METHOD FOR PREPARING BIODEGRADABLE MICROCAPSULES AND MICROCAPSULES OBTAINED IN THIS MANNER

TECHNICAL FIELD OF THE INVENTION

The present description relates to the field of microcapsules, and more particularly to methods for manufacturing microcapsules with a view to enclosing active substances actives such as essential oils. More specifically, it relates to a method for preparing biodegradable microcapsules. This method performs interfacial polymerization of multifunctional compounds resulting in poly(beta-amino ester)s. The invention also relates to biodegradable microcapsules obtained with this method.

RELATED ART

Microencapsulation is a method for protecting a reactive, sensitive or volatile substance (referred to here as “active ingredient”) in a capsule in which the size can vary from a nanometer to a micrometer. The core of the capsule is therefore isolated from the external environment thereof by a wall. This makes it possible to delay the evaporation, release or degradation thereof; there are numerous applications which make use of these technical effects when the microcapsules are incorporated in a complex formulation or applied to a product.

For example, microcapsules can be used to disperse in a controlled manner the active ingredient contained therein, which can particularly be a biocidal agent, an insecticide, a disinfectant, or a fragrance; this can take place by diffusion through the wall or under the influence of an external force which ruptures the wall.

In some applications, the release of the active ingredient takes place under the influence of an external force which breaks the wall of the microcapsules; thus, it is possible to release an adhesive (see for example WO 03/016369—Henkel), or a reagent (see for example WO 2009/115671—Catalyse).

In further applications, the contents of the microcapsule cannot escape but the color change thereof under the effect of a variation of temperature (thermochromism) or of UV radiation (photochromism) is outwardly visible (see for example WO 2013/114 025—Gem Innov, or WO 2007/070118—Kimberly-Clark, or EP 1 084 860—The Pilot Ink Co.).

There are several techniques for preparing microcapsules. The main ones are spray-drying, interfacial polymerization, solvent evaporation, polymer self-assembly using the Layer-by-Layer (LbL) technique, and colloidosome preparation. All these techniques make it possible to obtain stable microcapsules of a mean diameter of 10 μm. Interfacial polymerization is nevertheless the predominant technique as it enables quick preparation in a single step of microcapsules in which the wall if strong enough for the latter to be isolated and thus be used in numerous applications.

The formation of microcapsules by interfacial polymerization is usually performed in 4 steps: (i) Preparing a first phase containing the active ingredient (for example an essential oil) and an organo-soluble monomer; (ii) Forming an emulsion by dispersing first phase in an aqueous medium containing surfactant, and which represents the second phase; (iii) Adding the water-soluble monomer to the second phase; (iv) Forming and maturing the membrane by reacting the monomers by polycondensation at the interface.

Several polymer families are conventionally used for manufacturing the wall of microcapsules (Perignon, C. et al., Journal of Microencapsulation 2015, 32 (1), 1-15), such as polyamides (PA), polyurethanes (PU) or polyureas. The preparation of PA microcapsule walls generally uses monomers of the diamine (hexamethylene diamine for example) and acyl chloride (sebacoyl chloride for example) type, whereas those in PU make use of monomers of the di-isocyanate (HDI, IPDI etc.) and diol type. In the case of polyureas, di-isocyanate and diamine type monomers or di-isocyanates alone are used wherein the hydrolysis at the interface produces amines enabling urea function synthesis.

For example, the document WO 2009/115671 cited above describes the formation of microcapsule walls by interfacial polycondensation, using different monomer mixtures: hexamethylene diisocyanate (HMDI) and ethylene diamine; tetraethylorthosilicate (TEO) and 3-(trimethoxysilyl)propylmethacrylate (MPTS); 2,4-tolylenediisocyanate (TDI) and 1,3 phenylenediamine; 2,4-toluene diisocyanate and 1,3-phenylene diamine.

There are already some works reporting the preparation of microcapsules by interfacial polymerization using other types of polymers. Mention can be made for example of the works by J. Bernard on the preparation of glyconanocapsules by copper-catalyzed azide-alkyne cycloaddition (R. Roux et al., J. ACS Macro Lett. 2012, 1 (8), 1074-1078), or the works by K. Landfester (Siebert et al. Chem. Commun. 2012, 48, 5470-5472). L. Shi et al. (J. Appl. Polym. Sci. 2016, 133 (36), 168-7) and D. Patton et al. (ACS Appl. Mater. Interfaces 2017, 9 (4), 3288-3293) who also prepared microcapsules by thiol-ene chemistry initiated by respectively a base and a photoinitiator.

A relatively broad spectrum of polymeric materials is therefore proposed to a person skilled in the art to select the suitable type of microcapsule for a given use. Thus, microcapsules are already used in numerous technical applications, but the application potential thereof has not yet been fully recognized, and it is a strongly emerging sector destined to grow significantly once the microcapsule wall meets increasingly stringent criteria in terms of toxicity and recyclability.

However, microcapsules represent microparticles of polymeric materials. For some years, polymeric material microparticles have been identified as an area of environmental concern, due to the wide dissemination thereof in ecosystems, in soils, in aquatic and maritime ecosystems, reaching distant locations from the place where they were introduced into the ecosystem. This wide dissemination harms not only as a general rule the organisms present in these ecosystems, but could also have harmful effects for human health. Increasingly stringent regulations are already being announced which restrict the use of plastics capable of forming microparticles during the degradation thereof in-situ in a natural environment, and especially of plastics used directly in the form of microparticles.

