Microcapsules for Controlling the Diffusion of Active Organic Compounds

Abstract

The present invention relates to microcapsules having a core consisting of a lipophilic phase surrounded by a gelled shell, wherein the core further contains at least one active organic compound, and to the use of said microcapsules in various application fields such as crop and / or seed treatment, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater pollution removal, detergents, and methods for treating crops and / or seeds.

Description

Technical Field

[0001] The present invention relates to microcapsules having a core composed of a lipophilic phase surrounded by a gelling shell, further containing at least one active organic compound in the core, and uses of the microcapsules in various application fields such as crop and / or seed treatment, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater pollution removal, and detergents.

Background Art

[0002] Semiochemicals are chemicals released by organisms into the environment as signals to other organisms. They may be released by plants or animals as part of interspecies (allelochemical compounds) and intraspecies (pheromones) interactions. Thus, pheromones are found among semiochemical compounds. Pheromones are natural substances secreted by an individual into the external environment, received by another individual of the same species, and causing a specific reaction. In most cases, they constitute olfactory signals that function as messengers within a population.

[0003] Pheromones make it possible to control the population of harmful insects by affecting their reproductive behavior. Currently, most of the pheromone biocontrol products in use are stored in dispensers (manually attached to trees and plants) made of plastic or other polymeric materials so that the pheromone can diffuse through the walls. These dispensers are effective for controlling specific insects, but their use requires a great deal of manual work and needs to be carried out several times per season, which makes the operation cumbersome. In fact, most of the existing systems containing polymer beads do not have a sufficient action time in the field.

[0004] For these compounds to be used as effective biocontrol tools, the pheromone needs to diffuse at a constant concentration over a relatively long period of several months corresponding to the flight period of the pest. However, current methods cannot achieve these periods. Therefore, the difficulty in developing a release control formulation that can release the pheromone at a constant rate over a long period is a factor limiting its use in controlling crop pests. Also, since existing products mainly use devices that immobilize the pheromone, it cannot actually be sprayed.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Therefore, the aim is to enable the controlled diffusion of active organic compounds over several weeks to several months. The acquisition of this ability makes it possible to develop a series of products with various characteristics to address various agricultural problems.

[0006] Furthermore, since pheromones are very expensive, it is preferable to carefully control their use to limit over-application and optimize the effectiveness of the pheromone. Using pheromones in a sprayable form allows for uniform treatment of a large area. The technical solution of the present inventors enables the spraying of pheromones and also enables diffusion at a constant rate over a long period.

Means for Solving the Problems

[0007] Therefore, the present invention proposes encapsulating an active organic compound in a capsule having a core containing a lipophilic phase to achieve these objectives.

[0008] By encapsulating the organic compound, it becomes possible to control diffusion, particularly by adjusting the partition coefficient of the compound between the lipophilic and aqueous phases and the shape of the capsule. This solution makes it possible to extend the diffusion time of, for example, pheromones from less than 10 days to 38 days or more.

[0009] Furthermore, the size of the capsules can be specifically selected to enable the application of the active agent by spraying, for example, spraying in the field. In fact, the size of these capsules is compatible with the use of conventional agricultural machinery.

[0010] Accordingly, the present invention relates to microcapsules having a core consisting of a lipophilic phase surrounded by a gelled shell, the microcapsules having an average diameter of 50 to 4000 μm in the hydrated form, and the core further containing at least one active organic compound.

[0011] The present invention also relates to the use of the microcapsules according to the invention for the treatment of plant crops and / or their seeds, nutrition and / or animal feed, human nutrition and / or food, and the formulation of cosmetics and / or pharmaceuticals. They are used for the preparation of compositions, the removal of soil and wastewater contamination, and the formulation of cleaning products.

[0012] The present invention also relates to a method for treating crops and / or seeds, including the application of the microcapsules according to the invention.

[0013] Detailed Description of the Invention Microcapsules As used herein, the term "microcapsules" means capsules having an average diameter of less than 10 mm and containing at least a core and a shell. Such capsules preferably contain a liquid or solid core encapsulated by a substantially solid gelled envelope. The core is preferably liquid. This type of capsule has been applied in many technical fields. The shell contains one or more compartments, whether concentric or not. Preferably, the microcapsules according to the present invention contain only a single core coated by a shell.

[0014] Therefore, since microbeads are mainly composed of a solid or gelled matrix containing a plurality of small inclusions, these microcapsules are significantly different from microbeads.

[0015] According to a preferred embodiment of the present invention, the microcapsules have a ratio of the core volume to the total volume of the microcapsules exceeding 20%. Thus, these microcapsules can contain a large amount of core, and thus an active organic compound, relative to a given volume of shell.

