Urea complexes of active ingredients

Abstract

The present invention relates to the technical field of agrochemical active ingredient or pharmaceutical active ingredient delivery systems. The present invention relates generally to certain solid state forms of compositions comprising as component (a) at least one agrochemical or pharmaceutical active ingredient, as component (b) urea, and as component (c) at least one non-ionic surfactant. The invention also relates to products obtainable or obtained by the method defined in the context of the invention. The invention further relates to formulations comprising these compositions or products, and to application mixtures obtainable or obtained by diluting these compositions or products with water or an aqueous surfactant-containing solution. The invention further relates to methods of making these compositions, products, formulations and application mixtures, as well as their use and methods of using these compositions, products, formulations and application mixtures.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 341,649, filed May 13, 2022. The entire contents of that application are hereby incorporated by reference in their entirety as if fully set forth herein. Technical Field

[0003] The invention relates to the technical field of agrochemical active ingredient or pharmaceutical active ingredient delivery system. The present invention mainly relates to certain compositions in solid form, which include as component (a) at least one agrochemical 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 obtainable or obtained by the method defined in the context of the present invention. The present invention further relates to preparations comprising these compositions or products, and application mixtures obtainable or obtained by diluting these compositions or products with water or an aqueous solution containing a surfactant. The present invention further relates to methods for preparing these compositions, products, preparations and application mixtures, as well as their uses and methods for using these compositions, products, preparations and application mixtures. Background Art

[0004] The delivery of poorly soluble active ingredients (active ingredients) to target organisms is a major challenge in both agronomy and pharmacology. In almost all cases, efficacy requires active molecules to reach the circulatory system of plants (for herbicides, systemic fungicides and pesticides) or human or veterinary patients. In pharmaceutical science, this is typically achieved by amorphous solid dispersions, such as described in Int. J. Pharm. 2020, 586, 11950. The active pharmaceutical ingredient (API) is impregnated into a polymer matrix using a solvent, and then the solvent is removed. The API diffuses out of the polymer and dissolves in the patient's stomach or small intestine, and this process is achieved due to the fact that the active ingredient is in a non-crystalline state in the polymer matrix. This accelerates dissolution and can reach an over-saturated concentration of the active ingredient. Similar formulation strategies, such as impregnation on silica gel, are also known in pharmacology.

[0005] Despite the presence of many active, low-solubility active ingredients in the agricultural sector, matrix encapsulation strategies used for pharmaceutical active ingredient types are ineffective in practical applications. Agricultural pesticides are almost always sprayed onto target plants or soil via water sprays. Unlike drug delivery, where matrix particles may remain in the gastrointestinal tract for hours, agricultural formulations are added to the spray mixture immediately before application, usually for only a few minutes. After spraying, the spray solution dries up quickly, and the active ingredient is only in contact with a thin layer of attached moisture on the leaf or soil surface. This hinders the transport of the active ingredient into the plant and its distribution in the soil.

[0006] There are some known strategies in the art to improve the absorption of low-solubility pesticides (especially low water solubility). In some cases, sufficient amounts of active ingredients can be dissolved in a suitable solvent that can carry the active ingredient into the leaves, such as a formulation type known as an emulsifiable concentrate. However, typically the active ingredient is ground to a few microns in size, suspended in water, and added to a spray barrel. The active ingredient is delivered from this type of formulation, which is known as a suspension, and is usually enhanced by adding a separate solvent to the spray mixture, typically a crop oil concentrate or soybean or rapeseed oil methyl esters.

[0007] Although these methods are widely used in commercial agriculture, they have significant limitations. Crop oil concentrates and other additives increase the cost and complexity of the application method and show inconsistent results (especially on soil). Oil adjuvants are not helpful for seed treatment. In addition, for particularly insoluble active ingredients, the solubilization of additives is insufficient. Therefore, a method is needed in agriculture to quickly release low-solubility agricultural active ingredients (typically pesticides) in spray mixtures, to show enhanced solubility with tiny, low-crystallinity particles and to deliver active ingredients to plants, soil, fungi or other targets.

[0008] Currently, most new active ingredients, especially active agrochemical ingredients or active pharmaceutical ingredients, exhibit poor solubility characteristics and subsequent reduced bioavailability. In the field of active pharmaceutical ingredients (APIs), one approach to overcome these problems is to embed the amorphous API in water-soluble polymers to form amorphous solid dispersions (ASDs), as these can improve 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 improve the bioavailability of poorly water-soluble APIs. A major challenge in the administration of these APIs is the high inter-individual variability in drug properties. Another inherent problem of amorphous solid dispersions is the instability of the solid state, which leads to a tendency for the drug and / or excipients to recrystallize during storage. This can be accompanied by a decrease in solubility and bioavailability.

[0009] IN 369969 relates to urea complexes of insecticides (chlorpyriphos, malathion, bifenthrin and cypermethrin) for improving safety handling and other properties.

[0010] US 4,065,289 discloses a herbicide composition containing a plant fertilizer.

[0011] US 5,714,157 teaches certain water-dispersible granular agricultural compositions formed by extrusion, comprising an active ingredient, a base, urea, a urea modifier and optionally other additives.

[0012] US 5,474,971 relates to certain rapidly disintegrating granular compositions which are prepared by extruding a dry premix through a die or screen at elevated temperature and which contain an active ingredient, a water-soluble diluent and at least two other additives.

[0013] WO 2014 / 093522 discloses (a production method) an extruded pesticide granule composition suitable for preparing a nearly stable micro-emulsion, the granule composition comprising urea, a non-ionic surfactant, a pesticide active ingredient and water.

[0014] US2016 / 0050913 relates to a method for manufacturing certain agricultural and horticultural granular formulations by molding a powdered composition into granules by a transverse extrusion granulator.

[0015] J. Pharm. Sci. 1966, (55), 581-583 studied the dissolution rate and gastrointestinal absorption of chloramphenicol-urea samples prepared by solid solution and eutectic mixture.

[0016] IN 182620 relates to a process for preparing urea complexes of vitamin E and its esters.

[0017] International Journal of Pharmaceutics 1997, 156, 175-180 aims to improve the dissolution rate of the poorly water-soluble drug ofloxacin by using urea or mannitol solid dispersion system.

[0018] J. Pharm. Sci., 2008, Vol. 97, No. 3, 1191-1201 reported the addition reaction of amiloride hydrochloride in urea.

[0019] J. Pharmacy Pharmacology, 2007, 59, 1501-1507 discloses a urea inclusion complex of enalapril maleate to improve pharmaceutical properties.

[0020] J. Incl. Phenom. Macrocycl. Chem. 2008, 60, 203-209 studied the urea co-inclusion complex of glipizide to improve the solubility characteristics.

[0021] J. Pharm, Innov., 2008, 3, 249-57 discussed the method of using hexagonal urea to reduce the moisture sensitivity / hygroscopicity of moisture-sensitive drugs through urea inclusion reaction (using nicorandil as a model drug).

[0022] Powder Technology 2014, 257, 168-174 evaluated clarithromycin-urea solid dispersions prepared by solvent evaporation, electrospraying and freeze drying.

[0023] J. Incl. Phenom. Macrocycl. Chem. 2015, 81, 105-120 reported the study of urea co-inclusion complex of simvastatin to improve the pharmaceutical properties.

[0024] Drug Development and Industrial Pharmacy 2015, 41(9), 1401-1415 provides a review on the classification of solid dispersions: relevance to (i) stability and solubility and (ii) preparation and characterization techniques.

[0025] Drug Delivery 2020, Vol.27, No.1, 110-127 reviews the mechanisms of increasing bioavailability through amorphous solid dispersions.

[0026] Mol.Pharmaceutics 2021, 18, 1905-1919 reports the characterization of amorphous solid dispersions (ASDs).

[0027] WO 95 / 08987 relates to a process for the preparation of solid dispersions and deposits and solid forms of calcium antagonists of the dihydropridine class, such as nimodipine.

[0028] WO 2021 / 156172 relates to a pharmaceutical composition comprising regorafenib and a stabilizer. Summary of the invention

[0029] It is found that a composition based on a solid form of urea and comprising an active ingredient having specific structure and physical properties and a certain amount and ratio of a nonionic surfactant can be rapidly dissolved in water or an aqueous diluent, thereby increasing or improving the bioavailability of the active ingredient.

[0030] Briefly, certain aspects of the present invention relate to specific solid compositions comprising: (a) a total amount of at least about 5% by weight of one or more pesticide or pharmaceutical active ingredients having a melting point of at least 55° C. and a solubility of 50 g / L or less in deionized water, wherein component (a) is not present in the form of a salt with an inorganic counterion; (b) a total amount of at least about 50% by weight of urea; and (c) a total amount of at least about 1% by weight of one or more non-ionic surfactants, wherein the ratio of the total amount of component (c) to the total amount of component (a) is about 0.8 or less.

[0031] In certain embodiments, the solid composition according to the present invention exists in the form of inclusion compound or solid solution. In other embodiments, the composition in the solid form according to the present invention, after dilution with water, will produce nanoparticles of active ingredient or produce active ingredient in liquid form. In other embodiments, the solid composition according to the present invention, after adding an aqueous solution of an emulsifying surfactant, will produce an active ingredient in emulsified form.

[0032] Other aspects of the invention relate to products obtainable or obtained from these solid compositions by processes such as (hot melt) extrusion, melting and cooling, spray drying, spray cooling, granulation (Prilling), spheronization or combinations thereof.

[0033] In another aspect, the present invention relates to a process for the preparation of a composition according to the invention, and an application mixture obtainable or obtained according to a composition or product according to the invention.

[0034] Further aspects of the invention relate to methods for controlling unwanted vegetation, plant pests, (phytopathogenic) fungi or (phytopathogenic) nematodes and the corresponding uses thereof.

[0035] Further aspects of the invention relate to compositions, products or administration mixtures as defined above and below the invention for use as medicaments in the treatment of animals or humans, as well as corresponding methods and uses. DETAILED DESCRIPTION

[0036] Generally, the present invention relates to a composition in solid form at 25°C and 1013 mbar, comprising:

[0037] (a) at least about 5% by weight of one or more pesticide or pharmaceutical active ingredients having a melting point of at least 55°C (at 1013 mbar) and a solubility in deionized water of 50 g / L or less (at a pH of about 7, 25°C and 1013 mbar), component (a) not being present in the form of a salt with an inorganic counter ion (i.e., component (a) not being present in the form of a salt with an inorganic counter ion, such as a monovalent metal ion, a divalent metal ion, a trivalent metal ion or an ammonium counter ion);

[0038] (b) a total amount of at least about 50 weight percent urea;

[0039] (c) at least about 2% by weight of a total amount of one or more non-ionic surfactants; wherein the ratio of the total amount of component (c) to the total amount of component (a) is about 0.8 or less; and

[0040] The amounts used are in each case based on the total weight of the composition.

[0041] In the context of the present invention, the composition or product of the present invention is sometimes also referred to as a complex.

[0042] In the context of the present invention, many embodiments of the compositions or products according to the present invention are defined by the amounts of the components contained therein. These amounts are typically expressed in ranges of weight percent (wt%) based on the total amount of the composition. It will be appreciated by those skilled in the art that the sum of these amounts does not (and by definition cannot) exceed 100%.

[0043] The composition of the present invention mainly comprises one or more pesticides or active pharmaceutical ingredients with the above-mentioned characteristics in urea, typically agricultural pesticides, together with nonionic surfactants, and optional other ingredients, such as dispersants that help the wetting and dissolution of the urea granular matrix and the dispersion of the active ingredients. Importantly, urea is very soluble in water (about 100g per 100ml of water) and dissolves within a few seconds. In this process, the active ingredient is released rapidly, for example, forming small and disordered particles, which are more bioavailable than crystalline solids ground into suspensions. The use of certain polymer dispersants promotes some active ingredients to form particularly small particles, as described in more detail in the examples below. In particularly favorable cases, the active ingredient will not crystallize quickly and form an oil dispersed in water.

[0044] In practice, the composite of the present invention can be prepared from molten or nearly molten urea, wherein one or more active ingredients of component (a) are dissolved, and then rapidly and fully cooled, typically in less than one minute, to prevent or minimize phase separation when urea solidifies. In some cases, fine amorphous particles of one or more active ingredients of component (a) present in the urea matrix are observed before hydrolysis, which is also satisfactory because these particles can also provide enhanced bioavailability when released. This process is compatible with well-known and commercially practiced methods for large-scale production of agricultural formulations, including (hot melt) extrusion, spray drying and granulation. In addition, the method is suitable for those pharmaceutical active ingredients in which relatively high loading and rapid release of active ingredients are beneficial relative to amorphous solid dispersions.

[0045] In the methods and compositions known in the prior art, pesticides can be co-extruded with urea to form a mechanical mixture of pesticides with a melting point lower than that of urea ("dense dispersion"). In these cases, a solid solution of the pesticide is not formed. In other methods of the prior art, urea and active ingredient particles are mixed and heat-melted rather than forming a single phase.

[0046] The present invention differs from the prior art, in which urea is typically used as a binder or "carrier" for the active granules, in that there is clear evidence of a molecular-scale interaction between urea and the pesticide, which can be described as "solvation". In the prior art, there is no mention of mixing of urea with the active ingredient at the molecular level: urea is sometimes used only as a coating and carrier for the active granules, not as a "solvent" for the active ingredient.

