Urea complex as an active ingredient

Abstract

The present invention relates to the technical field of delivery systems for agrochemical or pharmaceutical active ingredients. The present invention mainly relates to a specific composition in solid form comprising at least one agrochemical or pharmaceutical active ingredient as component (a), urea as component (b), and at least one non-ionic surfactant as component (c). The present invention also relates to products that can be obtained by the method defined in relation to the present invention, or the products obtained. The present invention further relates to formulations comprising these compositions or products, and application mixtures that can be obtained or are obtained by diluting these compositions or products with water or an aqueous surfactant solution. The present invention further relates to methods for preparing these compositions, products, formulations and application mixtures, as well as their use, and methods of using these compositions, products, formulations and application mixtures.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit and priority of U.S. Provisional Application No. 63 / 341,649, filed on May 13, 2022, and all of its contents are incorporated herein by reference as if fully set forth herein.

[0002] Field of the Invention The present invention relates to the technical field of delivery systems for agrochemical active ingredients or pharmaceutical active ingredients. The present invention mainly relates to a specific composition in solid form comprising, as component (a), at least one agrochemical active ingredient or pharmaceutical active ingredient, as component (b), urea, and as component (c), at least one non - ionic surfactant. The present invention also relates to products that can be obtained by the methods defined in relation to the present invention, or products obtained. The present invention further relates to formulations containing these compositions or products and application mixtures that can be obtained or are obtained by diluting these compositions or products with water or an aqueous surfactant solution. The present invention further relates to methods for preparing these compositions, products, formulations and application mixtures, as well as their uses, and methods of using these compositions, products, formulations and application mixtures.

Background Art

[0003] Background Art The delivery of poorly soluble active ingredients (active substances) to the target organism is a major challenge in both agriculture and pharmacology. In virtually all cases, efficacy requires the active molecule to reach the plant (for herbicides and systemic fungicides and insecticides) or the circulatory system of human or veterinary patients. In pharmaceutical science, this is typically achieved via Amorphous Solid Dispersions, as described, for example, in Int.J.Pharm.2020,586,11950. The active pharmaceutical ingredient (API) is impregnated into the polymer matrix using a solvent that is subsequently removed. The API diffuses from the polymer and dissolves in the patient's stomach or small intestine, a process enabled by the fact that the active substance is in an amorphous form in the polymer matrix. This accelerates dissolution and allows for the achievement of supersaturated concentrations of the active substance. Similar formulation strategies, such as impregnation into silica, are also known in pharmacology.

[0004] There are many active low-solubility active ingredients in the agricultural field, but the type of matrix encapsulation strategy used for pharmaceutical active substances is actually ineffective. Agricultural pesticides are, in most cases, sprayed onto the target plant or soil by water spraying. Unlike pharmaceutical delivery where matrix particles can be present in the gastrointestinal tract for several hours, agricultural formulations are often added to the spray mixture for only a few minutes immediately prior to application. After spraying and rapid drying of the spray solution, the active substance only contacts the thin layer of variable moisture on the leaf or soil surface. This inhibits the transport of the active substance into the plant and its distribution in the soil.

[0005] Several strategies are known in the art for enhancing the uptake of pesticides having low solubility, particularly low water solubility. In some cases, for example as a formulation type known as an emulsifiable concentrate, it is possible to dissolve a sufficient amount of the active substance in a suitable solvent that can carry the active substance to the leaves. However, in most cases, the active substance is ground to a size of several microns, suspended in water, and added to the spray tank. Delivery of the active substance from this formulation type, known as a suspension concentrate, is often enhanced by the addition of a separate solvent to the spray mixture, typically a soybean oil concentrate or a methyl ester of soybean oil or rapeseed oil.

[0006] These methods are widely practiced in commercial agriculture but have significant limitations. Crop oil concentrates and other additives add cost and complexity to the application process and provide inconsistent results, particularly with respect to the soil. Oil adjuvants are not useful for seed treatment. Furthermore, solubilization by additives is insufficient, particularly for insoluble active substances. Accordingly, there is a need in agriculture for a method of rapidly releasing low-solubility agricultural active substances, typically pesticides, in a spray mixture as fine, low-crystalline particles that exhibit enhanced solubility and delivery of the active substance to plants, soil, fungi, or other targets.

[0007] Today, most of the new active ingredients, especially active pesticidal or pharmaceutical ingredients, exhibit the property of low solubility and subsequently reduced bioavailability. In the field of Active Pharmaceutical Ingredients (APIs), one approach to overcome these problems is to embed amorphous APIs into water-soluble polymers to form Amorphous Solid Dispersions (ASDs), as these can increase the oral bioavailability of poorly soluble drugs. When these systems come into contact with the gastrointestinal medium, dissolution occurs and a supersaturated state is reached, which is more or less stabilized by the polymer. This so-called "spring and parachute" approach has been shown to significantly enhance the bioavailability of poorly soluble APIs. One of the major challenges in the administration of these APIs is the high inter-individual variability in drug performance. Another inherent problem of amorphous solid dispersions is the solid-state instability that leads to the tendency of the drug and / or excipients to recrystallize during storage. This can be accompanied by a decrease in solubility and bioavailability.

[0008] Indian Patent No. 369969 relates to urea complexes of the insecticides chlorpyrifos, malathion, bifenthrin, and cypermethrin for improving safe handling and other properties.

[0009] U.S. Patent No. 4,065,289 discloses a herbicidal composition containing a plant fertilizer.

[0010] U.S. Patent No. 5,714,157 teaches a specific water-dispersible granular agricultural composition comprising an active ingredient, a base, urea, a urea conditioner, and optionally, further additives formed by extrusion.

[0011] U.S. Patent No. 5,474,971 relates to a specific rapidly disintegrating granular composition produced by extruding a dry premix through a die or screen at high temperature and comprising an active ingredient, a water-soluble diluent, and at least two further additives.

[0012] International Publication No. WO 2014 / 093522 pamphlet discloses a method for producing an extruded pesticide granular composition suitable for preparing a substantially stable microemulsion, wherein the granular composition contains urea, a nonionic surfactant, a pesticidal active ingredient, and water.

[0013] U.S. Patent Application Publication No. 2016 / 0050913 relates to a method for producing specific agricultural and horticultural granular formulations by forming a powder composition into granules using a horizontal extrusion granulator.

[0014] J.Pharm.Sci. 1966, (55), 581 - 583 investigates the dissolution rate and gastrointestinal absorption via solid solutions and eutectic mixtures of chloramphenicol - urea samples.

[0015] Indian Patent No. 182620 relates to a method for producing a urea complex of vitamin E and its esters.

[0016] International Journal of Pharmaceutics 1997, 156, 175 - 180 aimed to improve the dissolution rate of the poorly water - soluble drug ofloxacin by a solid dispersion system containing urea or mannitol.

[0017] J.Pharm.Sci., 2008, Vol.97, No.3, 1191 - 1201 reports on the addition of amiloride hydrochloride in urea.

[0018] J.Pharmacy Pharmacology, 2007, 59, 1501 - 1507 discloses a urea inclusion compound of enalapril maleate for improving pharmaceutical properties.

[0019] J.Incl.Phenom.Macrocycl.Chem. 2008, 60, 203 - 209 studied the urea co - inclusion compound of glipizide for improving the dissolution profile.

[0020] J.Pharm.Innov., 2008, 3, 249 - 57 investigated the use of hexagonal urea as a means for reducing the hygroscopicity / uptake of hygroscopic drugs through addition into urea, using nicorandil as a model drug.

[0021] Powder Technology 2014, 257, 168 - 174 evaluated clarithromycin - urea solid dispersions prepared by solvent evaporation, electrospray, and freeze - drying methods.

[0022] J.Incl.Phenom.Macrocycl.Chem.2015, 81, 105 - 120 reported a study on the urea co - inclusion complex of simvastatin for improving pharmaceutical properties.

[0023] Drug Development and Industrial Pharmacy 2015, 41(9), 1401 - 1415 provided a review on the classification of solid dispersions: (i) stability and solubility (ii) correlation with preparation and characterization techniques.

[0024] Drug Delivery 2020, Vol.27, No.1, 110 - 127 outlined the mechanism of increased bioavailability via amorphous solid dispersions.

[0025] Mol.Pharmaceutics 2021, 18, 1905 - 1919 reported on the characterization of amorphous solid dispersions (ASD).

[0026] WO 95 / 08987 relates to the preparation of solid dispersions and crystals and solid forms containing dihydropyridine - type calcium antagonists such as nimodipine.

[0027] WO 2021 / 156172 relates to a pharmaceutical composition containing legolasfenib and a stabilizer.

Prior Art Documents

Patent Documents

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Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Patent Document 8

Patent Document 9

Non-Patent Document

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Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

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Non-Patent Document 5

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Non - Patent Document 11

Summary of the Invention

Problems to be Solved by the Invention

[0030] Summary of the Invention It has been found that a solid - form composition based on urea, containing an active ingredient having specific structural and physical properties and a specific amount and ratio of a non - ionic surfactant, enables rapid dissolution in water or an aqueous diluent, resulting in an enhancement or improvement in the bioavailability of the active ingredient.

Means for Solving the Problems

[0031] Briefly, a particular aspect of the present invention relates to a specific solid composition comprising: (a) one or more agrochemical or pharmaceutical active ingredients having a melting point of at least about 55 °C and a solubility in deionized water of 50 g / L or less, with a total amount of at least about 5% by weight, and wherein component (a) does not exist in the form of a salt with an inorganic counterion; (b) urea with a total amount of at least about 50% by weight; and (c) one or more non - ionic surfactants with a total amount of at least about 1% by weight, where the weight ratio of the total amount of component (c) to the total amount of component (a) is about 0.8 or less.

[0032] In certain embodiments, the solid composition according to the invention is in the form of an inclusion complex or a solid solution. In other embodiments, when the solid composition according to the invention is diluted with water, nanoparticles of the active ingredient are obtained, or an active ingredient in liquid form is obtained. In yet further embodiments, when the solid composition according to the invention is added to an aqueous solution of an emulsifying surfactant, an active ingredient in emulsified form is obtained.

[0033] Another aspect of the invention relates to products that can be obtained from these solid compositions, or are obtained, by methods such as (hot melt) extrusion, melting and cooling, spray drying, spray cooling, granulation, spheronization, or combinations thereof.

[0034] In a further aspect, the invention relates to a method for preparing a composition according to the invention, and to an application mixture that can be obtained from, or is obtained from, a composition or product according to the invention.

[0035] A further aspect of the invention relates to a method for controlling unwanted vegetation, plant pests, (phytopathogenic) fungi or (phytopathogenic) nematodes, and to the corresponding use.

[0036] A further aspect of the invention relates to a composition, product or application mixture as defined in relation to the invention for use as a medicament, for use in the treatment of the body of an animal or a human, and to the corresponding methods and uses.

Embodiments for Carrying Out the Invention

[0037] Detailed Description of the Invention Generally, the invention relates to a composition that is in solid form at 25 °C and 1013 mbar and that: (a) At least one pesticidal or pharmaceutical active ingredient having a melting point of at least 55 °C at 1013 mbar with a total amount of at least about 5% by weight and having a solubility of 50 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar, wherein component (a) does not exist as a salt with an inorganic counterion (i.e., component (a) does not exist as a salt with an inorganic counterion such as a monovalent metal ion, a divalent metal ion, a trivalent metal ion, or an ammonium counterion), component, (b) Urea in a total amount of at least about 50% by weight, (c) At least one nonionic surfactant in a total amount of at least about 2% by weight comprising, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is about 0.8 or less, and wherein the amounts indicated in each case relate to the composition, based on the total weight of the composition.

[0038] In respect of the present invention, the composition or product of the present invention may sometimes also be referred to as a complex.

[0039] In respect of the present invention, many embodiments of the composition or product of the present invention are defined by the amounts of the components contained therein. These amounts are typically indicated in the range of weight percentages (wt%) based on the total weight of the composition. It will be understood by those skilled in the art that the sum of these amounts does not exceed (and cannot exceed by definition) 100%.

[0040] The composition of the present invention mainly comprises, in urea together with a non-ionic surfactant, one or more pesticidal or pharmaceutical active ingredients having the above-described properties, typically agricultural pesticides, and optionally further components such as a dispersant that aids in the wetting and dissolution of the urea particles matrix and the dispersion of the active ingredient. Importantly, urea is highly soluble in water (about 100 g per 100 ml of water) and dissolves within seconds. The active substance is rapidly released in this process and forms small, disordered particles that are more bioavailable than, for example, crystalline solids that are micronized to form a suspension concentrate. The use of certain polymeric dispersants promotes the formation of particularly small particles of some active substances, as described in more detail by the following examples. In particularly preferred cases, the active substance does not crystallize too rapidly and forms an oil dispersed in water.

[0041] In practice, the composite of the present invention can be prepared from molten or nearly molten urea in which one or more active substances of component (a) are dissolved and then cooled sufficiently rapidly, typically in less than 1 minute, to prevent or minimize phase separation when the urea solidifies. In some cases, fine amorphous particles of one or more active substances of component (a) present in the urea matrix prior to hydrolysis are observed, which is also satisfactory since these particles also provide improved bioavailability when they are released. This method is compatible with well-known and commercially implemented methods for the production of agricultural formulations on a scale that includes (hot melt) extrusion, spray drying, and prilling. In addition, this method is suitable for pharmaceutical active substances for which a relatively high loading of the active substance and rapid release are beneficial compared to amorphous solid dispersions.

[0042] Methods and compositions known from prior art pesticides can co-extrude with urea to form a mechanical mixture (a "tight dispersion") of pesticides having a melting point lower than that of urea. In these cases, a solid solution of the pesticide is not formed. In other methods from the prior art, the urea and active ingredient particles are mixed and thermally fused rather than forming a single phase.

[0043] The distinction between the present invention and the prior art, where urea is typically used as a binder or "carrier" for the active particles, is clear evidence of a molecular-scale interaction between urea and the agrochemical, which can be described as "solvation". The prior art does not suggest that urea and the active substance mix at the molecular level: urea may act only as a coating and carrier for the active substance, rather than as a "solvent" for the active substance.

[0044] In contrast, the composites of the present invention are typically prepared from a molten or nearly molten mixture of the active ingredient and urea, although it is sometimes advantageous to add a small amount of water to lower the melting point of urea and thus the processing temperature. As will be described later, one or more additional components, such as dispersants, wetting agents, or other surfactants, are often components of the melt to provide wetting when the composite is added to water and for other purposes. One or more active substances of component (a) must be organic compounds, not in the form of inorganic salts, typically having a molecular weight of less than 800 daltons and a melting point of 55 °C or higher. One or more active substances of component (a) must have sufficient thermal stability for such processing, which usually means that no significant degradation should occur at temperatures in the range of about 75 °C to 110 °C for up to 30 minutes.

[0045] The present invention can also be regarded as an improved version of an approach used in both the agricultural and pharmaceutical fields known as "matrix encapsulation". The active ingredient is dissolved in a water-soluble matrix, typically a polymer, and released in molecular form when dissolved in a spray tank (for agricultural sprays) or the stomach (for pharmaceuticals). Although other methods have been demonstrated, it has now been found that, for example, by forming a solution in a molten solution and rapidly cooling, a surprisingly wide range of agricultural agrochemicals can be incorporated into a urea matrix.

[0046] The compositions or products of the present invention differ in that they are mainly solutions of active substances in urea and are formed in a molten, semi-molten or almost molten (softened) state. Thus, the compositions or products of the present invention can be prepared from the melt, both by casting on the surfaces or melt extrusion described below, or, for example, by prilling and spray drying, or by hot melt extrusion. According to the present invention, the particles of the active ingredient mainly do not exist as a mechanical mixture with urea, but are formed when urea is dissolved in water or an aqueous surfactant solution (for example, when generating an application mixture). In this way, the active substance can be obtained with a much smaller particle size and improved bioavailability compared to the prior art.

[0047] The object of the present invention was not only to achieve a rapid release of the active substance from the urea complex and a high or improved bioavailability of the active substance, but also to enable a higher efficacy of the active substance, in particular a high filling amount of the active substance in the composition or complex. Such a higher filling amount can be achieved in the urea matrix in the present invention since the dissolution process is carried out at a high temperature. The filling amount of conventional emulsifiable concentrate (EC) formulations is limited by the solubility of the active substance at room temperature (about 25 °C).

[0048] The urea complex (composition or product) of the present invention containing an agrochemical active ingredient is superior to the conventional methods for enhancing the activity of agrochemical active ingredients having low solubility in water, which is much cheaper than the polymers usually used for matrix encapsulation by urea, enables a moderate high filling amount of the composition according to the present invention (typically in the range of about 10% to about 30% by weight based on the total weight of the composition or product), and has value both as a phytohormone and as an adjuvant for improving the uptake of the active ingredient from the leaf surface. In addition, when formulated, the urea complex in powder form exhibits excellent dissolution and dispersion properties.

[0049] Urea complexes of herbicides such as atrazine, tembotrione, and mesotrione have been prepared. For example, the atrazine complex has shown improved control of velvetleaf weeds in greenhouses. Urea matrix encapsulation according to the present invention has been demonstrated to stabilize mesotrione and tembotrione against degradation. Also, complexes of fungicides and nematicides have been prepared.

[0050] The compositions of the present invention typically Component (a) in a total amount in the range of 5 wt% or more, 6 wt% or more, 7 wt% or more, typically 8 wt% or more, more typically 10 wt% or more, typically from 5 wt% to 35 wt%, 6 wt% to 33 wt%, 7 wt% to 32 wt%, 8 wt% to 31 wt%, or 10 wt% to 30 wt%, and / or Component (b) in a total amount in the range of 50 wt% or more, 60 wt% or more, typically from 50 to 90 wt%, 60 to 85 wt%, often 65 to 80 wt%, and / or Component (c) in a total amount of 2 wt% or more, 3 wt% or more, 4 wt% or more, 5 wt% or more, 8 wt% or more, often 10 wt% or more comprising, wherein the amounts indicated in each case are based on the total weight of the composition.

