Microcapsules controlling the diffusion of an active organic compound

Abstract

The present invention relates to a microcapsule having a core comprising a lipophilic phase surrounded by a gelled shell, the core further comprising at least one active organic compound, the uses of said microcapsule in various fields of applications such as crop and / or seed treatment, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater decontamination, cleaning products, and a crop and / or seed treatment method.

Description

[0001] DESCRIPTION

[0002] TITLE: Microcapsules controlling the diffusion of an active organic compound

[0003] The present invention relates to a microcapsule with a core comprising a lipophilic phase surrounded by a gelled shell, and in which the core further comprises at least one active organic compound, the uses of said microcapsule in various fields of application such as the treatment of crops and / or seeds, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater decontamination, cleaning products.

[0004] Semiochemical compounds are chemical substances emitted by an organism into the environment as a signal with other organisms. They can be emitted by plants or animals, in the context of interspecific interactions (allelochemical compounds) and intraspecific interactions (pheromones). Among the semiochemical compounds we therefore find pheromones. Pheromones are natural substances secreted into the external environment by an individual and received by a second individual of the same species in which they provoke a specific reaction. They most often constitute an olfactory signal acting as a messenger within a population.

[0005] Pheromones can be used to control pest insect populations, particularly by influencing their reproductive behavior. Currently, most pheromone-based biocontrol products are stored in plastic or other polymer dispensers (manually attached to trees or plants) that allow the pheromone to diffuse through their walls. Although these dispensers have been effective in controlling some insects, their application requires a lot of manual labor and must be carried out several times per season, making the operation tedious. Indeed, most existing systems, including polymer beads, do not have a sufficient duration of action in the field.

[0006] For these compounds to be used as an effective biocontrol tool, the pheromones must be released at constant concentrations over relatively long periods of time, a few months, corresponding to the pests' flight period. However, current methods cannot achieve these durations. Thus, the difficulty in developing controlled-release formulations that can release pheromones at a constant rate over an extended period has been a factor limiting their use in the control of crop pests. Moreover, since existing products are mainly devices on which the pheromone is immobilized, they are, in fact, not sprayable.

[0007] The objective is to enable controlled diffusion of active organic compounds over periods of several weeks to several months. Acquiring this capability will enable the development of a range of products with varied properties to address different agronomic issues.

[0008] Furthermore, pheromones are quite expensive, so it is preferable that the use of pheromones is finely controlled in order to limit overconsumption and optimize their effectiveness. A sprayable form of pheromones would allow for uniform treatment of large areas. The inventors' solution, in addition to allowing the spraying of pheromones, allows diffusion at a constant speed over a long period.

[0009] Thus, the invention proposes to encapsulate active organic compounds in a capsule with a core comprising a lipophilic phase in order to meet these objectives.

[0010] Encapsulation of organic compounds allows diffusion to be controlled by adjusting the partition coefficient of the compound between the lipophilic phase and the aqueous phase and the geometry of the capsule. This solution allows, for example, the diffusion time of pheromones to be extended from less than 10 days to more than 38 days.

[0011] In addition, the size of the capsules can be specifically chosen to allow application of the active ingredient by spraying, for example for spraying in open fields. Indeed, the size of these capsules is adapted to the use of standard agricultural equipment.

[0012] Thus the invention relates to a microcapsule with a core comprising a lipophilic phase surrounded by a gelled shell, in which the microcapsule has an average diameter of between 50 and 4000 μm when in hydrated form, and in which the core further comprises at least one active organic compound.

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

[0014] The invention also relates to a method of treating crops and / or seeds comprising the application of microcapsules according to the invention. detailed description of the Microcapsule invention

[0015] By "microcapsule" is meant here a capsule with an average diameter of less than 10 mm and comprising at least a core and a shell. Such capsules preferably comprise a liquid or solid core encapsulated by a substantially solid gelled envelope. The core is preferably liquid. This type of capsule has applications in numerous technical fields. The shell encompasses one or more compartments, concentric or not. Preferably, the microcapsules according to the invention comprise only a single core coated by the shell.

[0016] These microcapsules are therefore very different from microbeads, because microbeads are mainly made up of a solid or gelled matrix comprising multiple small inclusions.

[0017] According to a preferred embodiment of the invention, the microcapsules have a core volume to total microcapsule volume ratio greater than 20%. These microcapsules thus make it possible to contain a large volume of core and therefore of active organic compounds, for a given shell volume.

[0018] Microcapsules are well known to those skilled in the art and can be formed by different techniques and have different shell compositions.

[0019] Typically, the microcapsules used in the context of the invention are produced according to the manufacturing process described in French patent no. 2939012.

[0020] When the microcapsules according to the invention are suspended in an aqueous solution, they have an average diameter of between 50 and 4000 pm, preferably between 50 and 2000 pm, more particularly between 50 and 800 pm, advantageously between 100 and 400 pm. This average diameter can be measured by various techniques well known to those skilled in the art such as particle size analysis based on laser light diffraction, sieve fractionation or optical microscopy imaging. This diameter is particularly suitable for application by spraying.

