Process for the preparation of biodegradable polyurea microparticles suspension and polyurea microparticles suspension so obtained

Abstract

The present invention relates to a process for the preparation of polyurea microparticles suspension encapsulating hydrophobic active ingredients in polyurea eco-friendly microsystems. The present invention relates also to polyurea microparticles suspension obtainable by the process of the invention and their use for delivering said active ingredient in agriculture.

Description

[0001] P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0002] PROCESS FOR THE PREPARATION OF BIODEGRADABLE POLYUREA MICROPARTICLES SUSPENSION AND POLYUREA MICROPARTICLES SUSPENSION SO OBTAINED

[0003] ***** ***** *****

[0004] FIELD OF THE INVENTION

[0005] The present invention relates to a process for the preparation of a suspension of polyurea microparticles encapsulating hydrophobic active ingredients in polyurea eco-friendly microsystems.

[0006] The present invention relates also to polyurea microparticles suspension obtainable by the process of the invention and their use for delivering said active ingredient in agriculture.

[0007] STATE OF THE ART

[0008] Microplastics is a general term indicating solid polymeric particles less than 5 mm in length according to the European Chemicals Agency (ECHA). Once in the environment, not biodegradable microplastics are accumulated in marine, freshwater, and terrestrial ecosystems which lead to a big impact on the wildlife as well as on the whole food chain.

[0009] Many species mistake microplastics for food, leading to ingestion and potential health problems such as starvation, suffocation, and entanglement as reported by different researchers in the last decades. Furthermore, in an environment dominated by particulate material, microplastics can alter soil chemistry and affect soil organisms’ fitness and function.

[0010] In the literature it is shown that microplastics are frequently detected also in human samples since people are potentially exposed to microplastics through oral intake, inhalation, and skin contact as common ways. The effects connected with their introduction in human body mainly consist of oxidative stress, DNA damage, organ dysfunction, metabolic disorder, immune response, neurotoxicity, as well as reproductive and developmental toxicity. In addition, epidemiological evidence suggests that a variety of chronic diseases may be related to microplastics exposure.P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0011] In light of the above, in 2023, the European Commission adopted a REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) restriction on microplastics intentionally added to products and a proposal for a Regulation on preventing plastic pellet losses to the environment.

[0012] The Ell aims to reduce microplastic releases by 30% by 2030. This will be achieved by

[0013] - reducing plastic pollution (as these degrade into microplastics),

[0014] - restricting the use of intentionally added microplastics to products, and

[0015] - reducing unintentional microplastic releases

[0016] The regulation defines synthetic polymer microplastic as: “polymers that are solid and which either are contained in particles and constitute at least 1 % by weight of those particles, or build a continuous surface coating on particles, where at least 1 % by weight of those particles fulfill either of the following conditions:

[0017] (a) All dimensions of the particles are equal to or less than 5 mm.

[0018] (b) The length of the particles is equal to or less than 15 mm and their length to diameter ratio is greater than 3.”

[0019] However, some exceptions are included, such as:

[0020] • degradable or water-soluble (>2 g / l) polymers and natural polymers that have not been chemically modified,

[0021] • biodegradable polymers, and

[0022] • polymers with no carbon atoms within their own structure.

[0023] Crop protection compounds, including herbicides, insecticides, fungicides, and plant nutrients are often encapsulated either in polymeric matrices or within a core-shell system in their formulation form to achieve one or more purposes listed below:

[0024] • obtaining an active ingredient-controlled release for optimum effectiveness, • retarding the losses of volatile components,

[0025] • protecting the active ingredient against light and oxidation,

[0026] • protecting either employers or final users from harmful or unpleasant materials,

[0027] • preventing premature chemical reactions with other mixture components,P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0028] and

[0029] • reducing actives side effects such as crop toxicity and drifting.

[0030] Nowadays, synthetic polymers such as polyacrylates, polyamides, polyureas or polyurethanes represent the most common materials for encapsulating pesticides. Unfortunately, such materials lack of the required REACH characteristics described above, and the development of new environmentally friendly products is needed. Nevertheless, polyurea materials are still widely used in agrochemical industry since such polymer class possess unique attributes which make them ideal for entrapping specific active ingredients. These attributes include a wide range of physical and mechanical properties, chemical functionality, and diversity in specific polymer characteristics.

[0031] Looking at the prior knowledge, no methods have been described to obtain polyurea microparticles from relatively harmless starting materials and having an adequate biodegradation profile.

[0032] WO 2021 / 260017 illustrates a process to produce microcapsules from NCO terminated polyester-polyol polyisocyanate prepolymer containing at least 2 isocyanate groups and a polyamine as reagent materials. However, polyesters are known to undergo hydrolysis after some time in the environment. In fact, the biodegradability of the examples shown in the document described that the maximum value reached for the products was 38.8%. This result is not in compliance with the Commission Regulation 2023 / 2055 of 25 September 2023 amending Annex XVII to Regulation (EC) No 1907 / 2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) as regards synthetic polymer microparticles. According to the above, a tested item is considered to meet the biodegradation requirement if 60% mineralization is measured as consumed O2 or evolved CO2.

[0033] Moreover, the examples within the document describe the use of aromatic polyisocyanate (i.e. MDI, pMDI, TDI) as preferred reagents which are classified as extremely toxic, sometimes lethal by inhalation, materials (EC regulation 1272 / 2008). The aforesaid issues may result in difficulties on product handling asP024102WO-01 Notarbartolo & Gervasi S.p.A.

[0034] well as a concern for soil and aquatic environment.

[0035] It is an object of the invention to provide improved biodegradable microparticles for use in agriculture having improved properties, such as improved stability and a controlled and tunable release as well as minimizing the toxicity of the active ingredients, specifically for toxic active ingredients having a high volatility.

[0036] SUMMARY OF THE INVENTION

[0037] It has now been unexpectedly found by the present inventors that it is possible to produce a polyurea microparticles suspension (CS) suitable for agricultural use, comprising at least one active ingredient which is encapsulated within a pulyurea biodegradable shell polymer.

[0038] The use of such polyurea microparticles suspensions permits the tuned and controlled delivery of active ingredients ensuring a long-term formulation stability and excellent flowing behavior at the same time.