For environmental reasons, it may seem contradictory to seek to develop a novel product consisting of polymeric microparticles. It has hence emerged as desirable to have microcapsules made of degradable polymeric material. It is noted that microcapsules, used in numerous special applications and capable of being incorporated in numerous products in common use (such as textile materials, cosmetic or phytosanitary products) or technical use (such as paints, varnishes, inks), will not normally undergo end-of-life collection, and therefore cannot undergo biodegradation by composting, as can be envisaged for collected plastic products. Thus, the degradability of the plastics forming the wall of microcapsules cannot be based on chemical mechanisms which take place during composting. In this context, the question as to whether the degradability of the microcapsules involves a biological mechanism is somewhat unimportant; what is important is the degradability thereof in an ecosystem, regardless of the chemical mechanism of this degradation. For example, a fermentation would be a biodegradation, while a simple degradation in an ecosystem under the effect of light could be a photochemical reaction independent of the ecosystem; in reality, the situation will often be a combination, especially if the degradation takes place in stages. We use the expression “(bio)degradable” hereinafter to denote the characteristic of a material of degrading in a natural environment on a relatively brief scale (of the order of weeks or a year), according to the characteristics of this natural environment and the exposure of the material to the various agents present in this natural environment.

It is observed that all the microcapsules previously developed result in the preparation of polymer chains (polyamide, polyurea, polyurethane, etc.) which will be either physically interlocked in the case of a reaction between bifunctional compounds, or crosslinked in the case of one or more multifunctional compounds (functionality 3). In any case, the walls are not (bio) degradable due to the nature of the polymer chain. The problem addressed by the present invention is that of providing a novel type of microcapsules, which is easy to synthesize, without making use of toxic and/or costly raw materials, is (bio)degradable in the natural environment, can be used with a large number of active ingredients, and provides good external protection for the active ingredient that it is intended to contain.

Subject Matter of the Invention

During their research work, the inventors discovered that one possibility for obtaining degradable microcapsules would be to prepare walls made of polyester, which is a polymer known for the (bio)degradability thereof. The literature shows that studies have already been conducted on this theme, and it has been demonstrated that the rate of reaction between acid chlorides and diols was very slow. This system is thus unsuitable for interfacial polymerization (see E. M. Hodnett and D. A. Holmer, J Polym Sci, 1962, 58, 1415-21). Specific conditions such as the use of bisphenol A as diol and/or a reaction at very high pH made it possible to obtain microcapsules (see W. Eareckson, J Polym Sci, 1959, 399-406; see also P. W. Morgan and S. L. Kwolek, J Polym Sci, 1959, 299-327) but these conditions are overly restrictive for numerous internal phases and/or applications. Furthermore, the slow rate of polymerization reactions impedes the industrial use thereof in economic terms and in terms of short or even continuous production cycles.

Thus, the inventors did not pursue this avenue. According to the invention, the problem is solved using microcapsules made of poly(beta-amino)ester (abbreviated here as PBAE). According to the invention, these microcapsules are synthesized in a single reaction step via an addition reaction of amine functions to acrylate functions (reaction known as “Michael addition”), by interfacial polymerization. This reaction results in the micro-encapsulation of the organic phase without forming by-products (see reaction diagram in FIG. 6). The presence of ester functions in the PBAE backbone gives the polymer good degradation properties via hydrolysis.

Poly(beta-amino ester)s are known per se and have been used substantially in recent years (Lynn, D. M.; Langer, R. J. Am. Chem. Soc. 2000, 122 (44), 10761-10768; Liu, Y.; Li, Y.; Keskin, D.; Shi, L. Adv. Healthcare Mater. 2018, 2 (2), 1801359-24) thanks to the biocompatibility and biodegradability properties thereof, and they now represent a family of materials which have numerous applications as biomaterials (for example as anticancer drug vector, as antimicrobial material, and for tissue engineering).

The areas of application of poly(beta-amino ester)s are very vast (see FIG. 9).

Generally, it is known that aza-Michael addition type reactions can be performed in a wide range of solvents ranging from halogenated nonpolar solvents (dichloromethane or chloroform for example) to polar solvents such as dimethyl sulfoxide (DMSO) for example (Liu, Y.; Li, Y.; Keskin, D.; Shi, L. Adv. Healthcare Mater. 2018, 2 (2), 1801359-24). In practice, the PBAEs are essentially prepared in solution and are subsequently formulated to produce for example micelles, particles, gel/hydrogels, or films (so-called Layer-by-Layer technique). Oligo-PBAEs have also been crosslinked in a second phase, either by photopolymerization (Brey, D. M.; Erickson, I.; Burdick, J. A. J. Biomed. Mater. Res. 2008, 85A (3), 731-741.7), or in the presence of di-isocyanates.

It is also known that linear or crosslinked PBAEs are relatively stable in neutral medium but are degraded more rapidly by ester function hydrolysis at acid and/or basic pH. This hydrolysis phenomenon results in the release of small molecules such as bis(β-amino acid)s and diols when linear PBAEs are used; these molecules are known to be non-toxic with respect to mammalian cells, and to have a weak influence on the metabolism of healthy cells.

According to an essential feature of the present invention, the microcapsules having a PBAE wall are synthesized by interfacial polymerization.

More specifically, according to the invention, the problem is solved by a method wherein the Michael polycondensation reaction between amine functions and acrylate functions is used to obtain Poly(Beta-Amino Esters) (PBAEs) by interfacial polymerization. The inventors discovered that this method, applicable to various active ingredients to be encapsulated, makes it possible to prepare stable microcapsules capable of being isolated by drying and which have the property of being (bio) degradable.

The microencapsulation method according to the invention comprises the following steps:

(a) Dispersion of one or more compounds having at least two acrylate functions in an organic solution (also referred to here as “oily phase”, in the context of an emulsion) forming the phase to be encapsulated (and comprising, where applicable, the active ingredient);

(b) Addition of an excess with respect to the preceding volume of an aqueous phase comprising one or more surfactants, followed by an emulsification;

(c) Addition to the emulsion obtained in step (b) of one or more compounds including at least one primary amine function and/or two secondary amine functions and polymerization reaction at a temperature between about 20° C. and 100° C.;

(d) Collection, washing and drying of the microcapsules.