[0021] Preferably, the microcapsules according to the invention are free, that is to say that they are not included in another structure such as a film, a bead, a gel or encapsulated a second time, but that they are in direct contact with the medium which surrounds them, typically a liquid (if they are in suspension for example) or a gas.

[0022] The heart

[0023] The core of the microcapsules according to the invention is a core comprising a lipophilic phase, preferably comprising predominantly a lipophilic phase. Thus, the core comprising a lipophilic phase of the microcapsules according to the invention may be an oily core, that is to say it is composed solely of oil, or alternatively be in the form of an oil-in-water (O / W) emulsion, for example an oil-in-water microemulsion. In this case, the core of the microcapsule is therefore predominantly composed of an oil or a mixture of oils, preferably oils of vegetable, mineral or synthetic origin or a mixture thereof. The term "oil" means a fatty substance that is liquid at room temperature (25°C) and atmospheric pressure.

[0024] The core comprising a lipophilic phase may also be a core comprising or consisting of solid fatty substances at ambient temperature and pressure, notably chosen from waxes, pasty fatty substances, butters; and mixtures thereof.

[0025] In a preferred embodiment, the core is liquid at room temperature, or liquid at a temperature between 15°C and 30°C.

[0026] In one embodiment of the invention, the core does not comprise wax.

[0027] The core of the microcapsule is therefore mainly composed of a lipophilic phase. In particular, the core is mainly composed of fatty compounds of animal, vegetable, mineral or synthetic origin or a mixture of these.

[0028] In a preferred embodiment, the core of the microcapsule according to the invention is an oily core comprising an oil chosen from isopropyl myristate, a paraffin oil and mixtures thereof. In a preferred embodiment, the core of the microcapsules according to the invention is an oily core composed mainly of an oil, paraffins and mixtures thereof.

[0029] In a preferred embodiment, the core comprises one or more elements selected from: fatty acids (saturated fatty acids such as palmitic acid, mono-polyunsaturated fatty acids such as linolenic acid), simple lipids (glycerides such as oils and butter and steroids), complex lipids (phospholipids, sphingolipids and lipoproteins), and isoprene lipids (steroids and terpenes).

[0030] Preferably, the composition of the core is biodegradable.

[0031] According to a preferred embodiment of the invention, the viscosity of the core is less than 2000 mPa.s.

[0032] The core of the microcapsules according to the invention comprises at least one active organic compound. By "active organic compound" is meant an active substance, an active principle or active ingredient which is known and / or used for a particular purpose and one of the constituent chemical elements of which is carbon.

[0033] Preferably, said at least one active organic compound is a volatile compound.

[0034] “Volatile organic compound” means any organic compound, excluding methane, having a vapor pressure greater than or equal to 0.01 kPa at a temperature of 293.15 K (20°C) or having a corresponding volatility under particular conditions of use (pressure and temperature).

[0035] More preferably, the active organic compound according to the invention is a semiochemical compound, possibly volatile.

[0036] By "semiochemical compound" or "semiochemical" is meant an active substance, a chemical substance emitted by an organism into the environment as a signal with other organisms. Preferably, said at least one semiochemical compound of the microcapsule is chosen from pheromones, allomones, kairomones and synomones. More particularly, the semiochemicals of the microcapsule may be of natural or chemical origin, i.e. extracted from a living organism or chemically synthesized.

[0037] In one embodiment, said at least one semiochemical compound is an oxygenated hydrocarbon, of a size between 10 and 20 carbons, which may be unsaturated and have other functions such as for example an alcohol, acetate and / or aldehyde function.

[0038] In one embodiment, the semiochemical according to the invention is a sex pheromone. Thus, preferably, the semiochemical is the sex pheromone of the pest targeted by a biocontrol treatment. In one embodiment, the semiochemical is a sex pheromone of Lobesia botrana (Eudemis vine), Eupoecilia ambiguella (commonly known as Cochylis), Cydia pomonella (Codling moth), Grapholita molesta (Oriental leafroller), Anarsia lineata (Lesser peach tree leafroller), Tuta absolute (Tomato leafroller) or Thaumetopoea pityocampa (Pine processionary moth).

[0039] In one embodiment, the semiochemical according to the invention is a kairomone, for example a kairomone targeting the faba bean weevil.

[0040] In one embodiment, the semiochemical is selected from Z-13-hexadecen-1 1 -yn-1 -yl acetate, (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24O2), and (Z)-9-dodecenyl acetate (C 14 H 26 O2). In one embodiment, the oily core of the microcapsule has a semiochemical mass concentration of between 0.1% and 10%, more preferably between 0.2% and 5%.

[0041] The hull

[0042] The microcapsules according to the invention preferably comprise at least one liquid core encapsulated by a substantially solid gelled envelope called the shell.

[0043] Preferably, the shell of the microcapsules according to the invention is mainly composed of a biopolymer having gelling properties, this biopolymer in the majority proportion in the shell is hereinafter called the main biopolymer. Such biopolymers having gelling properties are for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.

[0044] The materials that make up the shell are preferably biodegradable and bio-sourced. The shell is preferably semi-permeable to gases and low molecular weight molecules.

[0045] Shell-forming gels can be chemical or physical, i.e. formed by coacervation or by polymerization.