[0047] 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 the urea and thereby lower the processing temperature. As described below, one or more additional components, such as dispersants, wetting agents or other surfactants, are typically components of the melt to provide wetting when the composite is added to water and for other purposes. The one or more active ingredients of component (a) must be organic compounds rather than inorganic salt forms, typically have a molecular weight of less than 800 Daltons, and a melting point of 55°C or higher. The one or more active ingredients of component (a) must have sufficient thermal stability to undergo such processing, which generally means that it will not significantly degrade over a temperature range of about 75°C to 110°C for a period of up to 30 minutes.

[0048] The present invention may also be viewed as an improvement on a method used in the agricultural and pharmaceutical fields known as "Matrix encapsulation". The active ingredient is dissolved in a water-soluble matrix (typically a polymer) which dissolves in a spray tank (for agricultural sprays) or in the stomach (for pharmaceuticals), releasing the active ingredient in molecular form. It has now been found that an unexpectedly wide range of agricultural pesticides can be incorporated into a urea matrix, for example by forming a solution in a molten solution and rapidly cooling it, although other methods have been described.

[0049] The composition or product of the present invention are different in that these are mainly solutions of active ingredients in urea, formed in a molten, semi-molten or near molten (softened) state. Therefore, the composition or product of the present invention can be prepared by casting or melt extrusion (as described below) of a melt on the surface, or, for example, prepared by granulation and spray drying or hot melt extrusion. According to the present invention, the active ingredient particles are mainly formed when urea is dissolved in water or an aqueous surfactant solution (for example, when preparing an application mixture), rather than existing as a mechanical mixture with urea. In this way, the active ingredient obtained has a smaller particle size and a bioavailability improved compared to the prior art.

[0050] The purpose of the present invention is not only to achieve a rapid release of the active ingredient from the urea complex and to achieve a high or improved bioavailability of the active ingredient, but also to achieve a higher efficacy of the active ingredient, in particular a high loading of the active ingredient in the composition or complex. Such a higher loading can be achieved in the urea matrix of the present invention because the dissolution process is carried out at a higher temperature. The loading of conventional emulsifiable concentrate (EC) formulations is limited by the solubility of the active ingredient at room temperature (about 25° C.).

[0051] The urea complex (composition or product) containing the pesticide active ingredient of the present invention is superior to previous methods for enhancing the activity of agrochemical active ingredients with low solubility in water because urea is much cheaper than the polymers commonly used for matrix encapsulation, allowing the composition according to the present invention to achieve reasonably high loadings (typically ranging from about 10% to about 30% based on the total weight of the composition or product) and has value as a plant nutrient and as an adjuvant that helps to improve the absorption of foliar active ingredients. In addition, when formulated, the urea complex in powder form exhibits excellent solubility and dispersibility.

[0052] Urea complexes of herbicides such as atrazine, tembotrione and mesotrione have been prepared. For example, atrazine complexes showed improved control of the weed velvetleaf in greenhouses. Urea matrix encapsulation according to the invention has been shown to stabilize mesotrione and tembotrione against decomposition. In addition, complexes of fungicides and nematicides have been prepared.

[0053] The compositions of the present invention typically include:

[0054] The total amount of component (a) is 5 wt % or more, 6 wt % or more, 7 wt % or more, typically 8 wt % or more, more typically 10 wt % or more, typically ranging from 5% to 35%, 6% to 33%, 7% to 32%, 8% to 31% or 10% to 30%,

[0055] and / or

[0056] The total amount of component (b) is 50 wt% or more, 60 wt% or more, typically ranging from 50 wt% to 90 wt%, 60 wt% to 85 wt%, often ranging from 65 wt% to 80 wt%,

[0057] and / or

[0058] The total amount of component (c) is 2% by weight or more, 3% by weight or more, 4% by weight or more, 5% by weight or more, 8% by weight or more, often 10% by weight or more,

[0059] Therein, the amounts indicated are in each case based on the total weight of the composition.

[0060] The compositions of the present invention typically include:

[0061] The total amount of component (a) ranges from 5% to 35%, 6% to 33% or 7% to 32%,

[0062] and / or

[0063] The total amount of component (b) ranges from 50 wt% to 90 wt%, 60 wt% to 85 wt%, or 65 wt% to 80 wt%,

[0064] and / or

[0065] The total amount of component (c) ranges from 4 wt % or more, 5 wt % or more, or 8 wt % or more;

[0066] Therein, the amounts indicated are in each case based on the total weight of the composition.

[0067] The compositions of the present invention typically include:

[0068] The total amount of component (a) ranges from 7% to 32%, 8% to 31%, or 10% to 30%;

[0069] The total amount of component (b) ranges from 50 wt% to 90 wt%, 60 wt% to 85 wt%, or 65 wt% to 80 wt%;

[0070] and

[0071] The total amount of component (c) ranges from 5 wt % or more, 8 wt % or more, or 10 wt % or more;

[0072] Therein, the amounts indicated are in each case based on the total weight of the composition.

[0073] The melting point of component (a) in the composition according to the invention is typically in the range of about 55° C. to about 350° C. (at 1013 mbar).

[0074] The melting point of component (a) in the composition according to the invention is more typically in the range of about 60° C. to about 300° C. (at 1013 mbar).

[0075] The molecular weight of the active ingredient or ingredients of component (a) in the compositions according to the invention is typically less than about 800 Daltons.

[0076] The molecular weight of the active ingredient or ingredients of component (a) in the composition according to the invention is typically in the range of about 200 Daltons to about 800 Daltons.

[0077] The molecular weight of the active ingredient or ingredients of component (a) of the composition according to the invention is typically in the range of about 200 Daltons to about 700 Daltons.

[0078] The molecular weight of the active ingredient or ingredients of component (a) of the composition according to the invention is typically in the range of about 210 Daltons to about 600 Daltons.

[0079] The molecular weight of the active ingredient or ingredients of component (a) of the composition according to the invention is more typically in the range of about 210 Daltons to about 500 Daltons.

[0080] In certain cases, the molecular weight of the one or more active ingredients of component (a) of the composition according to the present invention is typically in the range of about 300 Daltons to about 600 Daltons.

[0081] In certain cases, the molecular weight of the one or more active ingredients of component (a) in the compositions according to the present invention is more typically in the range of about 320 Daltons to about 500 Daltons.

[0082] The solubility of the one or more active ingredients of component (a) in the composition according to the present invention in deionized water at a pH of about 7, 25° C. and 1013 mbar is typically 20 g / L or less.

[0083] The solubility of the one or more active ingredients of component (a) in the composition according to the present invention in deionized water at a pH of about 7, 25° C. and 1013 mbar is typically 10 g / L or less.

[0084] The solubility of the one or more active ingredients of component (a) in the composition according to the invention in deionized water at a pH of about 7, 25° C. and 1013 mbar is more typically 5 g / L or less.

[0085] Even more typically, the solubility of the one or more active ingredients of component (a) in the composition according to the invention in deionized water at a pH of about 7, 25° C. and 1013 mbar is 2 g / L or less.

[0086] Even more typically, the solubility of the one or more active ingredients of component (a) in the composition according to the invention in deionized water at a pH of about 7, 25° C. and 1013 mbar is 1 g / L or less.

[0087] The solubility of the one or more active ingredients of component (a) in the composition according to the invention in acetone at 25° C. and 1013 mbar is typically at least about 10 g / L.

[0088] The solubility of the one or more active ingredients of component (a) in the composition according to the invention in acetone at 25° C. and 1013 mbar is typically at least about 15 g / L.

[0089] The solubility of the one or more active ingredients of component (a) in the composition according to the present invention in acetone at 25° C. and 1013 mbar is more typically at least about 25 g / L.

[0090] The solubility of the one or more active ingredients of component (a) in the composition according to the present invention in acetone at 25° C. and 1013 mbar is more typically at least about 40 g / L.

[0091] In certain compositions according to the present 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.

[0092] In certain compositions according to the present 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.

[0093] In certain compositions according to the present 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 0.25 to about 0.50, based on the total weight of the composition.

[0094] In certain compositions of the present invention, the total amount of water in the composition is typically less than about 15 weight percent, based on the total weight of the composition.

[0095] In certain compositions of the present invention, the total amount of water in the composition is more typically less than about 10 weight percent, based on the total weight of the composition.

[0096] In certain compositions of the present invention, the total amount of water in the composition is even more typically less than about 5 weight percent, based on the total weight of the composition.

[0097] The compositions according to the present invention may contain water, and if present, typically the total amount of water is in the range of about 0.1 wt. % to about 5 wt. %, based on the total weight of the composition.

[0098] In certain compositions according to the present invention, the total amount of component (c) in the composition is typically at least about 4 weight percent, based on the total weight of the composition.

[0099] In certain compositions according to the present invention, the total amount of component (c) in the composition is typically at least about 5 weight percent, based on the total weight of the composition.

[0100] In certain compositions according to the present invention, the total amount of component (c) in the composition is more typically at least about 6 weight percent, based on the total weight of the composition.

[0101] In certain compositions according to the present invention, the total amount of component (c) in the composition is more typically at least about 7 weight percent, based on the total weight of the composition.

[0102] In certain compositions according to the present invention, the total amount of component (c) in the composition is even more typically at least about 8 wt %, based on the total weight of the composition.

[0103] In certain compositions according to the present invention, the total amount of component (c) in the composition is even more typically at least about 10 wt. %, based on the total weight of the composition.

[0104] Since the terminology used in the art is somewhat inconsistent, it is not easy to accurately describe the microstructure of the composition or product of the present invention. As discussed in the review of Chem. Commun., 2014, 50, 904-923, compositions similar to the present invention are variously described as "eutectics", "cocrystals" or "solid solutions". For urea, the terms "inclusion compounds" and "clathrates" are sometimes also used.

[0105] Eutectics are a class of long-known multi-component solids that have important and useful applications in everyday life. Compared to other multi-component crystalline solids (such as salts, solid solutions, molecular complexes and eutectics), eutectics are less studied in terms of molecular structural organization and bonding interactions. Traditionally, the definition of a eutectic is based on its low melting point compared to the individual components. The X-ray crystal structure of a eutectic 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 closer to the latter because their crystal arrangement is similar to that of the parent component but differs in terms of structural integrity. Solid solutions have structural homogeneity throughout the structure (single phase), while eutectics are heterogeneous aggregates of individual components whose crystal structures resemble those of discontinuous solid solutions (phase separation). Therefore, a eutectic mixture can be better defined as an aggregate of solid solutions. Structural analysis of eutectics, solid solutions, and eutectic mixtures has led us to understand that materials with strong adhesive (heterogeneous) interactions between the different components will form eutectics, while those with stronger cohesive (homogeneous / self) interactions will more often form solid solutions (for similar component structures) and eutectic mixtures (for dissimilar component structures).

[0106] Powder X-ray diffraction data obtained to date indicate that the compositions of the present invention retain the general structure of urea and can best be described as solid solutions.

[0107] Therefore, without being bound by the definition of "solid solution" or "clathrate" in a certain literature, the composition of the present invention has a single-phase appearance under a microscope, a lower melting point relative to urea, and most importantly, the active ingredient can be quickly released from the urea matrix as a liquid or nano-solid, and has improved biological activity after hydrolysis, so it is easy to functionally identify and distinguish it from the prior art. The seemingly similar materials in the prior art do not have these characteristics because urea here only acts as a binder or carrier for relatively large particles of the active ingredient.

[0108] As further described in the examples, the properties and hydrolysis behavior of the urea compositions and products of the present invention differ significantly from prior art compositions in which urea primarily acts as a binder.

[0109] in particular:

[0110] - When the composition or product of the invention is dissolved in water, some water-insoluble active ingredients are released from urea in liquid form, even though they are solid at room temperature. This behavior has not been described before and suggests that the active ingredients are present as dispersed molecules rather than as particles in the urea matrix, since the particles would be released as solids. As described in the examples below, this behavior was observed for urea complexes of the invention containing pesticide active ingredients such as fluopyram, tetraniliprole and tembotrione;

[0111] - The compositions and products of the present invention exhibit a single phase appearance and are free of inclusions when observed under a microscope. It is believed that discrete active particles larger than about 5 microns are excluded from the compositions and products of the present invention; and

[0112] - When viewed under a microscope, discrete particles of one or more active ingredients are demonstrated to be substantially absent, and inclusions of 3 microns in diameter or greater can be identified when viewed under an optical microscope with sufficient resolution. Typically, this requires a magnification of 20 times (20x).

[0113] In the context of the present invention, the term "substantial" or "substantially" refers to 90%, typically 95%, based on the total weight of the composition or product.

[0114] Compositions and products of the invention comprising active ingredients such as fluopyram exhibit eutectic behavior, allowing extrusion at temperatures of about 90°C, well below the melting point of urea or the active ingredient alone.

[0115] In certain embodiments, the melting point of a composition or product according to the invention is depressed by at least 2°C below that of pure urea, as measured by differential scanning calorimetry (DSC). This technique is known in the art and is illustrated in Example A9 below.