[0039] Therefore, the invention relates to a process for the preparation of a suspension of at least one polyurea microparticle, wherein said at least one polyurea microparticle encapsulates at least one active ingredient, said process comprising the step of: a) preparing an oil phase by dissolving the L-lysine ethyl ester diisocyanate in at least one active ingredient;

[0040] b) preparing an aqueous phase;

[0041] c) preparing an oil in water (O / W) emulsion by mixing the oil phase of step a) and aqueous phase of step b);

[0042] d) adding at least one diamine compound cross-linking agent to the O / W emulsion of step c);

[0043] e) obtaining a suspension of at least one polyurea microparticle encapsulating the at least one active ingredient of step a).

[0044] The inventors found out an inventive process that allows to obtain a polyurea microparticles suspension, wherein the microcapsules encapsulate at least one active ingredient for a tuned delivery in agriculture.

[0045] In the present invention the terms capsule, microcapsule, microsphere, and microparticle are used to mean a particle made of a polymer and in the particle sizeP024102WO-01 Notarbartolo & Gervasi S.p.A.

[0046] range of 1- 1000 pm as measured by microscopy, laser diffraction and sieving methods.

[0047] The inventors of the present invention hence found out that the process according to the invention allows to obtain polyurea microparticles suspensions.

[0048] Moreover, advantageously the process of the invention uses lysine ethyl ester diisocyanate as cross-linking reagent rather than toxic aromatic polyisocyanates in order to reduce the toxicity concerns during production stages of polyurea particles as well as to improve the biodegradability of the final polymeric product useful to encapsulate very different crop protection agents.

[0049] The use of eco-friendly encapsulating material allows the avoidance of the use of microplastics and meet the requirements of the REACH restriction adopted by the European Commission.

[0050] The inventors faced the problem of encapsulating very highly volatile liquid active ingredients and with active ingredients having a low solubilization rate.

[0051] The inventors advantageously found out the process for obtaining microspheres / microcapsules suitable for encapsulating highly volatile liquid active ingredients. The microparticles so obtained are solid and very stable in an aqueous medium and can be delivered as a suspension according to the present invention. In a preferred embodiment the inventors found a one-step polymerization method to provide improved polyurea microparticles suspensions for use in agriculture having enhanced properties in terms of physical stability and user-handling characteristics

[0052] In another aspect the invention relates to a suspension of polyurea microparticles encapsulating the at least one active ingredient obtainable from the process of the invention.

[0053] In a preferred and advantageous embodiment, the invention relates to a suspension of polyurea microparticles encapsulating the at least one active ingredient, wherein the at least one active ingredient is a highly volatile liquid compound, preferably clomazone.

[0054] The inventors advantageously found out a process for obtaining microparticlesP024102WO-01 Notarbartolo & Gervasi S.p.A.

[0055] suitable for encapsulating highly volatile liquid active ingredients. The microparticles so obtained are solid and very stable.

[0056] The inventors also found out advantageously a process for preparing microcapsules of polyurea by adding to the O / W emulsion of step c)at least one diamine compound cross-linking agent selected from the group consisting of a chitosan or gelatin. Preferably, the gelatine is gelatine 50-300 g Bloom, more preferably gelatine 80-120 g Bloom.

[0057] The microcapsule so obtained was advantageously biodegradable with no phytotoxicity without incurring in problems of viscosity that could negatively affect the formation of the final microcapsules through interfacial polymerization.

[0058] In a very advantageous and preferred embodiment the active ingredient is clomazone.

[0059] The polyurea microparticles suspensions encapsulating the at least one active ingredient obtainable by the process of the invention are suitable for delivering the active ingredients in agriculture field.

[0060] In a very advantageous and preferred embodiment the active ingredients are selected from the group selected from clomazone, bixlozone, lambda-cyhalothrin and triallate. In an even more advantageous and preferred embodiment the active ingredient is clomazone.

[0061] In a preferred and advantageous embodiment, the capsule suspension of the invention comprises as the active ingredient clomazone. In a more preferred and advantageous embodiment, the encapsulated clomazone is in amount from 10 to 60% w / w, preferably from 20 to 40% w / w with respect to the total amount of the formulation.

[0062] The water dispersible dry microparticles obtainable by the process of the invention are suitable for delivering the active ingredients in agriculture field.

[0063] Advantageously the microparticles of the invention allow a tuned and controlled release of the active ingredient, depending on the action of the active principle. In a further aspect, the present invention relates to the use of said polyurea microparticles suspension in agriculture for delivering one or more activeP024102WO-01 Notarbartolo & Gervasi S.p.A.

[0064] ingredients.

[0065] DESCRIPTION OF THE DRAWINGS

[0066] Figure 1 shows the results of Example 1: appearance of plant plots for visual inspection after 14 days. Untreated com and OSR pots (Panel A); post treatment com samples (Panel B) post treatment OSR samples (Panel C).

[0067] Figure 2 shows the percentage of phytotoxicity and efficacy according to Example 1.

[0068] Figure 3 shows the results of the evaluation of the biodegradability according to Example 8.

[0069] DETAILED DESCRIPTION OF THE INVENTION

[0070] Therefore, the invention relates to a process for the preparation of a suspension of at least one polyurea microparticle, wherein said at least one polyurea microparticle encapsulates at least one active ingredient, said process comprising the step of: a) preparing an oil phase by dissolving the L-lysine ethyl ester diisocyanate in at least one active ingredient;

[0071] b) preparing an aqueous phase;

[0072] c) preparing an oil in water (O / W) emulsion by mixing the oil phase of step a) and aqueous phase of step b)

[0073] d) adding at least one amine compound cross-linking agent to the O / W emulsion of step c);

[0074] e) obtaining a suspension of polyurea microparticles encapsulating the at least one active ingredient of step a).

[0075] In the present description the following terms and definitions will be used:

[0076] - “microparticle” means a particle made of a polymer and in the particle size range of 1- 1000 pm as measured by microscopy, laser diffraction and sieving methods and comprises in its definition the “microsphere”, “capsule”, and “microcapsule”; - the term “active ingredient” refers to any hydrophilic or hydrophobic chemical or biological component (ora combination thereof), the application of which causes or provide a beneficial and / or useful effect in agriculture including, but not limited toP024102WO-01 Notarbartolo & Gervasi S.p.A.

[0077] fertilizers and pesticides including acaricides, fungicides, herbicides, insecticides, and nematicides;

[0078] - “g Bloom” is a unit that measures the gel strength of gelatin, defined as the number of grams of force required to depress a standard plunger 4 mm into a gelatin gel of fixed concentration and temperature; and

[0079] - “highly volatile liquid” means a liquid having a vapour pressure equal to or above 1 10’4mm Hg at 25°C.