[0046] The gelation of these biopolymers can be achieved by a variation in temperature (gellan gum), a variation in pH (chitosan, collagen, pectin) or ionic (alginate, carrageenan).

[0047] Preferably, the shell of the microcapsules according to the invention is mainly composed of a biopolymer having gelling properties by ionic or temperature variation.

[0048] Preferably, the shell of the microcapsules according to the invention is mainly composed of alginate.

[0049] The shell may further comprise one or more other biopolymers than the main biopolymer such as starch (in its various forms, for example pregelatinized, or amylose), potato protein, or another biopolymer than the main biopolymer having gelling properties, such as for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.

[0050] Preferably, the shell of the microcapsules according to the invention comprises a gel containing water, one or more biopolymers having gelling properties, and optionally a surfactant resulting from its manufacturing process. Preferably, the shell of the microcapsules according to the invention comprises a gel containing water, alginate, and optionally a surfactant resulting from its manufacturing process.

[0051] In a preferred embodiment, the shell of the microcapsules according to the invention does not comprise any polymer other than alginate.

[0052] Preferably, the alginate is sodium alginate or potassium alginate. Alginates are produced from brown algae called laminaria, also known as "sea weed". Such alginates advantageously have an aL-guluronate content greater than approximately 50%, preferably greater than 55%, or even greater than 60%.

[0053] The surfactant is advantageously an anionic surfactant, a non-ionic surfactant, a cationic surfactant or a mixture thereof. The molecular weight of the surfactant is between 150 g / mol and 10000 g / mol, advantageously between 250 g / mol and 1500 g / mol.

[0054] In the case where the surfactant is an anionic surfactant, it is for example chosen from an alkyl sulfate, an alkyl sulfonate, an alkylarylsulfonate, an alkali metal alkylphosphate, a dialkylsulfosuccinate, an alkaline earth metal salt of saturated or unsaturated fatty acids. These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic anionic group, such as a sulfate, a sulfonate or a carboxylate linked to one end of the hydrophobic chain. In the case where the surfactant is a cationic surfactant, it is for example chosen from an alkylpyridium or alkylammonium halide salt such as n-ethyldodecylammonium chloride or bromide, cetylammonium chloride or bromide (CTAB).These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic cationic group, such as a quaternary ammonium cation. In the case where the surfactant is a non-ionic surfactant, it is for example chosen from polyoxyethylenated and / or polyoxypropylenated derivatives of fatty alcohols, fatty acids, or alkylphenols, arylphenols, or from alkyl glucosides, polysorbates, cocamides.

[0055] In one embodiment, the surfactant is sodium lauryl sulfate (LSS) also called sodium dodecyl sulfate and / or polyoxyethylene sorbitan monooleate (Polysorbate 80).

[0056] Preferably, the surfactant is polyoxyethylene sorbitan monooleate (Polysorbate

[0057] 80). In one embodiment, the mass content of surfactant in the shell is greater than 0.001% and is advantageously greater than 0.1%. Advantageously, the mass concentration of surfactant is approximately 0.3%.

[0058] The shell of the microcapsules according to the invention may further comprise stabilizers, densifying particles or agents limiting sedimentation, such as silica or talc.

[0059] The thickness of the shell is a factor influencing the robustness of the microcapsule and the diffusion kinetics of the active organic compound. Thus, the thickness of the shell can be chosen to obtain a desired diffusion kinetics. Preferably, the thickness of the shell is at least 10 μm, preferably it is between 20 μm and 500 μm, more preferably between 20 and 150 μm.

[0060] The shell of the microcapsule preferably has a thickness of between 0.1% and 20%, advantageously between 1% and 20% and more particularly between 10% and 20% of the diameter of the capsule.

[0061] The diffusion of the active organic compound is also dependent on the partition coefficient between the lipophilic core of the microcapsule and the aqueous phase of the shell.

[0062] Preferably, the microcapsule according to the invention is suitable for the diffusion of the active organic compound over a period of more than 3 weeks, more preferably more than 6 weeks and preferably more than 2 months. Thus the invention relates to the use, preferably non-therapeutic, of the microcapsule according to the invention for the diffusion of the active organic compound over a period of more than 3 weeks, more preferably more than 6 weeks and preferably more than 2 months.

[0063] Preferably, the microcapsule according to the invention is suitable for the diffusion of the active organic compound over the duration corresponding to the flight period of the targeted pest.

[0064] Thus, in the case where the microcapsule comprises as an active organic compound a semiochemical and more particularly a sexual pheromone of a given flying pest, then the microcapsule is suitable for the diffusion of said pheromone over the duration of the flight period of said pest.

[0065] By "suitable for the diffusion of the active organic compound over a period of time" is meant that during said period the active organic compound continues to diffuse outside the microcapsule at a substantially constant non-zero speed.

[0066] The microcapsule may further comprise other components, such as, for example, antioxidant compounds, UV filters, pigments, dyes, stabilizers, densifying particles such as silica or talc, essential oils or other additives.

[0067] Uses and methods

[0068] The definitions defined in the microcapsule section apply here as well.

[0069] Preferably, in the methods and uses according to the invention, the microcapsules are used as such, that is to say that they are not included in another structure (such as a film, a bead, a gel or encapsulated a second time), but that they are used directly, possibly in suspension in a liquid.

