Microcapsules capable of controlling diffusion of active organic compounds

Abstract

The present invention relates to a microcapsule, the core of which comprises a lipophilic phase and is wrapped by a gel shell, the core further comprising at least one active organic compound, and furthermore, the gel shell comprises at least one active organic compound. The invention also relates to the use of said microcapsules in various fields of application (e.g. Crop and / or seed treatment, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater purification, maintenance products) and to a crop and / or seed treatment method.

Description

[0001] The invention relates to microcapsules whose core comprises a lipophilic phase and is surrounded by a gel shell, wherein the core also comprises at least one active organic compound, and furthermore to the use of said microcapsules in various fields of application, such as crop and / or seed treatment, human and / or animal nutrition, cosmetics and pharmaceuticals, soil and wastewater purification, care products.

[0002] Semiochemicals are chemical substances released by organisms into the environment as signals between them and other organisms. They can be released by plants or animals within the scope of interspecific (xenochemicals) and intraspecific (pheromones) interactions. Pheromones are among the semiochemicals. Pheromones are natural substances that are secreted by one individual into the external environment and received by other individuals of the same species, causing the latter to produce a specific reaction. They usually constitute olfactory signals and act as messengers within a population.

[0003] Pheromones can be used, in particular, to control pest populations by influencing their reproductive behavior. Currently, most pheromone-based biocontrol products are stored in dispensers made of plastic or other polymer materials that are manually fixed to trees or plants, allowing the pheromones to diffuse through their inner walls. Although these dispensers are effective in controlling certain insects, their application is labor-intensive, must be performed multiple times per season, and is a tedious process. In fact, most existing systems, including polymer pellets, do not work long enough in the field.

[0004] In order for these compounds to be used as effective biological control tools, pheromones must diffuse at a constant concentration over a relatively long period of time, lasting for several months, covering the entire flight period of the pest. However, current methods cannot meet this requirement. Therefore, the difficulty in developing controlled-release formulations that can release pheromones at a constant rate for a long time is a factor that limits their use in crop pest control. In addition, since existing products mainly fix pheromones in one location, spraying of pheromones cannot be achieved.

[0005] In summary, the goal is to allow for the controlled diffusion of active organic compounds over a period of weeks to months. Once this is solved, a range of products can be developed with a variety of properties to address a variety of agronomic challenges.

[0006] Furthermore, since pheromones are expensive, it is best to use them with fine control to limit overconsumption and optimize their effectiveness. Spraying pheromones allows for uniform treatment of large areas. The inventors' solution, in addition to spraying pheromones, also ensures that they diffuse at a constant rate over a long period of time.

[0007] The present invention therefore proposes encapsulating the active organic compound in a capsule, the core of which comprises a lipophilic phase, in order to meet these objectives.

[0008] Encapsulating organic compounds allows the diffusion of compounds to be controlled by taking advantage of the partition coefficient of the compound between the lipophilic and aqueous phases and the geometry of the capsule. For example, this solution can extend the diffusion duration of pheromones from less than 10 days to more than 38 days.

[0009] Furthermore, the size of the capsules can be selected on a case-by-case basis to apply the active agent by spraying, for example for field spraying. In fact, the size of these capsules is suitable for use with common agricultural equipment.

[0010] The present invention therefore relates to a microcapsule whose core comprises a lipophilic phase and is surrounded by a gel shell, wherein the average diameter of the microcapsules when in hydrated form is between 50 and 4000 μm and wherein the core further comprises at least one active organic compound.

[0011] The invention also relates to the use of the microcapsules according to the invention for treating plant crops and / or their seeds, for animal nutrition and / or feed, for human nutrition and / or food, for formulating cosmetic and / or pharmaceutical compositions, for purifying soil and wastewater and for formulating care products.

[0012] The present invention also relates to a method for treating crops and / or seeds, which can be applied to the microcapsules of the present invention.

[0013] Detailed description of the invention

[0014] Microcapsules

[0015] The term "microcapsule" herein refers to a capsule having an average diameter of less than 10 mm and comprising at least a core and a shell. Preferably, such capsules have a liquid or solid core, which is encapsulated by a nearly solid gel wrap. Preferably, the core is liquid. Such capsules are used in many technical fields. The shell comprises one or more concentric or non-concentric compartments. Preferably, the microcapsule according to the present invention comprises only one core wrapped by a shell.

[0016] Therefore, these microcapsules are very different from microspheres, as microspheres are primarily composed of a solid or gel matrix containing multiple small inclusions.

[0017] According to a preferred embodiment of the present invention, the ratio of the core volume of the microcapsule to the total volume of the microcapsule is greater than 20%. Therefore, for a given volume of the shell, these microcapsules can accommodate a large volume of the core and the active organic compound.

[0018] Microcapsules are well known to those skilled in the art and can be made by different techniques and with shells having different compositions.

[0019] Typically, the microcapsules used in the present invention are produced according to the manufacturing method described in French Patent No. 2939012.