[0116] In many cases, the compositions and products according to the invention are substantially homogeneous (i.e., components (a) and (b), and at least substantially or all of component (c) are present in the same phase). Typically, the compositions and products according to the 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 largely on the nature of component (a).

[0117] In this context we have observed in our analysis that the composition according to the invention may be in the form of a solid solution mixed with a portion of solid, non-complexed component (a).

[0118] In a particularly preferred embodiment, the uncomplexed portion comprises an anionic dispersant or a combination of an anionic dispersant and certain nonionic dispersants. Since ionic compounds (e.g., ionic dispersants) are insoluble in urea, these components form a separate phase. Preferably, the dispersant in this phase is readily soluble in water. The presence of a second phase comprising an anionic dispersant accelerates the dispersion of the formulation when added to water. It is believed that this phase subdivides the urea solid solution phase into smaller regions, thereby accelerating its dissolution.

[0119] Examples of preferred anionic components in the uncomplexed phase include: alkylated diphenyl oxide disulfonates in the form of sodium salt solutions from Dow and Pilot Chemical Selling, sulfosuccinic acid monoesters and sulfosuccinic acid diesters (such as docusate sodium or Solvay's surfactants), lignin sulfonates, alkylnaphthalene sulfonates, and copolymers of maleic acid and olefins (e.g., BASF's CP-9).

[0120] Examples of polymeric or highly branched nonionic surfactants suitable for (also suitable for) the uncomplexed phase include tristyrylphenol ethoxylates, castor oil ethoxylates, ethylene oxide and propylene oxide block copolymers (e.g., BASF's series) and polyglycidyl ether polyethylene glycol block copolymers (Evonik DA 675).

[0121] In a further embodiment, the composition or product according to the invention is an inclusion compound.

[0122] In yet a further embodiment, the composition or product according to the invention is a solid solution.

[0123] In a further embodiment, the composition or product is added to water at a pH of about 7, 25° C. and 1013 mbar, the amount of water being at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product, and the composition or product according to the invention forms nanoparticles of one or more active ingredients of component (a) having a particle diameter of 100 nm or less, as measured by dynamic light scattering.

[0124] In other embodiments, the composition or product is added to water at a pH of about 7, 25° C. and 1013 mbar, the amount of water being at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product, and one or more active ingredients of component (a) of the composition or product according to the present invention are substantially present in liquid form.

[0125] In certain other embodiments, the composition or product is added to a 1 wt % aqueous solution containing one or more emulsifying surfactants (e.g., typical tristyrylphenol ethoxylates), at 25° C. and 1013 mbar, the amount of aqueous solution being at least about 5 times the weight of the composition or product, for example about 10 times the weight of the composition or product, and one or more active ingredients of component (a) of the composition or product according to the present invention are substantially present in liquid form.

[0126] In certain other embodiments, the composition or product is added to water at a pH of about 7, 25° C. and 1013 mbar or to an aqueous solution containing 1% by weight of an emulsifying surfactant (e.g., a typical tristyrylphenol ethoxylate) at 25° C. and 1013 mbar, and one or more active ingredients of component (a) of the composition or product according to the present invention are substantially present in liquid form, 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, wherein the active ingredients of component (a) are substantially present in the form of an (emulsified) liquid for at least 30 minutes.

[0127] It should be noted that oleic acid used in some urea-based compositions described in the prior art is not a nonionic surfactant.

[0128] Typically, in the composition or product according to the present invention, the at least one nonionic surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 3 or higher.

[0129] Typically, in the composition or product according to the present invention, the at least one nonionic surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 4 or higher.

[0130] Typically, in the composition or product according to the present invention, the at least one nonionic surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 5 or greater.

[0131] Typically, in the composition or product according to the present invention, the at least one nonionic surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 6 or greater.

[0132] More typically, in the compositions or products according to the present invention, component (c) has a hydrophile-lipophile balance (HLB) value of about 3 or greater.

[0133] More typically, in the compositions or products according to the present invention, component (c) has a hydrophile-lipophile balance (HLB) value of about 4 or greater.

[0134] More typically, in the compositions or products according to the present invention, component (c) has a hydrophile-lipophile balance (HLB) value of about 5 or greater.

[0135] More typically, in the compositions or products according to the present invention, component (c) has a hydrophile-lipophile balance (HLB) value of about 6 or greater.

[0136] 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 phosphates and (poly)alkoxylated tristyrylphenols.

[0137] The (poly)alkoxylated phosphates are essentially phosphates in the form of free acids, ie not in the form of salts. Therefore, the (poly)alkoxylated phosphates are not neutralized.

[0138] In certain compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from: (poly)alkoxylated linear saturated or monounsaturated C 12 -C 18 -alcohols and linear saturated or monounsaturated C 12 -C 18 (Poly)alkoxylated phosphoric acid esters of -alcohols.

[0139] 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 of between about 2 and about 14.

[0140] 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 between about 4 and about 10.

[0141] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from: (poly)ethoxylated linear saturated or monounsaturated C 12 -C 18 -alcohols and linear saturated or monounsaturated C 12 -C 18 (Poly)ethoxylated phosphate esters of -alcohols.

[0142] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants containing from about 2 to about 14 ethylene glycol units (PEG-2 to PEG-14).

[0143] 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).

[0144] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from tristyrylphenol ethoxylates.

[0145] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from tristyrylphenol ethoxylates containing from about 6 to about 80 ethylene glycol units (PEG-6 to PEG-80).

[0146] In other compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from tristyrylphenol ethoxylates containing from about 10 to about 60 ethylene glycol units (PEG-10 to PEG-60).

[0147] In certain compositions and products of the present invention, the total amount of component (c) ranges from about 2 wt % to 20 wt %, based on the total weight of the composition.

[0148] In certain compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from ethoxylated linear saturated or monounsaturated C 12 -C 18 -alcohol, and 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.

[0149] In various compositions and products of the present invention, component (c) comprises or consists of one or more nonionic surfactants selected from: linear saturated or monounsaturated C 12- C 18 -alcohol ethoxylated phosphate esters, and 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.

[0150] Suitable linear alcohol ethoxylates as component (c) of the compositions and products of the present invention are commercially available from a number of sources, such as Shell Chemical (Neodol TM )、Dow(Tergitol TM ) or Croda (Brij TM and Synperonic TM ) and BASF (Lutensol TM ).

[0151] These surfactants are incorporated into the same urea matrix as the active ingredient (component (a)). One function of the nonionic surfactant (s) of component (c) in the composition or product of the present invention is to stabilize the urea complex structure, and these nonionic surfactants are incorporated into the urea complex, resulting in a harder composition or product, which is easier to handle and, for example, can be better extruded.

[0152] It has been found that while oleyl and other unsaturated alcohol ethoxylates can be used effectively in the context of the present invention, 12 -C 18 ) are suitable by virtue of the desired (superior) hardness of the resulting composition or product of the present invention.

[0153] The second function of the nonionic (neutral) surfactant in 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 making the composition or product harder after extrusion are C12-C18 linear saturated alcohols functionalized with PEG-5 to PEG-10 chains. Particularly suitable examples of this type are Synperonic TM 13 / 6 (Tridecyl alcohol PEG-6, Croda), Synperonic TM A7 (C12-15 alcohol, PEG-7, Croda) and Lutensol TM TDA 6 (Tridecyl alcohol PEG-6, BASF).

[0154] For certain active ingredients, such as those that require the presence of an acid to remain stable, nonionic surfactants typically contain unneutralized acidic groups. Phosphate surfactants in their acidic form are suitable for this purpose because they can be easily incorporated into the urea matrix along with the active ingredient. Phosphate surfactants are well known in the art and are commercially available, for example, from BASF and Croda. Polyethylene glycol (PEG) chains may be preferred to mixed chains of polyethylene glycol and polypropylene glycol. Agnique TM PE TDA 9 (Tridecyl Phosphate PEG-9, BASF) and Crodafos TM O5A (oleyl phosphate PEG-5, Croda) is an example of a suitable phosphate ester surfactant for use in component (c) of this aspect of the invention.

[0155] In the composition or product of the present invention, the phosphate surfactant is incorporated into urea in an acidic form (i.e., unneutralized) and enhances the stability of certain pH-sensitive active ingredients, such as triketone herbicides (e.g., tembotrione or mesotrione). The stability of these active ingredients is improved by incorporating the phosphate surfactant in an acidic form, as will be further described in the examples.

[0156] As described in the examples, incorporation of certain acids such as phosphoric acid (available as a liquid (e.g., 85% aqueous solution) or solid) or methanesulfonic acid (available as a liquid (e.g., 70% aqueous solution) or solid) into the compositions or products of the present invention is an effective means of stabilizing pH-sensitive active ingredients (e.g., mesotrione, cyproconazole or isoxaflutole). Phosphoric acid is preferably incorporated into the compositions or products of the present invention, which contain active ingredients (e.g., mesotrione, cyproconazole or isoxaflutole) that require a low pH value to ensure chemical stability. The amount of these acids used depends on the amount of active ingredient in the composition or product of the present invention and the number and type of other components therein. Typically, the amount of phosphoric acid or methanesulfonic acid used in each case ranges from about 0.3% to about 1.5% by weight, with a typical range of about 0.6% to about 1.2% by weight, based on the total weight of the composition or product of the present invention.

[0157] Optionally, the compositions and products of the present invention comprise as component (d) one or more polymeric dispersants different from component (c).

[0158] Additional embodiments of the present invention include conducting the hydrolysis of the urea complex in the presence of a water-soluble dispersant polymer. A suitable polymer concentration in the hydrolysis mixture is 0.1% to 0.6% based on solubility. It has been found that urea complexes of certain active ingredients form small particles with enhanced bioavailability when hydrolyzed in a solution of a suitable polymer dispersant. Urea complexes of, for example, prothioconazole and tampronone are particularly suitable for this embodiment, as described in the Examples. Amphiphilic water-soluble polymers such as Sokalan TM CP 9 (BASF) and Geropon TM TA / 72 (Solvay) is a suitable water-soluble polymer dispersant.

[0159] Typically, one or more dispersants are added to stabilize the suspension of particles. Polymeric dispersants such as Sokalan TM CP 9 (BASF), Atlox TM 4914 and Atlox TM 4915 (Croda) and DA-647 (Evonik) are suitable dispersants for this aspect of the invention, as are lignin sulfonates, such as those sold by Borregaard and Ingevity.

[0160] Another aspect of the present 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 when the urea complex is hydrolyzed. Therefore, incorporating a dispersant into the composition or formulation of the present invention helps maintain the suspension of the active particles in water. Typically, a powdered lignin sulfonate dispersant is dry mixed with the urea complex in an amount of about 10% to about 30% by weight. Such dispersants are known in the art and are used to maintain particle suspension and inhibit aggregation. A dry powder dispersant particularly suitable for this aspect of the present invention is Agnique TM DDL (BASF) and Ultrazine TM NA (Borregaard).

[0161] If present in the composition or product according to the invention, component (d) comprises or consists of one or more polymeric dispersants different from component (c), wherein component (d) is selected from polycarboxylates and their salts, maleic anhydride-isobutylene copolymers and their salts, (block) copolymers of styrene oxide and ethylene oxide, lignin sulfonates, and mixtures thereof.

[0162] If present in the composition or product according to the invention, component (d) comprises or consists of one or more polymeric dispersants different from component (c), wherein component (d) is more typically selected from polycarboxylates and their sodium salts, maleic anhydride-isobutylene copolymers and their sodium salts, (block) copolymers of styrene oxide and ethylene oxide, and mixtures thereof.

[0163] Particularly suitable polymeric dispersants for use in the present invention are, for example TA / 72 (Solvay), water-soluble sodium polycarboxylate; CP 9 (BASF), sodium salt of copolymer of maleic acid and olefins and / or DA-647 (Evonik), non-ionically modified copolymer of styrene oxide and ethylene oxide.

[0164] Typically, the molecular weight M of the polymer dispersant of component (d) is n About 1000 g / mol or higher, for example, in the range of about 1000 g / mol to about 200000 g / mol.

[0165] If present in a composition or product according to the present invention, the total amount of component (d) is typically in the range of about 1 wt% to about 15 wt%, based on the total weight of the composition or product.

[0166] If present in a composition or product according to the present invention, the total amount of component (d) is more typically in the range of about 2 wt% to about 12 wt%, based on the total weight of the composition or product.

[0167] If present in a composition or product according to the present invention, the total amount of component (d) is more typically in the range of about 3 wt% to about 9 wt%, based on the total weight of the composition or product.

[0168] Optionally, the compositions and products of the present invention include as component (e) one or more wetting agents different from components (c) and (d).

[0169] Examples of suitable wetters include: branched alcohol ethoxylates, particularly those marketed by BASF as Lutensol TM Guerbet alcohol ethoxylates sold as XL50-XL80. Alkyl polyglucosides such as Agnique from BASF TM PG 8105 and Agnique™ PG 264 are also suitable wetting agents, but these materials are provided in water and therefore tend to result in a softer rheology in the composition or product.