[0016] Microcapsules are known to those skilled in the art and can be formed by different techniques and can have different shell compositions.

[0017] Typically, the microcapsules used in connection with the present invention are manufactured according to the manufacturing process described in French Patent Invention No. 2939012.

[0018] When the microcapsules according to the present invention are suspended in an aqueous solution, they have an average diameter of 50 to 4000 μm, preferably 50 to 2000 μm, more specifically 50 to 800 μm, and advantageously 100 to 400 μm. This average diameter can be measured by various techniques well known to those skilled in the art, such as particle size distribution based on laser light diffraction, fractionation by sieving, or imaging by optical microscopy. This diameter is particularly suitable for spray coating.

[0019] Preferably, the microcapsules according to the present invention are free, i.e., not included in another structure such as a film, beads, gel, or second encapsulation, but are in direct contact with the surrounding medium, typically a liquid (e.g., in the case of a suspension) or a gas.

[0020] Core The core of the microcapsules according to the present invention is a core containing a lipophilic phase and preferably mainly contains a lipophilic phase.

[0021] Therefore, the core constituting the lipophilic phase of the microcapsules according to the present invention can be an oil core, i.e., a core composed only of oil, or can be in the form of an oil-in-water (O / W) emulsion, for example, an oil-in-water microemulsion. Therefore, in this case, the core of the microcapsules is mainly composed of oil or a mixture of oils, preferably oils of plant, mineral or synthetic origin, or mixtures thereof. "Oil" means a fatty substance that is liquid at room temperature (25°C) and atmospheric pressure.

[0022] The core consisting of the lipophilic phase can also be a core selected from, or consisting of, fats that are solid at normal temperature and pressure, especially waxes, pasty fats and butters, and mixtures thereof.

[0023] In a preferred embodiment, the core is liquid at room temperature or is liquid at a temperature between 15°C and 30°C. In one embodiment of the present invention, the core does not contain wax.

[0024] Therefore, the core of the microcapsules is mainly composed of a lipophilic phase. In particular, the core is mainly composed of fatty compounds of animal, plant, mineral or synthetic origin, or mixtures thereof.

[0025] In a preferred embodiment, the core of the microcapsules according to the present invention is an oil core containing an oil selected from isopropyl myristate, paraffin oil and mixtures thereof. In a preferred embodiment, the core of the microcapsules according to the present invention is an oil core composed of oil, paraffin and mixtures thereof.

[0026] In a preferred embodiment, the core consists of one or more elements selected from fatty acids (saturated fatty acids such as palmitic acid, monounsaturated fatty acids such as linolenic acid), simple lipids (glycerides such as oils and butters, steroids), complex lipids (phospholipids, sphingolipids, lipoproteins), and isoprenoid lipids (steroids, terpenes).

[0027] Preferably, the composition of the core is biodegradable.

[0028] According to a preferred embodiment of the present invention, the viscosity of the core is less than 2000 mPa·s.

[0029] The core of the microcapsule according to the present invention contains at least one active organic compound.

[0030] "Active organic compound" means an active substance, active ingredient or active component that is known and / or used for a specific purpose and one of the constituent chemical elements is carbon.

[0031] Preferably, the at least one active organic compound is a volatile compound.

[0032] "Volatile organic compound" means any organic compound other than methane that has a vapor pressure of 0.01 kPa or more at a temperature of 293.15 K (20 °C) or has a corresponding volatility under specific use conditions (pressure and temperature).

[0033] More preferably, the active organic compound according to the present invention is probably a volatile semiochemical compound.

[0034] "Semiochemical compound" or "semiochemistry" means an active substance, a chemical substance that an organism releases into the environment as a signal to other organisms. Preferably, at least one semiochemical of the microcapsule is selected from pheromones, allomones, kairomones, and synomones. More specifically, the semiochemical of the microcapsule can be of natural or chemical origin, that is, extracted from a living body or chemically synthesized.

[0035] In one embodiment, the at least one semiochemical compound is an oxygenated hydrocarbon having a size of 10 to 20 carbon atoms, which may be unsaturated and may have other functions such as alcohol, acetate and / or aldehyde functional groups.

[0036] In one embodiment, the semiochemical according to the present invention is a sex pheromone. Therefore, preferably, the semiochemical is the sex pheromone of a pest targeted for biocontrol treatment. In one embodiment, the semiochemical is the sex pheromone of Lobesia botrana (Eudemis botrana, family Vitaceae), Eupoecilia ambiguella (commonly known as the codling moth), Cydia pomonella (the codling moth), Grapholita molesta (the oriental fruit moth), Anarsia lineatella (a small moth of the family Gelechiidae), Adoxophyes orana (the leafroller), Tuta absoluta (the tomato leafminer) or Thaumetopoea pityocampa (the pine processionary moth).