Thus, the invention firstly relates to a method for manufacturing microcapsules containing a so-called active substance, in which method:

an aqueous solution of a surfactant, an oily phase comprising said active substance and at least a first monomer X, and a polar phase comprising at least a second monomer Y are provided;

an O/W type emulsion is prepared by adding said oily phase to said aqueous solution of the surfactant;

said polar phase is added to said O/W emulsion, in order to obtain a polymer by polymerizing said monomers X and Y;

from this reaction mixture, said microcapsules including a wall formed by said polymer and containing said active substance are isolated;

said method being characterized in that said polymer is a poly(beta-amino ester).

Said first monomer X is selected from (multi)acrylates, particularly (multi)acrylates of formula X′—(—O(C═O)—CH═CH₂)_nwhere n≥2 and where X′ is a molecule whereon n acrylate structural units are grafted.

Said first monomer X is, preferably, selected from (multi)acrylates of formula X′—(—O(C═O)—CH═CH₂)_nwhere n≥4 and where X′ is a molecule whereon n acrylate structural units are grafted. More specifically, it is advantageously selected from the group formed by:

diacrylates, and preferably those described in the article by Nayak et al. (Polymer-Plastics Technology and Engineering, 2018, 57, 7, 625-656);

triacrylates, particularly C₁₅O₆H₂O (CAS No. 15625-89-5, i.e. trimethylolpropane triacrylate), tetraacrylates, pentaacrylates, hexaacrylates, mixtures of these different acrylates of type O[CH₂C(CH₂OR)₃]₂where R is H or COCH═CH₂;

(multi)acrylates described in the article by Nayak et al. (Polymer-Plastics Technology and Engineering, 2018, 57, 7, 625-656);

polymers carrying pendant acrylate functions;

functional oligo-PBAEs, prepared for example by reacting diacrylate compounds with a functional primary amine and/or a functional secondary diamine;

the mixture of different compounds described above.

Said second monomer Y is selected from amines. More specifically, it is advantageously selected from the group formed by:

primary amines R—NH₂;

primary diamines of type NH₂(CH₂)_nNH₂where n is an integer which can typically be between 1 and 20, and

which is preferably 2 or 6;

secondary diamines comprising an aromatic core such as meta-xylylene diamine;

primary (multi)amines such as tris(2-aminoethyl) amine;

secondary diamines such as piperazine;

(multi)amines containing primary and secondary amine functions such as tetraethylene pentamine;

polymers containing primary and/or secondary amine functions such as polyethylene imine.

In an embodiment, said polymerization of said monomers is performed under stirring at a temperature between 20° C. and 100° C., and preferably between 30° C. and 90° C.

The invention further relates to a microcapsule containing a so-called active substance, characterized in that the wall thereof consists of poly(beta-amino ester).

The invention further relates to a microcapsule that can be obtained with the method according to the invention.

The wall of the microcapsules thus prepared can be modified by adding a polymer layer deposited on the surface of the microcapsules. This deposition can be performed by adding a polymer dispersed in an aqueous phase which will be deposited on the surface of the capsules. Among these polymers, mention can be made of polysaccharides (for example, cellulose, starch, alginates, chitosan) and derivatives thereof.

Another possibility for modifying the wall of the microcapsules is that of modifying it by adding a radical initiator either in the aqueous phase or in the oily phase. A final possibility is that of reacting the residual surface amine functions with water-soluble monofunctional acrylates to modify the surface condition of the microcapsules.

FIGURES

FIGS. 1 to 18 illustrate certain aspects of the invention, but do not restrict the scope thereof. FIGS. 2 to 5 refer to example 1. FIG. 7 refers to example 2, FIG. 8 to example 3, FIG. 8 to example 3, FIG. 10 to example 6, FIG. 11 to example 7, FIG. 12 to example 10, FIG. 13 to example 11, FIG. 14 to example 13, FIG. 15 to example 14, FIG. 16 to example 15, FIG. 17 to example 17, and FIG. 18 to example 18.

FIGS. 2 to 5 and 10 to 14 are optical micrographs; the horizontal bar at the bottom left of the image represents a length of 50 82 m. FIGS. 17 and 18 are also optical micrographs.

FIG. 1 shows the general diagram of the method according to the invention. The four-digit reference numbers denote steps of this method.

FIG. 2 shows an optical micrograph of microcapsules obtained according to example 1, after 5 hours of reaction.

FIG. 3 shows a Fourier transform infrared (FTIR) spectrum of the wall of the microcapsules isolated in slurries after 6 hours of reaction.

FIG. 4 shows an optical micrograph of microcapsules obtained according to example 1, after drying on a glass strip.

FIG. 5 shows two optical micrographs of microcapsules obtained according to example 1, after drying on a glass strip. The left micrograph was obtained in grazing incidence light, the right micrograph under fluorescent light after adding some drops of a fluorescent dye.

FIG. 6 illustrates the reaction diagram of the reaction according to the invention.

FIG. 7 shows that the thermochromic microcapsules are stable after a 30-min oven passage and that the thermochromic function thereof is preserved.

FIG. 8 illustrates the degradability of the walls of the microcapsule with an accelerated degradation test.

FIG. 9 illustrates the different fields of application of poly(beta-amino ester)s.

FIG. 10 shows that the microcapsules are stable after 24 hours, and the mean diameter thereof is between 10 μm and 30 μm.

FIG. 11 shows a similar image to FIG. 10, and leads to the same conclusion, for another example.

FIG. 12 shows the result of the use of the microcapsules according to the invention in a carbonless copy paper.

FIG. 13 shows a photograph of microcapsules according to another example of the invention.