[0070] The invention relates to the use of microcapsules according to the invention for the treatment of plant cultures and / or their seeds.

[0071] By "treatment of plant crops and / or their seeds" is meant treatments that can take place before, during or after cultivation, and here more particularly with the aim of preventing and / or limiting pest attacks or reducing their impacts. It also means treatments that can take place in green spaces, such as gardens or parks. The invention relates in particular to the use of microcapsules according to the invention as a pesticide.

[0072] The invention therefore relates in particular to the use of microcapsules for the treatment of plant cultures and / or their seeds, in which the active organic compound is a biocontrol agent.

[0073] The invention comprises a method of treating crops and / or seeds comprising the application of microcapsules according to the invention.

[0074] By "crop" or "plant crop" is meant here a plant production derived from the exploitation of the land. In one embodiment, the plant crops are chosen from wheat, corn, rapeseed, vines and beetroot.

[0075] The invention relates in particular to a method for treating crops and / or seeds comprising spreading, foliar spraying or coating seeds with microcapsules according to the invention, preferably microcapsules according to the invention in which the active organic compound is a biocontrol agent. In this method, the microcapsules can be used in suspension in a liquid. By "pests" is meant herein mainly animal pests, such as insects, arachnids or small mammals and more preferably insects.More specifically, the pests are chosen from Lobesia botrana (the vine moth), Eupoecilia ambiguella (commonly called Cochylis), Cydia pomonella (codling moth), Grapholita molesta (oriental leafroller), Anarsia lineata (small peach moth), Tuta absolute (tomato leafminer), Thaumetopoea pityocampa (pine processionary moth), Bruchus rufimanus (bean bruchid), or even aphids, midges, corn borers, sesamia, small and large flea beetles, terminal bud weevil, cryptoblabes, or leafhoppers.

[0076] By "pesticide" we mean a formulation intended to eliminate insects, rodents or weeds.

[0077] In another embodiment, the invention relates to the use, preferably non-therapeutic, of microcapsules according to the invention for animal and / or human nutrition and / or feed. In this embodiment, the active organic compounds used are preferably not therapeutic active agents, that is to say they have an interest from a nutritional or dietary point of view but they do not make it possible to prevent or treat diseases of the subject consuming them. Preferably, the active organic compounds used are edible agents, preferably with organoleptic or nutritional properties. Thus, in this use, the active agents preferably have an interest from a nutritional or dietary point of view but do not make it possible to prevent or treat diseases of the subject consuming them.

[0078] By "food" we mean the habitual or frequent intake of food. Indeed, microcapsules can contain active organic compounds that can improve the properties of a food product, such as its organoleptic properties (for example by the diffusion of aromas such as essential oils) or its shelf life (for example by controlling the diffusion of the organic compound).

[0079] By "nutrition" we mean the taking, often more occasional or as part of a treatment, of a food supplement typically to avoid or compensate for a deficiency. Indeed, the microcapsules according to the invention may contain, for example, vitamins.

[0080] By "animal" is meant a wild or domesticated animal. Preferably the animal is a domesticated, farmed or companion animal. In particular, the animals according to the invention are chosen from companion animals such as dogs, cats, fish, rabbits, horses, turtles, livestock species such as: cattle (cow, ox), sheep (mutton), goats, rabbits, pigs (pig), camels, and birds raised in poultry farming (chicken, quail, etc.).

[0081] The invention also relates to the use of microcapsules according to the invention for the formulation of cosmetics. In this embodiment, the active organic compounds used are preferably not therapeutic active agents, that is to say they have an interest from a cosmetic point of view but they do not make it possible to prevent or treat diseases of the subject using them.

[0082] Thus, for example, the microcapsules according to the invention may comprise conventional adjuvants of cosmetic compositions such as: hydrophilic or lipophilic cosmetic active ingredients, preservatives, antioxidants, perfumes and odor-absorbing agents.

[0083] The invention also relates to the use of microcapsules according to the invention for the formulation of pharmaceutical compositions. In this embodiment, the active agents used are preferably therapeutic active agents, that is to say they make it possible to prevent or treat diseases of the subject consuming them.

[0084] Indeed, the use of microcapsules according to the invention makes it possible to facilitate the storage, packaging or preparation of cosmetic or pharmaceutical formulations while maintaining good quality of the active organic compound.

[0085] Pharmaceutical compositions and therapeutic application

[0086] The invention also relates to a pharmaceutical composition comprising a microcapsule according to the invention. The application also relates to a microcapsule according to the invention for its use as a medicament.

[0087] The present invention also relates to a method of treating a subject, comprising administering a therapeutically effective amount of microcapsules according to the invention to a subject in need thereof.

[0088] In this embodiment, the microcapsule according to the invention advantageously comprises a therapeutic active compound.

[0089] By "therapeutic active agent" is meant an active agent as defined in the microcapsule section above which is furthermore known and / or used for a particular therapeutic purpose, i.e. it is known and / or used in the treatment or prevention of diseases. By "pharmaceutical compositions" is meant compositions having curative or preventive properties with respect to human or animal diseases. In particular, the capsules according to the invention may comprise insect repellent semiochemicals, making it possible to prevent or limit the arrival of parasites on animals or humans.