[0037] In one embodiment, the semiochemical according to the present invention is a kairomone, for example, a kairomone targeting the cowpea weevil.

[0038] In one embodiment, the semiochemicals are selected from Z-13-hexadecen-11-yn-1-yl acetate, (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24 O2), and (Z)-9-dodecenyl acetate (C 14 H 26 O2).

[0039] In one embodiment, the oily core of the microcapsule has a semiochemical mass concentration between 0.1% and 10%, more preferably between 0.2% and 5%.

[0040] Shell The microcapsule according to the present invention preferably comprises at least one liquid core encapsulated by a substantially solid gelled envelope called a shell.

[0041] Preferably, the shell of the microcapsules according to the present invention is mainly composed of a biopolymer having gelation properties. This biopolymer, which occupies most of the shell, is hereinafter referred to as the main biopolymer. Such biopolymers having gelation properties are, for example, alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.

[0042] The material constituting the shell is preferably biodegradable and of biological origin. The shell is preferably semi-permeable to gases and low molecular weight molecules.

[0043] The gel forming the shell may be chemical or physical, i.e., formed by coacervation or polymerization.

[0044] The gelation of these biopolymers can be carried out by a change in temperature (gellan gum), a change in pH (chitosan, collagen, pectin), or ions (alginate, carrageenan).

[0045] Preferably, the shell of the microcapsules according to the present invention is mainly composed of a biopolymer having gelation properties by an ion change or a temperature change.

[0046] Preferably, the shell of the microcapsules according to the present invention is mainly composed of alginate.

[0047] The shell may also be composed of starch (in various forms, such as pre-gelatinized, amylose), potato protein, or a biopolymer other than the main biopolymer having gelation properties, for example, one or more biopolymers other than the main biopolymers such as alginic acid, gellan gum, xanthan gum, pectin, chitosan, agar, carrageenan, etc.

[0048] Preferably, the shell of the microcapsules according to the present invention consists of 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 present invention comprises a gel containing water, alginate, and optionally a surfactant resulting from its manufacturing process.

[0049] In a preferred embodiment, the shell of the microcapsules according to the present invention does not contain polymers other than alginate.

[0050] Preferably, the alginate is sodium alginate or potassium alginate. Alginate is produced from brown algae called kelp, which is called "seaweed" in English. Such alginate preferably has an α-L-guluronic acid content of more than about 50%, preferably more than 55%, and even more preferably more than 60%.

[0051] The surfactant is preferably an anionic surfactant, a nonionic surfactant, a cationic surfactant or a mixture thereof. The molecular weight of the surfactant is from 150 g / mol to 10,000 g / mol, preferably from 250 g / mol to 1500 g / mol.

[0052] When the surfactant is an anionic surfactant, it is selected from, for example, alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkaline alkyl phosphates, dialkyl sulfosuccinates, alkaline earth salts of saturated or unsaturated fatty acids. These surfactants preferably have at least one hydrophobic hydrocarbon chain having 5 or more, and more preferably more than 10 carbon atoms, and at least one hydrophilic anionic group such as sulfate, sulfonate or carboxylate bonded to one end of the hydrophobic chain. When the surfactant is a cationic surfactant, it is selected from, for example, alkylpyridinium or alkylammonium halide salts such as n-ethyldodecylammonium chloride or n-ethyldodecylammonium bromide, cetylammonium chloride or bromide (CTAB). These surfactants preferably have at least one hydrophobic hydrocarbon chain having 5 or more, and more preferably more than 10 carbon atoms, and at least one hydrophilic cationic group such as a quaternary ammonium cation. When the surfactant is a nonionic surfactant, it is selected from, for example, aliphatic alcohols, fatty acids, or polyoxyethylenated and / or polyoxypropylenated derivatives of alkylphenols, arylphenols, or from alkyl glucosides, polysorbates, cocamides.

[0053] In one embodiment, the surfactant is sodium lauryl sulfate (LSS), also called sodium dodecyl sulfate, and / or polyoxyethylene sorbitan monolaurate (polysorbate 80).

[0054] Preferably, the surfactant is polyoxyethylene sorbitan monooleate (polysorbate 80).

[0055] In one embodiment, the mass content of the surfactant in the shell is greater than 0.001%, preferably greater than 0.1%. Preferably, the mass concentration of the surfactant is about 0.3%.

[0056] The shell of the microcapsules according to the invention is further a stabilizer, a densifying particle, or an agent that limits sedimentation such as silica or talc.