[0051] The compositions of the present invention typically Component (a) in a total amount in the range of 5% to 35%, 6% to 33%, or 7% to 32%, and / or Component (b) in a total amount in the range of 50 to 90 wt%, 60 to 85 wt%, 65 to 80 wt%, and / or Component (c) in a total amount of 4 wt% or more, 5 wt% or more, 8 wt% or more comprising, wherein the amounts indicated in each case are based on the total weight of the composition.

[0052] The compositions of the present invention typically Component (a) in an amount in the range of 7% to 32%, 8% to 31%, or 10% to 30%, Component (b) in an amount in the range of 50 to 90% by weight, 60 to 85% by weight, or 65 to 80% by weight and Component (c) in an amount of 5% by weight or more, 8% by weight or more, or 10% by weight or more comprising, wherein the amounts indicated in each case are based on the total weight of the composition.

[0053] The melting point of component (a) of the composition according to the invention is typically in the range of about 55 °C to about 350 °C at 1013 mbar.

[0054] The melting point of component (a) of the composition according to the invention is more typically in the range of about 60 °C to about 300 °C at 1013 mbar.

[0055] One or more active ingredients of component (a) of the composition according to the invention typically have a molecular weight of less than about 800 Daltons.

[0056] One or more active ingredients of component (a) of the composition according to the invention typically have a molecular weight in the range of about 200 Daltons to about 800 Daltons.

[0057] One or more active ingredients of component (a) of the composition according to the invention typically have a molecular weight in the range of about 200 Daltons to about 700 Daltons.

[0058] One or more active ingredients of component (a) of the composition according to the invention more typically have a molecular weight in the range of about 210 Daltons to about 600 Daltons.

[0059] One or more active ingredients of component (a) of the composition according to the invention more typically have a molecular weight in the range of about 210 Daltons to about 500 Daltons.

[0060] In some cases, one or more active ingredients of component (a) of the composition according to the invention typically have a molecular weight in the range of about 300 Daltons to about 600 Daltons.

[0061] In some cases, one or more active ingredients of component (a) of the composition according to the invention typically have a molecular weight in the range of about 320 Daltons to about 500 Daltons.

[0062] One or more active ingredients of component (a) of the composition according to the invention typically have a solubility of 20 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0063] One or more active ingredients of component (a) of the composition according to the invention typically have a solubility of 10 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0064] One or more active ingredients of component (a) of the composition according to the invention more typically have a solubility of 5 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0065] One or more active ingredients of component (a) of the composition according to the invention even more typically have a solubility of 2 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0066] One or more active ingredients of component (a) of the composition according to the invention even more typically have a solubility of 1 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0067] One or more active ingredients of component (a) of the composition according to the invention have a solubility of typically at least about 10 g / L in acetone at 25 °C and 1013 mbar.

[0068] One or more active ingredients of component (a) of the composition according to the invention have a solubility of typically at least about 15 g / L in acetone at 25 °C and 1013 mbar.

[0069] One or more active ingredients of component (a) of the composition according to the invention have a solubility of more typically at least about 25 g / L in acetone at 25 °C and 1013 mbar.

[0070] One or more active ingredients of component (a) of the composition according to the invention have a solubility of more typically at least about 40 g / L in acetone at 25 °C and 1013 mbar.

[0071] In a particular composition according to the invention, the weight ratio of the total amount of component (c) to the total amount of component (a) is typically in the range of about 0.1 to about 0.65, based on the total weight of the composition.

[0072] In a particular composition according to the invention, the weight ratio of the total amount of component (c) to the total amount of component (a) is more typically in the range of about 0.2 to about 0.55, based on the total weight of the composition.

[0073] In a particular composition according to the invention, the weight ratio of the total amount of component (c) to the total amount of component (a) is even more typically in the range of about 0.25 to about 0.50, based on the total weight of the composition.

[0074] In a particular composition according to the invention, the total amount of water in the composition is typically less than about 15% by weight, based on the total weight of the composition.

[0075] In a particular composition according to the invention, the total amount of water in the composition is more typically less than about 10% by weight, based on the total weight of the composition.

[0076] In a particular composition according to the invention, the total amount of water in the composition is even more typically less than about 5% by weight, based on the total weight of the composition.

[0077] The composition according to the present invention can contain water, and when present, based on the total weight of the composition, typically the total amount is in the range of about 0.1% by weight to about 5% by weight.

[0078] In a specific composition according to the present invention, the total amount of component (c) in the composition is typically at least about 4% by weight based on the total weight of the composition.

[0079] In a specific composition according to the present invention, the total amount of component (c) in the composition is typically at least about 5% by weight based on the total weight of the composition.

[0080] In a specific composition according to the present invention, the total amount of component (c) in the composition is more typically at least about 6% by weight based on the total weight of the composition.

[0081] In a specific composition according to the present invention, the total amount of component (c) in the composition is more typically at least about 7% by weight based on the total weight of the composition.

[0082] In a specific composition according to the present invention, the total amount of component (c) in the composition is even more typically at least about 8% by weight based on the total weight of the composition.

[0083] In a specific composition according to the present invention, the total amount of component (c) in the composition is even more typically at least about 10% by weight based on the total weight of the composition.

[0084] An exact description of the microstructure of the compositions or products of the present invention is not easy due to the somewhat inconsistent nomenclature used in this technical field. As described in Chem. Commun., 2014, 50, 904 - 923, compositions similar to those of the present invention have been variously described as "eutectics", "cocrystals", or "solid solutions", and in the case of urea, the terms "inclusion compounds" and "clathrate" may also be used.

[0085] Eutectics are a long-known type of multi-component solid with important and useful applications in daily life. Compared to other multi-component crystalline solids such as salts, solid solutions, molecular complexes, and cocrystals, eutectics have been less studied from the perspectives of molecular structure organization and binding interactions. Classically, eutectics are defined based on their low melting points compared to the individual components. The X-ray crystal structure of cocrystals is different from that of the individual components, while the unit cell of a solid solution is similar to that of one of the components. Eutectics are close to the latter type in that the crystal arrangement resembles that of the parent components, but they differ in terms of structural integrity. Solid solutions have structural uniformity throughout the entire structure (single phase), while eutectics have a crystal structure that is a heterogeneous aggregate of individual components like a discontinuous solid solution (phase separation). Therefore, it may be more appropriate to define eutectics as an aggregate of solid solutions. Structural analysis of cocrystals, solid solutions, and eutectics has shown that materials with strong adhesive (hetero) interactions between different components result in cocrystals, while materials with stronger cohesive (homo / self) interactions more often result in solid solutions (when the structures of the components are similar) and eutectics (when the structures of the components are different).

[0086] The powder X-ray diffraction data obtained so far suggest that the compositions of the present invention retain the general structure of urea and are best explained as solid solutions.

[0087] Thus, without being restricted by one or another literature definition of "solid solution" or "inclusion complex", the compositions of the present invention can be readily and functionally recognized and distinguished from the prior art by their single-phase appearance under the microscope, their low melting point compared to urea, and most importantly, the rapid release of the active substance from the urea matrix as a liquid or as a nanoparticle solid with improved biological activity upon hydrolysis. Apparent similar materials in the prior art do not share these properties because urea only acts as a binder or carrier for relatively large active ingredient microparticles.

[0088] As further described in the examples, the properties and hydrolysis behavior of the urea compositions and products of the present invention are significantly different from those of the prior art compositions in which urea mainly acts as a binder.

[0089] In particular - When the composition or product of the present invention is dissolved in water, certain water-insoluble active substances are released as a liquid from the urea, even though the active substance is solid at room temperature. This behavior has not been explained heretofore and indicates that the active substance exists as a dispersed molecule rather than as microparticles in the urea matrix since the microparticles are released as solids. This behavior has been observed for the urea complexes of the present invention having pesticidal active ingredients such as fluopyram, tetraniliprole, and tembotrione as described in the examples below; - When examined under the microscope, a single-phase appearance of the compositions and products of the present invention was observed and the presence of inclusions was not observed. Discrete active microparticles larger than about 5 microns can be reliably excluded in the compositions and products of the present invention; and - Proven by the virtual absence of discrete microparticles of one or more active ingredients when viewed under an optical microscope having a resolution sufficient to identify inclusions having a diameter of 3 microns or more. Typically, a magnification of 20 times is required for this.

[0090] With respect to the present invention, the terms "substantial" or "substantially" refer to 90%, typically 95%, based on the total weight of the composition or product.

[0091] The eutectic behavior of the compositions and products of the present invention containing active substances such as fluopyram enables extrusion at a temperature of about 90 °C, which is considerably lower than the melting points of urea or the active substance alone.

[0092] In certain embodiments, when the decrease in the melting point of the composition or product according to the present invention is measured by differential scanning calorimetry (DSC), it is at least 2 °C lower than the melting point of pure urea. This technique is known in the art and is illustrated in Example A9 below.

[0093] In many cases, the compositions and products according to the present invention are substantially homogeneous (i.e., components (a) and (b), and at least a substantial amount or all of component (c) are present in the same phase). Typically, the compositions and products according to the present invention are substantially single-phase compositions or single-phase products, sometimes also referred to in the art as solid dispersions or solid solutions. The microstructure depends significantly on the properties of component (a).

[0094] In this regard, it has been observed in the analysis by the inventors that the compositions according to the present invention can be in the form of a solid solution in a mixture with a part of the solid non-complexed component (a).

[0095] In a particularly preferred embodiment, the non-complexed portion comprises an anionic dispersant or a combination of an anionic dispersant and a specific non-ionic dispersant. Ionic compounds such as ionic dispersants are not soluble in urea, so these components form a separate phase. Preferably, the dispersant in this phase is readily soluble in water. The presence of a second phase containing an anionic dispersant promotes the dispersion of the formulation when added to water. This phase is thought to divide the urea solid solution phase into smaller regions and facilitate their dissolution.

[0096] Preferred anionic components of the non-complexed phase include, for example, alkylated diphenyl ether disulfonates, doxate sodium, or mono- and diester-sulfosuccinates such as Aerosol® surfactants from Solvay, lignosulfonates, alkylnaphthalene sulfonates, and copolymers of maleic acid and alkenes, such as Sokalan® CP-9 from BASF, which are commercially available as sodium salt solutions from Dow (Dowfax®) and Pilot Chemical (Calfax®).

[0097] Suitable polymers or highly branched nonionic surfactants for the non-complexed phase include block copolymers of ethylene oxide and propylene oxide such as tristyrylphenol ethoxylate, castor oil ethoxylate, the Pluronic® series from BASF, and the polyglycidyl ether polyethylene glycol block copolymer Break-thru® DA 675 from Evonik.

[0098] In a further embodiment, the composition or product according to the invention is an inclusion complex.

[0099] In a further embodiment, the composition or product according to the invention is a solid solution.

[0100] In a further embodiment, when the composition or product according to the invention is added to water having a pH of about 7 at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product, nanoparticles of one or more active ingredients of component (a) having a particle size of 100 nm or less are formed as determined by dynamic light scattering.

[0101] In other embodiments, one or more active ingredients of component (a) of the composition or product according to the invention are present substantially in liquid form when the composition or product is added to water having a pH of about 7 at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product.

[0102] In certain other embodiments, one or more active ingredients of component (a) of the composition or product according to the invention are present substantially in liquid form when the composition or product is added to a 1 wt% solution of one or more emulsifying surfactants in water, for example typically tristyrylphenol ethoxylate, at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product.

[0103] In other embodiments, one or more active ingredients of component (a) of the composition or product according to the invention are present substantially in liquid form when the composition or product is added to water having a pH of about 7 at 25 °C and 1013 mbar or to a 1 wt% solution of one or more emulsifying surfactants (e.g., typically tristyrylphenol ethoxylate) in water at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product, where the active ingredient of component (a) is present substantially in (emulsified) liquid form for at least 30 minutes.

[0104] It should be noted that oleic acid used in some urea-based compositions described in the prior art is not a non-ionic surfactant.

[0105] Typically in the composition or product according to the invention, at least one non-ionic surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 3 or more.

[0106] Typically, in the compositions or products according to the present invention, at least one nonionic surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 4 or more.

[0107] Typically, in the compositions or products according to the present invention, at least one nonionic surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 5 or more.

[0108] Typically, in the compositions or products according to the present invention, at least one nonionic surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 6 or more.

[0109] More typically, in the compositions or products according to the present invention, component (c) has a hydrophilic-lipophilic balance (HLB) value of about 3 or more.

[0110] More typically, in the compositions or products according to the present invention, component (c) has a hydrophilic-lipophilic balance (HLB) value of about 4 or more.

[0111] More typically, in the compositions or products according to the present invention, component (c) has a hydrophilic-lipophilic balance (HLB) value of about 5 or more.

[0112] More typically, in the compositions or products according to the present invention, component (c) has a hydrophilic-lipophilic balance (HLB) value of about 6 or more.

[0113] In certain compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of (poly)alkoxylated alcohols, (poly)alkoxylated phosphate esters, and (poly)alkoxylated tristyrylphenols.

[0114] The above (poly)alkoxylated phosphate ester is a phosphate ester in a substantially free acid form, i.e., not in a salt form. Therefore, the above (poly)alkoxylated phosphate ester is not neutralized.

[0115] In certain compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of (poly)alkoxylated linear saturated or monounsaturated C 12 -C 18 -alcohols and (poly)alkoxylated phosphate esters of linear saturated or monounsaturated C 12 -C 18 -alcohols.

[0116] In various compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants having a degree of alkoxylation in the range of about 2 to about 14.

[0117] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants having a degree of alkoxylation in the range of about 4 to about 10.

[0118] In another embodiment, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of (poly)ethoxylated linear saturated or monounsaturated C 12 -C 18 -alcohols and (poly)ethoxylated phosphate esters of linear saturated or monounsaturated C 12 -C 18 -alcohols.

[0119] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants containing about 2 to about 14 ethylene glycol units (PEG-2 to PEG-14).

[0120] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants containing from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10).

[0121] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of tristyrylphenol ethoxylates.

[0122] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of tristyrylphenol ethoxylates containing from about 6 to about 80 ethylene glycol units (PEG-6 to PEG-80).

[0123] In still other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of tristyrylphenol ethoxylates containing from about 10 to about 60 ethylene glycol units (PEG-10 to PEG-60).

[0124] In certain compositions and products of the present invention, the total amount of component (c) is in the range of about 2 wt% to 20 wt% based on the total weight of the composition.

[0125] In certain compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of ethoxylated linear saturated or monounsaturated C 12 -C 18 -alcohols having from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10), wherein the total amount of component (c) is in the range of about 4 wt% to about 20 wt% based on the total weight of the composition.

[0126] In the various compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of ethoxylated phosphate esters of linear saturated or mono-unsaturated C 12 -C 18 -alcohols having from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10), wherein the total amount of component (c) is in the range of about 2 wt% to about 10 wt% based on the total weight of the composition.

[0127] Suitable linear alcohol ethoxylates as component (c) of the compositions and products of the present invention are commercially available from many sources such as Shell Chemical (Neodol™), Dow (Tergitol™), or Croda (Brij™ and Synperonic™), and BASF (Lutensol™).

[0128] These surfactants are co-formulated in the same urea matrix as the active ingredient (component (a)). One function of the nonionic surfactant of component (c) of the composition or product of the present invention is to stabilize the urea complex structure, and the nonionic surfactant is incorporated into the urea complex, resulting in a more easily handled, e.g., harder composition or product that allows for better extrusion.

[0129] Oleyl and other unsaturated alcohol ethoxylates can be effectively used with respect to the present invention, but ethoxylated linear saturated alcohols containing 12 to 18 carbons (C 12 -C 18 ) have been found to be suitable for the desired (excellent) hardness of the resulting composition or product of the present invention.

[0130] The second function of the non-ionic (neutral) surfactant of component (c) is to provide wetting when the composition or product of the present invention is added to water. Particularly suitable surfactants for providing effective wetting and a harder extruded composition or product are C12 - C18 linear saturated alcohols functionalized with PEG-5 to PEG-10 chains. Examples of this particularly suitable class are Synperonic™ 13 / 6 (tridecyl alcohol PEG-6, Croda), Synperonic™ A7 (C12-15 alcohol, PEG-7, Croda) and Lutensol™ TDA 6 (tridecyl alcohol PEG-6, BASF).

[0131] For certain active substances, such as active substances stabilized by the presence of an acid, the non-ionic surfactant typically contains an acidic group that is not neutralized. Acid form phosphate ester surfactants are suitable for this purpose as they can be easily incorporated into the urea matrix together with the active substance. Phosphate ester surfactants are well known in the art and are commercially available from, for example, BASF and Croda. The polyethylene glycol (PEG) chain may be preferred over a mixed chain of polyethylene glycol and polypropylene glycol. For this aspect of the present invention, Agnique™ PE TDA 9 (tridecyl phosphate PEG-9, BASF) and Crodafos™ O5A (oleyl phosphate PEG-5, Croda) are suitable phosphate ester surfactants for component (c).

[0132] These phosphate ester surfactants in acid form (i.e., without neutralization) are co-incorporated into the urea in the composition or product of the present invention, enhancing the stability of certain pH-sensitive active substances such as triketone herbicides like tembotrione or mesotrione. The stability of these active substances is improved by the incorporation of the acid form phosphate ester surfactant, as further described in the examples.