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

[0021] Preferably, the microcapsules of the invention are free, that is, they are not contained in other structures such as membranes, pellets, gels or secondary encapsulations, but are in direct contact with the surrounding medium, typically a liquid (for example if they are in suspension) or a gas.

[0022] core

[0023] The core of the microcapsule of the present invention comprises a lipophilic phase, preferably, mainly comprises a lipophilic phase.

[0024] Thus, for the microcapsules according to the invention, the core comprising a lipophilic phase may be an oily core, that is to say it consists exclusively of oil, or may be in the form of an oil-in-water (O / W) emulsion, such as an oil-in-water microemulsion. In this case, the core of the microcapsules consists essentially of oil or an oil mixture, preferably of vegetable, mineral or synthetic origin or a mixture thereof. "Oil" refers to a fatty substance that is liquid at ambient temperature (25° C.) and atmospheric pressure.

[0025] The core comprising a lipophilic phase may also be a core containing or consisting of a solid fatty substance (at ambient temperature and pressure), in particular chosen from waxes, pasty fatty substances and butters; and mixtures thereof.

[0026] In a preferred embodiment, the core is liquid at ambient temperature, or is liquid at a temperature between 15°C and 30°C.

[0027] In one embodiment of the invention, the core contains no wax.

[0028] The core of the microcapsule is therefore composed predominantly of a lipophilic phase. In particular, the core consists predominantly of fatty compounds of animal, vegetable, mineral or synthetic origin or mixtures thereof.

[0029] In a preferred embodiment, the core of the microcapsule of the present invention is an oily core comprising an oil selected from isopropyl myristate, paraffin oil and a mixture thereof. In a preferred embodiment, the core of the microcapsule of the present invention is an oily core mainly composed of oil, paraffin and a mixture thereof.

[0030] In a preferred embodiment, the core comprises one or more of the following components: fatty acids (saturated fatty acids, such as palmitic acid, and mono / polyunsaturated fatty acids, such as linolenic acid), simple lipids (glycerides, such as oils and butters, and steroids), complex lipids (phospholipids, sphingolipids and lipoproteins) and prenylated lipids (steroids and terpenes).

[0031] Preferably, the composition of the core is biodegradable.

[0032] According to a preferred embodiment of the present invention, the viscosity of the core is less than 2000 mPa.s.

[0033] The core of the microcapsule of the present invention comprises at least one active organic compound.

[0034] "Active organic compound" refers to an active substance, active molecule or active ingredient known and / or used for a specific purpose, one of the chemical constituent elements of which is carbon.

[0035] Preferably, said at least one reactive organic compound is a volatile compound.

[0036] The term "volatile organic compound" refers to any organic compound having a vapor pressure greater than or equal to 0.01 kPa at 293.15 K (20° C.) or a corresponding volatility under specific conditions of use (pressure and temperature), except methane.

[0037] More preferably, the active organic compound of the present invention is a semiochemical, which may be volatile.

[0038] "Semiochemical" or "semiochemical" is an active substance, a chemical substance released by an organism into the environment as a signal between organisms and other organisms. Preferably, at least one semiochemical in the microcapsule is selected from pheromones, egotropins, kairomones and mutualists. More specifically, the semiochemical of the microcapsule can be of natural or chemical origin, i.e. extracted from organisms or chemically synthesized.

[0039] In one embodiment, the at least one semiochemical is an oxygenated hydrocarbon, which is between 10 and 20 carbons in size, may be unsaturated and have other functional groups, such as an alcohol, acetate and / or aldehyde functional group.

[0040] In one embodiment, the semiochemical of the present invention is a sex pheromone. Therefore, preferably, the semiochemical is a sex pheromone of pests, which is used in the field of biological control. In one embodiment, the semiochemical is a sex pheromone of Lobesia botrana (grape flower moth), Eupoecilia ambiguella (commonly known as ring needle moth), Cydia pomonella (codling moth), Grapholita molesta (pear borer), Anarsia lineata (peach moth), Tuta absoluta (tomato leaf miner) or Thaumetopoea pityocampa (pine moth).

[0041] In one embodiment, the semiochemical of the present invention is a kairomone, such as a kairomone from Vicia faba.

[0042] In one embodiment, the semiochemical is selected from Z-13-hexadecene-11-yn-1-yl acetate, (E)-7-(Z)-9-dodecadienyl acetate (C14H24O2) and (Z)-9-dodecenyl acetate (C14H26O2).

[0043] In one embodiment, the mass concentration of the semiochemical substance in the oily core of the microcapsule is between 0.1% and 10%, more preferably, between 0.2% and 5%.

[0044] shell

[0045] Preferably, the microcapsule of the present invention comprises at least one liquid core, which is encapsulated by a nearly solid gel wrapper (called a "shell").

[0046] Preferably, the shell of the microcapsule of the present invention is mainly composed of a biopolymer with gelling properties, which accounts for a large proportion of the shell and is hereinafter referred to as the "main biopolymer". For example, the biopolymer with gelling properties can be alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.

[0047] Preferably, the material constituting the shell is biodegradable and bio-based. Preferably, the shell is semi-permeable to low molecular weight gases and molecules.