[0080] The microencapsulation procedure as it will be clear from the examples used in this process consists of interfacial polymerization. When compared with bulk polymerization, interfacial polymerization occurs at the interface of two immiscible phases. Hence a primary emulsion must be obtained prior the encapsulation of the active ingredient in a solid matrix.

[0081] The process comprises the step a) of preparing an oil phase by dissolving the crosslinking agent L-lysine ethyl ester diisocyanate in at least one active ingredient. Preferably the at least one active ingredient is a highly volatile liquid active ingredient, a compound, solid or liquid, having a low solubilization rate, harmful compounds for workers and final users or compounds which need a controlled release.

[0082] More preferably, the at least one active ingredient can be selected from the group consisting of fertilizers, pesticides, comprising preferably acaricides, fungicides, herbicides, insecticides, and nematicides.

[0083] Specifically and preferably, the at least one active ingredient can be selected from the group consisting of

[0084] - an herbicide selected from the group consisting of clomazone, bixolozone, pyroxasulfone and fenoxasulfone;

[0085] - a thiocarbamate herbicide, preferably triallate, diallate, butylate, cycloate, EPTC and molinate;

[0086] - a pyrethroid, preferably cyfluthrin, lambda-cyhalothrin, bifenthrin, permethrin and resmethrin;P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0087] - a dinitroaniline, preferably pendimethalin, trifluralin, ethalfluralin, oryzalin, butralin, benefin / benfluralin and prodiamine

[0088] - a terpen and / or terpeoid, preferably d-limonene, azadirachtins, carvacrol, 1,8-cineole, anisole, limonene, [3-pinene, linalool, menthone, a-pinene, pulegone, myrcene eugenol, borneol, menthol, isomenthol, anethole, camphor, carvone, menthyl acetate, linalyl acetate, thymol, p-cymene, y-terpinene, a-terpineol, 4-terpineol, citronellol and geraniol and

[0089] - an essential oil, preferably cinnamon oil, citronella oil, clove oil, eucalyptus oil, lemongrass oil, mint oil, mint oil, orange oil, peppermint oil, rosemary oil and thyme oil.

[0090] More preferably the at least one active ingredient is selected from the group consisting of:

[0091] - an isoxazoline-derivate herbicides, still more preferably clomazone, bixolozone, pyroxasulfone, fenoxasulfone and even more preferably clomazone;

[0092] - a thiocarbamate herbicide, still more preferably triallate, diallate, butylate, cycloate, EPTC and molinate; and

[0093] - a pyrethroid, still more preferably cyfluthrin, lambda-cyhalothrin, bifenthrin, permethrin and resmethrin.

[0094] In a preferred and advantageous embodiment, the at least one active ingredient is a highly volatile liquid compound.

[0095] In a more preferred and advantageous embodiment, the at least one active ingredient is selected from the group consisting of clomazone, bixolozone, triallate and lambda-cyhalothrin.

[0096] The most preferred active ingredient is clomazone.

[0097] Clomazone, the common name for 2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone, is an active ingredient in highly effective herbicides that are selective against perennial weeds, including grasses and broadleaves. Clomazone works by inhibiting the biosynthesis of carotenoids in the plant; a plant affected by clomazone exhibits progressive whitening with increased dosage. Herbicides containing clomazone are applied to the soil for control of weeds on beans,P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0098] cabbage, cucumbers, cotton, melons, mint, peas, peppers, rice, soybeans, squash, sugarcane, sweet potatoes, tobacco and tuberous vegetables. Such herbicides are selective against perennial weeds, including grasses and broadleaves.

[0099] Clomazone is a highly volatile compound and therefore it is a problematic active ingredient.

[0100] The same can be repeated for bixolozone, that is a highly volatile liquid herbicide characterized by high vapor tension, hence a significant volatility. Lambda-cyhalothrin, common name of (RS)-alpha-cyano-3-phenoxybenzyl 3-(2-chloro-3,3,3-trifluoropropenyl)-2,2, -dimethylcyclopropanecarboxylate is a synthetic pyrethroid insecticide and acaricide used to control a wide range of pests in a variety of applications. Pests controlled include aphids, Colorado beetles and butterfly larvae. Crops on which it may be applied include cotton, cereals, hops, ornamentals, potatoes, vegetables, or others.

[0101] Triallate, IIIPAC name S-(2,3,3-trichloroprop-2-enyl) N,N-di(propan-2-yl) carbamothioate, belongs to the thiocarbamate chemical class. It is a pre-emergence selective herbicide used to control grass weeds in fields and pulse crops. It is used selectively to control wild oats, black grass, and annual meadow grass in barley, wheat, peas, lentils, rye, maize, beets, brassicas, carrots, and onions.

[0102] Triallate needs to be finely released from capsules to carry out a proper weed control with no side effect on crops therefore it is a problematic active ingredient.

[0103] Lambda-cyhalothrin, common name of (RS)-alpha-cyano-3-phenoxybenzyl 3-(2-chloro-3,3,3-trifluoropropenyl)-2,2, -dimethylcyclopropanecarboxylate is a synthetic pyrethroid insecticide and acaricide used to control a wide range of pests in a variety of applications. Pests controlled include aphids, Colorado beetles and butterfly larvae. Crops on which it may be applied include cotton, cereals, hops, ornamentals, potatoes, vegetables, or others.

[0104] Lambda-cyhalothrin has a high toxicity degree and it is potentially lethal by inhalation and therefore it is a problematic active ingredient.

[0105] L-lysine ethyl ester diisocyanate, the cross-linking agent of step a) of the process of the invention, is dissolved in the at least one active ingredient in a weight ratio inP024102WO-01 Notarbartolo & Gervasi S.p.A.

[0106] the range from 1 :2.5 to 1 : 10 (w / w), preferably 1 :5 (w / w), between L-lysine ethyl ester diisocyanate and the at least one active ingredient

[0107] In a preferred embodiment, the oil phase of step a) comprises the cross-linking agent L-lysine ethyl ester diisocyanate in the range from 5% to 50%, preferably from 7% to 17% (w / w) with respect to the total weight of the oil phase.

[0108] In a preferred embodiment the oil phase of step a) comprises the at least one active ingredient in the range from 25% to 95%, preferably from 80% to 90% (w / w) with respect to the total weight of the oil phase.

[0109] Step a) can be carried out preferably in the optional presence of a catalyst.

[0110] When present, the catalyst is preferably selected from the group consisting of dibutyltin dilaurate, 1,4-diazabicyclo [2.2.2] octane, cobaltous stearate, triethylenediamine, stannous 2-ethylhexoate, more preferably it is 1,4-diazabicyclo [2.2.2] octane.