[0133] As also described in the examples, incorporating certain acids such as phosphoric acid (which can be used as a liquid (e.g., 85% in water) or as a solid) or methanesulfonic acid (which can be used as a liquid (e.g., 70% in water) or as a solid) into the compositions or products of the present invention is an effective means for stabilizing pH-sensitive active ingredients such as mesotrione, tembotrione, or isoxaflutole. Phosphoric acid, which is preferably incorporated into the compositions or products of the present invention containing active ingredients that require a low pH for chemical stability, such as mesotrione, tembotrione, or isoxaflutole. The amount of these acids depends on the amount of active ingredient present in the composition or product of the present invention, as well as the amount and type of further components therein. Generally, the amount of phosphoric acid or methanesulfonic acid is in the range of about 0.3 wt% to about 1.5 wt%, typically in the range of about 0.6 wt% to about 1.2 wt%, based on the total amount of the composition or product of the present invention.

[0134] Optionally, the compositions and products of the present invention include, as component (d), one or more polymer dispersants different from component (c).

[0135] A further embodiment of the present invention involves the hydrolysis of urea complexes in the presence of a water-soluble dispersant polymer. A suitable polymer concentration in the hydrolysis mixture is 0.1% to 0.6% on a soluble basis. It has been found that urea complexes of certain active substances form small particles with improved bioavailability when hydrolysis is carried out in a solution of a suitable polymer dispersant. As described in the examples, for example, prothioconazole and tembotrione urea complexes are particularly suitable for such embodiments. Amphiphilic water-soluble polymers such as Sokalan™ CP 9 (BASF) and Geropon™ TA / 72 (Solvay) are suitable water-soluble polymer dispersants.

[0136] Typically, one or more dispersants are added to stabilize the particle suspension. Polymer dispersants such as Sokalan™ CP 9 (BASF), Atlox™ 4914 and Atlox™ 4915 (Croda) and Break-thru™ DA-647 (Evonik) are suitable dispersants for this aspect of the invention, as are lignosulfonates such as those sold by Borregaard and Ingevity.

[0137] A further aspect of the invention is particularly applicable to urea complexes prepared by slow cooling, as described below and in the examples. Compositions and formulations prepared by slow cooling tend to form larger active particles upon hydrolysis of the urea complex. Thus, incorporation of a dispersant into the composition or formulation of the invention can be beneficial in maintaining the suspension of active particles in water. Typically, a lignosulfonate dispersant in powder form is dry mixed with the urea complex in an amount of from about 10 wt% to about 30 wt%. Dispersants of these classes are well known in the art for maintaining particle suspension and suppressing aggregation. Particularly suitable dry powder dispersants for this aspect of the invention are Agnique™ DDL (BASF) and Ultrazine™ NA (Borregaard).

[0138] When present in a composition or product according to the invention, component (d) comprises or consists of one or more polymer dispersants different from component (c), and component (d) is selected from the group consisting of polycarboxylates and their salts, maleic anhydride-isobutylene copolymers and their salts, and (block) copolymers of styrene oxide and ethylene oxide, lignosulfates, and mixtures thereof.

[0139] When present in the composition or product according to the invention, component (d) comprises or consists of one or more polymer dispersants different from component (c), and component (d) typically consists of a group selected from polycarboxylates and sodium salts, maleic anhydride-isobutylene copolymers and their sodium salts, and (block) copolymers of styrene oxide and ethylene oxide, and mixtures thereof.

[0140] Particularly preferred polymer dispersants in the specification according to the invention are, for example, Geropon™ TA / 72 (Solvay), water-soluble sodium polycarboxylate, Sokalan™ CP 9 (BASF), copolymers of maleic acid and olefins as sodium salts, and / or Break-thru™ DA-647 (Evonik), nonionic modified copolymers of styrene oxide and ethylene oxide.

[0141] Typically, the polymer dispersant of component (d) has a molecular weight M of about 1000 g / mol or more n , for example, in the range of about 1000 g / mol to about 200000 g / mol n having.

[0142] When present in the composition or product according to the invention, the total amount of component (d) is typically in the range of about 1 to about 15% by weight, based on the total weight of the composition or product.

[0143] When present in the composition or product according to the invention, the total amount of component (d) is more typically in the range of about 2 to about 12% by weight, based on the total weight of the composition or product.

[0144] When present in the composition or product according to the invention, the total amount of component (d) is more typically in the range of about 3 to about 9% by weight, based on the total weight of the composition or product.

[0145] Optionally, the compositions and products of the present invention include, as component (e), one or more wetting agents that are optionally different from (c) and (d).

[0146] Suitable examples of such wetting agents (wetters) include ethoxylates of branched alcohols, in particular Guerbet alcohol ethoxylates commercially available as Lutensol® XL50 - XL80 from BASF. Alkyl polyglucosides such as Agnique® PG 8105 and Agnique® PG 264 (BASF) are also suitable wetting agents, but since these substances are supplied in water, they tend to result in a softer rheology of the composition or product.

[0147] Therefore, effective wetting agents that are commercially available in the form of dry powders and are readily soluble in water are particularly suitable in this aspect of the present invention. Particularly suitable dry wetting agents having a non - linear structure include, for example, Morwet® D - 425 (alkylnaphthalenesulfonate condensate, Nouryon) and Agnique® ANS 3DNPW (BASF). Another example of a particularly suitable wetting agent is Morwet® EFW (alkylnaphthalenesulfonate condensate, Nouryon).

[0148] When present in the composition or product of the present invention, component (e) typically comprises or consists of one or more wetting agents having a non - linear structure, and component (e) is different from components (c) and (d).

[0149] When present in the composition or product of the present invention, component (e) comprises or consists of one or more wetting agents that are different from components (c) and (d), and component (e) is typically selected from the group consisting of Guerbet alcohol ethoxylates, alkyl polyglucosides, alkylnaphthalenesulfonate condensates, and mixtures thereof.

[0150] When present in the composition or product of the present invention, component (e) comprises or consists of one or more wetting agents different from components (c) and (d), wherein component (e) is more typically selected from the group consisting of ethoxylated branched alcohols.

[0151] When present in the composition or product of the present invention, component (e) comprises or consists of one or more wetting agents different from components (c) and (d), and component (e) is more typically selected from the group consisting of alkylnaphthalenesulfonate condensates.

[0152] When present in the composition or product according to the present invention, the total amount of component (e) is typically in the range of about 5 to about 30% by weight, based on the total weight of the composition or product.

[0153] When present in the composition or product according to the present invention, the total amount of component (e) is typically in the range of about 5 to about 20% by weight, based on the total weight of the composition or product.

[0154] Optionally, the compositions and products of the present invention comprise, as component (f), one or more water-soluble polymer binders different from components (c), (d) and (e).

[0155] In certain embodiments, the urea complex of the present invention is typically prepared from a melt. The components of the melt can be prepared by mixing in an open or closed container, by circulation in an extruder, by use of a sigma mixer or a planetary mixer, or by any other common mixing technique known in the art that can control the temperature. When the composition or product according to the present invention is obtained by extrusion with mixing, it may be advantageous to first add one or more surfactants to provide lubrication.

[0156] When water is added to lower the melting point of the mixture, it is typically less than 10% by weight of the total mass of the composition. In particular, during extrusion molding, an aqueous solution of a water-soluble polymer that can act as a binder can be used.

[0157] When present in the composition or product of the present invention, component (f) is typically selected from the group consisting of cellulose ethers and their salts, and comprises or consists of one or more water-soluble polymer binders different from components (c), (d) and (e).

[0158] When present in the composition or product of the present invention, component (f) is typically selected from the group consisting of methylcellulose polymers, water-soluble hydroxypropylmethylcellulose, their salts, and mixtures thereof, and comprises or consists of one or more water-soluble polymer binders different from components (c), (d) and (e).

[0159] Suitable cellulose ethers as the water-soluble polymer binder of component (f) are available, for example, under the trade name Methocel® from International Flavors and Fragrances. Methocel® J12MS is a particularly suitable binder in the context of the present specification.

[0160] When present in the composition or product according to the present invention, the total amount of component (f) is typically in the range of about 0.5 to about 3% by weight, based on the total weight of the composition or product.

[0161] In a particular composition or product of the present invention, the total amount of methanol in the composition or product is less than about 1% by weight, based on the total weight of the composition or product.

[0162] In a particular composition or product of the present invention, the total amount of ethanol in the composition or product is less than about 1% by weight, based on the total weight of the composition or product.

[0163] In other compositions or products, C in the composition or product 1 -C 6 The total amount of alcohol is less than about 1% by weight based on the total weight of the composition or product.

[0164] In a specific composition or product of the present invention, the total amount of oleic acid in the composition or product is less than about 1% by weight based on the total weight of the composition or product.

[0165] In various compositions or products of the present invention, the total amount of the components in salt form in the composition or product is about 10% by weight or less based on the total weight of the composition or product.

[0166] In other compositions or products of the present invention, the total amount of the components in salt form in the composition or product is about 5% by weight or less based on the total weight of the composition or product.

[0167] Therefore, the compositions or products of the present invention typically do not substantially contain components in salt form.

[0168] When component (a) contains or consists of one or more pesticidal active ingredients, these can be selected from the group consisting of pesticidal active ingredients that meet the structural and physical criteria defined for the present invention.

[0169] Typically, component (a) of the compositions, products and application mixtures according to the present invention contains or consists of one or more pesticidal active ingredients, and component (a) typically contains or consists of one or more active ingredients selected from the group consisting of fungicides, herbicides, insecticides, nematicides, acaricides, molluscicides, bactericides, and phytotoxicity reducing agents.

[0170] The pesticidal active ingredients (pesticides), phytotoxicity reducing agents, and general names used herein that can be used as component (a) of the compositions, products, and application mixtures according to the present invention are known in the art; see, for example, "The Pesticide Manual", 16th Edition, British Crop Protection Council 2012; these include known stereoisomers (especially racemates and pure isomers of enantiomers) and derivatives such as salts or esters, especially commercially customary forms when the criteria for component (a) as defined in the present invention are met. Unless otherwise restricted, when a pesticide is generally referred to herein by its common name, the pesticide includes all forms known in the art such as salts, esters, free acids and free bases, and their stereoisomers.

[0171] Component (a) comprises or consists of one or more herbicides, and the one or more herbicides are acetyl-CoA carboxylase (ACCase) inhibitors, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitors, glutamine synthetase inhibitors, auxins, photosystem I (PS I) inhibitors, photosystem II (PS II) inhibitors, acetolactate synthase (ALS) or acetohydroxyacid synthase (AHAS) inhibitors, mitotic inhibitors, protoporphyrinogen oxidase (PPO) inhibitors, 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors, cellulose inhibitors, oxidative phosphorylation uncouplers, dihydropteroate synthase inhibitors, fatty acid and lipid biosynthesis inhibitors, auxin transport inhibitors and carotenoid biosynthesis inhibitors, their salts and esters, their racemic mixtures and resolved isomers, and mixtures thereof.

[0172] When component (a) contains or consists of one or more insecticides, the one or more insecticides can be selected from the group consisting of organic (thio) phosphates, carbamates, pyrethroids, insect growth regulators, chitin synthesis inhibitors, insect steroid hormone antagonists, juvenoids, lipid biosynthesis inhibitors, nicotinic acetylcholine receptor disruptors, allosteric modulators, biopesticides, GABA antagonist compounds, mitochondrial electron transport inhibitors, uncouplers, oxidative phosphorylation inhibitors, molting disruptors, oxidase inhibitors, sodium channel blockers, ryanodine receptor inhibitors, their esters, their racemic mixtures and resolved isomers, and mixtures thereof.

[0173] When component (a) contains or consists of one or more fungicides, the one or more fungicides can be selected from the group consisting of respiration inhibitors (such as inhibitors of complex II, inhibitors of complex III, etc.), sterol biosynthesis inhibitors (such as C14 demethylase inhibitors, delta14-reductase inhibitors, inhibitors of 3-ketoreductase, etc.), nucleic acid synthesis inhibitors (phenylamides or acylamino acid fungicides, other nucleic acid inhibitors), inhibitors of cell division and the cytoskeleton (such as tubulin inhibitors or other cell division inhibitors, etc.), inhibitors of amino acid and protein synthesis (such as methionine synthesis inhibitors, protein synthesis inhibitors, etc.), signal transduction inhibitors (MAP / histidine kinase inhibitors, G protein inhibitors), lipid and membrane synthesis inhibitors (such as phospholipid synthesis inhibitors, lipid peroxidation inhibitors, phospholipid biosynthesis and cell wall deposition inhibitors, acid amide hydrolase inhibitors, etc.), multi-site acting inhibitors, cell wall inhibitors (such as glucan synthesis inhibitors, melanin synthesis inhibitors, etc.), plant defense inducers, their racemic mixtures and resolved isomers, and mixtures thereof.

[0174] The phytotoxicity reducing agent related to the present invention is typically a herbicide phytotoxicity reducing agent. Typically, the phytotoxicity reducing agent is selected from the group consisting of benoxacor, cloquintocet and its agriculturally acceptable esters, cinmethylin, cyprosulfamide, dichlormid, dicyclonon, dietholate, fenchlorazole and its agriculturally acceptable esters, fenclorim, flurazole, fluxofenim, furilazole, isoxadifen and its agriculturally acceptable esters, mefenpyr and its agriculturally acceptable esters, mefenate, metcamifene, naphthalic anhydride, oxabetrinil, and mixtures thereof.

[0175] Regarding the present invention, component (a) typically contains or consists of an agrochemical active substance selected from the group consisting of chlorotriazine herbicides, pyridine fungicides, aryloylcyclohexanedione herbicides, carbamate herbicides, conazole fungicides, pyridylpyrazole insecticides, and mixtures thereof.

[0176] Regarding the present invention, component (a) more typically contains or consists of an active substance selected from the group consisting of atrazine, cyprosulfamide, fluopyram, isoxaflutole, mesotrione, fenmedifam, prothioconazole, tembotrione, tetraniliprole, and mixtures thereof.

[0177] In a specific embodiment of the present invention, component (a) contains or consists of tembotrione, mesotrione, fenmedifam, or a combination thereof.

[0178] In another embodiment of the present invention, component (a) contains or consists of fluopyram.

[0179] In another embodiment of the present invention, component (a) contains or consists of tetraniliprole.

[0180] When the component (a) contains or consists of one or more pharmaceutically active ingredients, these can be selected from the group of pharmaceutically active ingredients that meet the structural and physical criteria defined for the present invention.

[0181] Suitable pharmaceutically active ingredients are, for example, blood coagulation inhibitors such as rivaroxaban, which can reduce the risk of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and similar conditions.

[0182] Suitable pharmaceutically active ingredients are, for example, anticancer and anti-angiogenic agents such as regorafenib, which have various activities including inhibitory activity against VEGFR, PDGFR, raf, p38, and / or flt-3 kinase signaling molecules, and can be used for the treatment of various diseases and conditions such as hyperproliferative diseases like cancer, tumors, lymphomas, sarcomas, and leukemia.

[0183] Other suitable pharmaceutically active ingredients are, for example, dihydropyridine-type calcium antagonists such as nitrendipine, nimodipine, or lacidipine. Nimodipine is, for example, an antihypertensive agent that can reduce brain damage caused by bleeding from ruptured blood vessels.

[0184] In a further aspect, the present invention relates to a product that can be obtained or is obtained by extrusion of a composition as defined for the present invention, wherein the extrusion temperature is typically in the range of about 85°C to about 110°C, and then the molten composition is cooled to a temperature below 55°C.

[0185] In a further aspect, the present invention relates to a product that can be obtained or is obtained by melting a composition as defined for the present invention and then cooling the molten composition to a temperature below 55°C, wherein typically the melting of the composition is carried out such that the temperature of the molten composition is in the range of about 75°C to about 110°C.

[0186] The product according to the invention typically contains methanol and / or ethanol in a total amount of less than about 1% by weight, based on the total weight of the product.

[0187] The product according to the invention typically contains C 1 -C 6 alcohol in a total amount of less than about 1% by weight, based on the total weight of the product.

[0188] The product according to the invention typically contains oleic acid in a total amount of less than about 1% by weight, based on the total weight of the product.

[0189] In a further aspect, the invention relates to a formulation comprising a composition or product as defined herein with respect to the invention, further comprising one or more additional components selected from the group consisting of adjuvants, liquid components at 25°C and 1013 mbar, solid active components at 25°C and 1013 mbar, and mixtures thereof.

[0190] The adjuvant is typically selected from the group of substances well-known as adjuvants in the field of agricultural formulations. Adjuvants that can be included in the formulations of the invention are, for example, antifreeze agents such as alkylene glycols. Suitable antifreeze agents are glycerol or propylene glycol, typically included in an amount in the range of about 3% to about 20% by volume, typically in the range of about 5% to about 15% by volume.

[0191] The formulations of the invention are typically formulations selected from the group consisting of wettable granules (WG), wettable powders (WP), and oil-dispersible wettable powders (OD).

[0192] When the formulation of the invention is an oil-dispersible wettable powder (OD) formulation, the one or more formulation adjuvants are typically selected from the group consisting of oily active ingredients, vegetable oils, oily solvents, and mixtures thereof.

[0193] In one embodiment, the formulation of the present invention is an oil-based dispersible wettable powder (OD) formulation containing an oily solvent, and the oily solvent contains or is a long-chain fatty acid methyl ester, typically soy methyl (soy methyl ester).

[0194] In another embodiment, the formulation of the present invention is an oil-based dispersible wettable powder (OD) formulation containing an oily herbicide, and the oily herbicide contains or is acetochlor.