[0048] The gel forming the shell may be formed by chemical or physical processes, ie by coacervation or polymerization.

[0049] The gelation of these biopolymers can be achieved by temperature changes (gellan gum), pH changes (chitosan, collagen, pectin), or ionic changes (alginate, carrageenan).

[0050] Preferably, the shell of the microcapsule of the present invention is mainly composed of a biopolymer that obtains gel properties through ion or temperature changes.

[0051] Preferably, the shell of the microcapsule of the present invention is mainly composed of alginate.

[0052] The shell may also include one or more biopolymers in addition to the primary biopolymer, such as starch (in various forms, such as pregelatinized starch or amylose), potato protein, or another biopolymer having gelling properties in addition to the primary biopolymer, such as alginate, gellan gum, xanthan gum, pectin, chitosan, agar, or carrageenan.

[0053] Preferably, the shell of the microcapsule of the present invention comprises a gel containing water, one or more biopolymers with gelling properties, and a surfactant that may be produced by its production method. Preferably, the shell of the microcapsule of the present invention comprises a gel containing water and alginate, and a surfactant that may be produced by its production method.

[0054] In a preferred embodiment, the shell of the microcapsule of the present invention does not contain any polymer other than alginate.

[0055] Preferably, the alginate is sodium alginate or potassium alginate. Alginate is produced by brown algae, the latter being known as Laminaria japonica, the English term "sea weed". The α-L-guluronic acid content of such alginates is advantageously greater than about 50%, preferably greater than 55% or even greater than 60%.

[0056] Advantageously, the surfactant is an anionic surfactant, a nonionic surfactant, a cationic surfactant or a mixture thereof.The molecular weight of the surfactant is between 150 g / mol and 10,000 g / mol, advantageously between 250 g / mol and 1500 g / mol.

[0057] In the case where the surfactant is an anionic surfactant, for example, it is selected from alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl phosphates, dialkyl sulfosuccinates, alkaline earth salts of saturated or unsaturated fatty acids. Advantageously, these surfactants have at least one hydrophobic hydrocarbon chain with a carbon number greater than 5 or even 10 and at least one anionic hydrophilic group, such as sulfate, sulfonate or carboxylate connected to one end of the hydrophobic chain. In the case where the surfactant is a cationic surfactant, for example, it is selected from alkyl pyridine or alkyl ammonium halide salts, such as n-ethyl dodecyl ammonium chloride or ammonium bromide or hexadecyl ammonium chloride and ammonium bromide (CTAB). Advantageously, these surfactants have at least one hydrophobic hydrocarbon chain with a carbon number greater than 5 or even 10 and at least one cationic hydrophilic group, such as quaternary ammonium cations. In the case where the surfactant is a nonionic surfactant, for example, it is selected from polyoxyethylene and / or polyoxypropylene derivatives of fatty alcohols, fatty acids or alkylphenols, arylphenols, or selected from alkyl glucoside, polysorbate and coconut amide.

[0058] In one embodiment, the surfactant is sodium lauryl sulfate (SLS, also known as sodium cocoyl sulfate) and / or polyoxyethylene sorbitan monoester (polysorbate 80).

[0059] Preferably, the surfactant is polyoxyethylene sorbitan monoester (polysorbate 80).

[0060] In one embodiment, the mass content of the surfactant in the shell is greater than 0.001%, advantageously greater than 0.1%. Advantageously, the mass concentration of the surfactant is about 0.3%.

[0061] The shell of the microcapsules according to the invention may also contain stabilizers, dense particles or agents which limit precipitation, such as silicon dioxide or talc.

[0062] The thickness of the shell is a factor that affects the firmness of the microcapsules and the diffusion movement of the active organic compound. Therefore, the thickness of the shell can be selected to obtain the desired diffusion movement. 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.

[0063] The shell thickness of the microcapsules is preferably between 0.1% and 20%, advantageously between 1% and 20%, more particularly between 10% and 20%, of the capsule diameter.

[0064] The diffusion of the active organic compound also depends on the partition coefficient between the lipophilic core of the microcapsule and the aqueous phase of the shell.

[0065] Preferably, the active organic compound diffusion duration of the microcapsules of the present invention is more than 3 weeks, more preferably more than 6 weeks, and preferably more than 2 months. Therefore, preferably, the present invention relates to non-therapeutic uses of the microcapsules of the present invention, and the active organic compound diffusion duration is more than 3 weeks, more preferably more than 6 weeks, and preferably more than 2 months.

[0066] Preferably, the active organic compound applicable to the microcapsules of the present invention has a diffusion duration corresponding to the entire flight period of the target pest.

[0067] Thus, if the microcapsules contain an active organic compound as a semiochemical, more specifically a sex pheromone of a given flying insect pest, the microcapsules are suitable for diffusing said pheromone throughout the flight period of said pest.

[0068] The term "suitable active organic compound diffusion duration" means that the active organic compound continues to diffuse to the outside of the microcapsules at a substantially constant non-zero rate during the said time.

