emulsion (E3) obtained in Example 1 was poured into a 500 ml beaker and irradiated with a maximum light intensity of 1 W / cm at a wave length of 365 nm. 2 The resulting microcapsules were irradiated with a UV light source (Dymax LightBox ECE 2000) for 15 minutes. The microcapsules obtained were essentially monodisperse, but some coalescence of the droplets was observed. The conversion of the reactive groups was less than 75%.

[0125] Example 3

[0126] Preparation of double emulsion according to US2020129948

[0127] Step a): Preparation of the first emulsion (E1)

[0128] [Table 4]

[0129]

[0130] Composition C2 has the following characteristics:

[0131] The CN component 1963 has 2 reactive acrylate functional groups per molecule and an average molecular weight of less than 5000 g / mol. The crosslinker SR 399 has 5 reactive acrylate functional groups per molecule and a molecular weight of 524.5 g / mol. The Darocur 1173 photoinitiator has no reactive functional groups and a molecular weight of 164 g / mol. Under stirring at 2000 rpm, the composition C1 is added dropwise to the composition C2 in a ratio of 3:7. Thus, a first emulsion (E1) is obtained.

[0132] Step b): Preparation of the second emulsion (E2)

[0133] [Table 5]

[0134]

[0135] The composition C3 was stirred at 1000 rpm until completely homogenized and then left to stand at room temperature for one hour. The first emulsion (E1) was then added dropwise to the composition C3 under stirring at 1000 rpm. This gave the second emulsion (E2).

[0136] Step c): Refine the size of the second emulsion

[0137] The second polydisperse emulsion (E2) obtained in the previous step was stirred at 1000 rpm for 10 minutes. Thus, a monodisperse emulsion (E3) was obtained.

[0138] Example 4 - Photopolymerization according to the present invention

[0139] As described in Example 3 above, a double emulsion E3 with a volume of 3000 mL was prepared. -1 A quartz flask with a useful volume of 1000 mL and a stirring device with a shear rate of 1000 mL was charged with the double emulsion E3 obtained as described above, wherein the transmittance of the double emulsion E3 was 0.9 and the viscosity was 5000 mPa*s. Stirring was started to provide a mixed double emulsion E4, and a light source arranged perpendicular to the flask wall, emitting at 365 nm and having a maximum light intensity of 1 W / cm 2 The mixed polymerized double emulsion was continuously withdrawn at a flow rate of 300 mL / min through the withdrawal line, while fresh double emulsion was fed through the feed line at the same rate. The obtained microcapsules were monodisperse. Essentially no coalescence of droplets was observed. The conversion rate of reactive groups was at least 80%.

[0140] Example 4a

[0141] The method of Example 4 was followed, except that the withdrawn mixed double emulsion was allowed to flow through a quartz tube of 5 cm in diameter, which was illuminated by a laser emitting at 365 nm and having a maximum intensity of 1 W / cm 2 The quartz tube further comprises a rotor-stator mixer. The obtained microcapsules are monodisperse. Essentially no agglomeration of droplets is observed. The conversion rate of reactive groups is at least 90%.

[0142] Example 4b

[0143] The process of Example 4 was carried out, but in addition the flask was equipped with a recirculation line, through which 50% of the withdrawn stream was recirculated. The feed rate of the double emulsion E3 was adjusted accordingly. The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0144] Example 4c

[0145] Double emulsion E3 was continuously introduced into a flask equipped with a static mixer (which provided 70 s -1 The mixed double emulsion was then fed into the feed line of the flask at a rate of 300 ml / min and irradiated as described in Example 2. The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0146] Example 4d

[0147] The process of Example 4c was carried out, but the mixed double emulsion was irradiated in a quartz tube according to Example 4a instead of a flask. The microcapsules obtained were monodisperse. Essentially no coalescence of the droplets was observed. The conversion of the reactive groups was at least 80%.

[0148] Comparative Example 2

[0149] 200 ml of the double emulsion (E3) obtained in Example 3 was poured into a 500 ml beaker and irradiated for 15 minutes with the aid of a UV light source (Dymax LightBox ECE 2000) with a maximum light intensity of 1 W / cm2 at a wave length of 365 nm. The microcapsules obtained were essentially monodisperse, but some coalescence of the droplets was observed. The conversion of the reactive groups was less than 75%.