[0170] Therefore, effective wetting agents which are commercially available in dry powder form and which dissolve rapidly in water are particularly suitable in this aspect of the invention. An example of a particularly suitable dry powder wetting agent having a non-linear structure is Morwet TM D-425 (alkyl naphthalene sulfonate condensate, Nouryon) and Agnique TM ANS 3DNPW (BASF). Another particularly suitable example of a wetting agent is Morwet TM EFW (alkyl naphthalene sulfonate condensate, Nouryon).

[0171] If 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, wherein component (e) is different from components (c) and (d).

[0172] If 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 typically selected from Guerbet alcohol ethoxylates, alkyl polyglucosides, alkyl naphthalene sulfonate condensates, and mixtures thereof.

[0173] If 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 ethoxylated branched chain alcohols.

[0174] If 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 alkylnaphthalene sulfonate condensates.

[0175] If present in a composition or product according to the present invention, the total amount of component (e) is typically in the range of about 5 wt% to about 30 wt%, based on the total weight of the composition or product.

[0176] If present in a composition or product according to the present invention, the total amount of component (e) is typically in the range of about 5 wt% to about 20 wt%, based on the total weight of the composition or product.

[0177] 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).

[0178] 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, circulating in an extruder, using a sigma mixer or planetary mixer or any other conventional mixing technique known in the art, provided that the temperature can be controlled. If the composition or product according to the present invention can be obtained by extrusion with mixing, it may be advantageous to first add one or more surfactants to provide lubrication.

[0179] If water is added to lower the melting point of the mixture, typically no more than 10% by weight of the total composition is added. Aqueous solutions of water-soluble polymers which can act as binders may be used, particularly in extrusion.

[0180] If present in the composition or product of the invention, component (f) typically comprises or consists of one or more water-soluble polymeric binders different from components (c), (d) and (e) selected from cellulose ethers and salts thereof.

[0181] If present in the composition or product of the present invention, component (f) typically comprises or consists of one or more water-soluble polymer binders different from components (c), (d) and (e), selected from methylcellulose polymers, water-soluble hydroxypropyl methylcellulose, salts thereof and mixtures thereof.

[0182] Cellulose ethers suitable as water-soluble polymeric binders for component (f) are available, for example, from International Flavors and Fragrances under the Methocel™ brand. TM J12MS is a particularly suitable adhesive.

[0183] If present in the composition or product of the present invention, the total amount of component (f) is typically in the range of 0.5 wt% to 3 wt%, based on the total weight of the composition or product.

[0184] In certain compositions or products of the present invention, the total amount of methanol in the composition or product is less than about 1 weight percent, based on the total weight of the composition or product.

[0185] In certain compositions or products of the present invention, the total amount of ethanol in the composition or product is less than about 1 weight percent, based on the total weight of the composition or product.

[0186] In other compositions or products of the present invention, the total amount of C1-C6 alcohols in the composition or product is less than about 1 weight percent, based on the total weight of the composition or product.

[0187] In certain compositions or products of the present invention, the total amount of oleic acid in the composition or product is less than about 1 weight percent, based on the total weight of the composition or product.

[0188] In various compositions or products of the present invention, the total amount of components present in the composition or product in salt form is generally about 10 wt % or less, based on the total weight of the composition or product.

[0189] In other compositions or products of the present invention, the total amount of components present in the composition or product in salt form is generally about 5 wt % or less, based on the total weight of the composition or product.

[0190] Thus, the compositions or products of the present invention are typically substantially free of components present in salt form.

[0191] If component (a) comprises or consists of one or more pesticidally active ingredients, these ingredients may be selected from pesticidally active ingredients that meet the structural and physical criteria defined in the context of the present invention.

[0192] Typically, component (a) in the compositions, products and application mixtures according to the invention comprises or consists of one or more pesticidal active ingredients, wherein component (a) typically comprises or consists of one or more active ingredients selected from the group consisting of fungicides, herbicides, insecticides, nematicides, acaricides, molluscicides, bactericides and safeners.

[0193] The pesticidal active ingredients (pesticides) and safeners which can be used as component (a) of the compositions, products and application mixtures according to the invention, and the common names used herein are all known in the art, see for example The Pesticide Manual 16th edition, British Crop Protection Council, 2012. These include - provided that the criteria for component (a) defined in the context of the present invention are met - the known stereoisomers (in particular racemates and enantiomerically pure isomers) and derivatives thereof, such as salts or esters, in particular the commercially customary forms. A pesticide is referred to herein by its common name, unless otherwise limited, and then the pesticide includes all forms known in the art, such as salts, esters, free acids and free bases, and stereoisomers thereof.

[0194] If component (a) comprises or consists of one or more herbicides, the one or more herbicides may be selected from the group consisting of acetyl-CoA carboxylase (ACCase) inhibitors, 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, cell mitosis 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.

[0195] If component (a) comprises or consists of one or more pesticides, the one or more pesticides may be selected from: organo(thio)phosphates, carbamates, pyrethroids, insect growth regulators, chitin synthesis inhibitors, insect steroid hormone antagonists, juvenile hormone analogs (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, esters, racemic mixtures and resolved isomers thereof, and mixtures thereof.

[0196] If component (a) comprises or consists of one or more fungicides, the one or more fungicides may be selected from the group consisting of respiratory inhibitors (e.g. Complex II inhibitors, Complex III inhibitors), sterol biosynthesis inhibitors (e.g. C 14 demethylase inhibitors, δ14-reductase inhibitors, 3-ketoreductase inhibitors), nucleic acid synthesis inhibitors (such as benzamide or acylamino acid fungicides, other nucleic acid inhibitors), cell division and cytoskeleton inhibitors (such as tubulin inhibitors or other cell division inhibitors), amino acid and protein synthesis inhibitors (such as methionine synthesis inhibitors, protein synthesis inhibitors), 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), multi-target inhibitors, cell wall inhibitors (such as glucan synthesis inhibitors, melanin synthesis inhibitors), plant defense inducers, and their racemic mixtures and resolved isomers, and mixtures thereof.

[0197] Safeners in the context of the present invention are typically herbicide safeners. Typically, safeners are selected from: benoxacor, cloquintocet and agriculturally acceptable esters thereof, cyometrinil, cyprosulfamide, dichlormid, dicyclonon, dietholate, fenchlorazole and agriculturally acceptable esters thereof, fenclorim, flurazole, fluxofenim, furilazole, isoxadifen and agriculturally acceptable esters thereof, mefenpyr and agriculturally acceptable esters thereof, mephenate, metcamifen, naphthalic anhydride, oxabetrinil, and mixtures thereof.

[0198] In the context of the present invention, component (a) typically comprises or consists of a pesticidal active ingredient selected from the group consisting of chlorotriazine herbicides, pyridine fungicides, aroylcyclohexanedione herbicides, carbamate herbicides, conazole fungicides, pyridylpyrazole insecticides, and mixtures thereof.

[0199] In the context of the present invention, component (a) more typically comprises or consists of an active ingredient selected from the group consisting of atrazine, cyproconazole, fluopyram, isoxathiapiprolin, mesotrione, phenmedipham, prothioconazole, tampoxadone, tetrazopyram, and mixtures thereof.

[0200] In certain embodiments of the present invention, component (a) comprises or consists of tembotrione, mesotrione, betaine, or a combination thereof.

[0201] In other embodiments of the present invention, component (a) comprises or consists of fluopyram.

[0202] In other embodiments of the present invention, component (a) comprises or consists of tetrazopyridam.

[0203] If component (a) comprises or consists of one or more pharmaceutically active ingredients, these ingredients may be selected from pharmaceutically active ingredients that meet the structural and physical criteria defined in the context of the present invention.

[0204] Suitable pharmaceutical active ingredients are, for example, blood thinners, such as Rivaroxaban, which can reduce the risk of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE) and similar conditions.

[0205] Suitable pharmaceutical active ingredients, for example, anticancer and antiangiogenic agents, such as Regorafenib, have multiple activities, including inhibitory activity on VEGFR, PDGFR, raf, p38 and / or flt-3 kinase signaling molecules, and can be used to treat various diseases and conditions, such as cancer, tumors, lymphomas, sarcomas and hyperproliferative diseases such as leukemia.

[0206] Other suitable active pharmaceutical ingredients are, for example, dihydropyridine calcium antagonists, such as nitrendipine, nimodipine or lacidipine. For example, nimodipine is an antihypertensive drug that can reduce brain damage caused by bleeding from ruptured blood vessels.

[0207] In a further aspect, the invention relates to a product obtainable or obtained by extruding a composition as defined hereinbefore or after, wherein the extrusion temperature is typically in the range of about 85°C to about 110°C, followed by cooling the molten composition to a temperature below 55°C.

[0208] In a further aspect, the present invention relates to a product obtainable or obtained by melting a composition as defined in the context of the present invention, followed by cooling the molten composition to a temperature below 55°C, wherein the melting of the composition is typically carried out so that the temperature of the molten composition is in the range of about 75°C to about 110°C.

[0209] The product according to the present invention typically comprises methanol and / or ethanol in a total amount of less than about 1 wt %, based on the total weight of the product.

[0210] Products according to the present invention typically contain C1-C6 alcohols in a total amount of less than about 1 wt %, based on the total weight of the product.

[0211] Products according to the present invention typically contain oleic acid in a total amount of less than about 1 wt %, based on the total weight of the product.

[0212] In a further aspect, the invention relates to a formulation comprising a composition or product as defined in the context of the invention, additionally comprising one or more further components selected from adjuvants, liquid ingredients at 25°C and 1013 mbar, solid active ingredients at 25°C and 1013 mbar, and mixtures thereof.

[0213] The adjuvant is typically selected from adjuvant substances known in the field of agricultural formulations. The formulations of the present invention may contain adjuvants such as antifreeze agents, such as alkylene glycols. Suitable antifreeze agents include glycerol or propylene glycol, typically contained in an amount ranging from about 3% to 20% by volume, typically from about 5% to 15% by volume.

[0214] The formulation of the present invention is typically a formulation selected from wettable granules (WG), wettable powders (WP) and oil dispersions (OD).

[0215] If the formulation of the invention is an oil dispersion (OD) formulation, the one or more formulation adjuvants are typically selected from the group consisting of an oily active ingredient, a vegetable oil, an oily solvent, and mixtures thereof.

[0216] In one embodiment, the formulation of the invention is an oil dispersion (OD) formulation comprising an oily solvent, wherein the oily solvent comprises or is a long chain fatty acid methyl ester, typically methyl soyate (soybean oil methyl ester).

[0217] In another embodiment, the formulation of the present invention is an oil dispersion (OD) formulation comprising an oily herbicide, wherein the oily herbicide comprises or is acetochlor.

[0218] In certain embodiments, the formulation of the present invention is a wettable granule (WG) formulation or a wettable powder (WP) formulation, wherein the adjuvant comprises or is a powder emulsifier or a powder dispersant.

[0219] In certain embodiments, the formulation of the invention is a wettable granule (WG) formulation or a wettable powder (WP) formulation, wherein the adjuvant comprises or is a dry powder emulsifier or a dry powder dispersant.

[0220] Another aspect of the invention, described in more detail in Example 1 below, is a method for preparing the urea complex of the invention by evaporating an alcohol solution. This method is particularly suitable for laboratory scale preparation without special equipment (such as an extruder or spray dryer). In this method, urea, an active substance and an organic compound typically containing 16 to 65 carbon atoms are mixed and completely dissolved in an alcohol solution. Examples of suitable organic compounds are soybean oil methyl ester and C 12 to C 18 Alcohol ethoxylates. Macol TM CSA 20 (Cetyl-Stearyl PEG-20, BASF) is also an organic compound suitable for this embodiment.

[0221] Another method for obtaining the composition of the present invention is shown in Example 3 below. The active ingredient is dissolved in a mixture of water, urea and a nonionic surfactant at an elevated temperature, typically in the range of about 80°C to about 110°C. When the active ingredient is completely dissolved, the active ingredient-urea mixture is added to an oily diluent at the same temperature (or higher) as the urea solution, accompanied by rapid stirring. 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 with a branched structure so as to minimize solubility in urea at a boiling point at least 10°C higher than the operating temperature. Isooctane is a particularly suitable oily diluent for this embodiment. Typically, an emulsifier with a branched structure and an HLB value of less than 14 is added to the oily diluent. Tween TM 61 (Sorbitan stearate PEG-4, HLB 10, Croda) is a suitable emulsifier for this method. The urea complex of the present invention can be separated by filtration.

[0222] Another aspect of the invention relates to a process for the preparation of a composition as defined above and below the present invention, characterized by the following steps:

[0223] 1. combining components (a), (b), (c), and optionally one or more further components selected from water and components (d), (e) and (f), as defined above,

[0224] 2. mixing the combination obtained in step 1 at a temperature range of about 60° C. to about 140° C., typically at a temperature range of about 75° C. to about 125° C., more typically at a temperature range of about 80° C. to about 110° C.,

[0225] 3. Cool the composition obtained in step 2.

[0226] The temperature in step 3 is lower than the temperature in step 2 to a certain extent, so that at least a semi-solid product can be obtained, which solidifies into the composition of the present invention after further cooling.

[0227] The mixing in step 2 can be performed, for example, by a stirrer, a twin-screw mixer or other suitable methods known in the art.