[0069] The microcapsules may also contain other components, such as antioxidant compounds, UV screeners, pigments, colorants, stabilizers, dense particles (such as silica or talc), essential oils or other additives.

[0070] Uses and methods

[0071] The definitions in the section on microcapsules also apply here.

[0072] Preferably, in the methods and uses according to the invention, the microcapsules are used as such, that is, they are not contained in another structure (such as a film, pellet, gel or secondary encapsulation), but are used directly, possibly suspended in a liquid.

[0073] The present invention relates to the use of the microcapsules according to the invention for treating plant crops and / or their seeds.

[0074] "Treatment of plant crops and / or their seeds" refers to a treatment which can be carried out before, during or after planting, where, more particularly, the aim is to prevent and / or limit attacks by pests or to reduce their impact. It also refers to a treatment which can be carried out in green areas such as gardens or parks. In particular, the present invention relates to the use of the microcapsules according to the present invention as insecticides.

[0075] The present invention therefore relates in particular to the use of microcapsules for treating plant crops and / or their seeds, wherein the active organic compound is a biological control agent.

[0076] The present invention includes a method for treating crops and / or seeds, which may be applied to the microcapsules of the present invention.

[0077] Herein, "crop" or "plant crop" refers to plant products obtained by cultivating land. In one embodiment, the plant crop is selected from wheat, corn, rapeseed, grapevine and sugar beet.

[0078] Specifically, the present invention relates to a method for treating crops and / or seeds, comprising broadcasting, foliar spraying or seed coating with the microcapsules of the present invention, preferably, in the microcapsules of the present invention, the active organic compound is a biological control agent. In this method, the microcapsules can be suspended in a liquid for use.

[0079] The term "pest" herein refers primarily to animal pests, such as insects, arachnids or small mammals, more preferably, to insects.

[0080] More specifically, the pest is selected from Lobesia botrana (Grape Flower-winged Leaf-roller), Eupoeciliaambiguella (commonly known as Grape and Apple Leaf-roller), Cydia pomonella (Cydling Moth), Grapholitamolesta (Pear Borer), Anarsia lineata (Peach Moth), Tuta absoluta (Tomato Leaf-miner), Thaumetopoea pityocampa (Pine Leaf-miner), Bruchus rufimanus (Bean Weevil), or aphids, gall midges, borers, corn borers, yellow and rape flea beetles, rape stem weevils, hidden borers or grape leafhoppers.

[0081] As used herein, "insecticide" refers to a preparation used to eliminate insects, rodents or weeds.

[0082] In another embodiment, the present invention relates to the use of the microcapsules of the present invention for nutrition and / or food for animals and / or humans, preferably for non-therapeutic uses. In this embodiment, preferably, the active organic compounds used are not therapeutically active agents, i.e., they have nutritional or food value, but cannot prevent or treat diseases in the consumer. Preferably, the active organic compounds used are edible agents, preferably edible agents with organoleptic or nutritional properties. Therefore, in this use, active agents with nutritional or food value, but cannot prevent or treat diseases in the consumer are preferred.

[0083] "Food" refers to food that is habitually or frequently ingested. In fact, the microcapsules can contain active organic compounds, thereby improving the properties of the food, such as its organoleptic properties (e.g. by diffusing fragrance, such as essential oils) or its shelf life (e.g. by controlling the diffusion of organic compounds).

[0084] "Nutrition" refers to the intake of dietary supplements during treatment or more often on a regular basis in order to avoid or compensate for the lack of essential nutrients. In fact, the microcapsules according to the invention may contain vitamins, for example.

[0085] "Animal" refers to wild or domesticated animals. Preferably, the animal is a domesticated, farmed animal or a pet. Specifically, the animal involved in the present invention is selected from pets, such as dogs, cats, fish, rabbits, horses, turtles, and farmed species, such as cattle (cows, bulls), sheep (sheep), goats, rabbits, pigs (boars), camels and birds raised in poultry farming (chickens, quails, etc.).

[0086] The invention also relates to the use of the microcapsules according to the invention for formulating cosmetics. In this embodiment, preferably, the active organic compounds used are not therapeutically active agents, ie they have cosmetic value but cannot prevent or treat diseases of the user.

[0087] Thus, for example, the microcapsules according to the invention may contain customary additives for cosmetic compositions, such as hydrophilic or lipophilic cosmetic active agents, preservatives, antioxidants, fragrances and odor absorbers.

[0088] The present invention also relates to the use of the microcapsules of the present invention in the formulation of pharmaceutical compositions. In this embodiment, the active agents used are preferably therapeutically active agents, ie they can prevent or treat diseases in the consumer.

[0089] In fact, the use of the microcapsules according to the invention makes it possible to facilitate the storage, packaging or preparation of cosmetic or pharmaceutical preparations while maintaining the good quality of the active organic compounds.

[0090] Pharmaceutical synthesis and therapeutic applications

[0091] The present invention also relates to a pharmaceutical composition comprising the microcapsules of the present invention. The present application also relates to using the microcapsules of the present invention as a drug.