[0057] The thickness of the shell is a factor that affects the robustness of the microcapsules and the diffusion rate of the active organic compound. Therefore, the thickness of the shell can be selected so as to obtain a desired diffusion rate. Preferably, the thickness of the shell is at least 10 μm, preferably between 20 μm and 500 μm, more preferably between 20 μm and 150 μm.

[0058] The shell of the microcapsules preferably has a thickness of 0.1% to 20% of the diameter of the capsule, advantageously 1% to 20%, more particularly 10% to 20%.

[0059] The diffusion of the active organic compound also depends on the partition coefficient between the lipophilic core of the microcapsules and the aqueous phase of the shell.

[0060] Preferably, the microcapsules according to the invention are suitable for diffusing the active organic compound over a period of at least 3 weeks, more preferably at least 6 weeks, most preferably at least 2 months. Thus, the invention relates to the use, preferably non-therapeutic, of the microcapsules according to the invention for diffusing the active organic compound over a period of at least 3 weeks, more preferably at least 6 weeks, most preferably at least 2 months.

[0061] Preferably, the microcapsules according to the invention are adapted to diffuse the active organic compound over a period corresponding to the flight period of the target pest.

[0062] When the active organic compound of the microcapsules is a semiochemical, in particular the sex pheromone of a given flying pest, the microcapsules are adapted to diffuse the pheromone over the flight period of the pest.

[0063] "Suitable for the diffusion of an active organic compound over a period of time" means that during said period, the active organic compound continues to diffuse from the microcapsules at a substantially constant non-zero rate.

[0064] The microcapsules may further contain other components such as, for example, antioxidants, UV filters, pigments, dyes, stabilizers, densified particles such as silica or talc, essential oils or other additives.

[0065] Uses and methods The definitions defined in the section on microcapsules apply equally here.

[0066] Preferably, in the methods and uses according to the invention, the microcapsules are used as such, i.e., the microcapsules are not contained in another structure (such as a film, beads, gel or second encapsulation), but are used directly, although in some cases they are used suspended in a liquid.

[0067] The present invention relates to the use of the microcapsules according to the invention for treating plant crops and / or their seeds.

[0068] "Treatment of plant crops and / or their seeds" means a treatment that can be carried out before, during or after cultivation, and here in particular means a treatment that can be carried out for the purpose of preventing and / or limiting attacks by pests or reducing the effects of pests. It also means treatments carried out in green spaces such as gardens and parks. The present invention relates in particular to the use of the microcapsules according to the invention as insecticides.

[0069] Accordingly, the present invention relates in particular to the use of microcapsules for treating plant crops and / or their seeds, wherein the active organic compound is a biocontrol agent.

[0070] The present invention includes a method for treating crops and / or seeds, including the application of the microcapsules according to the invention.

[0071] As used herein, the term "crop" or "plant culture" means plant production derived from a certain land use. In one embodiment, the plant crop is selected from wheat, corn, rapeseed, grapevine, and beet.

[0072] The present invention particularly relates to a method for treating crops and / or seeds, including spraying, foliar spraying, or coating seeds with the microcapsules according to the present invention, preferably the microcapsules according to the present invention in which the active organic compound is a biocontrol agent. In this method, the microcapsules can be used by suspending them in a liquid.

[0073] As used herein, the term "pest" mainly means pests such as insects, spiders, and small mammals, and more preferably insects. More specifically, the pests are Lobesia botrana (Eudemis of grapevine), Eupoecilia ambiguella (commonly called Cochylis), Cydia pomonella (apple codling moth), Grapholita molesta (Oriental fruit moth), Anarsia lineatella (small peach fruit moth), all absolute (tomato leaf miner), Thaumetopoea pityocampa (pine processionary), Bruchus rufimanus (broad bean weevil), or aphids, midges, moths, sesame moths, large and small scale insects, terminal bud weevils, Cryptoblabes, leafhoppers, etc.

[0074] As used herein, the term "insecticide" means a formulation intended to control insects, rodents, or weeds.

[0075] In another embodiment, the present invention relates to the use, preferably non-therapeutic, of the microcapsules according to the invention for animal and / or human nutrition and / or food. In this embodiment, the active organic compounds used are preferably not therapeutic active agents, i.e., they are interesting from a nutritional or dietary point of view but do not prevent or treat the diseases of the subjects who ingest them. Preferably, the active organic compounds used are edible agents and preferably have functional or nutritional properties. Thus, in this application, the active agents are preferably interesting from a nutritional or dietary point of view but cannot prevent or treat the diseases of the subjects who ingest them.

[0076] "Diet" means habitual or frequent food intake. The microcapsules can contain active organic compounds that improve the properties of food, such as organic properties (e.g., by diffusing scents like essential oils) or preservability (e.g., by controlling the diffusion of organic compounds).