[0090] The pharmaceutical compositions as defined herein therefore preferably further comprise pharmaceutically acceptable excipients.

[0091] By "pharmaceutically acceptable" is meant herein compositions and molecular entities which do not produce adverse, allergic or otherwise unwanted reactions when administered to a subject.

[0092] By "subject" we mean here a living being, preferably a mammal, and more particularly a human.

[0093] The term "therapeutically effective amount" herein means an amount effective, at doses and for periods of time necessary, to achieve the desired therapeutic result. This amount may vary depending on factors such as the disease, the extent of the disease, the age, sex, and weight of the subject, and the ability of the microcapsules to cause a desired therapeutic result. A therapeutically effective amount encompasses an amount in which any toxic or detrimental effects are outweighed by the therapeutically beneficial effects. A therapeutically effective amount also encompasses an amount sufficient to confer a benefit, for example, a clinical benefit.

[0094] Such pharmaceutical compositions are preferably adapted to the route of administration.

[0095] In a particular embodiment, the pharmaceutical compositions are suitable for oral, sublingual, buccal, intranasal or topical administration.

[0096] The invention also relates to the use of microcapsules according to the invention for the manufacture of a medicament. The invention also relates to the use of microcapsules according to the invention for the formulation of pharmaceutical compositions.

[0097] For these uses, the microcapsule according to the invention advantageously comprises a therapeutic active agent.

[0098] By "treatment" or "treat" is meant herein the achievement, partially or substantially, of one or more of the following results: partially or totally reducing the extent of the disease, improving a clinical symptom or indicator associated with the disease, delaying, inhibiting or preventing the progression of the disease. By "prevention" or "prevent" is meant herein the achievement, partially or substantially, of one or more of the following results: preventing or delaying the onset of the disease or at least one of its symptoms, preventing or delaying the deterioration of an indicator associated with the onset of the disease.

[0099] The invention also relates to the use of microcapsules according to the invention for the decontamination of soil or wastewater.

[0100] The invention also relates to the use of microcapsules according to the invention in cleaning products. By "cleaning products" is meant products for use in the private or professional setting for maintaining, cleaning and / or protecting surfaces.

[0101] The invention thus relates to the use of microcapsules according to the invention in the formulation of maintenance products, such as for example:

[0102] - in pesticides, insecticides or insect repellents that can be used indoors or outdoors,

[0103] - in air fresheners, for example textile deodorizers or room fragrances,

[0104] - in wood care products, for example to limit attack on wood by parasites.

[0105] In the following description and examples, unless otherwise indicated, percentages are percentages by weight and ranges of values ​​expressed as "between ... and ...", "from ... to ...", or "greater than ..." include the limits specified.

[0106] Throughout the application, the wording "comprising a" or "comprising a" means "comprising at least one" or "comprising at least" one unless otherwise specified.

[0107] The following examples are presented for illustrative purposes and are not intended to limit the scope of the invention.

[0108] Figures:

[0109] [Fig. 1] Figure 1: This graph represents the abundance of the main compound of the unencapsulated pheromone after preconcentration by the technique known as Solid Phase Micro-Extraction (SPME), separation of the pheromone compounds by gas chromatography and detection by mass spectrometry (GCMS) in a closed chamber at controlled temperature.

[0110] [Fig. 2] Figure 2: This graph represents the abundance of the main compound of the encapsulated pheromone after preconcentration by the technique called Solid Phase Micro-Extraction (SPME), separation of the pheromone compounds by gas chromatography and detection by mass spectrometry (GCMS) in a closed chamber at controlled temperature.

[0111] [Fig. 3] Figure 3: This graph represents the abundance of the pheromone peak at equilibrium of different capsule prototypes with continuous phases of different nature.

[0112] [Fig. 4] Figure 4: This graph represents the abundance of the pheromone peak at equilibrium over time, when the pheromone is unencapsulated. The ordinate represents the area under the characteristic peak of the pheromone. The abscissa represents the time of measurement in day (d1, d5) or week (W1 to W4).

[0113] [Fig. 5] Figure 5: This graph represents the abundance of the pheromone peak at equilibrium over time, when the pheromone is encapsulated in a microcapsule with a high-viscosity paraffin-based core and with a shell thickness equal to 25 pm. The ordinate represents the area under the characteristic peak of the pheromone. The abscissa represents the time of measurement in day (d1, d5) or week (W1 to W4).

[0114] [Fig. 6] Figure 6: This graph represents the abundance of the pheromone peak at equilibrium over time, when the pheromone is encapsulated in a microcapsule with a low-viscosity paraffin-based core and with a shell thickness equal to 30 pm. The ordinate represents the area under the characteristic peak of the pheromone. The abscissa represents the time of measurement in day (d1, d5) or week (W1 to W4).

[0115] [Fig. 7] Figure 7: This graph represents the abundance of the pheromone peak at equilibrium over time, when the pheromone is encapsulated in a microcapsule with a high-viscosity paraffin-based core and with a shell thickness equal to 100 μm. The ordinate represents the area under the characteristic peak of the pheromone. The abscissa represents the time of taking the measurement in day (d1, d5) or in week (W1 to W4). [Fig. 8] Figure 8: This graph represents the abundance of the pheromone peak at equilibrium over time, when the pheromone is encapsulated in a millimeter-sized microcapsule. The ordinate represents the area under the characteristic peak of the pheromone. The abscissa represents the time of taking the measurement in day (d1, d5) or in week (W1 to W4).