[0111] When present, the catalyst is preferably added in an amount in the range from 0.000000009% to 0.2, preferably 0.000001 to 0.1% (w / w) with respect to the oil phase of step a).

[0112] The process comprises the step b) of preparing an aqueous phase.

[0113] In step b) the aqueous phase is prepared preferably by adding an excipient selected from the group consisting of a wetting agent in water, an emulsifying agent, a dispersing agent and a preservative agent.

[0114] More preferably step b) can be carried out by adding to water at least one excipient selected from the group consisting of: a wetting agent, an emulsifying agent, a dispersing agent, and a preservative agent and their mixture.

[0115] Preferably, the wetting agent of step b) is selected from the group consisting of sodium dioctylsulfosuccinate, sodium lauryl sulfate, alkylbenzene sulfonates, alkylphenolethocylates, polysorbates, polyether alcohols and polypropylene glycolethylene oxide condensates more preferably it is sodium dioctylsulfosuccinate. The wetting agent of step b) is preferably dissolved in water in a weight percentage (%) in the range from 1% to 10%, preferably 2.30% (w / w) with respect to the total weight of the aqueous phase.P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0116] Preferably, the emulsifying agent of step b) is selected from the group consisting of calcium lignosulphonate, tristyrylphenol phosphate, castor oil ethoxylate, sodium lauryl sulfate, alkylbenzene sulfonates, alkylphenolethocylates, polysorbates, polyether alcohols and polypropylene glycol-ethylene oxide condensates.

[0117] The emulsifying agent of step b) is added in water in a weight percentage (%) in the range from 1 % to 30%, preferably from 2.45% to 11.30% (w / w) with respect to the total weight of the aqueous phase.

[0118] Preferably, the dispersing agent of sub step b) is selected from the group consisting of xanthan gum dispersion, fatty acid esters and ethoxylated fatty acid esters, sodium alkyl sulfosuccinates, allyloxybenzene sulfonates, poly(vinyl alcohol), guar gum and hydroxyethyl, more preferably it is a xanthan gum dispersion commercially available as AG RH 23 gel 2.7%.

[0119] The dispersing agent of step b) is added in water in a weight percentage (%) in the range from 1% to 20%, preferably from 2.74 to 11.64% (w / w) with respect to the total weight of the aqueous phase.

[0120] Preferably, the preservative agent of step b) is selected from the group consisting of 1 ,2-benzisothiazolin-3-one, sorbic acid, benzoic acid, propionic acid, parabens and benzalkonium chloride.

[0121] The preservative agent of step b) is added in water in a weight percentage (%) in the range from 0.05% to 0.3%, preferably from 0.14 to 0.19% (w / w) with respect to the total weight of the aqueous phase.

[0122] The process comprises the step c) of preparing an oil in water (O / W) emulsion by mixing the aqueous phase of step b) and the oil phase of step a). Preferably, the aqueous phase of step b) is added to the oil phase of step a) for preparing the oil in water (O / W) emulsion.

[0123] In the oil in water (O / W) emulsion, the above compounds are present preferably in the following amounts with respect to the total amount of the emulsion:

[0124] - L-lysine ethyl ester diisocyanate, the cross-linking agent of step a) is in an amount in the range from 1 to 7% (w / w), preferably from 2 to 5%, more preferably from 2.2% to 4.4% (w / w);P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0125] - the at least one active ingredient in the range from 5% to 50%, preferably from 15% to 45% (w / w);

[0126] - when present, the catalyst is in an amount in the range from 0.000000009% to 0.2%, preferably 0.000001% to 0.1% (w / w);

[0127] - the wetting agent is in the range from 0.1 % to 8%, preferably 1.8% (w / w). - the emulsifying agent is in the range from 1 % to 6%, preferably from 1.5% to 4.2% (w / w), more preferably from 1.8% to 4%;

[0128] - the dispersing agent is in the range from 1 % to 10%, preferably from 2.0% to 8.5% (w / w);

[0129] - the preservative agent is in the range from 0.01% to 1%, preferably about 0.1%(w / w).

[0130] Preferably, before step c) a pre-heating is carried out of the aqueous phase and the oil phase, independently from each other, more preferably at a temperature in the range from 20°C to 80°C, still more preferably at 50°C.

[0131] In an advantageous and preferred embodiment, the aqueous phase is poured dropwise into oil phase and homogenized. The homogenization can be carried out preferably with a speed in the range from 5000 to 13000 rpm for 3-20 minutes, more preferably at 10000 rpm for 5 minutes with a homogenizer known in the art.

[0132] The process comprises the step d) of adding at least one amine compound crosslinking agent to the O / W emulsion of step c).

[0133] The at least one amine compound cross-linking agent of step d) is preferably a water soluble amine compound selected from the group consisting of hexamethylenediamine, lysine HCI, ethylene diamine, polyethylene imine), piperazine, diethylene triamine, 1-4 cyclohexyl diamine, gelatin and a chitosan. The inventors also found out advantageously a process for preparing microcapsules of polyurea by adding to the O / W emulsion of step c) at least one diamine compound cross-linking agent selected from the group consisting of a chitosan or gelatin. Preferably, the gelatine is gelatine 50-300 g Bloom, more preferably gelatine 80-120 g Bloom.

[0134] The microcapsule so obtained was advantageously biodegradable with noP024102WG-01 Notarbartolo & Gervasi S.p.A.

[0135] phytotoxicity without incurring in problems of viscosity that could negatively affect the formation of the final microcapsules through interfacial polymerization.

[0136] In an advantageous and preferred embodiment, the at least one amine compound cross-linking agent of step d) is added to the O / W emulsion of step c) in a weight percentage (%) in the range from 1% to 10%, preferably in the range from 1.5% to 4.5% (w / w) with respect to the total weight of the emulsion.

[0137] Gelatin is a protein based material commonly derived from collagen taken from animal body parts (i.e. skin, cartilage, bone from fish, porcine and bovine source) . It is brittle when dry and rubbery when moist. It may also be referred to as hydrolyzed collagen, collagen hydrolysate, gelatine hydrolysate, hydrolyzed gelatine, and collagen peptides after it has undergone hydrolysis. The gelatin used in step d) is preferably derived from porcine skin by acidic hydrolysis, being a gelatin in the range of 80-120 g Bloom. The amount employed is comprised between 0.5 and 2% (w / w) dissolved in the aqueous phase, most preferable 1%.