[0195] In some embodiments, the formulation of the present invention is a wettable granule (WG) formulation or a wettable powder (WP) formulation, and the adjuvant contains or is an emulsifier powder or a powder dispersant.

[0196] In some embodiments, the formulation of the present invention is a wettable granule (WG) formulation or a wettable powder (WP) formulation, and the adjuvant contains or is a dry emulsifier powder or a dry powder dispersant.

[0197] Another aspect of the present invention described in detail by Example 1 below is a method for preparing the urea complex of the present invention by evaporation of an alcohol solution. This method is particularly suitable for laboratory-scale preparations that do not use special equipment such as extruders or spray dryers. In this method, urea, an active substance, and an organic compound typically containing 16 to 65 carbons are combined and completely dissolved in an alcohol solution. Examples of suitable organic compounds are soy methyl and ethoxylates of C12 - C18 alcohols. Macol (trademark) CSA 20 (cetyl-stearyl alcohol PEG-20, BASF) is also a suitable organic compound for this embodiment.

[0198] A further method of obtaining the composition of the present invention is illustrated in Example 3 below. The active substance is dissolved in a mixture of water, urea and a non-ionic surfactant at a high temperature, typically in the range of about 80°C to about 110°C. When the dissolution of the active substance is complete, the active ingredient-urea mixture is added to the oily diluent at the same temperature (or higher) as the urea solution while stirring rapidly. The stirring speed and the amount of oil are typically sufficient to provide a fine emulsion of the urea mixture. The oily diluent is typically a hydrocarbon having a branched structure in order to minimize its solubility in urea which has a boiling point at least 10°C higher than the operating temperature. Isooctane is an oily diluent particularly suitable for this embodiment. Typically, an emulsifier having a branched structure and an HLB of less than 14 is added to the oily diluent. Tween™ 61 (sorbitan stearate PEG-4, HLB 10, Croda) is an emulsifier suitable for this method. The urea complex of the present invention can be isolated by filtration.

[0199] In a further aspect, the present invention is a method for preparing a composition as defined with respect to the present invention, the method comprising the following steps: 1. Combining component (a), (b), (c) and optionally water and one or more further components selected from the group consisting of components (d), (e) and (f) as defined above; 2. Mixing the combination obtained from step 1 at a temperature in the range of about 60°C to about 140°C, typically in the range of about 75°C to about 125°C, more typically in the range of about 80°C to about 110°C; 3. Cooling the composition obtained from step 2. The method is characterized by the above steps.

[0200] The temperature in step 3 is lower than the temperature in step 2 to such an extent that at least a semi-solid product is obtained and it solidifies to the composition according to the invention when further cooled.

[0201] The mixing in step 2 can be carried out using, for example, a stirrer, a twin-screw mixer or other suitable methods known in the art.

[0202] Process 3 includes extrusion, spray drying, spray cooling, granulation, spheronization, combinations thereof, or other means known in the art.

[0203] In a further aspect, the invention relates to a product obtainable or obtained by the method as defined above, wherein when the product is added at 25°C to an amount of water sufficient to dissolve urea, one or more active ingredients of component (a) are substantially present as nanoparticles having a diameter of less than 100 nm as determined by dynamic light scattering.

[0204] In a further aspect, the invention relates to a product obtainable or obtained by the method as defined above, wherein when the product is added at 25°C to an aqueous emulsifier dilution in an amount sufficient to dissolve urea, an emulsion of a liquid of one or more active ingredients of component (a) is obtained, and this emulsion is stable with respect to crystallization of said one or more active ingredients of component (a) at 25°C for at least 30 minutes.

[0205] In a further aspect, the invention relates to an application mixture comprising - the composition or product of the invention as defined above, - water in an amount of at least 10-fold by weight, typically at least 25-fold by weight, more typically at least 50-fold by weight of said composition or product, and - one or more components selected from the group consisting of further adjuvants, other diluents, and other active ingredients and relates to an application mixture.

[0206] In certain embodiments, the application mixture is a spray application mixture.

[0207] In other embodiments, the application mixture is an agricultural spray application mixture.

[0208] In a further aspect, the invention relates to a composition, product or application mixture as defined in the invention, comprising a pesticidal active ingredient, for use in a method of controlling unwanted vegetation, phytophagous pests, (phytopathogenic) fungi or (phytopathogenic) nematodes.

[0209] In a further aspect, the invention relates to a method for controlling unwanted vegetation, phytophagous pests, phytopathogenic fungi or phytopathogenic nematodes, the method comprising applying a composition, product or application mixture as defined in the invention, comprising a pesticidal active ingredient, to the unwanted vegetation, phytophagous pests, phytopathogenic fungi or phytopathogenic nematodes.

[0210] In a further aspect, the invention relates to the use of a composition, product or application mixture as defined in the invention, comprising a pesticidal active ingredient, for controlling unwanted vegetation, phytophagous pests, phytopathogenic fungi or phytopathogenic nematodes.

[0211] In the context of the present invention, phytopathogenic nematodes are in particular plant parasites. Most nematodes that feed on higher plants are obligate parasites. Economically highly impactful plant parasites are for example Meloidogyne spp., Heterodera spp. and Globodera spp.

[0212] In a further aspect, the invention relates to a composition, product or application mixture as defined in the invention, comprising a pharmaceutical active ingredient, for use as a medicament.

[0213] In a further aspect, the invention relates to a composition, product or application mixture as defined in the invention, comprising a pharmaceutical active ingredient, for use in a method of treating the body of an animal or a human.

[0214] In a further aspect, the invention relates to a method of treating a subject in need thereof, the method comprising administering (typically orally) to the subject a pharmaceutically effective amount of a composition, product or application mixture as defined in the invention, comprising a pharmaceutical active ingredient.

[0215] In a further aspect, the invention relates to the use of a composition, product or application mixture as defined in the invention, comprising a pharmaceutically active ingredient, in the treatment of the body of an animal or a human, said composition, product or application mixture typically being orally administered to the body of said animal or human.

[0216] In a further aspect, the invention relates to an application mixture which can be obtained by diluting a composition or formulation of the invention with an appropriate amount of water, or which is obtained, typically for a composition, product or formulation in water, the weight ratio of water to the composition, product or formulation being in the range of from about 200:1 to about 10:1, typically in the range of from about 100:1 to about 20:1.

[0217] Such an application mixture may contain one or more further additives, formulation adjuvants and / or pesticides.

[0218] In a further aspect, the invention relates to a method of preparing an application mixture of the invention, which method is characterized in that a composition, product or formulation is (gently) stirred and (slowly) poured into water contained in a container, optionally containing one or more further additives, formulation adjuvants and / or pesticides in the application mixture.

[0219] Typically, in such a method of preparing an application mixture of the invention, the weight ratio of water to the composition, product or formulation of the invention is in the range of from about 200:1 to about 10:1, typically in the range of from about 100:1 to about 20:1.

[0220] The spraying application mixture of the present invention can be applied to a field or an application area in accordance with practices known to those skilled in the art. The spraying application mixture according to the present invention can be applied to the field at different stages of crop plants depending on the pesticidal active ingredient present in or as component (A). In some embodiments, the spraying application mixture is applied to the soil before planting the crop plants or after planting the crop plants but before emergence of the crop plants. In other embodiments, the spraying application mixture is applied after emergence of the crop plants.

[0221] Preferred crop plants according to the present invention are maize, soybean, cotton, wheat, oilseed rape, canola, and sugar beet. The compositions, products and spray application mixtures of the present invention can also be applied to other useful plants such as grapes, trees (such as palm trees), fruits (such as apples, pears, plums, bananas, etc.), nuts (such as almonds, pecans, peanuts, etc.), or vegetables (such as tomatoes, dry beans, snap beans, potatoes, etc.).

[0222] The compositions, products or application mixtures of the present invention comprising one or more herbicides as part of component (a) are useful for controlling a wide variety of weeds, i.e., plants considered to be a nuisance or competition to commercially important crop plants such as maize, soybean, cotton, wheat, brassica, canola, sugar beet, dry beans, snap beans, and potatoes. In some embodiments, the application mixture is applied before the weeds emerge (i.e., pre-emergence application).

[0223] Monocotyledonous weeds belong to, for example, the genera Echinochloa, Setaria, Panicum, Digitaria, Phleum, Poa, Festuca, Eleusine, Brachiaria, Lolium, Bromus, Avena, Cyperus, Sorghum, Agropyron, Cynodon, Monochoria, Fimbristylis, Sagittaria, Eleocharis, Scirpus, Paspalum, Ischaemum, Sphenoclea, Dactyloctenium, Agrostis, Alopecurus, and Apera.

[0224] Dicotyledonous weeds belong to, for example, the genera Sinapis, Lepidium, Galium, Stellaria, Matricaria, Anthemis, Galinsoga, Chenopodium, Urtica, Senecio, Amaranthus, Portulaca, Xanthium, Convolvulus, Ipomoea, Polygonum, Sesbania, Ambrosia, Kochia, Cirsium, Carduus, Sonchus, Solanum, Rorippa, Rotala, Lindernia, Lamium, Veronica, Abutilon, Emex, Datura, Viola, Galeopsis, Papaver, Centaurea, Trifolium, Ranunculus, Taraxacum, and Euphorbia.

[0225] Although the present invention has been described in detail, it will be apparent that modifications and changes can be made without departing from the scope of the invention as defined in the appended claims.

Examples

[0226] Examples The following non-limiting examples are provided to further illustrate the present invention.

[0227] Unless otherwise specified, all amounts and percentages are by weight.

[0228] Abbreviations and materials used: PEG = polyethylene glycol Macol® CSA20 = Cetostearyl (cetyl / stearyl) alcohol PEG-20 ether = Ceteareth-20 (BASF) MTBE = methyl-t-butyl ether Klearfac® AA270 = phosphate ester of polyoxyalkylated fatty alcohol [oxirane, 2-methyl-, polymer with oxirane, mono-C10-16-alkyl ether, phosphate, CAS No. 68649-29-6], 85% active, and 15% phosphoric acid (BASF) Lutensit® AE-P = phosphate ester of ethoxylated / propooxylated medium chain alcohol (BASF) Crodafos™ SG = PEG-10 PPG-5 cetyl phosphate = PPG-5-ceteth-10 phosphate (Croda) Phospholan™ PS-220 = C10-14 alcohol (30 EO) ethoxylate 104-phosphate ester (Nouryon) Brij® O20 = polyoxyethylene (20) oleyl ether = Oleth-20 (Croda) Crodafos™ O10A = complex ester of phosphoric acid and ethoxylated cosmetic grade oleyl alcohol (Croda) Tween61® = polyoxyethylene (4) sorbitan monostearate = sorbitan stearate PEG-4 (Croda) Ultrazine™ NA = sodium lignosulfonate dispersant (Borregaard) rpm = revolutions per minute Methocel™ J12MS = surface-treated hydroxypropyl methylcellulose (HPMC)-based polymer (International Flavors and Fragrances), typically used as a 2% aqueous solution Pluronic® P123 = Ethylene Oxide - Propylene Oxide Block Copolymer (BASF) Synperonic® A7 = Ethoxylate of fully saturated C12 - C15 alcohols. This water - soluble non - ionic surfactant is an effective wetting agent and detergent (Croda) Break - thru® EM O7 = Oleyl Alcohol PEG - 7 (Evonik) Agnique® DDL = Lignin sulfonate - based dispersant (BASF) Toximul® 8244 = PEG - 16 Polyethoxylated Castor Oil (Stepan) Pluronic® P123 = Poly(ethylene glycol) - block - poly(propylene glycol) - block - poly(ethylene glycol) (Sigma Aldrich) Agnique® PE TDA 9 = Tridecyl Alcohol Phosphate Ester, PEG - 9 (BASF) Agnique® ANS 3DNPW = Mixture of alkyl naphthalene sulfonates, wetting agent (BASF) Synperonic® 13 / 6 = Polyoxyethylene(6) Isotridecanol (Croda) Sokalan® = Sokalan® CP9 = Maleic Acid - Olefin Copolymer, 25% aqueous solution (BASF) Morwet® EFW = Sodium Alkyl Naphthalene Sulfonate Mixed Dispersant (Nouryon) AAtrex® Nine - O® = 88.2% Atrazine, 1.8% related compounds, 10% other ingredients (Syngenta) Laudis® = 34.5% Tembotrione, 65.5% other ingredients (Bayer) Callisto® = 40% Mesotrione, 60% other ingredients (Syngenta) Proline® = 41% Prothioconazole, 59% other ingredients (Bayer) Urea = 99% Urea (Fisher Scientific) Haake (trademark) Mini CTW = Hot melt extruder, ThermoFisher Scientific Malvern Nano-ZS Zetasizer = Dynamic light scattering device Break-thru (registered trademark) S233: Biodegradable trisiloxane surfactant (Evonik) Soprophor (registered trademark) FLK = Anionic tristyrylphenol ethoxylate phosphate ester emulsifier, aqueous solution of about 40% active substance (Solvay) Lutropur (registered trademark) MSA = 70% aqueous solution of methanesulfonic acid (BASF) Geropon (registered trademark) TA / 72 = Sodium polycarboxylate, CAS No. 223571-91-3, anionic surfactant, polymer dispersant (Solvay) Makon (registered trademark) TSP-60 = Tristyrylphenol ethoxylate PEG-60 (Stepan) Break-thru (registered trademark) DA-647 = Nonionic modified copolymer of styrene oxide and ethylene oxide (Evonik) Myrj (trademark) S8 = Polyoxyl 8 stearate = PEG-8 stearate (Croda) Steposol (registered trademark) OE = Methyl oleate Stepwet (registered trademark) DF-95 = Sodium lauryl sulfate (93%) (Stepan), dry powder Dowfax (registered trademark) 8390 = Diphenyl ether disulfonate, sodium salt, C16 alkylate (Dow Chemical) Dowfax (registered trademark) 3B2 = Diphenyl ether disulfonate, sodium salt, C10 alkylate (Dow Chemical) Stepfac (trademark) 8181 = Polyethylene glycol (6) tridecyl ether phosphate Makon (registered trademark) TSP-12 = Tristyrylphenol ethoxylate PEG-12 (Stepan) Toximul® 8320 = Butyl ethylene oxide - propylene oxide block copolymer (Stepan) (average MW 5500, HLB 12) Makon® TD - 12 = Tridecyl alcohol ethoxylate, PEG - 12 (Stepan) Crodafos® T6A = Tridecyl phosphate ester, PEG - 6 (Croda) Soprophor® CY / 8 = Non - ionic tristyrylphenol ethoxylate emulsifier (CAS No. 99734 - 09 - 05); HLB: 13.5, paste (Solvay) Soprophor® S - 25 / 80 = Non - ionic tristyrylphenol ethoxylate; HLB: 14.5; approximately 80% active substance in water, liquid (Solvay)

[0229] In the following examples, the compositions of the present invention are sometimes also referred to as complexes

[0230] Examples 1 - 11: Example 1: Preparation of atrazine urea complex by evaporation method The following components were mixed in a bottle as shown in Table 1 and placed in an oven at 55°C. The bottle was removed from the oven, stirred, and returned to the oven to be completely dissolved.

[0231] Table 1: Components used to form the urea complex of atrazine by the evaporation method

Table 1

[0232] After dissolution was complete, 7.0 g of Vistive® soy methyl ester was added to the flask. The bottle was shaken and the contents were transferred to a pear-shaped flask. The solvent was evaporated on a rotary evaporator until a white precipitate began to form, which occurred rapidly during evaporation. The precipitate was collected by filtration. The complex showed rapid and nearly complete precipitation, with only a small amount of complex forming in the filter flask, which was not recovered. The product was rinsed with MTBE and dried overnight at 55 °C under a vacuum of 24” Hg (≈0.81273 bar) while purging with nitrogen. 51.8 g of product (white powder) was recovered, which was found to contain 9.9% atrazine and 10.7% total triazine compounds. When added to water, the urea dissolved and the fine atrazine particles remained suspended in the turbid solution.

[0233] Example 2: Preparation of mesotrione urea complex with phosphate surfactant by evaporation method In four different 4-ounce (120 mL) bottles, 15 g of urea, 80 mL of methanol, and 0.5 g of Brij® O20 were combined with the caps on. The bottles were placed in an oven maintained at 55 °C, occasionally swirling until the contents were completely dissolved. The bottles were removed from the oven and a stir bar was added along with 1.6 g of mesotrione and 0.5 g of each phosphate ester shown in Table 2. In this case, the phosphate ester not only acts in the formation of the urea complex but also acts in stabilizing mesotrione against decomposition due to the acidity of the unneutralized phosphate ester. The bottles were stirred at room temperature for a short time until mesotrione was dissolved (about 5 minutes). Each bottle was swirled and the contents were transferred to a round-bottom flask, and 1.8 g of soy methyl ester was added to the flask. After a rapidly initiated and then rapidly occurring exothermic process with accelerated methanol evaporation, the solvent was evaporated using a rotary evaporator until white precipitate began to form. The precipitate was transferred to a Buchner funnel with a coarse frit. The filtrate was yellowish-brown. The remaining product in the flask was rinsed into the Buchner funnel with methyl-t-butyl ether and vacuum was applied. The product was a fine white powder that retained a significant amount of solvent even after vacuum filtration. It was dried overnight at 55 °C under a vacuum of 24” Hg (about 0.81273 bar) while purging with nitrogen. The filtrate was dark yellow. The product was weighed and pulverized in a mortar and pestle. The yields and mesotrione concentrations of each complex are shown in Table 2.