[0077] "Nutrition" usually means ingesting dietary supplements more frequently or during treatment to avoid or compensate for deficiencies. In fact, the microcapsules according to the present invention can contain, for example, vitamins.

[0078] "Animal" means wild animals or domestic animals. Preferably, the animals are domestic animals, breeding animals, or pets. In particular, the animals according to the present invention are selected from pet animals such as dogs, cats, fish, rabbits, horses, turtles, etc., and domestic animal species such as cows (cattle, cows), sheep (sheep), goats, rabbits, pigs (hogs), camels, and birds (chickens, quails, etc.) raised in poultry farming.

[0079] The present invention also relates to the use of the 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, they are interesting from a cosmetic point of view but cannot be used to prevent or treat the diseases of the subjects.

[0080] Thus, for example, the microcapsules according to the present invention may contain conventional adjuvants for cosmetic compositions such as hydrophilic or lipophilic cosmetic active ingredients, preservatives, antioxidants, fragrances and odor absorbers.

[0081] The present invention also relates to the use of the microcapsules according to the present invention for the formulation of pharmaceutical compositions. In this embodiment, the active agents used are preferably therapeutic active agents, i.e., they enable the prevention or treatment of the diseases of the subject taking them.

[0082] In fact, the use of the microcapsules according to the present invention makes it possible to facilitate the storage, packaging, or preparation of cosmetic or pharmaceutical formulations while maintaining the good quality of the active organic compounds.

[0083] Pharmaceutical compositions and therapeutic applications The present invention also relates to pharmaceutical compositions comprising the microcapsules according to the present invention. This application also relates to the microcapsules according to the present invention for use as a medicament.

[0084] The present invention also relates to a method of treating a subject comprising administering to the subject in need of treatment a therapeutically effective amount of the microcapsules according to the present invention.

[0085] In this embodiment, the microcapsules according to the present invention advantageously contain a therapeutic active compound.

[0086] "Therapeutic active agent" means an active agent as defined in the section on the microcapsules above and which is further known and / or used for a specific therapeutic purpose, i.e., an active agent known and / or used for the treatment or prevention of diseases.

[0087] "Pharmaceutical composition" means a composition having therapeutic or prophylactic properties against diseases in humans or animals. In particular, the capsules according to the invention can contain insect repellent semiochemicals, which makes it possible to prevent or limit the access of parasites to animals or humans.

[0088] Thus, the pharmaceutical composition as defined herein preferably also contains pharmaceutically acceptable excipients.

[0089] Here, "pharmaceutically acceptable" means compositions and molecular entities that do not cause side reactions, allergic reactions, or other undesirable reactions when administered to a subject.

[0090] Here, "subject" means an organism, preferably a mammal, more specifically a human.

[0091] "Therapeutically effective amount" means, in this specification, the effective amount in the dosage and period required to obtain the desired therapeutic result. This amount can vary depending on factors such as the disease, the degree of the disease, the age, sex and weight of the subject, and the ability of the microcapsules to produce the desired therapeutic result. A therapeutically effective amount includes any amount where the toxic or harmful effects are less important than the therapeutically beneficial effects. A therapeutically effective amount also includes an amount sufficient to confer a benefit, such as a clinical benefit.

[0092] Such pharmaceutical compositions are preferably compatible with the route of administration.

[0093] In certain embodiments, the pharmaceutical composition is suitable for oral, sublingual, buccal, intranasal or topical administration.

[0094] The invention also relates to the use of the microcapsules according to the invention for the manufacture of a medicament. The invention also relates to the use of the microcapsules according to the invention for the formulation of a pharmaceutical composition.

[0095] For these uses, the microcapsules according to the invention advantageously contain a therapeutic agent.

[0096] As used herein, "treatment" or "treating" means partially or substantially achieving one or more of the following results: partially or completely reducing the degree of a disease, improving clinical symptoms or indicators associated with the disease, delaying the disease, or suppressing or preventing the progression of the illness.

[0097] "Prevention" or "preventing" as used herein means partially or substantially achieving one or more of the following results: preventing or delaying the onset of a disease or at least one of its symptoms, and preventing or delaying the worsening of an indicator associated with the onset of the disease.

[0098] The present invention also relates to the use of the microcapsules according to the invention for the removal of soil or wastewater contamination.

[0099] The present invention also relates to the use of the microcapsules according to the invention in cleaning products. "Maintenance products" means products for use in private or professional environments for maintaining, cleaning, and / or protecting surfaces.

[0100] Accordingly, the present invention relates to the use of the microcapsules according to the invention in formulations of cleaning products such as, for example, the following. - Insecticides, pesticides, or repellents that can be used indoors or outdoors, - Deodorants such as fiber deodorants and interior perfumes, - Wood care products that, for example, limit attack of wood by parasites.