[0138] Chitosan is a linear polysaccharide composed of randomly distributed |3-(1 — >4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It is made by treating the chitin shells of shrimp and other crustaceans with an alkaline substance, such as sodium hydroxide. Chitosan used in step d) has a molecular weight preferably in the range of 150 and 700 KDa dissolved in acidic water (aqueous phase) in the range of 1-4% (w / w). Most preferably 2% of chitosan powder having a molecular weight between 300 and 500 KDa.

[0139] Preferably, after the addition of the at least one amine compound cross-linking agent to the O / W emulsion in step d), the resulting emulsion is heated and kept under magnetic stirring, thus avoiding also viscosity problems.

[0140] In an advantageous and preferred embodiment, the stirring is carried out preferably at a temperature in the range from 20°C to 80°C, preferably at 50°C, more preferably with a speed in the range from 200 to 500 rpm for 4 hours, still more preferably at 400 rpm for 4 hours with a stirrer known in the art.

[0141] The process comprises the step e) of obtaining a polyurea microparticles suspensions encapsulating the at least one active ingredient of step a).P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0142] Preferably, in step e) the emulsion of step d) is slowly cooled at room temperature and it is stirred at a speed in the range from 200 to 500 rpm, preferably 400 rpm, for 12 hours, preferably 12 hours.

[0143] The process of the invention allowed the encapsulation of very highly volatile liquid active ingredients and having a low solubilization rate.

[0144] The process of the invention advantageously permits the encapsulation of one or more active ingredients with a loading in the range from 25 to 95% (w / w), preferably from 30 to 90% (w / w) with respect to the total weight of the microparticle.

[0145] In the preferred and advantageous embodiment, wherein the active ingredient is clomazone, the encapsulated clomazone is in amount from 30 to 95 % (w / w), preferably from 40 to 95 % (w / w) with respect to the total weight of the microparticle. The use of an eco-friendly polyurea matrix allows to avoid the use of microplastics and meet the requirements of the REACH restriction adopted by the European Commission.

[0146] In another aspect, the invention relates to a suspension of polyurea microparticles encapsulating the at least one active ingredient obtainable from the process of the invention.

[0147] In a preferred and advantageous embodiment, the invention relates to a suspension of polyurea microparticles encapsulating the at least one active ingredient, wherein the at least one active ingredient is a highly volatile liquid compound, preferably clomazone.

[0148] Advantageously the suspension of the invention comprises a microcapsule capable to release an amount of the at least one active ingredient in the range from 1 to 100%, with respect to the whole amount of the microcapsule suspension.

[0149] The inventors advantageously found out a process for obtaining microparticles suitable for encapsulating highly volatile liquid active ingredients. The microparticles so obtained are solid and very stable.

[0150] In a very advantageous and preferred embodiment the active ingredient is clomazone.

[0151] The polyurea microparticles suspensions encapsulating the at least one activeP024102WG-01 Notarbartolo & Gervasi S.p.A.

[0152] ingredient obtainable by the process of the invention are suitable for delivering one or more active ingredients in agriculture field.

[0153] Advantageously the microparticles suspension of the invention allows a tuned and controlled release of the active ingredient, depending on the action of the active principle.

[0154] Preferably, the polyurea microparticle has a D50 in the range from 1 pm to 40 pm, more preferably 1-15 pm and D90 in the range from 10 pm to 100 pm, more preferably from 15 pm to 40 pm as measured by a laser diffraction analyzer (more preferably analyzer Malvern 3000, Malvern Panalytical, Malvern, UK).

[0155] In a further aspect, the present invention relates to the use of said polyurea microparticles suspension encapsulating the at least one active ingredient in agriculture for delivering one or more active ingredients.

[0156] EXPERIMENTAL PART

[0157] Example 1: Preparation and evaluation of the microparticle of the invention The microencapsulation procedure used consists of interfacial polymerization. When compared with bulk polymerization, interfacial polymerization occurs at the interface of two immiscible phases. Hence a primary emulsion must be obtained prior clomazone encapsulation in a solid matrix.

[0158] Firstly, an oil phase was prepared as follows.

[0159] L-Lysine ethyl ester diisocyanate (VWR, Milano, Italy) was dissolved in Clomazone (Sipcam Oxon, Mezzana Bigli, Italy) in a 1:5 ratio by weight, this mixture representing the oil phase of the primary emulsion.

[0160] Then the aqueous phase was prepared as follows.

[0161] 1.8 g of sodium dioctylsulfosuccinate (Geropon SDS, Solvay, Ospiate di Bollate, Italy) dissolved in 75.1 ml of deionized water obtaining the aqueous phase.

[0162] The two phases were pre-heated at 50°C, then the aqueous phase was poured dropwise into the dispersed phase and homogenized by an Ultraturrax T50, (IKA, Staufen, Germany) at 900 rpm to obtain a O / W emulsion. Afterwards, 1.5 g of crosslinking agent, hexamethylenediamine (Arpadis, Antwerpen, Belgium), was slowly added at the aforementioned emulsion and kept under magnetic stirring at 400 RPMP024102WG-01 Notarbartolo & Gervasi S.p.A.

[0163] and 50°C for 4h. Lastly, the temperature was dropped down at room temperature whereas the sample have been stirring overnight to obtain a capsule suspension. Table 1. O / W emulsion composition according to Example 1

[0164]

[0165] Physical appearance, active content, suspensibility, particle size distribution, viscosity, pH, and release profile were evaluated following CIPAC and FAO guidelines.

[0166] The loading of clomazone within the microparticles was found to be 15.9% (w / w) by HPLC considering the whole formulation.

[0167] Particle size analyses of D50 and D90 resulted 17.9 and 39.4 pm respectively as measured by a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK) using water as dispersing medium.

[0168] Clomazone release from the polyurea based microparticles analyses were performed by dispersing a known weight of powder in a fixed volume of hexane, the amount of released active ingredient was obtained by calculating the difference between the initial loading value and the clomazone amount measured in the supernatant normalized by the microparticle active ingredient concentration after 1, 5, 15, 30 and 60 minutes. The results are reported in Table 2.

[0169] Table 2. Clomazone releasing profile

[0170]

[0171] P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0172]

[0173] Suspensibility was analyzed as per the method mentioned for agricultural applications as per CIPAC handbook. 2.5 g sample of the formulation was weighed in a 100 ml beaker and 50 ml of water was added to it. The material was stirred, and the suspension obtained was allowed to remain for 4 minutes in a water bath at temperature of 30° C. Suspension was taken into a 250 ml cylinder with additional quantity of water and maintained up to the 250 ml mark. The cylinder was stoppered and inverted 30 times and kept undisturbed for 30 minutes. After 30 minutes, upper portion 225 ml (9 / 10) of the material was removed by siphon. Suspension remaining at base of the cylinder is transferred to a petri-dish, by rinsing with distilled water and dried to constant weight. Suspensibility was estimated by the following equation:

[0174]

[0175] where a is the mass of sample taken for analysis and b is the mass of sample remaining at bottom of the cylinder. The value obtained was 98.5%.