FIG. 14 shows a photograph of microcapsules according to another example of the invention.

FIG. 15 shows the biodegradation percentage as a function of time for dry microcapsules according to the invention.

FIG. 16 shows the biodegradation percentage as a function of time for the wall of the microcapsules according to the invention.

FIG. 17 shows a photograph of microcapsules according to another example of the invention.

FIG. 19 shows a photograph of a cotton fiber which has been placed in contact with microcapsules according to the invention in which the surface has been modified (b) or not (a).

DETAILED DESCRIPTION

In the following detailed description of embodiments of the present description, numerous specific details are disclosed in order to provide a more in-depth understanding of the present invention, and to enable a person skilled in the art to execute the invention. However, it will be obvious to a person skilled in the art that the present description can be implemented without these specific details. In other cases, well-known features have not been described in detail to avoid overburdening the description unnecessarily.

FIG. 1 shows a general diagram of the method according to the invention. The aqueous surfactant solution (1000) is prepared. An organic solution (also known as “oily phase”) is also prepared comprising the phase to be encapsulated (which comprises the so-called active substance) and the monomer X (1002). At step 1010, this oily phase 1002, which is an organic solution, is added to said aqueous solution 1000 and at step 1020 an O/W (oil-in-water, according to a term known to a person skilled in the art) type emulsion 1022 is obtained. In this emulsion, said organic solution is the so-called oily phase (O phase). At step 1030, an aqueous solution of the monomer Y 1024 is added to said emulsion 1022. At step 1040, the polymerization reaction results in a reaction mixture 1042 from which, at step 1050, a heterogenous mixture 1052 known as slurry is formed, which comprises, suspended in an aqueous base, the microcapsules containing the phase to be encapsulated.

Step 1050 involves as a general rule a temperature of the reaction mixture 1042 greater than about 20° C., typically between 20° C. and 100° C. A temperature between about 30° C. and about 90° C. is preferred, and even more preferably between about 40° C. and about 80° C.

This method can be applied to different monomers X and Y. According to the invention, the monomer X is a (multi)acrylate, and the monomer Y is an amine, preferably, a primary amine and/or a primary (multi)amine and/or a secondary diamine and/or a compound having primary and secondary amines.

The term (multi)acrylate denotes any compound of formula X′—(—O(C═O)—CH═CH₂)_nwhere n≥2 and where X′ is a molecule whereon n acrylate structural units are grafted.

The term primary (multi)amine denotes any compound comprising at least two primary amine functions.

As an acrylate, it is possible to use for example triacrylates (such as C₁₅O₆H₂O, CAS No. 15625-89-5); tetraacrylates; pentaacrylates; hexaacrylates; mixtures of these different acrylates cited. It is possible to use for example molecules of type O[CH₂C(CH₂OR)₃]₂where R can be H or COCH═CH₂.

As an amine, it is possible to use for example molecules of type NH₂(CH₂)_nNH₂where n is an integer which can typically be between 1 and 20, and which be for example 2 (ethylene diamine) or 6 (hexamethylene diamine, CAS number: 124-09-4). It is also possible to use piperazine, meta-xylylene diamine, pentaethylenehexamine, tris(2-aminoethyl)amine (TREN) or polyethylene imine (PEI).

The nature and the concentration of the amines and the acrylates can be varied.

The reagent function ratio of the monomers Y (—NH) and X (acrylate) is advantageously greater than 1, and typically between 1 and 5, preferably between 1.2 and 3.8.

According to a specific embodiment of the invention, the monomers X (acrylate) and/or Y (amine) are biosourced.

FIG. 6 shows the reaction diagram of the aza-Michael addition reaction between a secondary amine and an acrylate (reaction (a)) and the polyaddition reaction between a multifunctional acrylate compound and a multi-amine compound resulting in a cross-linked polymer (reaction (b)).

The organic core of the microcapsules can consist of an organic phase comprising an active substance. During the formation of the microcapsule, this organic (oily) phase will be enclosed by the polymeric wall of the microcapsule, which protects it from the environment. Said organic (oily) phase can consist of said active substance, or said active substance can be part of said organic (oily) phase, wherein it can be particularly dissolved. The expression “active substance” refers here to the specific purpose wherein the microcapsules are intended to be used; as a general rule, in view of the specificity of the microcapsule product, this purpose is always known during the manufacture thereof.

The active substance can be selected particularly from oils (pure or containing possibly other molecules in solution or in dispersion), such as essential oils, natural and edible oils, plant and edible oils, liquid alkanes, esters and fatty acids, or from dyes, inks, paints, thermochromic and/or photochromic substances, fragrances, products with biocidal effect, products with fungicidal effect, products with antiviral effect, products with phytosanitary effect, pharmaceutical active ingredients, products with cosmetic effect, adhesives; these active ingredients being optionally in the presence of an organic vector.

It is possible to use, non-restrictively, distillation extracts of natural products such as essential oils of eucalyptus, citronella, lavender, mint, cinnamon, camphor, aniseed, lemon, orange, which can be obtained by extraction from plant matter, or by synthesis.

It is also possible to use other substances such as long-chain alkanes (for example tetradecane), which can contain lipophilic solutions in solution.

As a general rule, and according to the function sought for the microcapsules, it is possible to use any hydrophobic compound, which will thus be naturally dispersed in the form of emulsion of hydrophobic droplets suspended in an aqueous phase.

Numerous additives enabling superior protection of the organic (oily) phase to be encapsulated, against infrared radiation, ultraviolet radiation, unintentional entry of specific gas or oxidation, can be incorporated in the microcapsule.