[0116] [Fig. 9] Figure 9: This graph represents the fraction of pheromone remaining after 4 weeks of diffusion (in percentage).

[0117] [Fig. 10] Figure 10: This graph represents the effect of the tested samples on the behavior of the male insect, therefore on its response. The mention "14 DAO" means 14 days after opening, that is to say that the bottle containing the tested capsules was opened and kept for 14 days in the incubator before carrying out the test.

[0118] [Fig. 11] Figure 1 1: This graph represents the fraction of pheromone remaining after 20 weeks of diffusion (in percentage).

[0119] [Fig. 12] Figure 12: This graph represents the fertility decline of couples placed near the samples. The mention "14 DAO" means 14 days after opening, that is to say that the bottle containing the tested capsules was opened and kept for 14 days in the oven before carrying out the test.

[0120] Examples:

[0121] Example 1

[0122] Capsules were formed by co-extrusion of two fluids:

[0123] - the core fluid consisting of paraffin oil in which the pheromone is solubilized at a mass concentration of 1%, and

[0124] - the shell fluid consisting of an alginate solution and a surfactant (SDS at a molar concentration of 8 mM).

[0125] The respective fluid flow rates between the core and shell fluids and the piezoelectric actuation parameters (voltage and frequency) applied to the co-flow were optimized in order to ultimately obtain core-shell type, single-core, calibrated-size and monodisperse capsules, with a homogeneous alginate shell in order to manipulate a homogeneous sample and to be able to characterize, in a reproducible manner, the diffusion phenomenon.

[0126] The study is carried out on the pine processionary moth pheromone, Z-13-hexadecen-1 1 -yn-1 -yl acetate. This compound, like all pheromones, is relatively expensive (€300 / g). A first effort by the inventors consisted of developing a method for injecting small volumes of heart, in the order of mL.

[0127] A segmented injection system has proven satisfactory. The sample containing the pheromone is placed between two small air bubbles separating it from the carrier oil.

[0128] An analytical method was developed to detect the main component of the pheromone. The low quantities of analytes led to the choice of a preconcentration method called Solid Phase Micro-Extraction (SPME) and gas chromatography-mass spectrometry (GCMS).

[0129] The inventors ensured that the pheromone diffused well outside the capsules, but also that the encapsulation made it possible to significantly extend the diffusion time of the pheromone, ranging from less than 10 days to more than 38 days (see figures 1 and 2).

[0130] Example 2: Closed system: study of thermodynamic equilibrium

[0131] In order to establish the diffusion profiles of the samples at short times and to have initial information on possible differences between the capsules, a study was carried out in a closed system.

[0132] The experiment consists of introducing the samples into hermetic 20 mL vials and monitoring the evolution of the quantity extracted by the SPME fiber over time, until equilibrium is reached. The measurements were initially carried out over short periods (one measurement every 45 minutes, this duration corresponding to the analysis time) then, once the maximum concentration is reached, the measurements are carried out at longer time intervals to ensure that equilibrium has been reached (one measurement every 2.5 hours).

[0133] These tests were carried out with the Eudémis pheromone, (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24 O2).

[0134] Formula (I), (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24 O2) a) Effect of encapsulation

[0135] The inventors observed that when the pheromone is encapsulated, equilibrium is reached after about 2 hours, while when it is not, equilibrium is not reached even after 50 hours, which means that the pheromone continues to be released. It would therefore appear that the presence of the alginate membrane has an effect on the thermodynamic equilibrium of the system when the pheromone is confined. b) Effect of core composition

[0136] The amount of pheromone adsorbed on the fiber also varies depending on the composition of the microcapsule core. Indeed, the inventors tested three oils as the core composition of the microcapsule: isopropyl myristate and two paraffin oils of different compositions and different viscosities.

[0137] The inventors observed that the quantities released of pheromones at equilibrium for paraffins are greater than for isopropyl myristate. In particular, the quantity of pheromone released at equilibrium is two to three times greater for paraffins than for isopropyl myristate. This suggests that the pheromone is retained to a greater or lesser extent depending on the nature of the core solution in which it is dispersed.

[0138] The structure of the volatile compound (particularly in terms of chain length and functional group) is closer to that of isopropyl myristate than to that of paraffins. The inventors therefore hypothesized that when the volatile compound has a greater affinity with the continuous phase, its diffusion out of the capsule is slowed. c) Effect of shell thickness

[0139] The inventors also compared capsules with a shell thickness of 25 μm to capsules with a shell thickness of 100 μm. The results obtained seem to indicate that if there is an effect of the variation in shell thickness, it is relatively weak or barely visible under these analysis conditions. Nevertheless, a trend emerges: when the shell thickness increases, diffusion seems to slow down slightly. d) Effect of capsule size

[0140] The inventors compared submillimeter-sized capsules to millimeter-sized capsules. Here, they observed a visible slowdown in diffusion in the case of millimeter-sized capsules. This could be explained by the exchange surface area, which is larger in the case of submillimeter capsules, for a given quantity of pheromone.