[0101] In this specification and the following examples, unless otherwise specified, % is by weight, and ranges of values expressed as "between... and...", "from... to...", or "greater than..." include the specified limits.

[0102] Throughout this application, the expression "comprising" or "comprises" means "including at least one" or "including at least one" unless otherwise specified.

[0103] The following examples are presented for illustrative purposes and are not intended to limit the field of the present invention.

Brief Description of the Drawings

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DETAILED DESCRIPTION OF THE INVENTION

[0105] Example: Example 1 The capsules were formed by co - extrusion of the following two fluids. - A core fluid consisting of paraffin oil in which the pheromone was solubilized at a mass concentration of 1%, and - A core fluid consisting of an alginate solution and a surfactant (SDS at a molar concentration of 8 mM).

[0106] The respective flow rates of the fluids between the core fluid and the shell fluid, and the parameters of the piezoelectric actuation (voltage and frequency) applied to co - forming were optimized to obtain single - core, monodisperse core - shell capsules of calibrated size with a homogeneous alginate shell so as to be able to handle homogeneous samples and characterize the diffusion phenomenon in a reproducible manner.

[0107] This study was conducted on (Z)-13 - hexadecen - 11 - en - 1 - yl acetate, which is the pheromone of the pine processionary moth. This compound, like other pheromones, is relatively expensive (300 euros / g). The first effort by the inventors was to develop a method for injecting a small amount of core, about 1 mL.

[0108] The segmented injection system has proven to be satisfactory. The sample containing the pheromone is placed between two small bubbles separated from the carrier oil.

[0109] An analytical method for detecting the main compound of the pheromone was developed. Due to the small amount of the specimen, solid - phase microextraction (SPME), a preconcentration method, and gas chromatography - mass spectrometry (GCMS) combined with mass spectrometry were selected.

[0110] The inventors confirmed that the pheromone diffused sufficiently outside the capsules, but it was also possible to significantly extend the diffusion period of the pheromone from less than 10 days to more than 38 days by encapsulation (see Figures 1 and 2).

[0111] Example 2: Closed System: Study of Thermodynamic Equilibrium The study was carried out in a closed system to establish the diffusion profile of the sample over a short period of time and obtain initial information regarding possible differences between the capsules.

[0112] The experiment consisted of introducing the sample into an airtight 20 mL vial and tracking the change over time in the amount extracted by the SPME fiber until equilibrium was reached. Measurements were first made over a short period of time (one measurement every 45 minutes, this period corresponding to the analysis time), then, once the maximum concentration had been reached, the measurements were made at longer time intervals, when the balance had been achieved (one measurement every 2.5 hours).

[0113] These tests were carried out using the Eudemis pheromone, (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24 O2). [Chemical formula] Formula (I), (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24 O2)

[0114] a) Effect of encapsulation The inventors observed that when the pheromone was encapsulated, equilibrium was reached after approximately 2 hours, whereas when it was not encapsulated, equilibrium was not reached even after 50 hours and the pheromone continued to be released. Thus, the presence of the alginate film is thought to affect the thermodynamic balance of the system when the pheromone is trapped.

[0115] b) Influence of the core composition Also, the amount of pheromone adsorbed onto the fiber varies depending on the composition of the core of the microcapsules. In fact, the inventors tested three oils as the core composition of the microcapsules, namely isopropyl myristate and two paraffin oils with different compositions and different viscosities.

[0116] The inventors observed that the amount of pheromone released at equilibrium is higher for paraffin than for isopropyl myristate. In particular, the amount of pheromone released at equilibrium is two to three times higher for paraffin than for isopropyl myristate. This suggests that the pheromone is retained more or less depending on the nature of the core solution in which it is dispersed.

[0117] The structure of this volatile compound (especially in terms of chain length and functional groups) is closer to that of isopropyl myristate than to that of paraffin. Therefore, the inventors hypothesized that when the volatile compound enhances its affinity with the continuous phase, the diffusion from the capsule slows down.

[0118] c) Influence of the shell thickness The inventors also compared capsules with a shell thickness of 25 μm and capsules with a shell thickness of 100 μm. The results obtained seem to indicate that the influence of the variation in shell thickness is relatively weak or hardly visible under these analysis conditions. Nevertheless, there is a tendency for the diffusion to become slightly slower as the shell thickness increases.

[0119] d) Influence of the capsule size The inventors compared submillimeter-sized capsules with millimeter-sized capsules. Here, they observed a visible deceleration of diffusion in the case of millimeter capsules. This can be explained by the fact that for a constant amount of pheromone, the exchange surface area is larger in the case of submillimeter capsules.