The wall of the microcapsules can be modified by adding a coating on the surface thereof. This deposition can be performed by adding a polymer dispersed in an aqueous phase which will be deposited on the surface of the capsules. Of these polymers, mention can be made of polysaccharides (cellulose, starch, alginates, chitosan, etc.) and derivatives thereof. This addition can be performed either hot or at ambient temperature at the end of the interfacial polymerization step.

The wall of the microcapsules can also be modified by adding a radical initiator either in the aqueous phase or in the organic (oily) phase. The addition in the organic phase can be performed before and/or after preparing the PBAE wall. If the addition is performed afterwards, the radical initiator can be diluted in acetone to promote transport in the microcapsules. These initiators can be azo compounds (such as azobis-isobutyronitrile and derivatives thereof) or peroxide compounds (lauroyl peroxide, etc.). In the case of initiators added in the aqueous phase, they can consist particularly of water-soluble azo compounds (such as 2,2′-Azobis(2-methylpropionamidine)dihydrochloride) red-ox systems (ammonium or potassium persulfate in combination with potassium metabisulfate for example). In an inert atmosphere, the radicals from the decomposition of the radical initiators can be added to the residual acrylate functions of the PBAE wall and reinforce it mechanically and/or modify the polarity thereof.

Another way to modify the wall of the microcapsules is to react the residual surface amine functions with water-soluble monofunctional acrylates. Without wishing to be bound to this hypothesis, the inventors believe that via Michael addition, an amino-ester bond would be formed and would anchor a functional group on the surface. Of the water-soluble acrylates suitable for use, mention can be made of acrylic acid, 2-carboxyethyl acrylate, 2-(dimethylamino) ethyl acrylate, 2-hydroxyethyl acrylate, poly(ethylene glycol) acrylates, 3-sulfopropyl acrylate potassium salt.

As surfactant, it is particularly possible to use those which are cited in Encyclopedia of Chemical Technology, volume 8, pages 912 to 915, and which have a hydrophilic-lipophilic balance (according to the HLB system) equal to or greater than 10.

Other macromolecular surfactants can also be used. Mention can be made for example of polyacrylates, methylcelluloses, carboxymethylcelluloses, polyvinyl alcohol (PVA) optionally partially esterified or etherified, polyacrylamide or synthetic polymers having anhydride or carboxylic acid functions such as ethylene/maleic anhydride copolymers. Preferably, polyvinyl alcohol can be used as a surfactant.

It may be necessary, for example in the case of aqueous solutions of a cellulose compound, to add a little alkaline hydroxide such as sodium hydroxide, in order to facilitate the dissolution thereof; such cellulose products can also be used directly in the form of the sodium salts thereof for example. Pluronics type amphiphilic copolymers can also be used. Generally, aqueous solutions containing from 0.1 to 5 wt. % of surfactant are used.

The size of the droplets is dependent on the nature and the concentration of the surfactant and the stirring speed, the latter being chosen particularly high in that smaller mean droplet diameters are sought.

In general, the stirring speed during the preparation of the emulsion is from 5000 to 10,000 rpm. The emulsion is usually prepared at a temperature between 15° C. and 95° C. Generally, when the emulsion has been obtained, impeller stirring is stopped and the emulsion is stirred using a common type of slower stirrer, for example of the frame stirrer type, typically at a speed of the order of 150 to 1500 rpm.

The method according to the invention thus results in homogeneous and fluid suspensions containing, according to the fillers introduced, generally from 20 wt. % to 80 wt. % of microcapsules having a mean diameter of 100 nm to 100 μm. The diameter of the microcapsules can be preferably between 1 μm and 50 μm, and more preferably between 10 μm and 40 μm.

The microcapsules, and in particular the wall thereof, according to the invention are (bio)degradable. The biodegradation can be determined for example by one of the methods described in the document “OECD Guidelines for Testing of Chemicals: Ready Biodegradability” (adopted by the OECD Council on Jul. 17, 1992). The manometric respirometry test (method 301 F) can preferably be used. Preferably, this test is used on emptied and washed microcapsules, so that the biodegradation of the content of the microcapsules does not interfere with the test which is aimed at characterizing the biodegradation of the material forming the wall of the microcapsules. Preferably, the microcapsule according to the invention, and/or the wall thereof, shows a biodegradation of at least 80%, preferably at least 83%, more preferably at least 85%, measured after 10 days of incubation using said method 301 F. With the same method, after 28 days of incubation, the microcapsules according to the invention preferably show a biodegradation of at least 90%, preferably at least 95%, and more preferably at least 98%.

EXAMPLES

To allow a person skilled in the art to reproduce the invention, examples of implementation are given here; they do not restrict the scope of the invention.

Example 1
Preparation of Fragranced Microcapsules Based on a Diamine (HMDA)

(i) Emulsion Preparation

11.0 g of essential oil (Eucalyptus) was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (0.39 g, 0.71 mmol) was dispersed in the essential oil under magnetic stirring (350 rpm). Stirring was maintained until the solution become homogeneous; a heating step was added if required.

The essential oil/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturraxm IKA T10 at 9500 rpm for 3 min at ambient temperature to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, preheated to 50° C., the previously prepared emulsion was introduced and stirred at a speed of 250 rpm. When the emulsion reached 50° C., the solution of diamine (Hexamethylene diamine HMDA) (0.17 g, 1.46 mmol) in 5 g of PVA 2 wt % solution was added dropwise using a syringe and under stirring (250 rpm). During the reaction, samples at different reaction times were taken and analyzed by optical microscopy and Fourier transform infrared (FTIR) spectroscopy in order to monitor the formation of the microcapsules.

The total quantity of monomers used was ˜0.56 g. The amine was used in excess with respect to the acrylate monomer so as to obtain a —NH/acrylate function ratio=1.6. The essential oil/water mass ratio is equal to 0.24. The microcapsules can be analyzed by microscopy after a drying step. This analysis makes it possible to ensure the stability of the microcapsules once isolated. A second analysis consists of adding some drops of a fluorescent dye (Nile Red) on the dried microcapsules. Nile Red, a lipophilic chromophore which only fluoresces in an organic phase, makes it possible to verify that the core of the microcapsule still contains organic phase and that the microcapsules are filled.