[0228] Step 3 includes extrusion, spray drying, spray cooling, granulation, spheronization, combinations thereof or other methods known in the art.

[0229] Another aspect of the invention relates to a product obtainable or obtained by the process as defined above, wherein, when the product is added to an amount of water sufficient to dissolve the urea at 25°C, the one or more active ingredients in component (a) are essentially present as nanoparticles having a diameter significantly below 100 nm, as determined by dynamic light scattering.

[0230] Another aspect of the invention relates to a product obtainable or obtained by the process as defined above, wherein, when the product is added to an aqueous emulsifier diluent at 25°C in an amount sufficient to dissolve urea, a liquid emulsion of one or more active ingredients of component (a) is obtained, which emulsion is stable and prevents crystallization of the one or more active ingredients of component (a) for at least 30 minutes at 25°C.

[0231] Another aspect of the present invention relates to an application mixture comprising

[0232] - a composition or product of the invention as defined above,

[0233] - water, at least 10 times, typically at least 25 times, more typically at least 50 times by weight of the composition or product,

[0234] as well as

[0235] - One or more components selected from other adjuvants, other diluents and other active ingredients.

[0236] In certain embodiments, the application mixture is a spray application mixture.

[0237] In other embodiments, the application mixture is an agricultural spray application mixture.

[0238] Another aspect of the invention relates to a composition, product or application mixture as defined in the context of the present invention comprising a pesticidal active ingredient for use in a method for controlling unwanted vegetation, plant pests, (phytopathogenic) fungi or (phytopathogenic) nematodes.

[0239] Another aspect of the invention relates to a method for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes, comprising applying a composition, product or application mixture comprising a pesticidal active ingredient as defined in the context of the present invention to the unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

[0240] Another aspect of the invention relates to the use of a composition, product or application mixture comprising a pesticidal active ingredient as defined in the context of the present invention for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

[0241] In the context of the present invention, phytopathogenic nematodes are in particular plant parasites. Most nematodes that feed on higher plants are obligate parasites. For example, plant parasites with a large economic impact are, for example, root-knot nematodes, cyst nematodes and pathological nematodes.

[0242] Another aspect of the invention relates to a composition, product or administration mixture as defined in the context of the present invention comprising a pharmaceutically active ingredient for use as a medicament.

[0243] Another aspect of the invention relates to a composition, product or administration mixture as defined above and below the invention comprising a pharmaceutically active ingredient for use in a method of treatment of an animal or human.

[0244] Another aspect of the invention relates to a method of treating a subject in need thereof, comprising administering to said subject (typically orally) a pharmaceutically effective amount of a composition, product or administration mixture as defined in the context of the present invention comprising a pharmaceutically active ingredient.

[0245] Another aspect of the invention relates to the use of a composition, product or administration mixture as defined above and below the invention comprising a pharmaceutically active ingredient for the treatment of an animal or a human, wherein the composition, product or administration mixture is typically administered orally to the animal or a human.

[0246] Another aspect of the invention relates to an application mixture obtainable or obtained by diluting the composition (referred to as a tank mix in the case of agricultural active ingredients). The product or formulation of the invention has an appropriate amount of water, wherein the weight ratio of water to the composition, product or formulation is typically in the range of about 200:1 to about 10:1, typically in the range of about 100:1 to about 20:1.

[0247] Such application mixtures may contain one or more additional additives, formulation adjuvants and / or pesticides.

[0248] Another aspect of the invention relates to a process for preparing an application mixture according to the invention, characterised in that the composition, product or preparation is (slowly) poured into a container containing water under (gentle) stirring, optionally one or more additional additives, formulation adjuvants and / or pesticides are added to the application mixture.

[0249] Typically, in such methods of preparing application mixtures of the invention, the weight ratio of water to the composition, product or formulation of the invention is in the range of about 200:1 to about 10:1, typically in the range of about 100:1 to about 20:1.

[0250] The spraying application mixture of the present invention can be applied to the field or application area according to the practice known to those skilled in the art. The spraying application mixture according to the present invention can be applied in the field of crops at different growth stages, depending on the active pesticide ingredient present in component (a) or as component (a). In certain embodiments, the spraying application mixture is applied to the soil before planting crop plants or after planting crop plants, but before the crop plants emerge. In other embodiments, the spraying application mixture is applied after the crop plants emerge.

[0251] In the context of the present invention, preferred crop plants include: corn, soybeans, cotton, wheat, rapeseed, canola and sugar beet. The compositions, products and spray-applied mixtures of the present invention can also be applied to other useful plants, such as vines, trees (e.g. palm trees), fruits (e.g. apples, pears, prunes, bananas, etc.), nuts (e.g. almonds, pecans, peanuts, etc.) or vegetables (e.g. tomatoes, dry beans, snap beans, potatoes, etc.).

[0252] The compositions, products or application mixtures of the present invention comprising one or more herbicides as (part of) component (a) are suitable for controlling various weeds, i.e., plants that are considered to be troublesome or competitive to commercially important crop plants, such as corn, soybeans, cotton, wheat, rapeseed, canola, sugar beets, dry beans, snap beans and potatoes, etc. In certain embodiments, the application mixture is applied before the weeds appear (i.e., pre-emergence application).

[0253] Monocotyledonous weeds belong, for example, to 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.

[0254] Dicotyledonous weeds belong, for example, to the genera Sinapis, Lepidium, Galium, Stellaria, Matricaria, Anthemis, Galinsoga, Chenopodium, Urtica, Senecio, Amaranthus, Portulaca, Xanthium, Convolvulus, Ipomoea, Polygonum, Sesbania, Ambrosia, Kochia, a), Cirsium, Carduus, Sonchus, Solanum, Rorippa, Rotala, Lindernia, Lamium, Veronica, Abutilon, Emex, Datura, Viola, Galeopsis, Papaver, Centaurea, Trifolium, Ranunculus, Taraxacum, and Euphorbia.

[0255] Having described the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of the invention as defined in the appended claims.

[0256] Example

[0257] The following non-limiting examples are provided to further illustrate the present invention.

[0258] Unless otherwise indicated, all amounts and percentages are by weight.

[0259] Abbreviations and materials used :

[0260] PEG = Polyethylene glycol

[0261] CSA 20 = PEG-20 cetearyl ether (cetyl / stearyl alcohol) = Ceteareth-20 (BASF)

[0262] MTBE = methyl-tert-butyl ether

[0263] AA 270 = Phosphoric acid esters of polyoxyalkylated fatty alcohols [ethylene oxide, 2-methyl-, polymer with ethylene oxide, mono-C10-16 alkyl ether, phosphate ester, CAS No. 68649-29-6], 85% active substance and 15% phosphoric acid (BASF)

[0264] AE-P = Phosphate esters of ethoxylated / propoxylated medium chain alcohols (BASF)

[0265] Crodafos TM SG = PEG-10 PPG-5 Cetyl Phosphate = PPG-5-Ceteth-10 Phosphate (Croda)

[0266] Phospholan TM PS-220 = C10-14 alcohol (30EO) ethoxylate 104-phosphate (Nouryon)

[0267] O20 = Polyoxyethylene (20) oleyl ether = Oleth-20 (Croda)

[0268] Crodafos TM O10A = Complex ester of phosphoric acid and ethoxylated cosmetic grade oleyl alcohol (Croda)

[0269] Tween =Polyoxyethylene (4) sorbitan monostearate =Sorbitan stearate PEG-4 (Croda)

[0270] Ultrazine TM NA = Sodium lignin sulfonate dispersant (Borregaard)

[0271] rpm = revolutions per minute

[0272] Methocel TM J12MS = Surface treated hydroxypropyl methylcellulose (HPMC) based polymer (International Flavors and Fragrances), typically used as a 2% aqueous solution

[0273] P123 = Ethylene oxide-propylene oxide block copolymer (BASF)

[0274] Synperonic TM A7 = fully saturated C12-C15 alcohol ethoxylate. This water-soluble nonionic surfactant is an effective wetting agent and detergent (Croda)

[0275] EM O7 = Oleyl PEG-7 (Evonik)

[0276] DDL = lignin sulfonate based dispersant (BASF)

[0277] 8244 = PEG-16 polyethoxylated castor oil (Stepan)

[0278] P123 = poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (SigmaAldrich)

[0279] PE TDA 9 = Tridecyl alcohol phosphate, PEG-9 (BASF)

[0280] ANS 3DNPW = Alkyl naphthalene sulfonate mixture (BASF), wetting agent

[0281] Synperonic TM 13 / 6 = Polyoxyethylene (6) isotridecanol (Croda)

[0282] = CP 9 = maleic acid-olefin copolymer, 25% aqueous solution (BASF)

[0283] EFW = Sodium alkylnaphthalene sulfonate mixed dispersant (Nouryon)

[0284] = 88.2% atrazine, 1.8% related compounds, 10% other ingredients (Syngenta)

[0285] = 34.5% tembotrione, 65.5% other ingredients (Bayer)

[0286] = 40% Mesotrione, 60% Other ingredients (Syngenta)

[0287] =41% prothioconazole, 59% other ingredients (Bayer)

[0288] Urea = 99% urea (Fisher Scientific)

[0289] Haake TMMini CTW = Hot Melt Extruder, ThermoFisher Scientific

[0290] Malvern Nano-ZS Zetasizer=Dynamic Light Scattering Equipment

[0291] S233: Biodegradable trisiloxane surfactant (Evonik)

[0292] FLK = anionic tristyrylphenol ethoxylated phosphate emulsifier, aqueous solution active about 40% (Solvay)

[0293] MSA = 70% methanesulfonic acid in water (BASF)

[0294] TA / 72 = sodium polycarboxylate, CAS No. 223571-91-3, anionic surfactant, polymer dispersant (Solvay)

[0295] TSP-60 = Tristyrylphenol Ethoxylate PEG-60 (Stepan)

[0296] DA-647 = Modified copolymer of nonionic styrene oxide and ethylene oxide (Evonik)

[0297] Myrj TM S8 = Polyoxyl (8) Stearate = PEG-8 Stearate (Croda)

[0298] OE = methyl oleate

[0299] DF-95 = Sodium lauryl sulfate (93%) (Stepan), dry powder

[0300] 8390 = Diphenyl oxide disulfonic acid sodium salt, C16 alkylate (Dow Chemical)

[0301] 3B2 = diphenyl oxide disulfonic acid sodium salt, C10 alkylate (Dow Chemical)

[0302] Stepfac TM 8181 = Polyethylene glycol (6) tridecyl ether phosphate

[0303] TSP-12 = Tristyrylphenol Ethoxylate PEG-12 (Stepan)

[0304] 8320 = butyl-based ethylene oxide-propylene oxide block copolymer (Stepan) (average MW 5500, HLB value 12)

[0305] TD-12 = Tridecyl alcohol ethoxylate, PEG-12 (Stepan)

[0306] T6A = Tridecyl Phosphate, PEG-6 (Croda)

[0307] CY / 8 = a nonionic tristyrylphenol ethoxylated emulsifier (CAS No. 99734-09-05); HLB: 13.5, paste (Solvay)

[0308] S-25 / 80 = a nonionic tristyrylphenol ethoxylate; HLB: 14.5; about 80% active ingredient in water, liquid (Solvay)

[0309] In the following examples, the composition of the present invention is sometimes also referred to as a complex.

[0310] Embodiment 1-11:

[0311] Example 1: Preparation of Urea Complex of Atrazine by Evaporation

[0312] As shown in Table 1 below, the following components were combined in a bottle and placed in an oven at 55° C. The bottle was removed from the oven, stirred and returned to the oven to complete dissolution.

[0313] Table 1. Components used to form urea complexes of atrazine by evaporation

[0314]

[0315] After complete dissolution, 7.0 g of Methyl soybean oil. After shaking the bottle, the contents were transferred to a pear-shaped flask and the solvent was evaporated on a rotary evaporator until a white precipitate began to form, which occurred suddenly during the evaporation. The precipitate was recovered by filtration. The complex showed rapid and nearly complete precipitation, with only a small amount of the complex formed in the filter flask and was not recovered. The product was rinsed with MTBE and dried overnight at 55°C and 24 inches of mercury (about 0.81273 bar) in a vacuum with a nitrogen purge. 51.8 g of white powdered product was recovered and was found to contain 9.9% atrazine and 10.7% of all triazine compounds. When added to water, the urea dissolved, leaving fine atrazine particles suspended in the turbid solution.

[0316] Example 2: Preparation of urea complex of mesotrione and phosphate surfactant by evaporation method

[0317] In four different 4 oz (120 mL) bottles, 15 g of urea, 80 mL of methanol, and 0.5 g of O20 is combined and sealed. The bottle is placed in an oven maintained at 55°C and rotated occasionally until the contents have completely dissolved. The bottle is removed from the oven and a stir bar is added as well as 1.6 g of mesotrione and 0.5 g of the corresponding phosphate (as shown in Table 2). In this case, the phosphate not only plays a role in the formation of the urea complex, but also helps to stabilize mesotrione and prevent decomposition due to the acidity of the unneutralized phosphate. The bottles are briefly stirred at room temperature until the mesotrione is dissolved (approximately five minutes). Each bottle is shaken and the contents are transferred to a round-bottom flask, and 1.8 g of soybean oil methyl ester is added to the flask. The solvent is evaporated on a rotary evaporator until a white precipitate begins to form in an exothermic step, accompanied by accelerated evaporation of methanol, which occurs quickly after a sudden start. The precipitate is transferred to a Buchner funnel with a coarse-pore filter plate. The filtrate is yellow-brown. The remaining product in the flask is rinsed into a Buchner funnel with methyl-t-butyl ether and a vacuum is applied. The product is a fine white powder, and a considerable amount of solvent is retained even after vacuum filtration. The mixture was dried overnight at 55°C, 24 inches of mercury (about 0.81273 bar) under vacuum conditions with nitrogen purge. The filtrate was dark yellow. The product was weighed and crushed in a mortar and pestle. The yield and mesotrione concentration of each complex are shown in Table 2.