[0092] The present invention also relates to a method for treating a subject, comprising administering a therapeutically effective amount of the microcapsules of the present invention to a subject in need thereof.

[0093] In this embodiment, advantageously, the microcapsules of the present invention contain a therapeutically active compound.

[0094] "Therapeutically active agent" refers to an active agent as defined above in the microcapsule section, which is known and / or used for a specific therapeutic purpose, ie, known and / or used to treat or prevent a disease.

[0095] The term "pharmaceutical composition" refers to a composition having therapeutic or preventive properties for human or animal diseases. Specifically, the capsule of the present invention may contain insect repellent semiochemical substances for preventing or limiting the entry of parasites into the body of an animal or human.

[0096] Therefore, preferably, the pharmaceutical composition herein also includes a pharmaceutically acceptable excipient.

[0097] "Pharmaceutically acceptable" herein means that these compounds and molecular entities do not cause side effects, allergies or other adverse reactions when administered to a subject.

[0098] The term "subject" herein refers to an organism, preferably a mammal, more specifically a human being.

[0099] The term "therapeutically effective amount" herein refers to an effective amount in the desired time period and dosage to achieve the desired therapeutic effect. The therapeutically effective amount may vary depending on factors such as the disease, the scope of the disease, the age, sex and weight of the subject, and the ability of the microcapsules to produce the desired therapeutic effect. The therapeutically effective amount includes an amount in which any toxic or harmful effects are offset by the beneficial therapeutic effects. The therapeutically effective amount also includes an amount sufficient to provide a benefit, such as a clinical benefit.

[0100] Preferably, the pharmaceutical composition is suitable for the route of administration.

[0101] In one embodiment, the pharmaceutical composition is suitable for oral, sublingual, buccal, intranasal or topical administration.

[0102] The present invention also relates to the use of the microcapsules of the present invention in the manufacture of drugs. The present invention also relates to the use of the microcapsules of the present invention in the preparation of pharmaceutical compositions.

[0103] For these uses, the microcapsules of the invention advantageously contain a therapeutically active agent.

[0104] "Treatment" here means partially or substantially achieving one or more of the following results: partially or completely reducing the scope of the disease, improving clinical symptoms or indicators related to the disease, delaying, inhibiting or preventing the progression of the disease.

[0105] "Prevention" herein refers to partially or substantially achieving one or more of the following results: preventing or delaying the onset of a disease or at least one symptom, and preventing or delaying the deterioration of indicators related to the onset of the disease.

[0106] The present invention also relates to using the microcapsule of the present invention for purifying soil or wastewater.

[0107] The invention also relates to the use of the microcapsules according to the invention in care products. "Care products" are products intended for maintaining, cleaning and / or protecting surfaces in a private or professional environment.

[0108] Therefore, the present invention relates to formulating the microcapsules of the present invention into skin care products, such as:

[0109] - prepare insecticides, insecticides or repellents for indoor or outdoor use,

[0110] - preparation of deodorizing agents, such as textile deodorizers or room perfumes,

[0111] - Formulate wood care products, e.g. to limit pest attack on wood.

[0112] In the specification and the following examples, unless otherwise indicated, percentages are percentages by weight, and numerical ranges are expressed in the format of "between ... and ...", "... to ..." or "greater than ..." (limits indicated).

[0113] Throughout the application, unless otherwise specified, "comprising a" or "including a" means "comprising at least one" or "including at least one".

[0114] The following examples present the field of the invention in an illustrative and non-limiting manner.

[0115] picture:

[0116] [ Figure 1 ] Figure 1 : This figure represents the abundance of major compounds of unencapsulated pheromones after pre-concentration by solid phase microextraction (SPME) technique, separation of pheromone compounds by gas chromatography and detection by mass spectrometry (GCMS) in a closed housing at controlled temperature.

[0117] [ Figure 2 ] Figure 2 : This figure represents the abundance of major compounds of encapsulated pheromones after pre-concentration by solid phase microextraction (SPME) technique, separation of pheromone compounds by gas chromatography and detection by mass spectrometry (GCMS) in a closed chamber at controlled temperature.

[0118] [ Figure 3 ] Figure 3 : This figure shows the abundance of pheromone peaks at equilibrium for different capsule prototypes with continuous phases of different properties.

[0119] [ Figure 4 ] Figure 4 : This graph shows the abundance of the pheromone peak at equilibrium over time when the pheromone is not encapsulated. The ordinate represents the area under the characteristic peak of the pheromone. The x-axis represents the time measured in days (D1, D5) or weeks (W1 to W4).

[0120] [ Figure 5 ] Figure 5: This figure shows the abundance variation of pheromone peaks over time at equilibrium when pheromones are encapsulated in microcapsules with a core based on high viscosity paraffin wax and a shell thickness equal to 25 μm. The ordinate represents the area under the characteristic peak of the pheromone. The x-axis represents the time measured in days (D1, D5) or weeks (W1 to W4).