FIG. 2 shows an optical microscopy image of the reaction medium after 5 hours of reaction. The microcapsules are spherical, with a diameter between about 10 μm and about 25 μm. FIG. 3 shows the FTIR spectrum of the microcapsules isolated from a slurry after 6 hours of reaction (after washing with acetone, followed by three centrifugation cycles and oven drying). Characteristic vibrations of N—H bonds are observed around 3300 cm⁻¹to 3400 cm⁻¹, along with a narrow band characteristic of a C═O bond around 1727 cm⁻¹.

FIG. 4 shows an optical micrograph of microcapsules dried on a glass strip. The diameter thereof is around 30 μm to 35 μm. FIG. 5 shows a micrograph of microcapsules dried on a glass strip in glazing incidence light (on left) and in fluorescent light (on right) after adding some drops of Nile Red fluorescent dye. The intense emission in fluorescent light shows that the core of the microcapsule contains an organic phase.

Example 2
Preparation of Fragranced Microcapsules Based on a Diamine (HMDA)

(i) Emulsion Preparation

11.0 g of a thermochromic solution (10° blue) was introduced into a beaker, placed in an oil bath and heated to 130° C. under magnetic stirring (350 rpm). Stirring was maintained until the thermochromic solution became homogeneous and transparent. The thermochromic solution was cooled, and when the temperature thereof reaches 50° C., the (multi)acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (0.39 g, 0.71 mmol) is dispersed under magnetic stirring (350 rpm). Stirring is maintained until the solution becomes homogeneous. The thermochromic/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturrax™ IKA T10 at 9500 rpm for 3 min at ambient temperature to form an emulsion.

(ii) Microencapsulation

The total quantity of monomers used was ˜0.56 g. The amine was used in excess with respect to the acrylate monomer so as to obtain a —NH/acrylate function ratio=1.6. The thermochromic solution/water mass ratio equals 0.24.

The dried microcapsules show a reversible color change with a reversible change of coloration at a temperature of 10° C. These same capsules can, furthermore, be heated in an oven at 130° C. for 30 min without modifying the thermochromic properties thereof (FIG. 7).

Example 3
Poly(beta-amino ester) Degradability Test

A first degradability test was performed according to the following procedure:

(1) Synthesis of poly(beta-amino ester)

In a beaker, the Hexamethylene diamine HMDA monomer (1.0 g, 8.6 mmol) was solubilized in THF (4.0 g) and added to a solution of (multi)acrylate (trimethylolpropane triacrylate) monomer (1.8 g, 6.1 mmol) solubilized in 2.5 g of THF. The mixture was placed in a pill box subsequently placed in an oil bath at 50° C.

The amine was used in excess with respect to the acrylate monomer so as to obtain a —NH/acrylate function ratio=2.

The polymer retrieved after 5 hours of reaction was washed three times with acetone and oven-dried.

(2) Poly(beta-amino ester) Degradation

The degradation of the poly(beta-amino ester) was performed according to the following protocol:

20 mg of polymer solubilized in 1 mL of a sodium hydroxide solution (3M, in deuterated water D₂O, pH˜14) is introduced into a flask equipped with a magnetic stirrer. As the polymer is crosslinked, it is not soluble in the aqueous phase.

FIG. 8 shows that the poly(beta-amino ester) is dissolved in the aqueous phase, characterizing an effective degradation of the polymer under these accelerated degradation conditions.

Example 4
Preparation of Fragranced Microcapsules Based on a Triamine (TREN)

(i) Emulsion preparation

11.0 g of essential oil (Eucalyptus) was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (0.39 g, 0.74 mmol) was dispersed in the essential oil under stirring. The essential oil/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturraxm IKA T10 to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced therein. An aqueous solution of tris(2-aminoethyl)amine TREN (0.145 g, 0.99 mmol) in 5 g of PVA 2 wt % solution was added under stirring at a temperature between 50° C. and 60° C.

Example 5
Preparation of Thermochromic Microcapsules Based on a Triamine (TREN)

(i) Emulsion preparation

11.0 g of a thermochromic solution was introduced into a beaker and stirred hot, the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (0.39 g, 0.74 mmol) was dispersed therein under stirring. The thermochromic/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an UltraturraxTM IKA T10 to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced at a temperature of about 50° C. to 60° C. An aqueous solution of tris(2-aminoethyl) amine TREN (0.145 g, 0.99 mmol) in 5 g of PVA 2 wt % solution was added under stirring at a temperature between 50° C. and 80° C.

Example 6
Preparation of Microcapsules Based on a Biogenic Monomer

(i) Emulsion preparation

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced, the aqueous solution of diamine (Butane-1,4-diamine (Putrescine)) (0.13 g, 1.47 mmol) in g of PVA 2 wt % was added under stirring at a temperature between 50° C. and 60° C.

FIG. 10 shows an optical microscopy image of the capsules after 24 hours of reaction. The microcapsules are spherical, with a mean diameter between about 10 μm and about 30 μm.

Example 7
Preparation of Microcapsules Based on Polyethylene Imine (PEI)

(i) Emulsion Preparation

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced. A solution of polyethylene imine (PEI) (1.78 g, 1.48 mmol) in 5 g of PVA 2 wt % solution was added under stirring at a temperature between 50° C. and 60° C.

FIG. 11 shows optical microscopy images of the capsules after 24 hours of reaction. The microcapsules are spherical, with a mean diameter between about 10 μm and about 30 μm.