[0176] The suspension viscosity was measured by transferring 50 ml of sample in a 100 ml beaker at 20°C. The value was obtained by a Brookfield Ametek DV-1+ Viscometer (IIRAI S.p.A., Milan, Italy) using a LV spindle #6 at shear rate of 12 rpm. the resulting viscosity was 1650 cPs.

[0177] The pH value was obtained by pouring 1g of formulation in 100 ml of water under magnetic stirring. And it resulted in 5.1.

[0178] Residual evaluation was performed by the “wet sieve method” described in CIPAC Handbook. Analysis of Technical and Formulated Pesticides”. The found residual amount employing both a 45 and 150 pm sieves was 0.05 and 0.15% respectively. Finally, the formulation density resulted 1.052 g / ml.P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0179] The microcapsules were also evaluated for efficacy and phytotoxicity as below explained.

[0180] Efficacy and phytotoxicity evaluations were also performed in glasshouse in order to evaluate the selectivity on oilseed rape (Delight variety, OSR) and com (PR36Y03 variety).

[0181] Echinochloa crus-galli (ECHCG) weed was used as target species and the formulation was compared against untreated sample pots and clomazone emulsifiable concentrates (EC, 500g / l). The dose applied for com was 80 g / ha, whereas 90 g / ha were chosen for oilseed rape treatment (dose n). The application took place just after the sowing of 15 seeds / container, and phytotoxicity symptoms (bleaching) had been evaluated for 14 days. From the date recorded during the whole trial period, it was observed that all the test items showed a significantly different bleaching profile as depicted in Figures 1.

[0182] More in detail, Panel A in figure 1 shows the appearance of untreated sample pots of both com and OSR respectively: no bleaching or other signs of toxicity were detected during the whole test. In panel B are shown com pots treated by Sirtaki CS (a commercial product based on non-biodegradable polyurethane microcapsules), an emulsifiable concentrate and new synthesized polylurethane CS formulation respectively treated using two different doses, namely 80 and 160 gai / ha.

[0183] From the pictures, it resulted clear that the emulsifiable concentrate treated plants resulted smaller and more whitened in comparison with the samples treated using encapsulated clomazone at both dosing. Different bleaching degree is also spotted between plants treated by Sirtaki and the new formulation where the latter showed a lower toxicity by visual inspection. A similar result was observed on oilseed rape, OSR, treated plants too (Panel C). In this case 90 and 180 gai / ha dosing were employed. A quantitative analysis confirmed the results of the above (Figure 2). The efficacy against ECHCG culture did not show any significant difference in all the samples considered since all the formulations reached the maximum value (black bars).P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0184] Anyway, a substantially variation in phytotoxicity, and hence selectivity, was observed among the formulations (white and grey bars for com and oilseed rape, OSR, samples respectively).

[0185] Obviously, the emulsifiable concentrate, EC, showed the highest phytotoxicity in both cultures as consequence of the fast active ingredient release on the soil ground.

[0186] On the other hand, a different scenario was observed in plants when encapsulated clomazone was tested: the commercial reference product Sirtaki showed a dosedependent bleaching on com culture treated with 80 and 160 g / ha of active respectively (namely 40.0 and 67.5%). On the contrary, no dose related toxic effect was observed on OSR (22.5% for both doses). Surprisingly, the toxicity level of the microparticle suspension herein described resulted substantially lower than the one observed in the reference product.

[0187] In fact, at the dose “n” only 15.0% and 3.8 % of phytotoxicity was detected (80 g / ha and 90 g / ha on com and OSR respectively) whereas such values increased up to 25.0% on com when treated with “2n” dose, far below if compared with Sirtaki treatment. No significant differences were observed on OSRs between Sirtaki and microparticles treatment dosing 180 g / ha.

[0188] In conclusion, the data confirm that the use of Lysine diisocyanate in the inventive process allowed to encapsulate the active ingredient in high amount and in effective way as well as to properly eradicate the weed growth process with negligible effects on crop cultures.

[0189] Example 2: Preparation and evaluation of a suspension of microparticles of the invention

[0190] A further microcapsule suspension, CS containing clomazone as encapsulated active ingredient was obtained following the procedure described above with some modifications regarding the O / W emulsion homogenization speed (1 ■ 104RPM) and the maturation magnetic stirring at 600 RPM.

[0191] Calcium lignosulphonate was used as emulsifying agent. A xanthan gum dispersion (AG RH 23 gel 2,7% (w / w), Azelis, Antwerp, Belgium) and the preservative agent 1,2-P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0192] benzisothiazolin-3-one, (Proxel GXL, Antwerp, Belgium) were added after microcapsule maturation occurred.

[0193] Table 3. O / W emulsion composition according to Example 2

[0194]

[0195] Physical appearance, active content, suspensibility, particle size distribution, viscosity, pH, and release profile were evaluated following CIPAC and FAO guidelines.

[0196] The loading of clomazone within the microcapsule suspension, CS was found to be 18.5% (w / w) by HPLC considering the whole formulation.

[0197] by a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK) using water as dispersing medium.

[0198] Particle size analyses of D50 and D90 resulted 3.5 and 8.7 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK).

[0199] Clomazone release from the microparticles analyses were performed by dispersing a known weight of formulation in a fixed volume of hexane, the amount of released active ingredient was obtained by calculating the difference between the initial loading value and the clomazone amount measured in the supernatant normalized by the microparticle concentration after 1, 5, 15, 30 and 60 minutes.

[0200] The total amount of clomazone encapsulated at time = 0 was fixed at 100%.

[0201] Release profiles are shown in Table 4.P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0202] Table 4. Clomazone releasing profile

[0203]

[0204] Suspensibility was analyzed as per the method mentioned for agricultural applications as per CIPAC handbook. 2.5 g sample of the formulation was weighed in a 100 ml beaker and 50 ml of water was added to it. The material was stirred, and the suspension obtained was allowed to remain for 4 minutes in a water bath at temperature of 30 C. Suspension was taken into a 250 ml cylinder with additional quantity of water and maintained up to the 250 ml mark. The cylinder was stoppered and inverted 30 times and kept undisturbed for 30 minutes. After 30 minutes, upper portion 225 ml (9 / 10) of the material was removed by siphon. Suspension remaining at base of the cylinder is transferred to a petri-dish, by rinsing with distilled water and dried to constant weight. Suspensibility was estimated by the following equation:

[0205]

[0206] where a is the mass of sample taken for analysis and b is the mass of sample remaining at bottom of the cylinder. The value obtained was 99.0%.