[0121] [ Figure 6 ] Figure 6 : This figure shows the abundance variation of pheromone peaks over time at equilibrium when pheromones are encapsulated in microcapsules with a core based on low viscosity paraffin wax and a shell thickness equal to 30 μm. The ordinate represents the area under the characteristic peak of the pheromone. The x-axis represents the time measured in days (D1, D5) or weeks (W1 to W4).

[0122] [ Figure 7 ] Figure 7 : This figure shows the abundance variation of pheromone peaks over time at equilibrium when pheromones are encapsulated in microcapsules with a core based on high viscosity paraffin wax and a shell thickness equal to 100 μm. The ordinate represents the area under the characteristic peak of the pheromone. The x-axis represents the time measured in days (D1, D5) or weeks (W1 to W4).

[0123] [ Figure 8 ] Figure 8 : This graph shows the abundance change of pheromone peaks over time at equilibrium when pheromones are encapsulated in millimeter-sized microcapsules. The ordinate represents the area under the characteristic peak of the pheromone. The x-axis represents the time measured in days (D1, D5) or weeks (W1 to W4).

[0124] [ Fig. 9 ] Fig. 9 : This graph shows the pheromone fraction (percentage) remaining after 4 weeks of diffusion.

[0125] [ Fig.10 ] Fig.10 : This graph shows the effect of the test sample on the behavior of male insects and thus on their response. The so-called "14DAO" means 14 days after opening, that is, the bottle containing the test capsules was opened and kept in the oven for 14 days before the test was carried out.

[0126] [ Fig.11 ] Fig.11 : This graph shows the pheromone fraction (percentage) remaining after 20 weeks of diffusion.

[0127] [ Fig.12 ] Fig.12 :This graph shows the reduction in fertility of male and female insects placed near the sample. The so-called "14DAO" refers to 14 days after opening, that is, the bottle containing the test capsules was opened and kept in the oven for 14 days before the test. Example:

[0128] Embodiment 1:

[0129] The capsules are formed by coextrusion of two fluids:

[0130] - the fluid of the core consists of paraffin oil in which the pheromone is dissolved at a concentration of 1% by mass, and

[0131] The fluid of the shell consisted of alginate solution and a surfactant (SDS, molar concentration 8 mM).

[0132] The flow rates of the respective fluids between the core and the shell, as well as the piezoelectric drive parameters (voltage and frequency) applied to the co-flow, have been optimized in order to finally obtain standardized core-shell capsules with a homogeneous alginate shell, of calibrated size and monodispersity, with a single core, allowing the manipulation of homogeneous samples and the characterization of diffusion phenomena in a reproducible way.

[0133] The study used the pheromone of the pine caterpillar, Z-13-hexadecene-11-yn-1-yl acetate. Like all pheromones, this compound is relatively expensive (300 euros per gram). The inventors' initial goal was to develop an injection method for small core volumes in the milliliter range.

[0134] The segmented injection system has been shown to meet the requirements. The sample containing the pheromone is placed between two small air bubbles, separating it from the carrier oil.

[0135] An analytical method has been developed for the detection of the main compounds of pheromones. Due to the small number of analytes, a pre-concentration method called solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GCMS) was chosen.

[0136] The inventors ensured that the pheromone diffused out of the capsule, and the encapsulation allowed the diffusion duration of the pheromone to be significantly extended, from less than 10 days to more than 38 days (see Figure 1 and Figure 2 ).

[0137] Embodiment 2: Closed Systems: Thermodynamic Equilibrium Studies

[0138] In order to develop diffusion profiles of the samples in a short time and to obtain preliminary information on possible differences between capsules, a study was performed in a closed system.

[0139] The test involves placing the sample in a 20 mL sealed bottle and measuring the amount of SPME fiber extraction over time until equilibrium is reached. Measurements are first made at short intervals (every 45 minutes, this duration corresponds to the analysis time) and then, after the maximum concentration is reached, at longer intervals to ensure equilibrium is reached (every 2 hours and 30 minutes).

[0140] The pheromone of the grape moth was tested, namely (E)-7-(Z)-9-dodecadienyl acetate (C 14 H 24 O2).

[0141]

[0142] a) Effect of Encapsulation

[0143] The inventors observed that when the pheromone was encapsulated, equilibrium was reached after about 2 hours, while when it was not encapsulated, equilibrium was not reached after 50 hours, which means that the pheromone continued to be released. Therefore, the presence of the alginate film seems to have an effect on the thermodynamic equilibrium of the system when the pheromone is confined.

[0144] b) Influence of core composition

[0145] The amount of pheromone adsorbed on the fibers also varied depending on the composition of the microcapsule core. In fact, the inventors tested three oils as core components of the microcapsules: isopropyl myristate and two paraffin oils of different composition and viscosity.

[0146] The inventors observed that paraffin wax released a greater amount of pheromone than isopropyl myristate at equilibrium. Specifically, paraffin wax released 2 to 3 times more pheromone than isopropyl myristate at equilibrium. This suggests that pheromones are more or less retained, depending on the nature of the core solution containing the pheromone.