Claims

1. A continuous process for preparing microcapsules having an active ingredient encapsulated in a crosslinked photopolymer shell, the process comprising: include: Providing a double emulsion comprising droplets of at least one active ingredient (C1) dispersed in a photopolymerizable composition C2, wherein the droplets are dispersed in a composition C3, wherein the compositions C2 and C3 are immiscible with each other; inducing a controlled shear rate in the double emulsion to provide a mixed double emulsion (C4); and irradiating the mixed double emulsion (C4) to prepare the microcapsules.

2. The method according to claim 1, wherein the induced shear rate is less than 200 s -1 , preferably 50 to 200s -1 .

3. A method according to claim 1 or 2, wherein the induced shear rate is such that the droplet breakup rate is less than 0.1%.

4. The method according to any one of claims 1 to 3, wherein the droplets of the double emulsion are monodisperse and the induced shear rate is such that the droplets of the mixed double emulsion remain monodisperse.

5. The method according to any one of claims 1 to 4, wherein the shear rate is induced using an agitator, a vortex mixer, a static mixer, a rotary mixer or a rotor-stator mixer.

6. The method of claim 5, wherein the shear rate is induced using an agitator.

7. The method of claim 6, wherein the agitator is selected from overhead mixers equipped with blades, including but not limited to spiral, sawtooth, cross blade, straight blade, pitched blade, annular blade, anchor, propeller, radial flow, cross, paddle, centrifugal, half-moon, coil, beater, chain paddle overhead mixers and any combination thereof.

8. The method of claim 5, wherein the shear rate is induced using a vortex mixer.

9. The method of claim 8, wherein the vortex mixer is selected from a tube rack vortex mixer of orbital, vertical or horizontal geometry.

10. The method of claim 5, wherein the shear rate is induced using a static mixer.

11. The method according to claim 10, wherein the static mixer is selected from the group consisting of a helical static mixer, a plate static mixer, a low pressure drop static mixer and an interfacial surface generator mixer.

12. The method of any one of claims 1 to 5 and 8 to 11, wherein the shear rate is induced using an in-line mixer.

13. The method according to claim 12, wherein the inline mixer is selected from a static inline mixer and a dynamic inline mixer.

14. The process according to any one of claims 1 to 13, wherein the irradiation is carried out in one or more continuous stirred tank reactors and / or continuous flow reactors.

15. The method of claim 14, wherein the irradiating is performed in one or more continuous stirred tank reactors.

16. The process according to claim 15, wherein a portion of the product stream withdrawn from the continuous stirred tank reactor is recycled to the continuous stirred tank reactor.

17. The process according to claim 15, wherein the product stream comprising microcapsules is continuously introduced into at least one further irradiation step in a continuous flow reactor.

18. The process according to claim 15, wherein the product stream comprising microcapsules is continuously introduced into at least one further irradiation step in one or more continuous stirred tank reactors.

19. The process according to any one of claims 15 to 18, wherein the shear rate in the continuous stirred tank reactor is induced using an agitator.

20. The method of claim 19, wherein the agitator is selected from overhead mixers equipped with blades, including but not limited to spiral, sawtooth, cross blade, straight blade, pitched blade, annular blade, anchor, propeller, radial flow, cross, paddle, centrifugal, half-moon, coil, beater, chain paddle overhead mixers, and any combination thereof.

21. The method of claim 14, wherein the irradiating is performed in one or more continuous flow reactors.

22. The method according to claim 21, wherein the continuous flow reactor is equipped with at least one device for applying a shear rate.

23. The process according to claim 22, wherein the continuous flow reactor is equipped with at least one vortex mixer and / or at least one static mixer.

24. The method of claim 23, wherein the continuous flow reactor is equipped with at least one vortex mixer.

25. The process of claim 23, wherein the continuous flow reactor is equipped with at least one static mixer.

26. The process of claim 23, wherein the continuous flow reactor is equipped with an in-line mixer.

27. A method according to any one of claims 23 to 26, wherein the vortex mixer or mixer is according to any one of claims 9, 11 or 13.

28. The process according to any one of claims 21 to 27, wherein a plurality of continuous flow reactors are used and the reactors are arranged in parallel and / or in series.