[0318] Table 2. Urea complexes of mesotrione and phosphate surfactants by evaporation

[0319]

[0320] Example 3: Preparation of urea complex of tembotrione by slow cooling in oil suspension

[0321] In a 250 ml round bottom flask, 85.8 g urea was mixed with 24.2 g water (equivalent to 110 g 78% urea aqueous solution) and 4 g Crodafos TM O10A combined. The flask was sealed and placed in an oven maintained at 85°C. Contains 2g Tween 3g The bottle of EM O7 and 400 mL of isooctane was also placed in the same oven along with a 1-liter beaker. Once the reagents were hot, the flask was placed in an oil bath at 85°C and stirred. Once the urea was completely dissolved, 10.0 g of tampoxone was added to the mixture. When dissolution was nearly complete (about 3 minutes), the isooctane solution was poured into the beaker and mechanical stirring was started in a fume hood without heating. The urea solution was then poured into the beaker and stirring continued for about five minutes while the emulsion slowly cooled. Precipitation was observed almost immediately (about 70°C). The urea complex was recovered by filtration through a Buchner funnel, which was slowed by clogging of the filter plate. The recovered urea complex was dried overnight at 65°C, 20 inches of mercury (about 0.67728 bar) under vacuum conditions with nitrogen purge and then crushed using a mortar and pestle. 85 g of the resulting material (from both batches) was mixed with the lignin sulfonate dispersant Ultrazine TM The content of tembotrione in the obtained product was 8.63%.

[0322] Example 4: Preparation of atrazine-urea complex by hot melt extrusion

[0323] In this case, the complex includes atrazine, urea and J12MS solution. Water lowers the melting point of urea, while A waxy ethylene oxide-propylene oxide block copolymer, P123 (BASF) was added to the extruder to provide lubrication and disperse the urea. Alcohol ethoxylates were added as nonionic surfactants (component (c)) which also provided wetting properties. Some compositions also used dispersants to promote the formation of fine atrazine particles during hydrolysis of the complex. The alcohol ethoxylates used were A7 and EM O7. Dispersant is DDL and 8244. The composition is in Haake TM The compositions were prepared in a Mini CTW hot melt extruder. This equipment is a small twin screw extruder in which the components of the composition can be circulated before extrusion. All compositions were prepared at an extruder temperature of 95°C and a screw speed of 90 rpm. When the extruder reached temperature and the screw was turning, the first P123 for lubrication, then add solution and dispersant. Urea and atrazine were added together. The alcohol ethoxylate was added last. The mixture was then circulated in an extruder until molten and homogeneous, which took about two minutes. These compositions were easily crushed into a fine powder using a mortar and pestle. All substances dissolved rapidly in water, forming atrazine particles of 1-5 microns as measured by optical microscopy. The sedimentation rate was slow. The corresponding atrazine contents in the compositions are shown in Table 3.

[0324] Table 3. Preparation of atrazine-urea complexes by hot melt extrusion

[0325]

[0326]

[0327] Example 5: Preparation of urea complex of tembotrione by pouring the completely molten mixture onto a cooled metal plate

[0328] The composition also includes a powdered wetting agent ANS 3DNPW, 2% A7 J12MS aqueous solution and alcohol ethoxylate 13 / 6. The composition was prepared on a scale of 80 g, see Table 4 below. Urea, phosphate ester, wetting agent and The J12MS solution was combined in a 250 mL round bottom flask equipped with a stir bar. The flask was sealed and preheated in an oven at 90 °C. The flask was transferred to an oil bath at 105 °C and tembotrione was added and stirred until the solution was homogeneous. 13 / 6, and the mixture was poured in batches onto an aluminum plate placed on ice. The thin layer of composition on the plate was scraped off and cut into small pieces. Dissolution was easy and complete. Three batches of sample pools prepared in this way were analyzed, which contained 16.8 wt.% of tembotrione.

[0329] Table 4. Preparation of urea complexes of tembotrione by pouring the fully molten mixture onto a cooled metal plate

[0330]

[0331] When the 2% When applied as a solution of CP 9, this formulation provided effective fungal control on peanut plants in the field without being phytotoxic.

[0332] Example 6: Preparation of urea complex of prothioconazole by rapid cooling of melt

[0333] Urea, solution and ANS 3DNPW was 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 transfer to an oil bath at 105°C, melting was complete and viscosity was low. Prothioconazole was added and allowed 10 minutes to completely dissolve before adding the alcohol ethoxylate. The composition was poured in two portions onto an aluminum plate placed on ice. Thin wafers were obtained. These wafers were broken into small pieces, which dissolved rapidly in water, releasing very fine particles of prothioconazole.

[0334] Table 5. Preparation of urea complexes of prothioconazole by rapid melt cooling

[0335]

[0336] Example 7: Enhanced herbicidal efficacy of the urea-atrazine complex of Example 1

[0337] This was compared to conventional atrazine used alone or in combination with the HPPD inhibitor herbicide mesotrione. 95 parts by weight of the composite (containing 9.9% atrazine and 10.7% total triazine compounds) and 5 parts of dispersant EFW was combined to provide a dispersible composition with a loading of 9.4% atrazine. The composition was dispersed in water and sprayed on Abuthin (ABUTH) at a dosage of 140 g / ha and 280 g / ha and was sprayed with a conventional commercial atrazine composition at the same dosage. A comparison was also made with herbicides containing mesotrione. Tank mix of Syngenta. On 6-9 leaf stage Abutilon plants, spray was applied at 93 L / ha using a 9501 flat fan nozzle. In some treatments, 1% vol / vol crop oil concentrate (COC) was added. The treatment with urea-atrazine was 17.5 g / ha at the lower atrazine dosage (140 g / ha) and 35 g / ha at the higher atrazine dosage (280 g / ha). Table 6 shows the control effect of conventional atrazine and urea-atrazine complex on velvetleaf.

[0338] Table 6. Control effect of different atrazine-containing materials on velvetleaf

[0339]

[0340] Example 8: Enhanced herbicidal effect of the urea-trimethylenetetramine complex in Example 3

[0341] The control effect of tembotrione complex on ABUTH was compared with that of conventional tembotrione preparations. No adjuvant was used at a dose of 17.5 g / ha, which is well below the commercially recommended dose of 90 g / ha. The tank mix was sprayed onto the velvetleaf plants at a rate of 15 gallons per acre (approximately 140 L / ha). Plants were visually assessed three weeks after spraying. At the time of assessment, The control effect of the urea complex composition was 13%, while the control effect of the urea complex composition was 22%.

[0342] Example 9: Stability study of the corresponding urea complexes of mesotrione and tembotrione in Examples 2 and 3

[0343] Stability was assessed by placing samples in an oven and taking samples periodically. The mesotrione complex was evaluated over a 6-week period in an oven at 54°C. All complexes showed acceptable stability, except for Phospholan TM PS-220 and Crodafos TM The SG complex performed particularly well.

[0344] Table 7. Shows the concentration of mesotrione in the urea complex of Example 2 after aging in an oven at 54°C.

[0345] Table 7. Results of a stability study of mesotrione concentrations in urea complexes at 54°C for 8 weeks

[0346]

[0347]

[0348] The tembotrione-urea complex of Example 3 was aged in an oven at 54°C for eight weeks for testing. As shown in Example 3, the acidic phosphate surfactant Crodafos TM O10A (PEG-10 oleyl phosphate, Croda) stabilizes tembotrione and mesotrione, preventing their chemical decomposition. Table 8 shows the tembotrione concentration in the urea complex at 54°C for 8 weeks.

[0349] Table 8. Results of a stability study of tembotrione concentrations in urea complexes at 54°C for 8 weeks

[0350]

[0351] Example 10: Treatment of corn seeds with the urea-prothioconazole complex of Example 6

[0352] First, add the urea composition to water or water- The mixture was added and vortexed briefly to completely dissolve. The pigment and standard seed treatment polymer were added to the centrifuge tube. After a brief vortex, 8.6 mL of the mixture was applied to 1 kg of corn seeds, equivalent to a rate of 12 fluid ounces per 100 pounds of seeds. The treatment time was approximately 33 seconds.

[0353] Treatments were carried out at doses of 0.021 mg and 0.085 mg of prothioconazole per seed. Both doses of the control composition were treated with prothioconazole suspension concentrate. For urea compositions, an equal amount of water or water- Mixture. 20% was used at a dose of 0.032 mg / seed -80% water, while 30% was used at a dose of 0.085 mg / seed -70% water (wt / wt). Use The prepared low dose seed treatment solution was transparent before the addition of the seed colorant due to the small size of the prothioconazole particles formed.

[0354] Even at high doses, there was no chalking of the seed surface due to urea, and no material was transferred to the gloves when the seeds were rubbed. Seeds treated with the hydrolyzed urea complex were significantly more lustrous than control seeds or seeds treated with the hydrolyzed urea complex alone.

[0355] Example 11. Dynamic Light Scattering

[0356] Example 11a: Dynamic light scattering of the urea complex of tembotrione in Example 5

[0357] The tembotrione composition from Example 5 was prepared by rapid cooling of the melt, treated with hydrolysis 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 a mixture containing 15 mL of water or 15 mL of 2% The solution was allowed to stand at room temperature for two hours before the particle size was measured. The aqueous hydrolyzate was very slightly turbid and The hydrolyzate was optically clear. Dynamic light scattering showed that the particle size distribution of both hydrolyzate mixtures was very narrow, with the average particle size of the water hydrolyzate being 298 nm and The average particle size of the hydrolyzate was 5 nm. To ensure accuracy, the significant Hydrolysis results.

[0358] Example 11b: Dynamic light scattering of the urea complex of prothioconazole from Example 6

[0359] Two batches of samples were prepared and the results were 15.0% and 14.5% prothioconazole respectively. When dispersed in water or 2% Dynamic light scattering shows The dispersion had a sharp peak at 1.5 microns, while hydrolysis in water alone had a broader peak between 1.2 microns and 2.1 microns. The solution was analyzed using a Malvern Nano-ZS Zetasizer as in Example 11a.

[0360] Embodiment: A1-A9:

[0361] Example A1: Urea complex of Tetraniliprole prepared by hot melt extrusion (without water)

[0362] This example describes the preparation of a urea complex of the insecticide tetrazolyl thiocarbamide. Extrusion is carried out at moderate temperatures, the loading of active ingredients is high, and no water needs to be added. This indicates that there is a eutectic phenomenon between tetrazolyl thiocarbamide and urea. The composition is intended to be used for treating seeds, delivering tetrazolyl thiocarbamide to the seed surface in the form of low crystallinity to increase its bioavailability. It is worth noting that when the composition is added to water, tetrazolyl thiocarbamide is released in a liquid state in the form of a stable emulsion, which is ideal for the intended application.

[0363] By using Haake TM Ten batches of 5 g of product were prepared by extruding the mixture using a Mini CTW extruder (as described in Example 4). Extrusion was carried out at a screw speed of 90 rpm and a temperature of 105° C. The composition was easily extruded as continuous “noodles” and easily crushed into a powder after cooling to room temperature.

[0364] Table A1. Compositions of urea complexes of tetrazobactam prepared by hot melt extrusion (without water)

[0365]

[0366] After crushing, the composition dissolved in water almost immediately, forming a bright white liquid tetrazobactam emulsion in water. After being left overnight at room temperature, no crystallization or deterioration of the emulsion quality was observed.

[0367] Example A2: Treatment of corn seeds with tetrazobactam in urea

[0368] The tetrazobactam in ten batches of urea composition from Example A1 was pooled and a portion was used to treat corn seeds. To treat 1 kg of corn seeds with the BT trait (Bacillus thuringiensis protein, which protects plants from insects), the ratio of treatment liquid to seed mass was 16 fluid ounces per hundred pounds of corn seeds. 1,600 corn seeds per pound were treated in a bowl treater with a urea complex solution containing Example A1, with 0.125 mg and 0.25 mg of tetrazobactam per seed, respectively. The treatment mixture also included the fungicide fluoxastrobin at 0.085 mg / seed, as well as pigments and adhesive polymers. In order to optimize the tetrazobactam emulsion, the treatment liquid also contained 0.6 fluid ounces per hundred pounds of FLK.