[0147] The structure of the volatile compounds is closer to that of isopropyl myristate than paraffin wax, especially in terms of chain length and functional groups. Therefore, the inventors hypothesized that when the volatile compounds have a greater affinity for the continuous phase, their diffusion from the capsules will be slowed down.

[0148] c) Effect of shell thickness

[0149] 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 small or not very significant under these analytical conditions. However, a trend is shown: diffusion seems to slow down slightly when the thickness of the shell increases.

[0150] d) Effect of capsule size

[0151] The inventors compared submillimeter-sized capsules with millimeter-sized capsules. Here, they observed a visible slowdown of diffusion for the millimeter-sized capsules. This could be explained by the exchange surface, which is larger for a given amount of pheromone in the case of submillimeter-sized capsules.

[0152] In conclusion to this example, the fact that the pheromone is encapsulated is advantageous. Encapsulation appears to have an effect on the thermodynamics and to modify the diffusion equilibrium. This modification depends on the chemical properties of the shell, namely the solubility of the target molecule in the shell; this parameter is represented by the partition coefficient K and is used to describe the molecular equilibrium between the two phases of a two-phase system consisting of two immiscible solvents.

[0153] The coefficient K also depends on the solubility of the target molecule in the continuous phase (core solution), that is, the affinity between the two. This explains the observed variations between different continuous phases.

[0154] Regarding the thickness of the shell, it determines the surface over which the gradient is established and gives the flux. In theory, the larger this area, the longer the molecules will be released.

[0155] Finally, as mentioned above, the differences obtained between submillimeter and millimeter capsules can be explained by the fact that the exchange surface of the submillimeter capsule samples is larger than that of the millimeter capsule samples, both containing the same amount of pheromone.

[0156] Example 3: Open system, kinetic study under "real" conditions

[0157] This test allows pheromones to diffuse in a ventilated oven at a controlled temperature (17°C) and detects changes in the amount of pheromones remaining in the sample over time. After the pre-set extraction and equilibrium time is reached, the abundance of the extracted pheromone is measured. The amount extracted is proportional to the mass of pheromones remaining in the capsule. In practice, for each prototype, a wet capsule is placed at the bottom of a sealed bottle of a specified volume (20 mL) for SPME analysis. Before each analysis, the sealed bottle is sealed on a Peltier temperature-controlled stand at 17°C for 3 hours to ensure that the measurement is performed after equilibrium is established.

[0158] Continue to monitor for spread through 20 weeks.

[0159] The production method of the capsules used in this example is similar to that of Example 1.

[0160] This embodiment is directed to grape leaf rollers: grape leaf rollers and grape and apple leaf rollers.

[0161] The main molecules that make up these two sex pheromones are (E)-7-(Z)-9-dodecadienyl acetate (C14H24O2, shown above) and (Z)-9-dodecenyl acetate (C14H26O2).

[0162]

[0163] Three oils were tested: isopropyl myristate and two paraffin oils of different composition and viscosity.

[0164] Finally, the diffusion of pheromones through the capsule shell (here, the alginate membrane) was analyzed by GC / MS, still after pre-concentration of the samples using the SPME technique. Thus, the inventors were able to monitor the release movement of multiple capsule samples and non-encapsulated controls (pheromones simply dissolved in paraffin oil).

[0165] The inventors have demonstrated that formulating pheromones in alginate capsules is advantageous. In fact, the results ( Figure 4 and 5 ) showed that encapsulation slowed down the release of pheromones, thereby increasing the duration of their diffusion from the capsules: after 4 weeks of diffusion, 88% of the initial amount of pheromone was released in the unencapsulated form, compared to only 47% in the encapsulated form ( Fig. 9 ).

[0166] After 20 weeks of diffusion, the inventors observed that 99.5% (9.95 mg) of the initial amount of pheromone was released in the unencapsulated form, while only 72% ( Fig.11 ). Figure 4 In the embodiment, the average diameter of the capsule is 495 μm, the shell thickness is 25 μm (e=25 μm), and the core is paraffin oil (here paraffin 1), hereinafter referred to as capsule B. For a given core phase, the inventors also changed the geometry of the capsule, i.e., the size of the capsule and the thickness of the alginate membrane.

[0167] By changing these parameters, different diffusion data can be obtained ( Figure 6 , 7 and 8).

[0168] exist Figure 6 In the experiment, capsules with a diameter of 490 μm, a shell thickness of 30 μm and a low viscosity paraffin core were tested (capsule A).

[0169] exist Figure 7 In the present study, capsules with a diameter of 505 μm, a shell thickness of 100 μm and a high viscosity paraffin core were tested.

[0170] exist Figure 8 In the experiment, capsules with a diameter of 4 mm, a shell thickness of 310 μm and a high viscosity paraffin core were tested (capsule D).

[0171] The table below lists the characteristics of the produced capsules for which the diffusion phenomena were studied:

[0172] [Table 1] Table 1:

[0173]

[0174]

[0175] By comparing the pheromone fraction remaining after four weeks of diffusion of the capsule prototype studied ( Fig. 9 ), the inventors came to two conclusions:

[0176] -The affinity of pheromones for the continuous phase (oil phase) is the most important thermodynamic factor controlling their diffusion;

[0177] - The geometry of the capsule (size and thickness of the alginate membrane) appears to have an influence on the release motion.