[0234] Table 2: Urea Complexes of Mesotrione and Phosphate Ester Surfactants by the Evaporation Method

Table 2

[0235] Example 3: Preparation of tembotrione urea complex by slow cooling method in oil suspension 85.8 g of urea was mixed in a 250 ml round-bottom flask with 24.2 g of water (equivalent to 110 g of 78% urea in water) and 4 g of Crodafos® O10A. The flask was capped and placed in an oven maintained at 85 °C. A bottle containing 2 g of Tween 61®, 3 g of Break-thru® EM O7, and 400 mL of isooctane was also placed in the same oven along with a 1 liter beaker. When the reagents had warmed up, the flask was placed in an 85 °C oil bath and stirred. When the urea had completely dissolved, 10.0 g of tembotrione was added to the mixture. As dissolution neared completion (about 3 minutes), the isooctane solution was poured into the beaker and mechanical stirring was started in the hood without heating. The urea solution was then poured into the beaker and stirring was continued for about 5 minutes so that the emulsion cooled slowly. Precipitation was observed almost immediately (around 70 °C). The urea complex was recovered by filtration through a Buchner funnel, which was slowed by clogging of the frit. The urea complex recovered in the filter was dried under vacuum at 65 °C overnight with nitrogen purge and then ground with a mortar and pestle. 85 g of the resulting material (from two batches) was combined with the lignosulfonate dispersant Ultrazine® NA. The resulting product had a tembotrione content of 8.63%.

[0236] Example 4: Preparation of atrazine urea complex by hot melt extrusion In this example, the complex contained a solution of atrazine, urea, and Methocel® J12MS. Moisture lowered the melting point of urea, while Methocel® functioned as a binder. The waxy ethylene oxide - propylene oxide block copolymer, Pluronic® P123 (BASF), was included to provide lubrication and disperse urea in the extruder. The alcohol ethoxylate was included as a non - ionic surfactant (component (c)), which also provided wetting properties. Some compositions also used a dispersant to promote the formation of fine atrazine particles when the complex was hydrolyzed. The alcohol ethoxylates used were Synperonic® A7 and Break - thru® EM O7. The dispersants were Agnique® DDL and Toximul® 8244. The compositions were prepared using a Haake® Mini CTW hot melt extruder. This device is a small twin - screw extruder that can circulate the components of the composition before extrusion. All compositions were prepared at an extruder temperature of 95 °C and a screw speed of 90 rpm. With the extruder at room temperature and the screw rotating, Pluronic® P123 was first added for lubrication, followed by the Methocel® solution and the dispersant. Urea and atrazine were added together. The alcohol ethoxylate was added last. The mixture was then circulated in the extruder for about 2 minutes until melted and homogeneous. The compositions were easily pulverized into fine powder using a mortar and pestle. All dissolved very rapidly in water, forming atrazine particles of 1 - 5 microns by optical microscopy. Sedimentation was slow. The atrazine content of each composition is shown in Table 3.

[0237] Table 3. Preparation of Atrazine - Urea Complexes by Hot - Melt Extrusion

Table 3

[0238] Example 5: Preparation of tembotrione urea complex by pouring the completely melted mixture onto a cooled metal plate The composition also contained a powder wetting agent, Agnique® ANS 3DNPW, a 2% solution of Methocel® A7 J12MS in water, and an alcohol ethoxylate, Synperonic® 13 / 6. The composition was prepared on an 80 g scale (see Table 4 below). Urea, phosphate ester, wetting agent, and Methocel® J12MS solution were combined in a 250 mL round-bottom flask equipped with a stir bar. The flask was capped and preheated in an oven at 90 °C. The flask was transferred to an oil bath at 105 °C, and Tebuthiuron was added and stirred until the solution was homogeneous. Synperonic® 13 / 6 was added and poured dropwise onto an aluminum plate placed on ice. A thin layer of the composition on the plate was scraped off and shredded into small pieces. Dissolution was easy and complete. Three batches of the pool prepared in this way were analyzed to contain 16.8 wt% Tebuthiuron.

[0239] Table 4. Preparation of urea complex of Tebuthiuron by pouring a completely melted mixture onto a cooled metal plate

Table 4

[0240] When applied in a 2% solution of Sokalan® CP 9, this formulation provided effective fungal control for peanut plants in the field without phytotoxicity.

[0241] Example 6: Preparation of prothioconazole urea complex by rapid cooling of the melt Urea, Methocel (registered trademark) solution, and Agnique (registered trademark) ANS 3DNPW were combined in a 100 mL round-bottom flask equipped with a stir bar and placed in an oven at 105 °C. See Table 5 below. After transferring to a 105 °C oil bath, melting was complete and the viscosity was low. Prothioconazole was added and it took 10 minutes to dissolve completely before adding the alcohol ethoxylate. The composition was poured out in two operations onto an aluminum plate placed on ice. A thin wafer was obtained. The wafer was crushed into small pieces, which were rapidly dissolved in water to release very fine prothioconazole particles.

[0242] Table 5: Preparation of urea complex of prothioconazole by rapid cooling of the melt

Table 5

[0243] Example 7: Enhanced herbicidal effect of the urea - atrazine complex of Example 1 This was compared to conventional atrazine when used alone or in combination with the HPPD inhibitor herbicide mesotrione. A dispersion composition having an atrazine loading of 9.4% was obtained by combining 95 parts by weight of the complex (containing 9.9% atrazine and 10.7% total triazine compounds) with 5 parts of the dispersant Morwet® EFW. The composition dispersed in water was sprayed onto velvetleaf (ABUTH) at rates of 140 and 280 g / ha and compared to the conventional commercially available atrazine composition AAtrex® Nine-O® at the same rates. Tank mixtures with the mesotrione herbicide Callisto® (Syngenta) were also evaluated. Spraying was carried out at 93 L / ha using a 9501 flat fan nozzle on velvetleaf plants at the 6 - 9 leaf stage. Crop oil concentrate (COC) was included at 1% volume / volume in some treatments. In the treatments containing Callisto®, the rate of mesotrione was 17.5 g / ha at a lower atrazine rate (140 g / ha) and 35 g / ha at a higher atrazine rate (280 g / ha). Table 6 shows the % control of velvetleaf by conventional atrazine and the urea - atrazine - complex.

[0244] Table 6. Control of Velvetleaf by Different Atrazine - containing Materials

[0245]

Table 6

[0246] Example 8: Enhanced herbicidal effect of the urea - tembotrione complex of Example 3 The control of velvetleaf (ABUTH) with the tembotrione complex was compared to rates well below the rate of 17.5 g / ha of the conventional tembotrione formulation, Laudis®, without adjuvant, i.e., the commercially recommended rate of 90 g / ha. The tank mixture was sprayed onto velvetleaf plants at 15 gallons per acre (about 140 L / ha). The plants were visually evaluated 3 weeks after spraying. At the time of evaluation, the control was 13% with Laudis® and 22% with the urea complex.

[0247] Example 9: Stability study of the urea complexes of mesotrione and tembotrione in Examples 2 and 3 respectively The stability was evaluated by putting the sample into an oven and sampling regularly. The mesotrione complex was evaluated in an oven at 54 °C for 6 weeks. All complexes showed acceptable stability, but the Phospholan™ PS-220 and Crodafos™ SG complexes functioned particularly well.

[0248] Table 7 shows the concentration of mesotrione in the urea complex of Example 2 after aging in an oven at 54 °C.

[0249] Table 7. Results of the 8-week stability test of the mesotrione concentration in the urea complex at 54 °C

Table 7

[0250] The tembotrione-urea complex of Example 3 was tested by aging in an oven at 54 °C for 8 weeks. As shown in Example 3, the inclusion of the acidic phosphate ester surfactant, Crodafos™ O10A (PEG-10 oleyl phosphate, Croda), stabilizes tembotrione and mesotrione against chemical decomposition. Table 8 shows the concentration of tembotrione in the urea complex over 8 weeks at 54 °C.

[0251] Table 8. Results of the stability test of the tembotrione concentration in the urea complex over 8 weeks at 54 °C

Table 8

[0252] Example 10: Treatment of corn seeds with the urea - prothioconazole complex from Example 6 First, the urea composition was added to the water or water-Sokalan® mixture in a plastic centrifuge tube and vortexed briefly to completely dissolve it. A colorant and a standard seed treatment polymer were added to the tube. After a brief vortex, 8.6 mL of the mixture was applied to 1 kg of corn seeds. This corresponds to a rate of 12 fluid ounces per 100 weight of seeds. The treatment time was approximately 33 seconds.

[0253] The treatments were carried out at rates of 0.021 and 0.085 mg of prothioconazole per seed. The control compositions at both rates were carried out using the prothioconazole suspension concentrate Proline®. Equal amounts of water or water-Sokalan® were used in the urea compositions. 20% Sokalan® - 80% water was used at a rate of 0.032 mg / seed and 30% Sokalan® - 70% water (weight / weight) was used at a rate of 0.085 mg / seed. The low-rate seed treatment solution prepared with Sokalan® was transparent before adding the seed colorant because the formed prothioconazole particle size was small.

[0254] Even at the high rate, there was no chalkiness on the surface due to urea, and nothing transferred to the gloved hand when the seeds were rubbed. At the high rate, the seeds treated with the urea complex hydrolyzed in Sokalan® were significantly glossier than the control seeds or the seeds treated with the urea complex hydrolyzed only in water.

[0255] Example 11. Dynamic light scattering Example 11a: Dynamic light scattering of the tembotrione urea complex of Example 5 The tembotrione composition from Example 5, prepared by rapid cooling from the melt, was hydrolyzed and the tembotrione particles were evaluated by dynamic light scattering using a Malvern Nano-ZS Zetasizer. 0.6 g of the complex was added to 15 mL of water or 15 mL of 2% Sokalan® in a 30 mL vial and shaken to disperse. The solution was allowed to stand at room temperature for 2 hours before measuring the particle size. The water hydrolysis was very slightly turbid and the Sokalan® hydrolysis was optically transparent. A narrow particle size distribution of both hydrolysis mixtures was measured by dynamic light scattering, with an average particle size of 298 nm for the water hydrolysis and 5 nm for the Sokalan® hydrolysis. The results of the significant Sokalan® hydrolysis were reproduced and its accuracy was ensured.

[0256] Example 11b: Dynamic light scattering of the prothioconazole urea complex from Example 6 Two batches analyzed as 15.0% and 14.5% prothioconazole were prepared. When dispersed in water or 2% Sokalan® by the method described in Example 11, dynamic light scattering showed a sharp peak at 1.5 microns for the Sokalan® dispersion and a broad peak from 1.2 to 2.1 microns for the hydrolysis with water alone. The solution was analyzed with a Malvern Nano-ZS Zetasizer as in Example 11a.

[0257] Examples A1 - A9: Example A1: Urea complex of tetraniliprole prepared by hot melt extrusion without using water In this example, the preparation of the urea complex of the insecticide tetraniliprole is described. Extrusion was carried out at moderate temperatures with high loading of the active ingredient without the need to add water. This is an indicator of the eutectic of tetraniliprole and urea. The composition is intended to be used in seed treatment to deliver tetraniliprole to the seed surface with low crystallinity to enhance bioavailability. Notably, when this composition is added to water, tetraniliprole is released in the form of a stable emulsion as a liquid, which is ideal for the intended use.

[0258] Ten batches of 5 g each of the following products were prepared by extrusion of the mixture using the Haake (trademark) Mini CTW extruder described in Example 4. Extrusion was carried out at 105 °C at a screw speed of 90 rpm. The composition was easily extruded as a continuous "noodle" and, after cooling to room temperature, was easily pulverized into a powder.

[0259] Table A1. Composition of the urea complex of tetraniliprole prepared by hot melt extrusion without using water [Table 9]

[0260] After pulverization, the composition dissolved almost instantaneously in water, forming a bright white emulsion of liquid tetraniliprole in water. No crystallization or loss of emulsion quality was observed after leaving it overnight at room temperature.

[0261] Example A2: Treatment of corn seeds with tetraniliprole in urea Ten batches of tetraniliprole in the urea composition of Example A1 were pooled, and a portion was used to treat corn seeds. Corn seeds with 1 kg of the BT trait (Bacillus thuringiensis protein that protects plants from insects) were treated at a ratio of 16 fluid ounces of treatment solution per 100 weight of corn seeds to the seed mass. Corn seeds (1600 seeds per pound) were treated in a bowl processor with a solution containing the urea complex of Example A1 at a rate of 0.125 and 0.25 mg of tetraniliprole per seed. The treatment mixture also contained 0.085 mg / seed of the fungicide fluoxastrobin as well as a colorant and a binder polymer. To optimize the tetraniliprole emulsion, the treatment solution further contained Soprophor® FLK at a ratio of 0.6 fluid ounces / 100 weight.

[0262] The treated seeds were found to exhibit warm germination and low-temperature germination equivalent to that of untreated seeds. However, due to the BT trait, they were not suitable for the efficacy test. Therefore, the treatment was repeated on a smaller scale using corn seeds without the BT trait at a rate of 0.063 and 0.125 mg of tetraniliprole per seed. Also, treatment was carried out with a conventional suspension concentrate of tetraniliprole ("SC", 480 g / L). These batches were used in the efficacy assay described in Example A3.

[0263] Example A3: Efficacy of the Tetraniliprole Complex in Urea as a Seed-Use Insecticide Non-BT seeds treated at 0.063 mg / seed as described in Example A2 were germinated and grown in pots. When the plants reached a height of approximately 1 foot, black cutworms were introduced and stem damage was measured. At low rates of tetraniliprole, as shown in Table A3-1, the urea complex to which Soprophor® FLK was applied provided better protection to the stems than the conventional suspension concentrate.

[0264] Table A3-1. Damage to the stems of corn seedlings treated with 0.063 mg / seed of tetraniliprole by Spodoptera litura [Table 10]

[0265] Non-BT seeds treated with 0.125 mg / seed as described in Example A2 were evaluated based on the reduction in the area of the third leaf due to feeding by Spodoptera litura. As shown in Table A3-2, the urea complex again showed superior performance compared to the conventional suspension concentrate.

[0266] Table A3-2. Reduction in the surface area of the third leaf of corn seedlings treated with 0.125 mg / seed of tetraniliprole after feeding by Spodoptera litura [Table 11]

[0267] Example A4: Tenbotrione compositions in urea incorporating different surfactants that affect the form of the active ingredient after hydrolysis This example describes the preparation of two tenbotrione complexes by hot melt by pouring the melt onto a cold metal plate. Furthermore, the two compositions incorporate different surfactants that induce different behaviors when each composition is added to water. One composition, A4-1, formed nanoparticles similar to those of the complex of Example 5 characterized by particle size in Example 11. The other composition, A4-2, formed an emulsion of liquid tenbotrione. Also, these compositions exemplify the incorporation of methanesulfonic acid (using Lutropur® MSA) to lower the pH and provide chemical stability. Similar to Example 5, the incorporation of non-neutralized phosphate ester, Agnique® PE TDA 9, provided additional acidity.

[0268] The complex A4-1 that forms nanoparticles was prepared from the melt on a 100 g scale similar to Example 5. Geropon, Agnique® PE TDA 9, Synperonic® 13 / 6, water, and urea were combined in a 250 mL flask equipped with a stir bar, capped, and held overnight in a furnace at 105 °C. The flask was transferred to an oil bath at 105 °C. 0.5 g of MSA was added, followed by addition of Tembotrione, and stirring was maintained until the Tembotrione dissolved and a good vortex was formed. The mixture was poured out in batches to form a sheet of soft material having a red color. The product was dried at 55 °C for 4 hours under 24” Hg (about 0.81273 bar) vacuum while purging with nitrogen.

[0269] The complex A4-2 is on a scale of about 5 g in a Haake™ CTW hot melt extruder. The components added to the extruder are shown in the table. Multiple batches were prepared at an extruder temperature of 90 °C and a screw speed of 90 rpm. The batches were pooled to enable an effectiveness test.

[0270] Table A4. Tembotrione composition containing methanesulfonic acid [Table 12]

[0271] For Tembotrione, the incorporation of a polymeric dispersant that stabilizes the solid particle surface results in nanoparticle formation by Composition A4-1. Geropon® TA / 72, a polymeric dispersant manufactured by Solvay, was used for this purpose.

[0272] In contrast, Composition A4-2 contains Makon® TSP-60, which promotes the formation of an emulsion and results in the formation of an emulsion of liquid Tembotrione when Complex A4-2 is added to water.

[0273] Example A5: Fullopyram complex in highly filled urea by hot melt extrusion This example illustrates the high loadings achievable in urea complexes of active substances having a melting point near the extrusion temperature, which are advantageous for eutectic formation. It also shows that the release of the active substance as a liquid when the complex is hydrolyzed is readily achieved while varying the emulsifier and alcohol ethoxylate in the composition.

[0274] Fluopyram is a fungicide with a melting point of 118 °C and has poor water solubility of 16 mg / L, but is highly soluble in polar organic solvents (>250 g / L in ethyl acetate or DMSO). Using a Haake™ Mini CTW hot melt extruder, approximately 30% (nominal) fluopyram in urea was prepared at 90 °C and a screw speed of 90 rpm. In all cases, extrusion was easy and produced a continuous “noodle” that was easily milled after cooling. Compositions were prepared on a scale of approximately 5 g.

[0275] 1.5 g of fluopyram, 2.7 g of urea granules, and variable amounts of alcohol ethoxylate, wetting agent, and emulsifier were added to the Haake™ Mini CTW, circulated until homogeneous, and then extruded under the above conditions.