[0369] It was found that the cold and warm germination rates of the treated seeds were comparable to those of the untreated seeds. However, due to the BT trait, it is not suitable for efficacy testing. Therefore, corn seeds without the BT trait were used and the treatment was repeated on a smaller scale at a dosage of 0.063 mg and 0.125 mg tetrazolyl thiocarbamide per seed. It was also treated with a conventional tetrazolyl thiocarbamide suspension concentrate ("SC", 480 g / L). These batches were used for the efficacy determination described in Example A3.

[0370] Example A3: Efficacy of tetrazobactam-urea complex as a seed-applied insecticide

[0371] Non-BT seeds treated with 0.063 mg / seed as described in Example A2 were germinated and grown in pots. When the plants were about one foot tall, black cutworms were introduced and the stems were measured for damage. As shown in Table A3-1, the urea complex and the The protection of stems by applying FLK together was better than that of conventional suspension concentrate.

[0372] Table A3-1. Damage to the stems of corn seedlings treated with 0.063 mg / seed of tetrazobactam and black cutworms

[0373]

[0374] Non-BT seeds were treated with 0.125 mg / seed as described in Example A2 and evaluated based on the reduction in third leaf area due to black cutworm feeding. As shown in Table A3-2, the urea complex again outperformed the conventional suspension concentrate.

[0375] Table A3-2. Reduction in the surface area of ​​the third leaf of corn seedlings treated with 0.125 mg / seed tetrazobactam after feeding by black cutworms

[0376]

[0377] Example A4: Compositions of tembotrione-urea containing different surfactants that affect the morphology of the active ingredient after hydrolysis

[0378] This example describes the preparation of two tembotrione complexes by hot melt method by pouring the melt onto a cold metal plate. In addition, the two compositions contain different surfactants, which lead to different behaviors when the respective compositions are added to water. One composition, A4-1, forms nanoparticles similar to the complex of Example 5, the particle size of which is characterized in Example 11. Another composition, A4-2, forms a liquid tembotrione emulsion. In addition, these compositions illustrate the use of methanesulfonic acid (using MSA) is added to lower the pH and provide chemical stability. As shown in Example 5, unneutralized phosphate is added PE TDA 9 provides additional acidity.

[0379] Composite A4-1, which forms nanoparticles, was prepared similarly to Example 5 in a 100 g scale melt. Geropon, PE TDA 9, 13 / 6, water and urea are combined in a 250mL flask equipped with a stirrer, sealed, and placed in an oven at 105°C overnight. The flask is transferred to an oil bath at 105°C. 0.5g MSA is added, followed by tampron and stirring is maintained until tampron is dissolved and a good vortex is established. The mixture is poured out in batches to form red soft material sheets. The product is dried under a vacuum condition of 55°C, 24 inches of mercury (about 0.81273 bar) with nitrogen purge for 4 hours.

[0380] The compound A4-2 in the Haake TM CTW hot melt extruder. The components added in 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. These batches were combined for effect testing.

[0381] Table A4: Compositions of tembotrione containing methanesulfonic acid

[0382]

[0383] For tembotrione, the addition of a polymeric dispersant capable of stabilizing the surface of the solid particles leads to the formation of nanoparticles in composition A4-1. For this purpose, a polymeric dispersant from Solvay was used. TA / 72.

[0384] In contrast, composition A4-2 comprises TSP-60, which promotes the formation of emulsions, leads to the formation of a liquid tembotrione emulsion when complex A4-2 is added to water.

[0385] Example A5: High-loaded fluopyram-urea complex by hot melt extrusion

[0386] This example illustrates the high loading that can be achieved in a urea complex of active ingredient with a melting point close to the extrusion temperature, which favors the formation of co-crystals. It also shows that release of the active ingredient in a liquid state can be easily achieved by varying the emulsifier and alcohol ethoxylate in the composition upon hydrolysis of the complex.

[0387] Fluopyram is a fungicide with a melting point of 118°C. It is poorly soluble in water at 16 mg / L, but highly soluble in polar organic solvents (>250 g / L in ethyl acetate or DMSO). TM Compositions of about 30% (nominal) fluopyram in urea were prepared on a Mini CTW hot melt extruder at 90°C and a screw speed of 90 rpm. Extrusion in all cases readily produced continuous "noodles" that were easily crushed after cooling. The compositions were prepared on a scale of about 5 g.

[0388] 1.5 g of fluopyram, 2.7 g of urea granules and different amounts of alcohol ethoxylate, wetting agent and emulsifier were added to Haake TM The mixture was circulated in the Mini CTW until homogeneous and then extruded under the above conditions.

[0389] The following three compositions A5-1, A5-2 or A5-3 were prepared:

[0390] Composition A5-1:

[0391] 1.5g Fluopyram + 2.7g Urea Granules + 0.4g TSP-60+0.4g 13 / 6

[0392] Composition A5-2:

[0393] 1.5g Fluopyram + 2.7g Urea Granules + 0.4g TSP-60+0.4g EMO7

[0394] Composition A5-3:

[0395] 1.5g Fluopyram + 2.7g Urea Granules + DA-647+0.3g Myrj S8+ ANS 3DNPW

[0396] All compositions produced emulsions of liquid fluopyram when added to water at a weight ratio of about 10:1 to composition A5-1, A5-2 or A5-3, respectively. The emulsions remained stable for about two hours, at which time some crystallization and sedimentation occurred. Fluopyram particles formed during this process redispersed easily under an optical microscope and showed no crystallinity.

[0397] Example A6: Preparation of atrazine-urea complex from the melt

[0398] This example describes the preparation of an atrazine-urea complex from a melt, as compared to evaporation or hot melt extrusion (see Examples 1 and 4, respectively). The composition also demonstrated significantly better pre-emergence efficacy than conventional suspension concentrates. At a 150 g scale, an atrazine-urea complex was formed using the components shown in Table A6.

[0399] Table A6: Atrazine-urea complexes obtained from the melt

[0400]

[0401]

[0402] All components (except atrazine and 3 mL of J12MS solution) in a 500 mL round bottom flask equipped with a stir bar. Seal the flask and place in an oven at 115°C overnight. Transfer the flask to an oil bath at 120°C and stir. Add the remaining J12MS solution and atrazine was added in portions while maintaining stirring. When dissolution was complete, the resulting mixture was poured onto an aluminum plate placed on an ice bed. After two pourings, 130.9 g of a white composition was recovered. The batch was annealed overnight at 70°C in a nitrogen atmosphere and the mass was reduced to 123.9 g. The annealed composition was crushed into a fine powder using a mortar and pestle. The final product had an atrazine content of 17% due to evaporation of water.

[0403] Example A7: Pre-emergence efficacy of atrazine and tembotrione urea complex on velvetleaf

[0404] This example demonstrates that the atrazine-urea complex of Example A6, alone or in combination with tembotrione-urea of ​​Example 5, exhibits superior pre-emergence control of the large-seeded broadleaf weed Abutilon (ABUTH) compared to conventional commercial suspension concentrate compositions of these active substances. In this experiment, a commercial product (Atrazine) and (trimethylenetetramine).

[0405] A spray solution of the composition was applied to the soil at a dosage of 15 gallons per acre (about 140 L / ha). The dosage of each herbicide is shown in Table A7. Six velvetleaf seeds were placed 1 / 2 inch below the soil surface in each treatment and allowed two weeks to germinate. For each seed, the ratio of the fresh weight of velvetleaf that emerged to the average fresh weight of the six velvetleaf seeds that were not treated with the herbicide was determined. The percentage control is shown in Table A7 and is calculated based on these values, where 100% control corresponds to zero fresh weight of velvetleaf that germinated.

[0406] The efficacy results show that the atrazine composition in Example A6 is far superior to conventional atrazine for controlling velvetleaf. Typically, large-seeded broadleaf weeds such as velvetleaf are the most challenging to control pre-emergence and provide a clear assessment of relative efficacy.

[0407] Table A7: Control of velvetleaf using atrazine as a single active ingredient or in combination with tembotrione

[0408]

[0409] Example A8: Efficacy of tembotrione released from a composition according to the invention in liquid form or as nanoparticles.

[0410] This example demonstrates that a urea complex that releases urea as nanoparticles or liquid when hydrolyzed can exhibit better foliar efficacy than conventional suspension concentrate compositions (which are suspensions of small solid particles of the active substance). This is illustrated by the tembotrione-urea composition in Example A4 above.

[0411] The post-emergence efficacy of the tembotrione-urea composition of Example A4 was evaluated in a greenhouse trial. Compositions A4-1 (releasing tembotrione nanoparticles) and A4-2 (releasing tembotrione in liquid form as an emulsion) were applied to Palmer amaranth (AMAPA) and Abutilon (ABUTH) plants at 1 / 3 and 1 / 2 of the usual dose (i.e., 30 g / ha and 46 g / ha of tembotrione). These compositions were mixed with a commercial tembotrione suspension concentrate. (Bayer) was applied to plants 4"-6" (10.16-15.24 cm). All applications were made using an XR9501R nozzle (Teejet) at a spray rate of 15 gallons per acre (about 140 L / ha). Plant injury was evaluated 21 days after treatment. Six plants were used for each treatment.

[0412] The average damage is shown in Table A8-1 below. Compositions A4-1 and A4-2 provided better control of both weeds than conventional suspension concentrates. In most cases, the liquid form of tembotrione released by composition A4-2 was more effective than the nanoparticle form of tembotrione released by composition A4-1.

[0413] The efficacy of three different tembotrione compositions was evaluated: for the commercial product Composition A4-1 (producing tembotrione nanoparticles) and composition A4-2 (producing liquid tembotrione) were used on Palmer amaranth (AMAPA) and Abutilon (ABUTH) at 30 g / ha and 46 g / ha tembotrione doses. The percentage of control level (injury) was evaluated 21 days after treatment (21 DAA).

[0414] Table A8-1: Control (injury) of 21DAA of Palmer amaranth (AMAPA) and velvetleaf (ABUTH) by different tembotrione combinations at a dosage of 30 g / ha and 46 g / ha

[0415]

[0416] Tembotrione is typically used with an adjuvant. Three compositions were also evaluated using the same protocol at a tembotrione dose of 30 g / ha with 0.25% (vol / vol) adjuvant AU-973 (Adjuvants Unlimited, Memphis TN) added to the spray mixture.

[0417] The efficacy of three different tembotrione complexes was evaluated: for the commercial product Compositions A4-1 (producing tembotrione nanoparticles) and A4-2 (producing liquid tembotrione) were dosed at 30 g / ha and 0.25% (vol / vol) of adjuvant AU-973 was added to the spray mixture to Palmer amaranth (AMAPA) and Abutilon (ABUTH). The percentage of control level (injury) was evaluated 21 days after treatment (21 DAA).

[0418] Table A8-2: Control (injury) of 21DAA of Palmer amaranth (AMAPA) and velvetleaf (ABUTH) by different tembotrione combinations at 30 g / ha and with additional adjuvants

[0419]

[0420] Comparison of the results shown in Table 8-2 with the results at 30 g / ha in Table 8-1 shows that the adjuvant improved weed control for both weeds and all compositions. When the adjuvant was used again, both compositions A4-1 and A4-2 outperformed the conventional composition, with composition A4-2 performing best.

[0421] Example A9: Differential Scanning Calorimetry (DSC) of Tetrazobactam-Urea Compositions

[0422] By adding another nonionic surfactant as an emulsifier to the composition TSP-60, the tetrazolyl thiocarbamide-urea composition of Example A1 was modified. Another surfactant, sodium lauryl sulfate ( DF-95) to further aid emulsification. This anionic surfactant may not be part of the urea-tetracycline phase.

[0423] The composition - as shown in Table A9 - produces a liquid tetrazolyl thiamethoxam emulsion that is stable overnight (about 16 hours) at ambient temperature (about 20°C) when the composition is hydrolyzed in 8 times the weight of water without adding an additional emulsifier. The composition of Table A9 is prepared by the same hot melt extrusion method as Example A1.

[0424] Table A9. Tetrazobactam-urea compositions prepared by hot melt extrusion, including an emulsifier TSP-60 and anionic surfactant DF-95.

[0425]

[0426] This composition and the urea granules used to prepare it were subjected to differential scanning calorimetry. The urea granules showed a simple melting peak at 134°C. The DSC data of the tetrazopyrim-urea composition in this example also showed a single melting peak, but the temperature was much lower, at about 125°C.

[0427] 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 tetrazolyl amide. Instead, the modified urea matrix containing the active ingredient and some surfactants constitutes the only detectable phase. The reduced melting point reflects the destruction of the urea structure due to the addition of other components.

[0428] These DSC data cannot exclude the possibility that a small amount of tetrazolin still exists as a separate phase (the melting point of tetrazolin is 228°C, which is beyond the DSC measurement range). However, the DSC data of urea granules and the tetrazolin-urea composition in Example A9 show that the urea phase in the starting material completely disappears and a low melting point phase of tetrazolin dispersed in urea is formed.

[0429] Examples B10-B19 and Comparative Examples:

[0430] Embodiment B10:

[0431] This example describes a high loading (32.6% phenmedipham) urea complex of the herbicide phenmedipham that is readily hydrolyzed to a miniemulsion. The composition was prepared on a 4.6 g scale by feeding a solid premix that had been ground in a knife mill to a Haake 1000 rpm screw at 80°C. TM Mini CTW extruder. The premix consists of 1.5g technical grade betaine, 0.5g TD-12 and 2.6 g urea. The knife mill treatment helped to disperse the liquid surfactant onto the solid components of the composition. The composition circulated well in the extruder and extruded into fine but brittle "noodles" that were easily crushed into powder.