[0178] In order to plot the pheromone release profile over time for each studied sample, multiple observations were performed.

[0179] First, the release of pheromones was more or less linear, depending on the sample. For the unencapsulated pheromone, this release was not linear. This was also true for the high-viscosity paraffin capsules (film thickness of 25 μm). On the contrary, for the low-viscosity paraffin capsules with a film thickness of 25 μm, the high-viscosity paraffin capsules with a film thickness of 100 μm, and the millimeter-sized capsules, the pheromone release was quite linear, with coefficients of determination (R2) of 0.97, 0.95, and 0.94, respectively.

[0180] By comparing the slopes of these linear regressions, the inventors found that for unencapsulated pheromones and encapsulated pheromones, the slope obtained for the former is at least three times that of the latter.

[0181] By comparing the slopes of the lines obtained for high viscosity paraffin capsules with a film thickness of 25 μm and 100 μm, the inventors observed fairly close values, indicating that the thickness of the film has no significant effect on the diffusion phenomena.

[0182] Finally, by comparing submillimeter and millimeter-sized capsules of 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 size is larger. This is due to the larger exchange surface in the case of submillimeter-sized capsules. This trend can also be observed when comparing submillimeter-sized capsules with different core phases: the slope of high viscosity paraffin capsules is twice that of low viscosity paraffin capsules.

[0183] In summary, the parameters that mainly affect the diffusion phenomenon are the properties of the core phase and the affinity and solubility of pheromones to the core phase; secondly, the geometric parameters of the capsule.

[0184] The inventors have thus shown that it is advantageous to formulate pheromones in capsules having a core comprising a lipophilic phase. They have also been able to characterize the diffusion process quite accurately and to deduce the parameters that have a significant influence on it.

[0185] Example 4: Tests on insects

[0186] The production method of the capsules used in this example is similar to that of Example 3.

[0187] To test the effect of the capsules on insects, a flight tunnel test was performed. The tunnel is a shell 150 cm long, 50 cm wide and 32 cm high, with a fan at each end of the tunnel to filter the air entering the tunnel (carbon filter). Here, the inventors studied the diffusion of chemical signals from their diffusion source to the receptor (male insect, grape flower moth) through the air flow. During the test, red light with an intensity of 80 lux was used for illumination, the temperature was 21°C, the relative humidity was 80%, and the wind speed was set to 0.35 m / s. Male insects were released on a stand 140 cm away from the diffusion source and 30 cm high. The behavior of male insects was measured for 2 minutes within a pre-set range. The diffusion source contained 220 mg of pheromone. Positive controls and commercial products were also tested under the same conditions. The positive control was a commercial control from Bioprox, i.e., containing 1 mg of pheromone in rubber. The commercial product is the RAK (Plastic Dispenser) pheromone diffuser.

[0188] The results obtained are as follows Fig.10 The so-called "14DAO" means 14 days after opening, that is, the bottle containing the test capsules has been opened and stored in the oven for 14 days before the test.

[0189] Through this testing, the inventors have shown that the parameters that have the greatest impact on male insect behavior are capsule shell thickness, core composition and capsule ageing.

[0190] Embodiment 5:

[0191] The effect of the microcapsules was also tested outdoors. The microcapsules were placed in an orchard, and three cages were placed near the orchard, each containing five pairs of grape flower-winged moths. Then, in this environment, the inventors measured the egg-laying of female insects after one night in the cages.

[0192] These tests can verify the outdoor use effect of the microcapsules of the present invention (see Fig.12 results).

[0193] Through these tests, the inventors have shown that the parameters that have the greatest impact on the reproduction of the grapevine moth are capsule age, core composition and shell thickness, in order of importance.

Claims

1. A microcapsule having a core and a shell, wherein the core comprises a lipophilic phase and is surrounded by a gel shell, and when the microcapsules are in hydrated form, the average diameter of the microcapsules is between 50 and 4000 μm, and wherein, The core also comprises at least one active organic compound.

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

3. The microcapsule according to claim 1 or 2, characterized in that The at least one semiochemical is selected from pheromones, egotropins, kairomones and mutualists.

4. The microcapsule according to any one of claims 1 to 3, characterized in that The at least one semiochemical is volatile.

5. The microcapsule according to any one of claims 1 to 4, characterized in that The thickness of the gel shell is at least 10 μm.

6. The microcapsule according to any one of claims 2 to 5, characterized in that The oily core is mainly composed of oil, paraffin and their mixtures.

7. The microcapsule according to any one of claims 1 to 6, characterized in that The diffusion duration of the at least one semiochemical is greater than 3 weeks.

8. Use of the microcapsules 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 their seeds comprising applying a microcapsule suspension according to any one of claims 1 to 7.

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

11. Use of the microcapsules 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 purifying soil or wastewater.

13. Use of the microcapsules according to any one of claims 1 to 7 in care products.

14. Microcapsules 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 medicament.

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