[0141] In conclusion of this example, the fact of encapsulating the pheromone is of interest. It appears that encapsulation has an effect on thermodynamics and modifies the diffusion equilibrium. This modification depends on the chemical nature of the shell and therefore on the solubility of the molecule of interest in the latter; this parameter is represented by the partition coefficient K which is recognized for its ability to describe the equilibrium of a molecule between the 2 phases of a biphasic system consisting of two immiscible solvents.

[0142] The K coefficient also depends on the solubility of the molecule of interest in the continuous phase (core solution) and therefore on the affinity between the two. This explains the variations observed between the different continuous phases.

[0143] Regarding the thickness of the shell, this defines the surface on which the gradient is established and gives the flow. In theory, the larger this surface, the longer the release time of the molecule will be.

[0144] Finally, as mentioned previously, the differences obtained between submillimeter and millimeter capsules are explained by the exchange surface which is greater for a sample of submillimeter capsules than for a sample of millimeter capsules, both containing the same quantities of pheromone.

[0145] Example 3: Open system, kinetic study in “real” conditions

[0146] The experiment consists of letting the pheromone diffuse in a ventilated oven at a controlled temperature (17°C) and monitoring the evolution of the quantity of pheromone remaining in the sample over time. After a pre-defined extraction and equilibrium time, the abundance of the extracted pheromone is measured. The extracted quantity is proportional to the mass of pheromone remaining in the capsules. In practice, for each prototype, the wet capsules are placed at the bottom of the hermetic bottles dedicated to SPME analysis of defined volume (20 mL). Before each analysis, the bottles are closed for 3 hours on a Peltier rack at 17°C to ensure that the measurements are carried out once equilibrium is established.

[0147] The broadcast monitoring took place over 20 weeks.

[0148] The capsules in this example are produced in a similar manner to Example 1. This example was carried out for the grapevine leafrollers: Eudémis and Cochylis.

[0149] The major molecules composing the sex pheromones of these two species are (E)-7-(Z)-9-dodecadienyl acetate (C14H24O2, shown above) and (Z)-9-dodecenyl acetate (C 14 H 26 O2).

[0150] Formula (II), (Z)-9-dodecenyl acetate (C 14 H 26 O2)

[0151] Three oils were tested: isopropyl myristate and two paraffin oils of different compositions and different viscosities.

[0152] Finally, the analysis of the diffusion of pheromones through the capsule shell (here the alginate membrane) was carried out by GC / MS, always passing through a step of pre-concentration of the sample using the SPME technique. The inventors were thus able to follow the release kinetics of several capsule samples and that of a non-encapsulated control (the pheromone being simply solubilized in paraffin oil).

[0153] The inventors demonstrated the benefit of formulating pheromones in alginate capsules. Indeed, the results (Figures 4 and 5) indicate that encapsulation slows down the release of the pheromone and therefore increases the duration during which it diffuses outside the capsules: after 4 weeks of diffusion, 88% of the initial quantity of pheromone has been released when it is not encapsulated; compared to only 47% for the encapsulated form (Figure 9).

[0154] After 20 weeks of diffusion, the inventors observed that 99.5% (9.95 mg) of the initial amount of pheromone was released when it was not encapsulated, compared to only 72% for the encapsulated form (Figure 11). The capsules in Figure 4 have an average diameter of 495 pm with a shell thickness of 25 pm (e=25 pm) and an oily paraffin core (here paraffin 1), hereinafter referred to as capsules B. The inventors also, for a given core phase, varied the geometry of the capsule, namely the size of the capsule and the thickness of the alginate membrane.

[0155] By varying these parameters, it is possible to obtain different diffusion profiles (Figures 6, 7 and 8).

[0156] In Figure 6, capsules of 490 pm diameter with a shell thickness of 30 pm and a low viscosity paraffin core are tested (capsules A).

[0157] In Figure 7, 505 pm diameter capsules with a shell thickness of 100 pm and a high viscosity paraffin core are tested.

[0158] In Figure 8, 4 mm diameter capsules with a shell thickness of 310 pm and a high viscosity paraffin core are tested (capsules D).

[0159] The characteristics of the capsules produced and on which the diffusion phenomenon was studied are presented in the following table:

[0160] [Table 1] Table 1:

[0161] By comparing the remaining pheromone fractions after four weeks of diffusion for the prototype capsules studied (Figure 9), the inventors drew two conclusions: the affinity of the pheromones for the continuous phase (oil phase) is the most important thermodynamic factor for controlling their diffusion; the geometry of the capsules (size and thickness of the alginate membrane) seems to have an effect on the release kinetics. By plotting the pheromone release curves over time for each of the samples studied, several observations are made.

[0162] The first is that depending on the samples, the release of the pheromone is more or less linear. For the non-encapsulated pheromone, this release is not linear. The same is true for high viscosity paraffin capsules (membrane thickness of 25 μm). On the contrary, for low viscosity paraffin capsules with a membrane thickness of 25 μm, high viscosity paraffin capsules with a membrane thickness of 100 μm and millimeter capsules, the release of the pheromone is quite linear with coefficients of determination (R 2 ) which are respectively 0.97, 0.95 and 0.94.