[0276] The following three compositions A5-1, A5-2, or A5-3 were prepared: Composition A5-1: 1.5 g of fluopyram + 2.7 g of urea granules + 0.4 g of Makon® TSP-60 + 0.4 g of Synperonic® 13 / 6 Composition A5-2: 1.5 g of fluopyram + 2.7 g of urea granules + 0.4 g of Makon® TSP-60 + 0.4 g of Break-thru® EM O7 Composition A5-3: 1.5 g of fluopyram + 2.7 g of urea granules + Break-thru® DA-647 + 0.3 g of Myrj S8 + Agnique® ANS 3DNPW When added to water at a weight ratio of about 10:1 to the water composition A5-1, A5-2 or A5-3, all the compositions each produced an emulsion of liquid fluoropyram. The emulsion was stable for about 2 hours, at which point some crystallization and sedimentation occurred. The fluoropyram particles formed in this process were easily redispersed and appeared non-crystalline by optical microscopy.

[0277] Example A6 : Atrazine complex in urea prepared from the melt This example describes the preparation of an atrazine complex in urea from the melt, in contrast to the evaporation method or hot melt extrusion in Examples 1 and 4 respectively. This composition has also been demonstrated to have significantly better pre-emergence efficacy than conventional suspension concentrates. On a 150 g scale, the atrazine complex in urea was formed with the components shown in Table A6.

[0278] Table A6. Atrazine complex in urea obtained from the melt

Table 13

[0279] All components except atrazine and 3 mL of Methocel® J12MS solution were combined in a 500 mL round bottom flask equipped with a stir bar. The flask was capped and placed in an oven at 115 °C overnight. The flask was transferred to a 120 °C oil bath and stirred. The remaining Methocel® J12MS solution was added and atrazine was added little by little with stirring. When dissolution was complete, the resulting mixture was poured out onto an aluminum plate placed on an ice bed. In two pourings, 130.9 g of a white composition was recovered. The batch was annealed under nitrogen at 70 °C overnight, reducing the mass to 123.9 g. The annealed composition was ground to a fine powder using a mortar and pestle. The resulting product had an atrazine content of 17% by evaporation of water.

[0280] Example A7:Pre-emergence efficacy of atrazine and tebumeton urea complexes against velvetleaf This example demonstrates that the atrazine complex in urea from Example A6, alone or in combination with tebumeton in urea from Example 5, shows superior pre-emergence control of the large-seeded broadleaf weed velvetleaf (ABUTH) compared to conventional commercially available suspension concentrate compositions of these active substances. In this test, commercial products of AAtrex® Nine-O® for atrazine and Laudis® for tebumeton were used.

[0281] The spray solution of the composition was applied to the soil at a rate of 15 gallons per acre (about 140 L / ha). The rates of each herbicide are shown in Table A7. For each treatment, six velvetleaf seeds were placed 1 / 2 inch below the soil surface and it took 2 weeks for emergence. For each seed, the ratio of the fresh weight of the emerged velvetleaf to the average fresh weight of six untreated velvetleaf seeds was determined. The control rates shown in Table A7 were calculated from these values, where 100% control corresponds to the fresh weight of the emerged velvetleaf being zero.

[0282] The results of efficacy show that the atrazine composition from Example A6 is far superior to conventional atrazine for the control of velvetleaf. Typically, large-seeded broadleaf weeds such as velvetleaf are the greatest challenge for pre-emergence control and provide a clear assessment of relative efficacy.

[0283] Table A7. Control of velvetleaf using atrazine as a single active ingredient or in combination with tebumeton

Table 14

[0284] Example A8: Efficacy of tebumeton released from the compositions of the invention in liquid form or as nanoparticles This example demonstrates that a urea complex that releases the active substance as nanoparticles or a liquid upon hydrolysis can exhibit improved foliar efficacy compared to conventional suspension concentrate compositions that are suspensions of small solid particles of the active substance. This is illustrated using the tebuthiuron composition in urea from Example A4 above.

[0285] The post-emergence efficacy of the tebuthiuron composition in urea from Example A4 was evaluated in greenhouse trials. Compositions A4-1 (releasing tebuthiuron nanoparticles) and A4-2 (releasing tebuthiuron in liquid form as an emulsion) were applied to Palmer amaranth (AMAPA) and velvetleaf (ABUTH) plants at 1 / 3 and 1 / 2 of the normal rate, i.e., 30 g / ha and 46 g / ha of tebuthiuron. Along with the commercial tebuthiuron suspension concentrate Laudis® (Bayer), the compositions were applied to 4” - 6” (10.16 - 15.24 cm) plants. All applications were made at a spray rate of 15 gallons per acre (about 140 L / ha) using an XR9501R nozzle (Teejet). Plant injury was evaluated 21 days after treatment. Six plants were used for each treatment.

[0286] The average injury is shown in Table A8-1 below. Both Compositions A4-1 and A4-2 provided excellent control of both weeds compared to the conventional suspension concentrate composition. In most cases, tebuthiuron released in liquid form from Composition A4-2 was more effective than tebuthiuron in nanoparticle form from Composition A4-1.

[0287] The efficacy of three different tebuthiuron compositions was evaluated: the commercial product Laudis®, Composition A4-1 (producing tebuthiuron nanoparticles), and Composition A4-2 (producing liquid tebuthiuron), applied at 30 g / ha and 46 g / ha of tebuthiuron to Palmer amaranth (AMAPA) and velvetleaf (ABUTH). The level of control (injury) was evaluated as a percentage 21 days after treatment (21 DAA).

[0288] Table A8-1. Control (damage) of Palmer amaranth (AMAPA) and velvetleaf (ABUTH) at 21 DAA at application rates of 30 g / ha and 46 g / ha of different tembotrione compositions.

Table 15

[0289] Tembotrione is typically used with an adjuvant. Three compositions were also evaluated using the same protocol at a rate of 30 g / ha of tembotrione with 0.25% v / v of adjuvant AU-973 (Adjuvants Unlimited, Memphis TN) in the applied spray mixture.

[0290] The efficacy of three different tembotrione compositions was evaluated. The commercial product Laudis®, and compositions A4-1 (producing tembotrione nanoparticles) and A4-2 (producing liquid tembotrione) were applied at 30 g / ha against Palmer amaranth (AMAPA) and velvetleaf (ABUTH) using 0.25% v / v of adjuvant AU-973 in the applied spray mixture. The level of control (injury) was evaluated as a percentage on the 21st day after treatment.

[0291] Table A8-2. Control (damage) of Palmer amaranth (AMAPA) and velvetleaf (ABUTH) at 21 DAA at an application rate of 30 g / ha of different tembotrione compositions using additional adjuvant

Table 16

[0292] When the results shown in Table 8-2 are compared with the results of 30 g / ha in Table 8-1, it is shown that the adjuvant improved weed control for both weeds and all compositions. When using the adjuvant, again, both Compositions A4-1 and A4-2 were superior to the conventional compositions, and Composition A4-2 showed the best performance among all.

[0293] Example A9: Differential Scanning Calorimetry (DSC) of the Tetraniliprole-Urea Composition The tetraniliprole-urea composition of Example A1 was modified by adding further non-ionic surfactant, Makon® TSP-60 as an emulsifier, into the composition. Further surfactant, sodium lauryl sulfate (Stepwet® DF-95) was also included to further assist emulsification. This anionic surfactant may not be part of the urea-tetraniliprole phase. This composition shown in Table A9 produced an emulsion of liquid tetraniliprole that was stable at ambient temperature (about 20 °C) overnight (about 16 hours) when hydrolyzed in water in an 8-fold weight amount without the need to add additional emulsifier. The composition of Table A9 was prepared by hot melt extrusion using the same procedure as in Example A1.

[0294] Table A9. Tetraniliprole-Urea Composition Prepared by Hot Melt Extrusion Containing Emulsifier, Makon® TSP-60, and Anionic Surfactant Stepwet® DF-95

Table 17

[0295] Differential scanning calorimetry was performed on this composition and the urea granules used to prepare it. The urea granules showed a simple melting peak at 134 °C. The DSC data of the tetraniliprole-urea composition in this example also showed a single melting peak but at a much lower temperature of about 125 °C.

[0296] The absence of a melting peak at 134 °C indicates that the product is not a mechanical mixture of the urea starting material (urea granules) and the active ingredient, tetraniliprole. Instead, a modified urea matrix structure incorporating the active ingredient and some surfactants constitutes the only detectable phase. The depressed melting point reflects the disruption of the urea structure by the incorporation of other components.

[0297] These DSC data do not rule out the possibility that a small amount of tetraniliprole still existed as a separate phase (tetraniliprole melting point, 228 °C, outside the DSC measurement range). However, the DSC data for the urea granules and the tetraniliprole composition in urea of Example A9 showed a complete disappearance of the urea phase from the starting material and the formation of a low melting point phase containing tetraniliprole as a dispersion in urea.

[0298] Examples B10 - B19 and Comparative Example: Example B10: This example describes a highly filled (32.6% fenmedifam) urea complex of the herbicide fenmedifam that readily hydrolyzes to form a fine emulsion. The composition was prepared on a 4.6 g scale by feeding a solid premix ground with a knife mill at 80 °C and a screw speed of 90 rpm using a Haake™ Mini CTW extruder. The premix consisted of 1.5 g of fenmedifam technical, 0.5 g of Makon® TD-12, and 2.6 g of urea. The knife mill treatment served to disperse the liquid surfactant over the solid components of the composition. The composition circulated well within the extruder, was easily ground into a powder, and was extruded as a brittle but good “noodle”.

[0299] Example B11: This example illustrates a process by which a composition equivalent to Example B10 can be prepared on a scale of 100 g or more in a mixer. Additionally, the scaled-up process allows for "flood feeding" of raw materials. This means that the feed, the powder, can flow freely and be taken up by the mixer's screw without manual intervention. Such a process, while convenient at the scale shown in this example, can be easily extended to larger equipment. A Readco Kurimoto RK1 twin-screw mixer was used. The Readco Kurimoto RK1 had a significantly higher throughput and was more powerful, but had a different design from the Haake™ Mini CTW extruder used in the previous example.

[0300] Approximately 56 g of urea granules were added to a 250 mL Waring spice grinder blending cup with a blade, followed by approximately 33 g of fenmedifam technical powder, and then approximately 11 g of molten Makon® TD-12 maintained at 60 °C was added. This was pulsed frequently with the spice grinder and blended while interrupting to scrape down the sides of the container, and it immediately became sticky. A lightly granular but soft material was poured out, and then the remainder was scraped from the sides and remixed before pouring out. This process was repeated for a total of 200 g of material. This feed was used to prepare a 100 g scale composition in a Readco Kurimoto RK-1 mixer with the following settings.

[0301]

Table 18

[0302] Once the barrel reached temperature, the sample was added to the hopper all at once and flood fed to the screw. The motor was then started and the screw rotated. The material extruded at a moderate pace was friable and left thick, flat (4 mm x 25 mm) "noodles" like shark skin. The product was off-white, of good quality, and had sufficient strength and brittleness for comminution. Comminution yielded a very fine powder that dispersed rapidly in water.

[0303] Example B12: This example describes a tembotrione-urea composition that has excellent dispersibility in water and is easy to scale up from a small extruder to production using a continuous mixer. The purity of the tembotrione technical used was 96%. The composition was as follows:

[0304]

Table 19

[0305] The composition was prepared on a 5 g scale using a Haake (trademark) Mini CTW extruder operating at 80 °C and a screw speed of 90 rpm. A blend of materials milled in a small knife mill could be easily flood fed to the extruder, resulting in a nearly ideal peak torque of 1.2 N-m. The product was extruded as soft "noodles" that hardened upon cooling.

[0306] The same composition was then prepared on a 125 g scale on a Readco Kurimoto RK-1 mixer operating at 81 °C with a screw speed of 90 rpm. After milling the material in a knife mill, the composition was flood fed to the inlet of the Readco Kurimoto RK-1 and appeared as a soft mass in about 1 minute, which was cooled and hardened. Due to the favorable flow characteristics of this composition, the power demand was low (5.7 A). The product was milled to a powder in a Waring blender.

[0307] Example B13: This example describes the preparation of a high-filled urea complex of the herbicide phytotoxicity reducer, cyprosulfamide. A premix of the following composition was ground in a Waring spice grinder for a short time. 5 g of the premix was fed to a Haake (trademark) Mini CTW twin-screw extruder operating at 80 °C with a screw speed of 90 rpm.

[0308]

Table 20

[0309] When the extruded product was added to water, cyprosulfamide was efficiently dispersed.

[0310] Example B14: This example describes the dispersion of the active ingredient when the composition of the present invention is hydrolyzed. 0.2 g of the formulation was added to 10 mL of water in a vial and vortexed for a short time. Urea dissolved, and as a result, the active ingredient was dispersed in water. The particle size distribution was measured immediately thereafter using a Malvern Mastersizer.

[0311] The particle size distributions of the fenmedifam composition of Example B11 and the cyprosulfamide composition of Example B13 were measured. Almost all of each active ingredient was present as a fine emulsion, having a volume-weighted mean diameter (VMD or Dv50) of 1.2 microns for fenmedifam and 0.8 microns for cyprosulfamide. The broad shoulder with a larger diameter corresponds to a small fraction of the formulation that has not completed dissolution.

[0312] The narrow distribution indicates that the active ingredient is dispersed as an emulsion rather than as a suspended solid. This is because a 1-micron size is characteristic of aqueous emulsions such as milk (oil-in-water emulsions), and the narrow size range represents an equilibrium compared to the particle size distribution expected from irreversible crystallization in a solid dispersion.

[0313] Example B15: This example describes the preparation of a formulation of the fungicide prothioconazole on a larger scale and its ability to form either a stable dispersion or a nano-dispersion. It also exemplifies the use of a second phase containing an anionic dispersant to facilitate the dispersion of the formulation in water. In this example, two anionic dispersants, Dowfax® 3B2 and Sokalan® CP-9, were used.

[0314] First, urea granules and the dry Sokalan® CP-9 dispersant were added, and then the liquid components were added to perform the first mixing of the following formulation on a 500 g scale in a Hobart planetary mixer. The prothioconazole technical powder was added last. After mixing, the resulting mixture appeared to be swollen urea granules.

[0315]

Table 21

[0316] The mixture was then processed in a Readco Kurimoto RK-1 twin screw mixer at 74 °C (165 °F) and a screw speed of 60 rpm. After cooling, the hard white product was ground in a Waring spice grinder and passed through an 850 micron sieve. The product immediately dissolved in water to form a stable milky dispersion overnight. When the product was dissolved in a 0.5% solution (solid basis) of the anionic Sokalan® CP-9, a transparent solution was obtained due to the formation of prothioconazole nanoparticles. The suspension remained transparent for over a week.

[0317] Example B16: This example describes the preparation of a formulation on a larger scale using an anionic dispersant to improve the dispersion of the product when added to water. A formulation of the herbicide isoxaflutole was prepared using the following composition. The isoxaflutole technical used had a purity of 99%, and as a result, a formulation with an overall filling amount of approximately 32.7% of isoxaflutole was obtained.

[0318]

Table 22

[0319] Urea granules were added to the bowl of a planetary mixer (Kitchen Aid), and the liquid component mixture (all materials except isoxaflutole) was mixed with continuous low stirring for about 3 minutes. Then, while continuing stirring, isoxaflutole technical was added over about 5 minutes. The urea granules appeared to be significantly swollen.

[0320] The product from the planetary mixer was gravity-fed to a Readco Kurimoto RK-1 twin screw mixer at a screw speed of 60 rpm and 75 °C (167 °F). Thin and brittle "noodles" were produced, easily pulverized, and quickly dissolved in water.

[0321] Example B17: This example demonstrates the excellent post-emergence efficacy of the tembotrione-urea composition A4-2 from Example A4 (releasing tembotrione in liquid form as an emulsion) against two difficult-to-control grasses: barnyardgrass (ECHCG) and crabgrass (DIGSA). The efficacy was evaluated at 1 / 3 and 1 / 2 of the normal rate, i.e., 30 g / ha and 46 g / ha of tembotrione, and compared with the commercially available tembotrione suspension concentrate Laudis® (Bayer). Applications were carried out at both rates without adjuvant, and in addition, a 0.25% v / v AU-973 (Adjuvants Unlimited, Memphis, TN) non-ionic surfactant was added to the spray mixture to evaluate the efficacy at 30 g / ha of tembotrione. All applications were made using an XR9501R nozzle (Teejet) at a spray rate of 15 gallons per acre (about 140 L / ha). The control level of each weed was evaluated as the percentage of damage at 21 days after treatment (21 DAA).

[0322] As shown in Table B17, the conventional formulation was ineffective against both grass species tested at both rates, but high efficacy was seen for Composition A4-2 from Example A4, particularly against Echinochloa crus-galli (ECHCG).

[0323] Table B17. Control (damage) evaluated at 21 DAA of Echinochloa crus-galli (ECHCG) and Digitaria sanguinalis (DIGSA) with different tembotrione compositions at application rates of 30 g / ha and 46 g / ha [Table 23]

[0324] Example B18: Example 9 demonstrated that pH-sensitive active ingredients such as mesotrione and tembotrione can be stabilized by inclusion in urea together with a nonionic surfactant such as an acid form of a phosphate ester surfactant. This Example B18 shows that stabilization can also be achieved by including phosphoric acid in the composition, regardless of the presence or absence of the phosphate ester. It also shows an improved, i.e., higher loading, of tembotrione.

[0325] Four compositions of tembotrione in urea were each prepared on a 5 g scale using a Haake™ Mini CTW extruder operated at 80 °C with a screw speed of 90 rpm. The purity of the tembotrione technical was 96%. Tristyrylphenol ethoxylate (Soprophor® S-25 / 80) and phosphoric acid were used to stabilize the tembotrione. The compositions also contained a linear nonionic surfactant, either a phosphate ester or a linear alcohol ethoxylate.

[0326] First, 0.3 g of each linear nonionic surfactant was added to the extruder. The remaining 4.7 g was premixed and treated in a small knife mill before addition to the extruder. All four compositions were extruded as good "noodles", which were ground to powder before performing the thermal stability test.