[0120] As a conclusion of this example, the fact of encapsulating the pheromone is interesting. Encapsulation seems to affect thermodynamics and change the diffusion equilibrium. This modification depends on the chemical nature of the shell and thus on the solubility of the target molecule in the shell. This parameter is represented by the partition coefficient K and is recognized as the ability to describe the equilibrium of molecules between two phases of a two-phase system composed of two immiscible solvents.

[0121] The coefficient K also depends on the solubility of the molecule of interest in the continuous phase (core solution) and thus also on the affinity between the two. This explains the variations observed between different continuous phases.

[0122] Regarding the shell thickness, a gradient is established, which defines the surface giving rise to the flow. Theoretically, the larger this surface area, the longer the molecule release time.

[0123] Finally, as mentioned above, the difference obtained between sub - millicapsules and millicapsules is explained by the larger exchange surface area of the sub - millicapsule samples compared to samples of millicapsules containing the same amount of pheromone.

[0124] Example 3: Kinetic study under "real" conditions in an open system This experiment consists of diffusing the pheromone in a ventilated oven at a controlled temperature (17 °C) and monitoring the change in the amount of pheromone remaining in the sample over time. After a predefined extraction and equilibration time, the amount of extracted pheromone is measured. The amount extracted is proportional to the mass of pheromone remaining in the capsule. In practice, for each prototype, a moist capsule is placed at the bottom of a hermetic bottle dedicated to SPME analysis with a defined volume (20 mL). Before each analysis, the vial is sealed on a Peltier effect rack at 17 °C for 3 hours to ensure that equilibrium is established before the measurement is made.

[0125] Diffusion monitoring was carried out over 20 weeks.

[0126] The capsules of this example are manufactured in the same way as in Example 1. This example was carried out on grape berry moths, Eudemis and Cochylis.

[0127] The main molecules constituting these two sex pheromones are (E)-7-(Z)-9 - dodecadienyl acetate (C 14 H 24O2, shown above) and (Z)-9-dodecenyl acetate (C 14 H 26 O2).

Chemical formula

[0128] Three oils, isopropyl myristate and two paraffin oils with different compositions and viscosities, were tested.

[0129] Finally, the analysis of the diffusion of the pheromone through the capsule shell (here an alginate film) was always carried out via a step of pre-concentration of the sample using SPME technology and then by GC / MS. Thus, the inventors were able to follow the release kinetics of several capsule samples and those of an unencapsulated control (where the pheromone is simply solubilized in paraffin oil).

[0130] The inventors demonstrated the advantages of formulating pheromones in alginate capsules. Indeed, the results (Figures 4 and 5) show that encapsulation can slow down the release of the pheromone, thus increasing the period during which the pheromone diffuses from the capsule. After four weeks of diffusion, 88% of the initial pheromone had decreased. This is the amount of pheromone released when the pheromone is not encapsulated. In contrast, it was only 47% in the encapsulated form (Figure 9).

[0131] After 20 weeks of diffusion, the inventors observed that 72% was released in the encapsulated form, compared to 99.5% (9.95 mg) of the initial amount of pheromone released when not encapsulated (Figure 11). The capsule of Figure 4 has an average diameter of 495 μm, a shell thickness of 25 μm (e = 25 μm) and an oily paraffin core (paraffin 1 here), and is hereinafter referred to as capsule B. The inventors also vary the shape of the capsule, i.e., the size of the capsule and the thickness of the alginate membrane, for a given core phase.

[0132] By changing these parameters, different diffusion profiles can be obtained (Figures 6, 7, 8).

[0133] In Figure 6, capsules with a diameter of 490 μm, a shell thickness of 30 μm and a low-viscosity paraffin core are being tested (capsule A).

[0134] In Figure 7, capsules with a diameter of 505 μm, a shell thickness of 100 μm and a high-viscosity paraffin core are being tested.

[0135] In Figure 8, capsules with a diameter of 4 mm, a shell thickness of 310 μm and a high-viscosity paraffin core are being tested (capsule D).

[0136] The properties of the capsules manufactured and studied for the diffusion phenomenon are shown in the following table.

[0137]

Table 1

[0138] By comparing the pheromone fractions remaining after 4 weeks of diffusion of the capsule prototypes studied (Figure 9), the inventors drew two conclusions. - The affinity of the pheromone for the continuous phase (oil phase) is the most important thermodynamic factor for controlling the diffusion of the pheromone. - The shape of the capsule (size and thickness of the alginate film) seems to affect the kinetics of release.

[0139] By tracking the release curves of the pheromones of each sample studied over time, several observations are made.