[0163] By comparing the slopes of these linear regressions, the inventors found that the slope obtained for the non-encapsulated pheromone is at least 3 times higher than that obtained when the pheromone is encapsulated.

[0164] By comparing the slopes of the lines obtained for high viscosity paraffin capsules with membrane thicknesses of 25 and 100 pm, the inventors observed fairly similar values, which suggests that the thickness of the membrane does not have a significant effect on the diffusion phenomenon.

[0165] Finally, by comparing submillimeter and millimeter capsules for the same given core phase (high viscosity paraffin) and the same core / shell ratio (Rq = 1), the inventors observed that the slope is half as large when the capsule is larger. This is due to the exchange surface which is larger in the case of submillimeter capsules. This trend is also observed when comparing submillimeter capsules with different core phases: the slope is twice as large for capsules with high viscosity paraffin than for capsules with low viscosity paraffin.

[0166] In conclusion, the parameter that mainly influences the diffusion phenomenon is the nature of the core phase and the affinity and solubility that the pheromone presents with the latter; and secondly, the geometric parameters of the capsules.

[0167] Thus, the inventors demonstrated the benefit of formulating pheromones in capsules with a core comprising a lipophilic phase. They were also able to characterize the diffusion process quite precisely and deduce the parameters having a significant influence on it. Example 4: tests carried out on insects

[0168] The capsules in this example are produced in a similar manner to Example 3.

[0169] To test the effect of the capsules on the insects, flight tunnel tests were carried out. The tunnel is an enclosure 150 cm long, 50 cm wide and 32 cm high, including a fan at both ends of the tunnel and in which the incoming air is filtered (carbon filter). The inventors here study the diffusion of the chemical signal by an air flow from its source to the receiver (a male insect, Lobesia botrana). During the tests, the illumination is carried out with red light at an intensity of 80 lux, the temperature is 21 °C, the relative humidity is 80% and the wind speed is set at 0.35 m / s. The male is released 140 cm from the source, on a support at a height of 30 cm. The male's behavior is measured according to a predefined scale for 2 min. The source contains 220 mg of pheromone. A positive control and a commercial product are also tested under the same conditions.The positive control is a commercial control from the company BIOPROX, containing 1 mg of pheromone contained in rubber. The commercial product is a rak (plastic dispenser) that diffuses pheromones.

[0170] The results obtained are presented in Figure 10. The mention “14 DAO” means 14 days after opening, that is to say that the bottle containing the capsules tested was opened and kept for 14 days in the oven before carrying out the test.

[0171] Thanks to this test, the inventors showed that the parameters which have the greatest influence on the observed behavior of the male are the thickness of the shell of the capsule as well as the composition of the core in relation to the aging of the capsules.

[0172] Example 5

[0173] The outdoor effect of the microcapsules was also tested. Microcapsules were placed in an orchard and three cages were placed nearby, each cage containing five pairs of Lobesia botrana. The inventors then measured the females' egg-laying after a night spent in the cage in this environment.

[0174] These tests made it possible to validate the microcapsules according to the invention for their outdoor use (see results in figure 12).

[0175] Thanks to these tests, the inventors have shown that the parameters which have the greatest influence on the reproduction of Lobesia botrana are, in order of importance, the aging of the capsules, the composition of the heart and the thickness of the shell.

Claims

DEMANDS 1. Microcapsule with a core comprising a lipophilic phase surrounded by a gelled shell in which the microcapsule has an average diameter between 50 and 4000 pm when in hydrated form, and in which the core further comprises at least one semiochemical compound.

2. Microcapsule according to claim 1, wherein the core is oily or is an oil-in-water (O / W) emulsion.

3. Microcapsule according to claim 1 or 2, wherein said at least one semiochemical compound is selected from pheromones, allomones, kairomones and synomones.

4. Microcapsule according to any one of claims 1 to 3, wherein said at least one semiochemical compound is volatile.

5. Microcapsule according to any one of claims 1 to 4, wherein the gelled shell has a thickness of at least 10 pm.

6. Microcapsule according to any one of claims 2 to 5, wherein the oily core is composed mainly of an oil selected from paraffins and their mixtures.

7. Microcapsule according to any one of claims 1 to 6, for its use for the diffusion over a period of more than 3 weeks of said at least one semiochemical compound.

8. Use of microcapsule according to any one of claims 1 to 7, for the treatment of plant crops and / or their seeds.

9. Method of treating crops and / or seeds comprising the application of microcapsules according to any one of claims 1 to 7.

10. Use of microcapsules according to any one of claims 1 to 7, for animal and / or human nutrition and / or food.

11. Use of microcapsules according to any one of claims 1 to 7, for the formulation of cosmetics or pharmaceutical compositions.

12. Use of microcapsule according to any one of claims 1 to 7, for the decontamination of soils or wastewater.

13. Use of microcapsule according to any one of claims 1 to 7, in cleaning products.

14. Microcapsule according to any one of claims 1 to 7, for use in animal and / or human nutrition and / or food.

15. Microcapsule according to any one of claims 1 to 7, for use as a medicinal product.

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