[0207] The suspension viscosity was measured by transferring 50 ml of sample in a 100 ml beaker at 20°C. The value was obtained by a Brookfield Ametek DV-1+ Viscometer (IIRAI S.p.A., Milan, Italy) using a LV spindle #6 at shear rate of 12 rpm. the resulting viscosity was 2400 cPs.P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0208] The pH value was obtained by pouring 1g of formulation in 100 ml of water under magnetic stirring. And it resulted in 5.0.

[0209] Residual evaluation was performed by the “wet sieve method” described in CIPAC Handbook. Analysis of Technical and Formulated Pesticides”. The found residual amount employing both a 45 and 150 pm sieves was 0.02 and 0.10% respectively. Finally, the formulation density resulted 1,0711 g / ml.

[0210] Example 3: Preparation and evaluation of the microparticle of the invention A further microcapsule suspension, CS, containing clomazone as encapsulated active ingredient was obtained following the procedure described in Example 2 with some modifications.

[0211] A mixture of tristyrylphenol phosphate and castor oil ethoxylate has been used as emulsifying agents whereas dibutyltin dilaurate was added in the oily phase as catalyst. HMDA was replaced by lysine HCI as polyamine monomer to allow the interfacial polymerization.

[0212] Formulation composition is listed in Table 5.

[0213] Table 5. O / W emulsion composition according to Example 3

[0214]

[0215] The loading of clomazone within the microcapsule suspension, CS was found to be 19.9% (w / w) by HPLC considering the whole formulation. Particle size analyses of d50P024102WO-01 Notarbartolo & Gervasi S.p.A.

[0216] and d90 resulted 17.2 and 43.0 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK) .

[0217] Release profiles as measured following the procedure described in example 1 are shown in Table 6.

[0218] Table 6. Clomazone releasing profile

[0219]

[0220] Example 4: Preparation and evaluation of the microparticle of the invention A further microcapsule suspension, CS, containing clomazone as encapsulated active ingredient was obtained following the procedure described in Example 3 with some modifications. Dibutyltin dilaurate was replaced by 1 ,4-Diazabicyclo [2.2.2] octane as catalyst; the amount of clomazone emulsified was increased up to 40%.

[0221] Formulation composition is listed in Table 7.

[0222] Table 7. O / W emulsion composition according to Example 4

[0223]

[0224] P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0225]

[0226] The loading of clomazone within the capsule suspension, CS was found to be 39.4% (w / w) by HPLC considering the whole formulation. Particle size analyses of d50 and d90 resulted 26.7 and 60.8 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK).

[0227] The release profile was evaluated with respect to the total amount of the active ingredient encapsulated according to the procedure described above.

[0228] Table 8. Clomazone releasing profile

[0229]

[0230] Example 5: Preparation and evaluation of the suspension of microparticles of the invention

[0231] A microcapsule suspension, CS, containing bixlozone (2-(2,4-Dichlorobenzyl)-4,4-dimethylisoxazolidin-3-one) as encapsulated active ingredient was also obtained. Bixlozone is a highly volatile liquid herbicide characterized by a high vapor tension, hence a significant volatility. The need to achieve an active ingredient-controlled release for optimum effectiveness as well as the reduction of side effects such as crop toxicity and drifting is necessary. The sample has been obtained following the procedures described in the Example 3.

[0232] Table 9 shows the amount as %w / w of each component of the formulation.P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0233] Table 9. 0 / W emulsion composition according to Example 5

[0234]

[0235] The loading of bixlozone within the microcapsule suspension, CS was found to be 19.3% (w / w) by HPLC considering the whole formulation. Particle size analyses of d50 and d90 resulted 14.7 and 29.7 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK)The release profile was evaluated following the method described in example 1 for clomazone.

[0236] In Table 10 the results of the release evaluation are reported.

[0237] Table 10. Bixlozone releasing profile

[0238]

[0239] Example 6: Preparation and evaluation of the suspension of the microparticles of the inventionP024102WG-01 Notarbartolo & Gervasi S.p.A.

[0240] A microcapsule suspension, CS, containing lambda cyhalothrin as encapsulated active ingredient was produced. Lambda cyhalothrin is a pyrethroid insecticide harmful to humans because of its severe side effects. The encapsulation of lambda cyhalothrin in a confined system is mandatory in several manufacturing processes to protect either employers or final users. The sample has been obtained following the procedures described in the Example 3.

[0241] Table 11 shows the amount as %w / w of each component of the formulation.

[0242] Table 11. O / W emulsion composition according to Example 6

[0243]

[0244] The loading of lambda cyhalothrin within the CS was found to be 19.3% (w / w) by HPLC considering the whole formulation. Particle size analyses of d50 and d90 resulted 14.7 and 29.7 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK).

[0245] The release profile of Lambda cyhalothrin from the microcapsules was evaluated by HPLC.

[0246] Active ingedient release from the microparticles analyses were performed by dispersing a known weight of formulation in a fixed volume of hexane, the amount of released active ingredient was obtained by calculating the difference between the initial loading value and the clomazone amount measured in the supernatant normalized byP024102WG-01 Notarbartolo & Gervasi S.p.A.

[0247] the microparticle concentration after 1, 5, 15, 30 and 60 minutes. The release profile was evaluated with respect to the total amount of the active ingredient encapsulated. The results are reported in Table 12.

[0248] Table 12. Lambda cyhalothrin releasing profile

[0249]

[0250] Example 7: Preparation of the suspension of the microparticles of the invention A microcapsule suspension, CS, containing triallate as encapsulated active ingredient was obtained following the procedure described in the Example 3. Triallate is an herbicide belonging to the thiocarbamate class and it needs to be finely released from capsules to carry out proper weed control with no side effect. Table 13 shows the amount as %w / w of each component of the formulation.

[0251] Table 13. O / W emulsion composition according to Example 7

[0252]

[0253] P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0254] The loading of triallate within the suspension of the microcapsules, CS, was found to be 19.3% (w / w) by HPLC considering the whole formulation. Particle size analyses of d50 and d90 resulted 14.7 and 29.7 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK).