[0140] The first is that, depending on the sample, the release of the pheromone occurs almost linearly. In the case of non-encapsulated pheromones, this release is not linear. The same is true for high-viscosity paraffin capsules (film thickness 25 μm). Conversely, for low-viscosity paraffin capsules with a film thickness of 25 μm, high-viscosity paraffin capsules with a film thickness of 100 μm, and millimeter capsules, the release of the pheromone has a coefficient of determination (R 2 ), 0.97, 0.95, and 0.94 respectively.

[0141] By comparing the slopes of these linear regressions, the inventors found that the slope obtained for non-encapsulated pheromones is at least three times greater than the slope obtained when the pheromone is encapsulated.

[0142] By comparing the slopes of the lines obtained for high-viscosity paraffin capsules with film thicknesses of 25 μm and 100 μm, the inventors observed fairly close values suggesting that the film thickness does not have a significant impact on the diffusion phenomenon.

[0143] Finally, by comparing submillimeter capsules and millimeter capsules for the same given core phase (high-viscosity paraffin) and the same core / shell ratio (Rq = 1), the inventors observed that when the size of the capsule is large, the slope is halved. This is because in the case of submillimeter capsules, the exchange surface area is large. This trend is also observed when comparing submillimeter capsules with different core phases. The slope of the capsules containing high-viscosity paraffin is twice as large as that of the capsules containing low-viscosity paraffin.

[0144] As a conclusion, the parameters that mainly affect the diffusion phenomenon are the properties of the core phase, the affinity and solubility of the pheromone with respect to the core phase. Next are the geometric parameters of the capsule.

[0145] Therefore, the inventors have shown the advantages of incorporating pheromones into capsules having a core containing a lipophilic phase. They were also able to very accurately characterize the diffusion process and estimate the parameters that have a significant impact on the diffusion process.

[0146] Example 4: Tests Conducted on Insects The capsules of this example are manufactured in the same manner as in Example 3.

[0147] To test the effect of the capsules on insects, a flight tunnel test was conducted. The tunnel is a housing with a length of 150 cm, a width of 50 cm, and a height of 32 cm, and there are fans at both ends of the tunnel, and the incoming air is filtered therein (carbon filter). The inventors are studying the diffusion of chemical signals by the flow of air from the source to the receiver (male insect Lobesia botrana). During the test, the illumination was carried out with red light of 80 lux intensity, the temperature was set at 21 °C, the relative humidity was 80%, and the wind speed was 0.35 m / s. The male is released on a post 30 cm high and 140 cm away from the source. The behavior of the male is measured for 2 minutes according to a pre-defined scale. The source contains 220 mg of pheromone. The positive control and the commercial product are also tested under the same conditions. The positive control is a commercial control from BIOPROX containing 1 mg of pheromone in rubber. The commercial product is a rack (plastic dispenser) pheromone diffuser.

[0148] The results obtained are shown in Figure 10. The description "14DAO" means 14 days after opening. That is, it means that the bottle containing the tested capsules was opened and stored in an oven for 14 days before the test was carried out.

[0149] From this test, the inventors showed that the parameters that most affected the observed behavior of the males were the thickness of the capsule shell and the composition of the core related to the aging of the capsule.

[0150] Example 5 The outdoor effect of the microcapsules was also tested. Microcapsules were placed in an orchard, and three cages were placed nearby, each containing five pairs of Lobesia botrana. Next, the inventors measured the egg-laying of the females after they had spent one night in the cages in this environment.

[0151] These tests made it possible to verify the outdoor use of the microcapsules according to the present invention (see the results in Figure 12).

[0152] From these tests, the inventors clarified that the parameters that most affected the reproduction of Lobesia botrana were, in order of importance, the aging of the capsule, the composition of the core, and the thickness of the shell.

Claims

1. A microcapsule having a core containing a lipophilic phase surrounded by a gelled shell, wherein the average diameter of the microcapsule in the hydrated form is 50 to 4000 μm, and the core further contains at least one semiochemical compound.

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

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

4. The microcapsule according to any one of claims 1 to 3, wherein the at least one semiochemical compound is volatile.

5. The microcapsule according to any one of claims 1 to 4, wherein the thickness of the gelled shell is at least 10 μm.

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

7. The microcapsule according to any one of claims 1 to 6, which is used for diffusing the at least one semiochemical compound over a period exceeding three weeks.

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

9. A method for treating crops and / or seeds, which includes applying the microcapsule according to any one of claims 1 to 7.

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

11. Use of the microcapsule according to any one of claims 1 to 7 for formulating cosmetic or pharmaceutical compositions.

12. Use of the microcapsule according to any one of claims 1 to 7 for removing soil or wastewater pollution.

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

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

15. The microcapsule according to any one of claims 1 to 7 for use as a medicine.

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