Example 8
Preparation of Fragranced Microcapsules (Shell /PI Ratio=3.4%)

(i) Emulsion Preparation

193.6 g of essential oil (Eucalyptus) was placed in a beaker, and the multi-acrylate monomer

(Dipentaerythritol penta-/hexa-acrylate mixture) (4.5 g, 8.5 mmol) was dispersed in the essential oil under stirring. The essential oil/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (255.9 g PVA 2 wt. %); the mixture was homogenized to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced. A solution of diamine

(Hexamethylene diamine HMDA) (2.01 g, 17.2 mmol) in 44.1 g of a PVA 2 wt % solution was added under stirring at a temperature between 50° C. and 60° C. The whole was left to react for 2 hours at 50° C. and for 5 hours at 60° C.

Example 9
Preparation of Fragranced Microcapsules

(i) Emulsion Preparation

11.0 g of a mixture of 80% Pineapple papaya fragrance (reference RS42370 from the company Technicoflor in Allauch (France)) and 20% methyl myristate was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (0.39 g, 0.74 mmol) was dispersed in the fragrance under stirring. The essential oil/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturrax™ IKA T10 to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced. A solution of diamine (Hexamethylene diamine HMDA) (0.17 g, 1.49 mmol) in 5 g of a PVA 2 wt % solution was added under stirring at a temperature between 50° C. and 60° C. The whole was left to react for 2 hours at 50° C. and for 5 hours at 60° C.

Example 10
Preparation of Microcapsules for Carbonless Copy Papers (Shell/PI Ration=3.4%)

(i) Emulsion Preparation

193.6 g of an internal phase (Dye) was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (4.5 g, 8.5 mmol) was dispersed in the internal phase under stirring. The whole was added gradually to the previously prepared aqueous surfactant solution (255.9 g PVA 2 wt. %); the mixture was homogenized to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, the previously prepared emulsion was introduced. An aqueous solution of diamine

(Hexamethylene diamine HMDA) was added, under stirring at a temperature between 50° C. and 60° C.

(iii) Use of the microcapsules in a carbonless copy paper

These microcapsules were applied on a sheet of paper, according to known methods, and used in a carbonless copy system. FIG. 12 shows the result, which is fully satisfactory.

Example 11
Preparation of Thermochromic Microcapsules Based on POSS@octa(acrylate) Monomer

(i) Emulsion Preparation

20.0 g of thermochromic, and polyoctahedral silsesquioxanes borne by eight acrylate functions (POSS@octa(acrylate), CAS No. 1620202-27-8, purchased from Hydridplastics, 1.48 g, 1.12 mmol) and Butylated

HydroxyToluene (BHT, 5.0 mg) thermal inhibitor, were placed in a beaker. The mixture was solubilized hot under magnetic stirring. Stirring was maintained until the solution became homogeneous. The thermochromic/POSS@octa(acrylate) assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturra™ IKA T10 to form an emulsion.

(ii) Microencapsulation

In a reactor, the previously prepared emulsion was introduced. The solution of Hexamethylene diamine (HMDA, 0.35 g, 3.01 mmol) in water was added dropwise using a syringe and under stirring. The whole was left to react at 50° C. for 1 hour and at 80° C. for 23 hours. FIG. 13 shows a photograph of these microcapsules.

Example 12
Preparation of Thermochromic Microcapsules Based on POSS@octa(acrylate) Monomer with Meta-Xylylenediamine

(i) Emulsion preparation

10.0 g of thermochromic, and polyoctahedral silsesquioxanes borne by eight acrylate functions (POSS@octa(acrylate), CAS No. 1620202-27-8, purchased from Hydridplastics, 1.50 g, 1.12 mmol) and Butylated HydroxyToluene (BHT, 5.0 mg) thermal inhibitor, were placed in a beaker. The mixture was solubilized hot under magnetic stirring. Stirring was maintained until the solution became homogeneous. The thermochromic/POSS@octa(acrylate) assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturraxm IKA T10 to form an emulsion.

(ii) Microencapsulation

In a reactor, the previously prepared emulsion was introduced. The solution of meta-xylylenediamine (CAS No. 1477-55-0, 0.60 g, 3.01 mmol) in 3 mL of water was added dropwise using a syringe and under stirring. The whole was left to react at 65° C. for 1 hour and at 80° C. for 17 hours.

Example 13
Preparation of Thermochromic Microcapsules Based on POSS@octa(acrylate) Monomer with POSS@Octammonium and Hexamethylene Diamine (HDMA)

(i) Emulsion Preparation

10.0 g of thermochromic, and polyoctahedral silsesquioxanes borne by eight acrylate functions (POSS@octa(acrylate), CAS No. 1620202-27-8, purchased from Hydridplastics, 1.40 g, 1.06 mmol) and Butylated HydroxyToluene (BHT, 5.0 mg) thermal inhibitor, were placed in a beaker. The mixture was solubilized hot under magnetic stirring. Stirring was maintained until the solution became homogeneous. The thermochromic/POSS@octa(acrylate) assembly was added gradually to the previously prepared aqueous surfactant solution (40 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturraxl™ IKA T10 to form an emulsion.

(ii) Microencapsulation

In a reactor, the previously prepared emulsion was introduced. Afterward, the solution of Hexamethylene diamine (HMDA, 0.70 g, 6.02 mmol), POSS@(octa)ammonium (CAS No. 150380-11-3, purchased from Hydridplastics, 0.30 g, 0.26 mmol), and potassium carbonate (0.16 g, 1.16 mmol) in water was added dropwise using a syringe, under stirring. The whole was left to react at 65° C. for 1 hour and at 80° C. for 17 hours.

FIG. 14 shows a photograph of these microcapsules.