[0327] Tenbotrione composition of Example B18: [Table 24]

[0328] The product in powder form was stored in an oven at 54 °C for 4 weeks. Samples were taken periodically and analyzed for their tenbotrione content. Due to the small preparation scale, there was a slight difference in the initial tenbotrione concentration, but all compositions showed excellent high-temperature stability of tenbotrione.

[0329] Table B18. Tenbotrione content (wt%) of the composition of Example B18 - storage at 54 °C [Table 25]

[0330] Example B19: The prothioconazole-urea composition of Example B15 was analyzed by differential scanning calorimetry (DSC) both after blending in a Hobart mixer and then after hot blending in a subsequent Readco Kurimoto RK-1 twin-screw mixer. The DSC data for both prothioconazole-urea compositions showed no trace of the crystalline prothioconazole peak, i.e., the crystalline prothioconazole used as a starting material for producing the prothioconazole-urea composition of Example B15 was no longer present. These DSC data prove that there is no crystalline prothioconazole in these prothioconazole-urea compositions and that a solid solution of prothioconazole in urea was formed. These DSC data also showed that the urea peak was replaced by a broader peak at a lower temperature.

[0331] Comparative Example: This example demonstrates that the composition of the present invention cannot be obtained by precipitation from methanol containing oleic acid.

[0332] This comparative example was conducted using the precipitation method in methanol containing oleic acid reported by Thakral, S.; Madan, A.K. in, for example, J. Pharmacy Pharmacology, 2007, 59, 1501 - 7, or J. Incl. Phenom. Macrocycl. Chem., 2008, 60, 203 - 9, or J. Pharm, Innov., 2008, 3, 249 - 57. The descriptions of the procedures used in these publications are almost identical.

[0333] In these procedures, a solution prepared by dissolving 0.5 g of each active ingredient (enalapril maleate, glipizide, nicorandil) and 5 g of urea in 30 mL of methanol was "gently heated", then 0.6 g of oleic acid was added and "immediately precipitated", and after standing for 2 - 3 hours, the precipitate was collected by vacuum filtration.

[0334] This procedure was adopted to attempt to obtain the tenbotriol - urea complex in the same way.

[0335] A solution of 0.5 g of tenbotriol and 5 g of urea in 50 mL of methanol was prepared by gently heating. Then, 0.6 g of oleic acid was added and the heating was stopped. No precipitation occurred either during the addition or after the mixture was cooled to room temperature.

[0336] In contrast to the methods and procedures described with respect to the present invention, the single - phase tenbotriol - urea complex could not be obtained according to the precipitation procedure in methanol containing oleic acid.

[0337] Embodiment For further illustration, further non - limiting embodiments of the present invention are described below.

[0338] Embodiment 1. A composition in solid form at 25 °C and 1013 mbar, comprising: (a) One or more pesticidal or pharmaceutical active ingredients having a melting point of at least 55 °C at 1013 mbar with a total amount of at least about 5% by weight and having a solubility of 50 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar, wherein component (a) does not exist in the form of a salt with an inorganic counterion (i.e., does not exist as a salt with an inorganic counterion such as a monovalent metal ion, divalent metal ion, trivalent metal ion, or ammonium counterion), pesticidal or pharmaceutical active ingredient, (b) Urea in a total amount of at least about 50% by weight, (c) One or more nonionic surfactants in a total amount of at least about 1% by weight comprising, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is about 0.8 or less, and in each case the amounts indicated are based on the total weight of the composition, a composition.

[0339] Embodiment 2. The composition according to Embodiment 1, Component (a) in a total amount of 5% by weight or more, 6% by weight or more, 7% by weight or more, preferably 8% by weight or more, more preferably 10% by weight or more, typically in the range of 5% to 35% by weight, preferably in the range of 6% to 33% by weight, preferably in the range of 7% to 32% by weight, preferably in the range of 8% to 31% by weight, more preferably in the range of 10% to 30% by weight, Component (b) in a total amount of 50% by weight or more, 60% by weight or more, typically in the range of 60% to 90% by weight, preferably in the range of 60% to 85% by weight, often in the range of 65% to 80% by weight, Component (c) in a total amount of 2% by weight or more, 3% by weight or more, 4% by weight or more, preferably 5% by weight or more, more preferably 8% by weight or more, often 10% by weight or more comprising, a composition.

[0340] Embodiment 3. The composition according to Embodiment 1, Component (a) in a total amount of 7% by weight or more, preferably 8% by weight or more, more preferably 10% by weight or more, and / or The composition contains component (c) in a total amount of 2% by weight or more, or 3% by weight or more wherein, in each case, the amounts indicated are based on the total weight of the composition. Composition, where the amounts indicated in each case are based on the total weight of the composition.

[0341] Embodiment 4. A composition according to Embodiment 1 or 2, wherein component (a) is present in a total amount in the range of 5% to 35% by weight, preferably in the range of 6% to 33% by weight, component (b) is present in a total amount in the range of 50 to 90% by weight, preferably in the range of 60 to 85% by weight, and component (c) is present in a total amount of 3% by weight or more, preferably 4% by weight or more wherein, in each case, the amounts indicated are based on the total weight of the composition. Composition, where the amounts indicated in each case are based on the total weight of the composition.

[0342] Embodiment 5. A composition according to any one of Embodiments 1 to 4, wherein component (a) is present in a total amount in the range of 8% to 35% by weight, or in the range of 10% to 33% by weight, and / or component (b) is present in a total amount in the range of 55 to 85% by weight or in the range of 60 to 85% by weight wherein, in each case, the amounts indicated are based on the total weight of the composition. Composition, where the amounts indicated in each case are based on the total weight of the composition.

[0343] Embodiment 6. A composition according to any one of Embodiments 1 to 5, wherein the melting point of component (a) is in the range of about 55°C to about 350°C at 1013 mbar.

[0344] Embodiment 7. A composition according to any one of Embodiments 1 to 5, wherein the melting point of component (a) is in the range of about 60°C to about 300°C at 1013 mbar.

[0345] Embodiment 8. A composition according to any one of Embodiments 1 to 7, wherein one or more active ingredients of component (a) have a molecular weight in the range of less than 800 Daltons, preferably in the range of 200 to 800 Daltons, preferably in the range of 200 to 700 Daltons, more preferably in the range of 210 to 600 Daltons, often in the range of 300 to 600 Daltons, or in the range of 320 to 500 Daltons.

[0346] Embodiment 9. A composition according to any one of Embodiments 1 to 8, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is in the range of about 0.1 to about 0.65 based on the total weight of the composition.

[0347] Embodiment 10. A composition according to any one of Embodiments 1 to 8, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is in the range of about 0.2 to about 0.55 based on the total weight of the composition.

[0348] Embodiment 11. A composition according to any one of Embodiments 1 to 8, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is in the range of about 0.25 to about 0.5 based on the total weight of the composition.

[0349] Embodiment 12. A composition according to any one of Embodiments 1 to 11, wherein one or more active ingredients of component (a) have a solubility of 20 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0350] Embodiment 13. A composition according to any one of Embodiments 1 to 11, wherein one or more active ingredients of component (a) have a solubility of 10 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0351] Embodiment 14. A composition according to any one of Embodiments 1 to 11, wherein one or more active ingredients of component (a) have a solubility of 5 g / L or less in deionized water having a pH of about 7 at 25 °C and 1013 mbar.

[0352] Embodiment 15. The composition according to any one of Embodiments 1 to 11, wherein one or more active ingredients of component (a) have a solubility of 2 g / L or less in deionized water having a pH of about 7 at 25°C and 1013 mbar.

[0353] Embodiment 16. The composition according to any one of Embodiments 1 to 11, wherein one or more active ingredients of component (a) have a solubility of 1 g / L or less in deionized water having a pH of about 7 at 25°C and 1013 mbar.

[0354] Embodiment 17. The composition according to any one of Embodiments 1 to 16, wherein the total amount of water in the composition is less than about 15% by weight based on the total weight of the composition.

[0355] Embodiment 18. The composition according to any one of Embodiments 1 to 16, wherein the total amount of water in the composition is less than about 10% by weight based on the total weight of the composition.

[0356] Embodiment 19. The composition according to any one of Embodiments 1 to 16, wherein the total amount of water in the composition is less than about 5% by weight based on the total weight of the composition.

[0357] Embodiment 20. The composition according to any one of Embodiments 1 to 19, wherein the composition contains water.

[0358] Embodiment 21. The composition according to any one of Embodiments 1 to 20, wherein one or more active ingredients of component (a) have a solubility in acetone of at least about 10 g / L at 25°C and 1013 mbar.

[0359] Embodiment 22. The composition according to any one of Embodiments 1 to 21, wherein the total amount of component (c) is at least about 5% by weight based on the total weight of the composition.

[0360] Embodiment 23. The composition according to any one of Embodiments 1 to 21, wherein the total amount of component (c) is at least about 10% by weight based on the total weight of the composition.

[0361] Embodiment 24. The composition according to any one of Embodiments 1 to 23, wherein components (a) and (b) are present in substantially the same phase.

[0362] Embodiment 25. The composition according to any one of Embodiments 1 to 24, wherein when measured by differential scanning calorimetry, the decrease in the melting point of the composition is at least 2 °C lower than the melting point of pure urea.

[0363] Embodiment 26. The composition according to any one of Embodiments 1 to 25, wherein the composition is an inclusion complex.

[0364] Embodiment 27. The composition according to any one of Embodiments 1 to 25, wherein the composition is a solid solution.

[0365] Embodiment 28. The composition according to any one of Embodiments 1 to 27, wherein the nanoparticles of one or more active ingredients of component (a) are formed when the composition is added to water having a pH of about 7 at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition.

[0366] Embodiment 29. The composition according to any one of Embodiments 1 to 28, wherein one or more active ingredients of component (a) are substantially present in liquid form when the composition is added to water having a pH of about 7 at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition.

[0367] Embodiment 30. The composition according to any one of Embodiments 1 to 28, wherein one or more active ingredients of component (a) are substantially present in liquid form when the composition is added to a 1 wt% solution of one or more emulsifying surfactants in water at 25 °C and 1013 mbar in an amount of at least about 5 times the weight of the composition.

[0368] Embodiment 31. The composition according to Embodiment 29 or 30, wherein the active ingredient of component (a) is substantially present in (emulsified) liquid form for at least 30 minutes.

[0369] Embodiment 32. The composition according to any one of Embodiments 1 to 31, wherein at least one surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 3 or more.

[0370] Embodiment 33. The composition according to any one of Embodiments 1 to 31, wherein at least one surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 4 or more.

[0371] Embodiment 34. The composition according to any one of Embodiments 1 to 31, wherein at least one surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 5 or more.

[0372] Embodiment 35. The composition according to any one of Embodiments 1 to 31, wherein at least one surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 6 or more.

[0373] Embodiment 36. The composition according to any one of Embodiments 1 to 31, wherein component (c) has a hydrophilic-lipophilic balance (HLB) of about 3 or more.

[0374] Embodiment 37. The composition according to any one of Embodiments 1 to 31, wherein component (c) has a hydrophilic-lipophilic balance (HLB) of about 4 or more.

[0375] Embodiment 38. The composition according to any one of Embodiments 1 to 31, wherein component (c) has a hydrophilic-lipophilic balance (HLB) of about 5 or more.

[0376] Embodiment 39. The composition according to any one of Embodiments 1 to 31, wherein component (c) has a hydrophilic-lipophilic balance (HLB) of about 6 or more.

[0377] Embodiment 40. The composition according to any one of Embodiments 1 to 39, wherein the component (c) contains or consists of one or more nonionic surfactants selected from the group consisting of (poly) alkoxylated alcohols, (poly) alkoxylated phosphate esters, and (poly) alkoxylated tristyrylphenols.

[0378] Embodiment 41. The composition according to any one of Embodiments 1 to 40, wherein the component (c) contains or consists of one or more nonionic surfactants selected from the group consisting of (poly) alkoxylated linear saturated or monounsaturated C12 - C18 - alcohols and (poly) alkoxylated phosphate esters of linear saturated or monounsaturated C12 - C18 - alcohols.

[0379] Embodiment 42. The composition according to any one of Embodiments 1 to 41, wherein the component (c) contains or consists of one or more nonionic surfactants having a degree of alkoxylation in the range of about 2 to about 14.

[0380] Embodiment 43. The composition according to any one of Embodiments 1 to 41, wherein the component (c) contains or consists of one or more nonionic surfactants having a degree of alkoxylation in the range of about 4 to about 10.

[0381] Embodiment 44. The composition according to any one of Embodiments 1 to 43, wherein the component (c) contains or consists of one or more nonionic surfactants selected from the group consisting of (poly) ethoxylated linear saturated or monounsaturated C12 - C18 - alcohols and (poly) ethoxylated phosphate esters of linear saturated or monounsaturated C12 - C18 - alcohols.

[0382] Embodiment 45. The composition according to any one of Embodiments 1 to 44, wherein the component (c) contains or consists of one or more nonionic surfactants containing about 2 to about 14 ethylene glycol units (PEG - 2 to PEG - 14).

[0383] Embodiment 46. The composition according to any one of Embodiments 1 to 45, wherein component (c) comprises or consists of one or more nonionic surfactants containing from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10).

[0384] Embodiment 47. The composition according to any one of Embodiments 1 to 46, wherein component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of tristyrylphenol ethoxylate.

[0385] Embodiment 48. The composition according to Embodiment 47, wherein component (c) comprises or consists of one or more nonionic surfactants containing from about 6 to about 80 ethylene glycol units (PEG-6 to PEG-80).

[0386] Embodiment 49. The composition according to Embodiment 47, wherein component (c) preferably comprises or consists of one or more nonionic surfactants containing from about 10 to about 60 ethylene glycol units (PEG-10 to PEG-60).

[0387] Embodiment 50. The composition according to any one of Embodiments 1 to 49, wherein the total amount of component (c) is in the range of about 2% to 20% by weight based on the total weight of the composition.

[0388] Embodiment 51. The composition according to any one of Embodiments 1 to 50, wherein component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of ethoxylated linear saturated or monounsaturated C12 - C18 - alcohols having from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10), and the total amount of component (c) is in the range of about 4% to about 20% by weight based on the total weight of the composition.

[0389] Embodiment 52. The composition according to any one of Embodiments 1 to 51, wherein component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of ethoxylated phosphate esters of linear saturated or mono-unsaturated C12-C18-alcohols having from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10), and the total amount of component (c) is in the range of about 2% to about 10% by weight based on the total weight of the composition.

[0390] Embodiment 53. The composition according to any one of Embodiments 1 to 52, further comprising as component (d) one or more polymer dispersants different from component (c).

[0391] Embodiment 54. The composition according to any one of Embodiments 1 to 53, further comprising as component (d) one or more polymer dispersants selected from the group consisting of polycarboxylates and their salts (preferably sodium salts), maleic anhydride-isobutylene copolymers and their salts (preferably sodium salts), block copolymers of styrene oxide and ethylene oxide, lignosulfates, and mixtures thereof, different from component (c).

[0392] Embodiment 55. The composition according to any one of Embodiments 1 to 54, wherein the composition comprises as component (d) one or more polymer dispersants different from component (c), and the total amount of component (d) is in the range of about 1% to about 15% by weight based on the total weight of the composition.

[0393] Embodiment 56. The composition according to any one of Embodiments 1 to 55, wherein the composition comprises as component (e) one or more wetting agents different from components (c) and (d), preferably the composition comprises as component (e) one or more wetting agents having a non-linear structure, and component (e) is different from components (c) and (d).

[0394] Embodiment 57. The composition according to any one of Embodiments 1 to 56, wherein the composition contains, as component (e), one or more wetting agents selected from the group consisting of gel ber alcohol ethoxylate, alkyl polyglucoside, alkyl naphthalene sulfonate condensate, and mixtures thereof, which are different from components (c) and (d).

[0395] Embodiment 58. The composition according to any one of Embodiments 1 to 56, wherein the composition contains, as component (e), one or more wetting agents selected from the group consisting of ethoxylated branched alcohols, which are different from components (c) and (d).

[0396] Embodiment 59. The composition according to any one of Embodiments 1 to 56, wherein the composition contains, as component (e), one or more wetting agents selected from the group consisting of alkyl naphthalene sulfonate condensates, which are different from components (c) and (d).

[0397] Embodiment 60. The composition according to any one of Embodiments 1 to 59, wherein the composition contains, as component (e), one or more wetting agents that are different from components (c) and (d), and the total amount of component (e) is in the range of about 5 to about 30% by weight based on the total weight of the composition.

[0398] Embodiment 61. The composition according to any one of Embodiments 1 to 60, wherein the composition contains, as component (f), a water-soluble polymer binder that is different from components (c), (d), and (e).

[0399] Embodiment 62. The composition according to any one of Embodiments 1 to 61, wherein the composition contains, as component (f), a water-soluble polymer binder selected from the group consisting of cellulose ethers and their salts, preferably water-soluble methylcellulose polymers, water-soluble hydroxypropylmethylcellulose polymers, and mixtures thereof, which are different from components (c), (d), and (e).

[0400] Embodiment 63. The composition contains, as component (f), a water-soluble polymer binder different from components (c), (d), and (e), in a total amount within the range of about 0.5% to about 3% by weight based on the total weight of the composition, the composition according to any one of Embodiments 1 to 62.

[0401] Embodiment 64. The total amount of methanol in the composition is less than about 1% by weight based on the total weight of the composition, the composition according to any one of Embodiments 1 to 63.

[0402] Embodiment 65. The total amount of ethanol in the composition is less than about 1% by weight based on the total weight of the composition, the composition according to any one of Embodiments 1 to 64.