[0255] Triallate release profile from the microparticles analyses were performed by dispersing a known weight of formulation in a fixed volume of hexane, the amount of released active ingredient was obtained by calculating the difference between the initial loading value and the clomazone amount measured in the supernatant normalized by the microparticle concentration after 1, 5, 15, 30 and 60 minutes.

[0256] The release profile was evaluated with respect to the total amount of the active ingredient encapsulated.

[0257] The results are reported in Table 14.

[0258] Table 14. Triallate releasing profile

[0259]

[0260] Example 8: Preparation of the suspension of the microparticles of the invention A microcapsule suspension, CS, containing clomazone as encapsulated active ingredient was obtained following the procedure described in the Example 3.

[0261] In such case, a natural derived protein (gelatin from porcine skin, 80-120 bloom obtained by Sigma Aldrich, Darmstadt, Germany) was used as polyamine source. Table 15 shows the amount as %w / w of each component of the formulation.

[0262] Table 15. O / W emulsion composition according to Example 8

[0263]

[0264] P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0265]

[0266] The loading of clomazone within the CS was found to be 20.4% (w / w) by HPLC considering the whole formulation. Particle size analyses of d50 and d90 resulted in 15.9 and 30 pm respectively as measured with a laser diffraction analyzer (Malvern 3000, Malvern Panalytical, Malvern, UK).

[0267] The release profile of Lambda cyhalothrin from the microcapsules was evaluated by HPLC.

[0268] Active ingredient release from the microparticles analyses were performed by dispersing a known weight of formulation in a fixed volume of hexane, the amount of released active ingredient was obtained by calculating the difference between the initial loading value and the clomazone amount measured in the supernatant normalized by the microparticle concentration after 1, 5, 15, 30 and 60 minutes. The release profile was evaluated with respect to the total amount of the active ingredient encapsulated. The results are reported in Table 16.

[0269] Table 16. clomazone releasing profile

[0270]

[0271] P024102WG-01 Notarbartolo & Gervasi S.p.A.

[0272] The aqueous biodegradation test was performed according to procedure described in ISO 14851 (2019), Annex A. The ThOD (Theoretical Oxygen Demand) was calculated from the chemical formula reported on the same procedure. The results are given in g / g. The test was also accomplished following the OECD Guideline for Testing of Chemicals 301 F - Manometric Respirometry Test (1992). The results of this test can be used to comply with the commission Regulation 2023 / 2055 of 25 September 2023 amending Annex XVII to Regulation (EC) No 1907 / 2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards synthetic polymer microparticles.

[0273] After 60 days, as measured by CO2 production, reference item sodium acetate has reached a biodegradation percentage of 100.4 % (figure 3) As such the 60% pass level for a valid test was achieved. The biodegradation of microparticles has shown an absolute biodegradation 61.1% reaching the 60% biodegradability requirement to comply with REACH regulation (Figure 3).

Claims

P024102WO-01 Notarbartolo & Gervasi S.p.A.CLAIMS1. A process for the preparation of a suspension of at least one polyurea microparticle, wherein said at least one polyurea microparticle encapsulates at least one active ingredient, said process comprising the step of:a) preparing an oil phase by dissolving the L-lysine ethyl ester diisocyanate in at least one active ingredient;b) preparing an aqueous phase;c) preparing an oil in water (O / W) emulsion by mixing the oil phase of step a) and aqueous phase of step b);d) adding at least one amine compound cross-linking agent to the O / W emulsion of step c);e) obtaining a suspension of polyurea microparticles encapsulating the at least one active ingredient of step a).

2. The process according to claim 1, wherein the at least one amine compound cross-linking agent of step d) is a water-soluble agent selected from the group consisting of hexamethylenediamine, lysine HCI, ethylene diamine, poly(ethylene imine), piperazine, diethylene triamine, 1 -4 cyclohexyl diamine, gelatin and chitosan.

3. The process according to claim 2, , wherein the at least one amine compound cross-linking agent of step d) is a chitosan or gelatin, preferably gelatine 50-300 g Bloom, more preferably gelatine 80-120 g Bloom.

4. The process according to anyone of claims 1-3, wherein the active ingredient is selected from the group consisting of- an herbicide selected from clomazone, bixolozone, pyroxasulfone and fenoxasulfone;- a thiocarbamate herbicide, preferably triallate, diallate, butylate, cycloate, EPTC and molinate;- a pyrethroid, preferably cyfluthrin, lambda-cyhalothrin, bifenthrin, permethrin and resmethrin;- a dinitroaniline, preferably pendimethalin, trifluralin, ethalfluralin, oryzalin, butralin, benefin / benfluralin and prodiamine32P024102WO-01 Notarbartolo & Gervasi S.p.A.- a terpen and / or terpeoid, preferably d-limonene, azadirachtins, carvacrol, 1,8-cineole, anisole, limonene, [3-pinene, linalool, menthone, a-pinene, pulegone, myrcene eugenol, borneol, menthol, isomenthol, anethole, camphor, carvone, menthyl acetate, linalyl acetate, thymol, p-cymene, y-terpinene, a-terpineol, 4-terpineol, citronellol and geraniol and- an essential oil, preferably cinnamon oil, citronella oil, clove oil, eucalyptus oil, lemongrass oil, mint oil, mint oil, orange oil, peppermint oil, rosemary oil and thyme oil.

5. The process according to anyone of claims 1-4, wherein the at least one active ingredient is a highly volatile liquid compound.

6. The process according to anyone of claims 1-4, wherein the at least one active ingredient is selected from the group consisting of clomazone, bixolozone, triallate and lambda-cyhalothrin, preferably it is clomazone.

7. The process according to anyone of claims 1-6, wherein a catalyst is present in step a).

8. The process according to anyone of claims 1 -7, wherein in step b) the aqueous phase is prepared by adding an excipient selected from the group consisting of a wetting agent in water, an emulsifying agent, a dispersing agent and a preservative agent.

9. The process according to anyone of claims 1-8, wherein the at least one amine compound cross-linking agent of step d) is added to the O / W emulsion of step c) in a weight percentage (%) in the range from 1 to 10, preferably in the range from 1.5 to 4.5% (w / w) with respect to the total weight of the emulsion.

10. A suspension of polyurea microparticles encapsulating the at least one active ingredient obtainable from the process according to claims 1-9.

11. The suspension of polyurea microcapsules according to claim 10, wherein the at least one active ingredient is a highly volatile liquid compound, preferably clomazone.

12. A use of the polyurea microparticles suspension according to claim 10 or 11 for delivering at least one active ingredient in the agriculture field.33

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