Example 14
Biodegradation Test

A batch of microcapsules prepared according to example 8 was provided. The dry microcapsules but containing essential oil (Eucalyptus) were subjected to the biodegradability test described in the document OECD 301 (“OECD Guidelines for Testing of Chemicals: Ready Biodegradability”) using method 301 F (Manometric respirometry test). After an incubation time of nineteen days, the biodegradation percentage was 83%.

FIG. 15 shows the progression of the biodegradation percentage as a function of time, over a 19-day duration. Curve (b) corresponds to the microcapsule, while curve (a) corresponds to a reference product (sodium acetate) processed separately under the same biodegradation conditions.

Example 15
Biodegradation Test

A batch of microcapsules prepared according to example 8 was provided. The microcapsules were opened, emptied and washed. Then they were subjected to the biodegradability test described in the document OECD 301 (“OECD Guidelines for Testing of Chemicals: Ready Biodegradability”) using method 301 F (Manometric respirometry test). After an incubation time of twenty-eight days, the biodegradation percentage was 93%.

FIG. 16 shows the progression of the biodegradation percentage as a function of time.

Example 16
Preparation of Fragranced Microcapsules Based on a Multiamine (Pentaethylenehexamine)

(i) Emulsion Preparation

19.7 g of essential oil (Eucalyptus) was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (1.2 g, 2.29 mmol) was dispersed in the essential oil under magnetic stirring (350 rpm) at 50° C. Stirring was maintained until the solution became homogeneous. The essential oil/organic monomer assembly was added gradually to the prepared aqueous surfactant solution (31.7 g, PVA 2 wt. %) previously heated to 50° C.; the mixture was homogenized using an Ultraturrax™ IKA T10 at 11,500 rpm for 3 min at 50° C. to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, preheated to 50° C., the previously prepared emulsion was introduced and stirred at a speed of 250 rpm. The solution of multiamine (Pentaethylenehexamine) (1.9 g, 8.00 mmol) in 5.5 g of PVA 2 wt % solution was added dropwise using a syringe and under stirring (250 rpm). The reaction mixture was kept under stirring for 2 hours at 50° C. then 5 hours at 60° C.

The total quantity of monomers used was 3.1 g. The amine was used in excess with respect to the acrylate monomer so as to obtain an Amine/acrylate molar ratio=3.5. The essential oil/water mass ratio is equal to 0.53.

Example 17
Preparation of Fragranced Microcapsules Based on an Aromatic Diamine (m-xylylene diamine)

(i) Emulsion preparation

22.0 g of fragrance was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (1.52 g, 2.90 mmol) was dispersed in the fragrance under magnetic stirring (350 rpm) at 50° C. Stirring was maintained until the solution became homogeneous. The fragrance/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (35.0 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturrax™ IKA T10 at 11,500 rpm for 3 min at 50° C. to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, preheated to 65° C., the previously prepared emulsion was introduced and stirred at a speed of 250 rpm. When the emulsion has reached 65° C., the solution of m-xylylenediamine (0.80 g, 5.88 mmol) in 5.0 g of PVA 2 wt % solution was added dropwise using a syringe and under stirring (248 rpm). The reaction mixture is kept under stirring for 5 hours at 65° C. and 1 hour at 80° C.

The total quantity of monomers used was 2.3 g. The amine was used in excess with respect to the acrylate monomer so as to obtain a —NH/acrylate function ratio=1.6. The fragrance/water mass ratio is equal to 0.55.

FIG. 17 shows a photograph of these microcapsules.

Example 18
Preparation of Fragranced Microcapsules with a Cellulose Fiber Coating

(i) Emulsion Preparation

22.0 g of fragrance was placed in a beaker, and the multi-acrylate monomer (Dipentaerythritol penta-/hexa-acrylate mixture) (1.52 g, 2.90 mmol) was dispersed in the fragrance under magnetic stirring (350 rpm) at 50° C. Stirring was maintained until the solution became homogeneous. The fragrance/organic monomer assembly was added gradually to the previously prepared aqueous surfactant solution (40.0 g, PVA 2 wt. %); the mixture was homogenized using an Ultraturrax™ IKA T10 at 11,500 rpm for 3 min at 50° C. to form an emulsion.

(ii) Microencapsulation

In a double-wall reactor, equipped with an IKA blade mechanical stirring system, preheated to 65° C., the previously prepared emulsion was introduced and stirred at a speed of 250 rpm. When the emulsion reached 65° C., the solution of m-xylylenediamine (0.80 g, 5.88 mmol) in 5.0 g of PVA 2 wt % solution was added dropwise using a syringe and under stirring (250 rpm). The reaction mixture is kept under stirring for 5 hours at 65° C. and 1 hour at 80° C.

The total quantity of monomers used was 2.3 g. The amine was used in excess with respect to the acrylate monomer so as to obtain a —NH/acrylate function ratio=1.6. The essential oil/water mass ratio is equal to 0.5.

(iii) Cellulose Coating

4 wt. % of cellulose microfiber (Exilva F 01-L) was preheated to a temperature between 65° C. and 70° C. then introduced into the hot slurry under stirring. The mixture is homogenized hot under stirring for 30 min and for 2 hours at ambient temperature.

A cotton fiber bonding test was performed: a cotton fiber was previously wetted and then steeped in the slurry. After washing vigorously and thoroughly in water to simulate rinsing, the fiber was dried at ambient temperature.

FIG. 18 shows a photograph (image (b)) of a cotton fiber after steeping in a slurry solution then drying for microcapsules in which the surface has been modified. The coating enhances the bonding of the microcapsules on the cotton fiber, compared to uncoated microcapsules (image (a)).

Number	Date	Country	Kind
1905127	May 2019	FR	national
1912148	Oct 2019	FR	national

METHOD FOR PREPARING BIODEGRADABLE MICROCAPSULES AND MICROCAPSULES OBTAINED IN THIS MANNER

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