[0403] Embodiment 66. The total amount of C1-C6 alcohols in the composition is less than about 1% by weight based on the total weight of the composition, the composition according to any one of Embodiments 1 to 63.

[0404] Embodiment 67. The total amount of oleic acid in the composition is less than about 1% by weight based on the total weight of the composition, the composition according to any one of Embodiments 1 to 66.

[0405] Embodiment 68. The total amount of components in salt form is, in each case, about 10% by weight or less, preferably about 5% by weight or less based on the total weight of the composition, the composition according to any one of Embodiments 1 to 67.

[0406] Embodiment 69. The composition contains phosphoric acid or methanesulfonic acid, the composition according to any one of Embodiments 1 to 68.

[0407] Embodiment 70. The total amount of phosphoric acid and methanesulfonic acid is, in each case, within the range of about 0.3% to about 1.5% by weight, preferably about 0.6% to about 1.2% by weight based on the total weight of the composition, the composition according to Embodiment 69.

[0408] The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of one or more pesticidal active ingredients.

[0409] The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of a pesticidal active ingredient selected from the group consisting of fungicides, herbicides, insecticides, and phytotoxicity-reducing agents.

[0410] The composition according to any one of Embodiments 1 to 70, wherein the component (a) is selected from the group consisting of chlorotriazine herbicides, pyridine fungicides, aryloylcyclohexanedione herbicides, carbamate herbicides, conazole fungicides, pyridylpyrazole insecticides, and mixtures thereof.

[0411] The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of a pesticidal active ingredient selected from the group consisting of atrazine, cyprosulfamide, fluopyram, isoxaflutole, mesotrione, fenmedifam, prothioconazole, tembotrione, tetraniliprole, and mixtures thereof.

[0412] The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of a pesticidal active ingredient selected from the group consisting of atrazine, fluopyram, mesotrione, fenmedifam, prothioconazole, tembotrione, tetraniliprole, and mixtures thereof.

[0413] The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of tembotrione, mesotrione, fenmedifam, or a combination thereof.

[0414] The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of fluopyram.

[0415] Embodiment 78. The composition according to any one of Embodiments 1 to 70, wherein the component (a) contains or consists of tetranylioprole.

[0416] Embodiment 79. A product that can be obtained or is obtained by extruding the composition defined in any one of Embodiments 1 to 78.

[0417] Embodiment 80. The product according to Embodiment 79, wherein the extrusion temperature is in the range of about 85°C to about 110°C, and subsequently the molten composition is cooled to a temperature below 55°C.

[0418] Embodiment 81. A product that can be obtained or is obtained by melting the composition defined in any one of Embodiments 1 to 78 and subsequently cooling the molten composition to a temperature below 55°C.

[0419] Embodiment 82. The product according to Embodiment 81, wherein the melting of the composition is carried out such that the temperature of the molten composition is in the range of about 75°C to about 110°C.

[0420] Embodiment 83. The product according to any one of Embodiments 79 to 82, wherein the total amount of methanol and / or ethanol in the product is less than about 1% by weight based on the total weight of the product.

[0421] Embodiment 84. The product according to any one of Embodiments 79 to 82, wherein the total amount of C1-C6 alcohols in the product is less than about 1% by weight based on the total weight of the product.

[0422] Embodiment 85. The product according to any one of Embodiments 79 to 84, wherein the total amount of oleic acid in the product is less than about 1% by weight based on the total weight of the product.

[0423] Embodiment 86. A method for preparing the composition defined in any one of Embodiments 1 to 78, comprising the following steps: 1. A step of combining components (a), (b), (c), and optionally one or more additional components selected from the group consisting of water and components (d), (e), and (f) defined in Embodiments 1 to 78. 2. A step of mixing the combination obtained from Step 1 at a temperature in the range of about 60°C to about 140°C, preferably in the range of about 75°C to about 125°C, more preferably in the range of about 80°C to about 110°C. 3. A step of cooling the composition obtained from Step 2. A method characterized by the above.

[0424] Embodiment 87. The method according to Embodiment 86, wherein Step 3 includes extrusion, spray drying, spray cooling, granulation, spheronization, or a combination thereof.

[0425] Embodiment 88. When the product is added to an amount of water sufficient to dissolve urea at 25°C, one or more active ingredients of component (a) substantially exist as nanoparticles having a diameter of less than 100 nm as determined by dynamic light scattering. Can it be obtained by the method according to Embodiment 86 or 87, or the obtained product.

[0426] Embodiment 89. When the product is added to an aqueous emulsifier diluent in an amount sufficient to dissolve urea at 25°C, an emulsion of one or more liquid active ingredients of component (a) is obtained, which is stable against crystallization of the one or more active ingredients of component (a) at 25°C for at least 30 minutes. Can it be obtained by the method according to Embodiment 86 or 87, or the obtained product.

[0427] Embodiment 90. An application mixture, as follows: - The composition or product defined in any one of Embodiments 1 to 85, 88, or 89. - Water in an amount at least 10 times, preferably at least 25 times, more preferably at least 50 times the weight of the composition or product. And One or more components selected from the group consisting of further adjuvants, other diluents, and other active ingredients An application mixture comprising

[0428] Embodiment 91. The application mixture according to embodiment 90, wherein the application mixture is a spray application mixture.

[0429] Embodiment 92. A formulation comprising a composition or product defined in any one of embodiments 1 to 85, 88, or 89, and one or more further components selected from the group consisting of adjuvants, components that are liquid at 25°C and 1013 mbar, active ingredients that are solid at 25°C and 1013 mbar, and mixtures thereof.

[0430] Embodiment 93. The formulation according to embodiment 92, wherein the formulation is selected from the group consisting of wettable granules (WG), wettable powders (WP), and oil-dispersible wettable powders (OD).

[0431] Embodiment 94. The formulation according to embodiment 92 or 93, wherein the formulation is an oil-dispersible wettable powder (OD) formulation, and one or more formulation adjuvants are selected from the group consisting of oily active ingredients, vegetable oils, oily solvents, and mixtures thereof.

[0432] Embodiment 95. The formulation according to embodiment 94, comprising an oily herbicide, wherein the oily herbicide comprises acetochlor or is acetochlor.

[0433] Embodiment 96. The formulation according to embodiment 94 or 95, comprising an oily solvent, wherein the oily solvent comprises a long-chain fatty acid methyl ester, preferably soybean methyl, or is the same.

[0434] Embodiment 97. The formulation according to embodiment 92 or 93, wherein the formulation is a wettable granule (WG) formulation or a wettable powder (WP) formulation, and the adjuvant comprises or is a dry emulsifier powder or a dry powder dispersant.

[0435] A composition, product, application mixture or formulation as defined in any one of Embodiments 1 to 85, 88 to 91 or 92 to 97, containing a pesticidal active ingredient, for use in a method of controlling unwanted vegetation, plant pests, (phytopathogenic) fungi or (phytopathogenic) nematodes.

[0436] Embodiment 99. A method for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes, the method comprising applying a composition, product, application mixture or formulation as defined in any one of Embodiments 1 to 85, 88 to 91 or 92 to 97, containing a pesticidal active ingredient, to the unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

[0437] Embodiment 100. Use of a composition, product, application mixture or formulation as defined in any one of Embodiments 1 to 85, 88 to 91 or 92 to 97, containing a pesticidal active ingredient, for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

[0438] Embodiment 101. A composition, product or application mixture as defined in any one of Embodiments 1 to 85 or 88 to 91, containing a pharmaceutical active ingredient, for use as a medicament.

[0439] Embodiment 102. A composition, product or application mixture as defined in any one of Embodiments 1 to 85 or 88 to 91, containing a pharmaceutical active ingredient, for use in a method of treating the body of an animal or a human.

[0440] Embodiment 103. A method of treating a subject in need of treatment, the method comprising administering to the subject a pharmaceutically effective amount of a composition, product or application mixture as defined in any one of Embodiments 1 to 85 or 88 to 91, containing a pharmaceutical active ingredient.

[0441] Use of a composition, product or application mixture as defined in any one of Embodiments 1 to 85 or 88 to 91, comprising a pharmaceutically active ingredient, in the treatment of the body of an animal or a human, wherein the composition, product or application mixture is preferably administered orally to the body of the animal or the human.

[0442] Exemplary embodiments are provided so that this disclosure will be thorough and will convey the full scope to those skilled in the art. Numerous specific details are set forth such as examples of specific components, assemblies, and methods, to provide a full understanding of embodiments of the disclosure. It will be apparent to those skilled in the art that specific details are not required and that the exemplary embodiments may be embodied in many different forms and neither should be construed to limit the scope of the disclosure. In some exemplary embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.

[0443] When introducing elements of the present disclosure or its preferred embodiments, the articles "a", "an", "the", and "said" are intended to mean that there are one or more elements. The terms "comprising", "including", and "having" are intended to be inclusive and mean that additional elements other than the listed elements may exist. The method steps, processes, and operations described herein need not necessarily be performed in the particular order described or illustrated, unless specifically specified as the order of performance. It will also be understood that additional or alternative steps may be employed.

[0444] Terms such as first, second, third, etc. may be used herein to describe various elements, components, seeds, members, and / or sections, but these elements, components, seeds, members, and / or sections should not be limited by these terms. These terms may only be used to distinguish one element, component, seed, member, or section from another element, component, seed, member, or section. When "first", "second", and other numerical terms are used herein, they do not imply an arrangement or order unless clearly indicated by the context. Thus, a first element, component, seed, member, or section described below could be termed a second element, component, seed, member, or section without departing from the teachings of the exemplary embodiments.

[0445] In view of the above, it will be appreciated that some objectives of the present invention are achieved and other advantageous results are achieved.

[0446] Without departing from the scope of the present invention, various changes can be made to the above products and methods, so all matters included in the above description should be construed as illustrative and not in a limiting sense.

Claims

1. A composition in solid form at 25°C and 1013 mbar: (a) One or more pesticide active ingredients or pharmaceutical active ingredients having a total amount of at least about 5% by weight, a melting point of at least 55°C at 10¹³ mbar, and a solubility of 50 g / L or less in deionized water having a pH of about 7 at 25°C and 10¹³ mbar, wherein component (a) does not exist in the form of a salt with an inorganic counterion, and one or more active ingredients of component (a) preferably have a molecular weight of less than 800 daltons, (b) Urea in total amount of at least about 50% by weight, (c) One or more nonionic surfactants in total amount of at least about 1% by weight Includes, Here, the weight ratio of the total amount of component (c) to the total amount of component (a) is approximately 0.8 or less, and The amount shown in each case is based on the total weight of the composition.

2. The composition according to claim 1, wherein component (a) is in a total amount of 5% by weight or more, 6% by weight or more, 7% by weight or more, preferably 8% by weight or more, more preferably 10% by weight or more, typically in the range of 5% by weight to 35% by weight, preferably in the range of 6% by weight to 33% by weight, preferably in the range of 7% by weight to 32% by weight, preferably in the range of 8% by weight to 31% by weight, more preferably in the range of 10% by weight to 30% by weight, and component (b) is in a total amount of 50% by weight or more, 60% by weight or more, typically in the range of 50% by weight to 90% by weight, preferably in the range of 60% by weight to 85% by weight, often in the range of 65% by weight, and / or The component (c) is added in a total amount of 2% by weight or more, 3% by weight or more, 4% by weight or more, preferably 5% by weight or more, more preferably 8% by weight or more, and often 10% by weight or more. Includes, composition.

3. The composition according to claim 1, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is in the range of about 0.1 to about 0.65, based on the total weight of the composition.

4. The composition according to claim 1, wherein the weight ratio of the total amount of component (c) to the total amount of component (a) is in the range of about 0.2 to about 0.55, based on the total weight of the composition.

5. A composition according to claim 1, wherein one or more active components of component (a) have a solubility of 20 g / L or less in deionized water having a pH of about 7 at 25°C and 10¹³ mbar, and / or one or more active components of component (a) have a solubility of at least about 10 g / L in acetone at 25°C and 10¹³ mbar.

6. The composition according to claim 1, wherein components (a) and (b) are substantially in the same phase.

7. The composition according to claim 1, wherein, when measured by differential scanning calorimetry, the decrease in the melting point of the composition is at least 2°C lower than the melting point of pure urea.

8. The composition according to claim 1, wherein the composition is an inclusion complex, or the composition is a solid solution.

9. The composition according to claim 1, wherein when the composition is added to water having a pH of about 7 at 25°C and 10¹³ mbar in an amount at least about five times the weight of the composition, nanoparticles of one or more active components of component (a) are formed.

10. The composition according to claim 1, wherein when the composition is added to water having a pH of about 7 at 25°C and 1013 mbar in an amount of at least about 5 times the weight of the composition, one or more active components of component (a) are present in substantially liquid form. or A composition in which, when the composition is added to a 1% by weight solution of one or more emulsifying surfactants in water at 25°C and 10¹³ mbar in an amount of at least five times the weight of the composition, one or more active components of component (a) are present in substantially liquid form.

11. The composition according to claim 1, wherein at least one surfactant of component (c) has a hydrophilic-lipophilic balance (HLB) value of about 3 or more.

12. Component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of (poly)alkoxylated alcohols, (poly)alkoxylated phosphate esters, and (poly)alkoxylated tristyrylphenols, and component (c) preferably is a (poly)ethoxylated linear saturated or monounsaturated C １２ -C １８ - Alcohols and linear saturated or monounsaturated C １２ -C １８ - The composition according to claim 1, comprising or comprising one or more nonionic surfactants selected from the group consisting of (poly)ethoxylated phosphate esters of alcohols.

13. The composition according to claim 1, further comprising, as component (d), one or more polymer dispersants different from component (c), preferably polycarboxylates and their salts (preferably sodium salts), maleic anhydride-isobutylene copolymers and their salts (preferably sodium salts), and one or more polymer dispersants selected from the group consisting of styrene oxide and ethylene oxide block copolymers, lignosulfates, and mixtures thereof.

14. The composition according to claim 1, wherein the composition comprises one or more wetting agents as component (e) that are different from components (c) and (d), and the composition comprises one or more wetting agents as component (e) preferably having a non-linear structure, and component (e) is different from components (c) and (d), and the total amount of component (e) is preferably in the range of about 5 to about 30% by weight based on the total weight of the composition.

15. The composition according to claim 1, wherein the composition comprises, as component (f), a water-soluble polymer binder different from components (c), (d), and (e), preferably a water-soluble polymer binder selected from the group consisting of cellulose ethers and salts thereof, more preferably a water-soluble methylcellulose polymer, a water-soluble hydroxypropyl methylcellulose polymer, and mixtures thereof.

16. A product that can be obtained by extruding the composition according to any one of claims 1 to 15.

17. A product that can be obtained by melting the composition according to any one of claims 1 to 15, and then cooling the molten composition to a temperature of less than 55°C.

18. A method for producing the composition according to any one of claims 1 to 15, comprising the following steps:

1. A step of combining components (a), (b), (c), and optionally water, and one or more further components selected from the group consisting of components (d), (e), and (f) as defined in claims 1 to 15.

2. A step of mixing the combination obtained from step 1 at a temperature in the range of approximately 60°C to approximately 140°C, preferably in the range of approximately 75°C to approximately 125°C, more preferably in the range of approximately 80°C to approximately 110°C.

3. A method characterized by a step of cooling the composition obtained from step 2.

19. A product can be obtained by the method of claim 18, or a product obtained by the method of claim 18, wherein when the product is added to a sufficient amount of water to dissolve urea at 25°C, one or more active components of component (a) are substantially present as nanoparticles having substantially less than 100 nm in diameter, as determined by dynamic light scattering.

20. The method described in claim 18, or the product obtained by adding the product at 25°C to an aqueous emulsifier dilution sufficient to dissolve urea, yields an emulsion of one or more active components of the liquid component (a), which is stable against crystallization of the one or more active components of component (a) for at least 30 minutes at 25°C.

21. Applicable mixture, - A composition as defined in any one of claims 1 to 15, - Water in an amount at least 10 times, preferably at least 25 times, and more preferably at least 50 times the amount of the composition, and - An application mixture comprising one or more components selected from the group consisting of further adjuvants, other diluents, and other active ingredients.

22. A formulation comprising a composition defined in any one of claims 1 to 15, and one or more further components selected from the group consisting of an adjuvant, a liquid component at 25°C and 10¹³ mbar, a solid active component at 25°C and 10¹³ mbar, and mixtures thereof.

23. A composition according to any one of claims 1 to 15, comprising an active pesticide component for use in a method of controlling undesirable vegetation, plant pests, (plant pathogenic) fungi, or (plant pathogenic) nematodes.

24. A method for controlling undesirable vegetation, plant pests, plant pathogenic fungi, or plant pathogenic nematodes, comprising applying a composition according to any one of claims 1 to 15, which contains a pesticide active ingredient, to the undesirable vegetation, plant pests, plant pathogenic fungi, or plant pathogenic nematodes.

25. Use of the composition according to any one of claims 1 to 15, comprising a pesticide active ingredient, for controlling undesirable vegetation, plant pests, plant pathogenic fungi, or plant pathogenic nematodes.

26. A composition according to any one of claims 1 to 15, comprising a pharmaceutically active ingredient for use as a pharmaceutical.

27. A composition according to any one of claims 1 to 15, comprising a pharmaceutically active ingredient for use in a method of treating the body of an animal or a human.

28. A method for treating a subject (excluding humans) in need of treatment, comprising administering to the subject a pharmaceutically effective amount of a composition defined in any one of claims 1 to 15, which contains a pharmaceutically active ingredient.

29. The composition according to claim 27, which is administered orally to the body of the animal or human.