29. The method according to any one of claims 1 to 28, wherein the photopolymerizable composition C2 is photopolymerized in the wavelength range from 100 to 500 nm, preferably from 300 to 400 nm.

30. The method according to any one of claims 1 to 28, wherein the photopolymerizable composition C2 comprises or consists of monomers capable of polymerization by free radical induction, optionally a crosslinker and a photoinitiator.

31. The method of claim 30, wherein the monomer comprises acrylate and / or methacrylate groups.

32. The method of claim 31 , wherein the monomer comprises at least 2, 3, 4, 5 or 6 acrylate and / or methacrylate groups.

33. The method according to any one of claims 30 to 32, wherein the composition C2 comprises or consists of 50% to 99%, preferably 60% to 95%, of monomers, 1% to 5%, preferably about 3%, of a photoinitiator, and optionally 1% to 49%, preferably 10% to 30%, of a crosslinker, all percentages being by weight relative to the total weight of the composition C2.

34. The method according to any one of claims 1 to 23, wherein the composition C3 has an absorbance of 0.5 to 3 in the wavelength range of 100 to 400 nm.

35. The method according to any one of claims 1 to 34, wherein the composition C3 has a viscosity at 25°C of 2000 to 100000 mPa*s.

36. The method according to any one of claims 1 to 35, wherein the irradiation is performed using at least one irradiation source emitting radiation in the wavelength range of 100 to 500 nm, preferably 300 to 450 nm, which irradiates the mixed double emulsion through a barrier showing transmittance at the emission wavelength.

37. The method of any one of claims 1 to 36, wherein the shear rate is induced prior to the irradiating.

38. The method of any one of claims 1 to 36, wherein the shear rate is induced during the irradiating.

39. The method of any one of claims 1 to 36, wherein the shear rate is induced before and during the irradiating.

40. The method according to any one of claims 1 to 39, wherein the irradiation is performed in a fluid, wherein a Reynolds number of less than 1, preferably between 0.00001 and 0.01, is maintained in the fluid.

41. The method according to any one of claims 1 to 40, wherein the irradiating is performed in a fluid under conditions providing a Bodenstein number of at least 50, preferably equal to or greater than 100, more preferably equal to or greater than 200.

42. The method according to any one of claims 1 to 41, wherein the average residence time of the irradiating step is from 20 to 600 s.

43. The method of any one of claims 1 to 42, wherein the mixed double emulsion has a thickness in the radiation propagation direction of 1 mm to 20 cm.

44. The method of any one of claims 1 to 43, wherein the irradiating is performed in a cylindrical, flat cylindrical, prismatic or cuboid chamber, or a combination thereof.

45. The method according to any one of claims 1 to 44, wherein the photopolymer forming the microcapsule shell is selected from the group consisting of polyethers, polyesters, polyurethanes, polyureas, polyethylene glycols, polypropylene glycols, polyamides, polyacetals, polyimides, polyolefins, polysulfides and polydimethylsiloxanes, and the polymer has at least one reactive functional group selected from the group consisting of acrylates, methacrylates, vinyl ethers, N-vinyl ethers, mercapto esters, thioenes, siloxanes, epoxides, oxetanes, urethanes, isocyanates and peroxides.

46. ​​The method of any one of claims 1 to 45, wherein the average diameter of the produced microcapsules is between 1 μm and 30 μm.

47. The method according to any one of claims 1 to 46, wherein the produced microcapsules have a solid encapsulating shell, and the thickness of the shell is preferably between 0.2 μm and 8 μm.

48. A series of microcapsules, each microcapsule having a core, the core containing a solid encapsulating shell of an active ingredient obtained by conversion of reactive groups, the thickness of the shell being between 0.2 μm and 8 μm, the microcapsules having an average diameter between 1 μm and 30 μm, and the standard deviation of the distribution of the diameters of the microcapsules being less than 50% or less than 1 μm, wherein the conversion rate of the reactive groups is at least 80%, and the distribution of the conversion rates has a standard deviation of not more than 5%.

49. The plurality of microcapsules of claim 48, wherein the conversion of the reactive groups is at least 90%.

50. A plurality of microcapsules according to claim 48 or 49, obtainable by a method according to any one of claims 1 to 47.

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