[0432] Embodiment B11:

[0433] This example illustrates a method by which a composition comparable to that of Example B10 can be prepared in a blender on a 100 g or larger scale. Furthermore, the scale-up method enables "flood feeding" of the raw materials. This means that the feed (powder) is free flowing and is taken up by the blender screw without manual intervention. This method can be easily scaled up to larger equipment whilst being convenient on the scale shown in this example. A Readco Kurimoto RK1 twin screw blender was used. Although more powerful and having a significantly higher output, the Readco Kurimoto RK1 is of a different design to the Haake TM The Mini CTW extruder is different.

[0434] In a 250 mL Waring spice grinder blade mixing cup, add about 56 g of urea granules, followed by about 33 g of technical grade betaine powder, and then about 11 g of molten TD-12. Mixing was done in a spice grinder with frequent pulse stirring and intermittent scraping down the sides of the container, which quickly became sticky. The slightly granular but soft material was poured out, and the remainder was then scraped down the sides and re-stirred before pouring. This process was repeated until a total of 200 g of material was obtained. This feed was used to prepare the composition on a Readco Kurimoto RK-1 blender at a 100 g scale, set up as follows.

[0435] Dosage 100g

[0436] Waste gate 20% open (4mm)

[0437] Screw speed 30rpm

[0438] Feed flooding

[0439] Barrel set point 200°F (about 93.3°C)

[0440] Cylinder temperature 200°F (about 93.3°C)

[0441] Product temperature 205°F (about 96.1°C)

[0442] Once the barrel has reached temperature, the sample is added to the hopper all at once, flood feeding the screw. The engine is then started and the screw is turned. The material is extruded at a moderate rate, forming brittle, sharkskin-like, thick flat (4mm x25mm) "noodles". The product is off-white and of good quality, with sufficient strength and brittleness for easy crushing. After grinding, a very fine powder is obtained, which can be quickly dispersed in water.

[0443] Embodiment B12:

[0444] This example describes a tembotrione-urea composition that has excellent dispersibility in water and can be easily scaled up from a small extruder to production using a continuous mixer. The technical grade tembotrione used has a purity of 96%. The composition is as follows:

[0445]

[0446] Using Haake TM The Mini CTW extruder was operated at 80°C and 90 rpm screw speed to prepare the composition on a 5 g scale. The material mixture, which had been ground in a small knife mill, could be easily flood fed to the extruder, producing a near ideal peak torque of 1.2 Nm. The product was extruded as soft "noodles" which hardened upon cooling.

[0447] Subsequently, the same composition was prepared on a Readco Kurimoto RK-1 mixer at a scale of 125 g, operating at 81° C. and 90 rpm. After grinding the material in a knife mill, the composition was flood fed to the Readco Kurimoto RK-1 feed port and emerged as a soft mass after about one minute, which was allowed to cool and harden. The energy consumption was low (5.7 A) because the composition had good flow properties. The product was ground into powder in a Waring mixer.

[0448] Embodiment B13:

[0449] This example describes the preparation of a high loading urea complex of the herbicide safener cyprosulfamide. A premix of the following composition was briefly ground in a Waring spice grinder. 5 g of the premix was fed to a Haake spice grinder operating at 80°C and 90 rpm screw speed. TM Mini CTW twin-screw extruder.

[0450] Technical Grade Cyclopropanesulfonamide 30%

[0451] TSP-12 10%

[0452] Urea granules 60%

[0453] When the extruded product was added to water, ciprosulfamide was able to disperse efficiently.

[0454] Embodiment B14:

[0455] 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 a test tube of 10 mL of water and vortexed briefly. The urea dissolved, causing the active ingredient to disperse in the water. The particle size distribution was then immediately measured using a Malvern Mastersizer.

[0456] The particle size distribution was measured for the betanin composition in Example B11 and the cyprosulfonamide composition in Example B13. Almost all of the corresponding active ingredients were present as miniemulsions, with a volume weighted mean diameter (VMD or Dv50) of 1.2 microns for betanin and 0.8 microns for cyprosulfonamide. The broad shoulders at higher diameters corresponded to a small portion of the formulation that was not completely dissolved.

[0457] A narrow distribution indicates that the active ingredient is dispersed as an emulsion rather than a suspended solid, not only because a size of 1 micron is characteristic of oil-in-water emulsions such as milk, but also because the narrow size range represents an equilibrium compared to the particle size distribution expected from irreversible crystallization in a solid dispersion.

[0458] Embodiment B15:

[0459] This example describes the preparation of a fungicide prothioconazole formulation at a larger scale and its ability to form a stable dispersion or nanodispersion. It also illustrates the use of a second phase comprising an anionic dispersant to accelerate the dispersion of the formulation in water. In this example, two anionic dispersants were used: 3B2 and CP-9.

[0460] The following composition was initially mixed in a Hobart planetary mixer at a 500 g scale, first adding urea granules and dry CP-9 dispersant, then add liquid ingredients. Finally, add technical grade prothioconazole powder. After mixing, the resulting mixture appears as expanded urea granules.

[0461]

[0462] The mixture was then processed on 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 using a Waring spice grinder and passed through an 850 micron screen. The product immediately dissolved in water to form a milky white dispersion that was stable overnight. When the product was dissolved in 0.5% anionic When the suspension was in CP-9 solution (solid-based), a clear solution was obtained due to the formation of prothioconazole nanoparticles. The suspension remained clear for more than one week.

[0463] Embodiment B16:

[0464] This example describes the use of anionic dispersants to prepare larger scale formulations to improve the dispersibility of the product when added to water. The following composition was used to prepare a herbicide isoxaflutole formulation. The purity of the technical grade isoxaflutole used was 99%, resulting in a total loading of isoxaflutole in the formulation of about 32.7%.

[0465]

[0466] Urea granules were added to the bowl of a planetary mixer (Kitchen Aid), and the mixture of liquid components (all materials except isoxathiapiprolin) was mixed with continuous low speed stirring for about three minutes. Technical grade isoxathiapiprolin was then added with continuous stirring for about 5 minutes. The urea granules showed significant expansion.

[0467] The product from the planetary mixer was gravity-fed to a Readco Kurimoto RK-1 twin screw mixer at 75°C (167°F) and a screw speed of 60 rpm. This produced thin, crisp "noodles" that were easily crushed and quickly dissolved in water.

[0468] Example B17: This example demonstrates the superior post-emergence efficacy of the tembotrione-urea composition A4-2 of Example A4 - delivering liquid tembotrione as an emulsion - against two difficult to control weeds: barnyardgrass (ECHCG) and crabgrass (DIGSA). Efficacy was evaluated at 1 / 3 and 1 / 2 the conventional dosage, i.e., 30 g / ha and 46 g / ha of tembotrione, and compared with a commercial tembotrione suspension concentrate. (Bayer) for comparison. No adjuvant was used for both doses of application. In addition, 0.25% vol / vol of AU-973 (Adjuvants Unlimited, Memphis, TN) nonionic surfactant was added to the spray mixture, and the efficacy was evaluated with 30g / ha of tembotrione. All applications were performed using an XR9501R nozzle (Teejet) at a spray rate of 15 gallons per acre (about 140L / ha). The percentage of control level of each weed was evaluated in the form of percentage of injury 21 days after treatment (21DAA).

[0469] As shown in Table B17, the conventional formulation was ineffective against both weeds tested at both dosages, whereas composition A4-2 in Example A4 showed high efficacy, particularly against barnyardgrass (ECHCG).

[0470] Table B17: Different tembotrione compositions at 21DDA doses of 30 g / ha and 46 g / ha were evaluated for control (injury) of barnyardgrass (ECHCG) and crabgrass (DIGSA).

[0471]

[0472] Example B18: Example 9 shows that pH sensitive active ingredients (e.g. mesotrione and tembotrione) can be stabilized by adding urea and a nonionic surfactant (e.g. a phosphate surfactant) in the acid form. This Example B18 shows that stabilization can also be achieved by adding phosphoric acid (with or without the presence of a phosphate ester) to the composition. It also shows an increased (i.e. higher) loading of tembotrione.

[0473] Using Haake TM Four compositions of tembotrione in urea were prepared on a 5 g scale on a Mini CTW extruder operating at 80 °C and 90 rpm screw speed. The purity of the technical grade tembotrione was 96%. Tristyrylphenol ethoxylate ( S-25 / 80) and phosphoric acid to stabilize tembotrione. These compositions also include linear nonionic surfactants, phosphate esters or linear alcohol ethoxylates.

[0474] First, 0.3 g of the corresponding linear nonionic surfactant was added to the extruder. The remaining 4.7 g had been premixed and processed in a knife grinder before being added to the extruder. All four compositions were extruded into good "noodles" and crushed into powders before being tested for thermal stability. Composition of tembotrione in Example B18:

[0475]

[0476] The powdered product was stored in an oven at 54°C for four weeks. Samples were taken regularly and analyzed for the tembotrione content. Due to the small scale of preparation, there was a small difference in the initial tembotrione concentration, but all compositions showed excellent high temperature stability of tembotrione.

[0477] Table B18. Tembotrione content (wt%) in the composition of Example B18 - stored at 54°C

[0478]

[0479] Example B19: The prothioconazole-urea compositions of Example B15 were analyzed by differential scanning calorimetry (DSC), both after mixing in a Hobart mixer and subsequently hot mixing in a 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, the starting material used to produce the prothioconazole-urea compositions of Example B15, was no longer present. These DSC data demonstrate that crystalline prothioconazole is absent in these prothioconazole-urea compositions and that a solid solution of prothioconazole in urea is formed. These DSC data also show that the urea peak has been replaced by a broader peak at lower temperatures.

[0480] Comparative Example: This example shows that the composition of the invention is not obtained by precipitation from methanol using oleic acid.

[0481] This comparative example was carried out using a method of precipitation from methanol using oleic acid, reported by Thakral, S. and Madan, AK, for example in 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 description of the methods used in these publications is substantially the same.

[0482] In these methods, a solution of 0.5 g of the corresponding active ingredient (enalapril maleate, glipizide and nicorandil) and 5 g of urea in 30 mL of methanol was prepared by gentle heating. Subsequently, 0.6 g of oleic acid was added resulting in immediate precipitation. After 2-3 hours of standing, the precipitate was collected by vacuum filtration.

[0483] This method was adapted in an attempt to similarly obtain the tembotrione-urea complex.

[0484] A solution of 0.5 g tamponic acid and 5 g urea in 50 mL methanol was prepared by gentle heating. Subsequently, 0.6 g oleic acid was added and heating was stopped. No precipitation occurred either during the addition or after the mixture was cooled to room temperature.

[0485] In contrast to the methods and procedures described in the context of the present invention, the method using oleic acid precipitation in methanol did not result in a single-phase tembotrione-urea complex.

[0486] Implementation

[0487] For further illustration, additional non-limiting embodiments of the present invention are described below.

[0488] Embodiment 1. A composition in solid form at 25° C. and 1013 mbar, comprising:

[0489] (a) one or more pesticide or pharmaceutical active ingredients, the total amount of which is at least about 5% by weight, having a melting point of at least 55°C at 1013 mbar, and a solubility of 50 g / L or less in deionized water at a pH of about 7 at 25°C and 1013 mbar, component (a) is not in the form of a salt with an inorganic counter ion (i.e., it is not a salt with an inorganic counter ion, such as a monovalent metal ion, a divalent metal ion, a trivalent metal ion or an ammonium counter ion, etc.),

[0490] (b) a total amount of at least about 50% by weight of urea,

[0491] (c) at least about 1% by weight in a total amount of one or more nonionic surfactants,

[0492] 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

[0493] Therein, the amounts stated in each case are based on the total weight of the composition.

[0494] Embodiment 2. A composition according to embodiment 1, comprising

[0495] The total amount of component (a) is 5 wt% or more, 6 wt% or more, 7 wt% or more, preferably 8 wt% or more, more preferably 10 wt% or more, typically in the range of 5 to 35 wt%, preferably in the range of 6 to 33 wt%, preferably in the range of 7 to 32 wt%, preferably in the range of 8 to 31 wt%, more preferably in the range of 10 to 30 wt%,

[0496] The total amount of component (b) is 50 wt% or more, 60 wt% or more, typically in the range of 50 to 90 wt%, preferably in the range of 60 to 85 wt%, usually in the range of 65 to 80 wt%, and

[0497] The total amount of component (c) is 2 wt% or more, 3 wt% or more, 4 wt% or more, preferably 5 wt% or more, more preferably 8 wt% or more, typically 10 wt% or more.

[0498] Embodiment 3. A composition according to embodiment 1, comprising

[0499] The total amount of component (a) is 7 wt% or more, preferably 8 wt% or more, more preferably 10 wt% or more,

[0500] and / or

[0501] The total amount of component (c) is 2% by weight or more, or 3% by weight or more, wherein the amounts stated in each case are based on the total weight of the composition.

[0502] Embodiment 4. A composition according to embodiment 1 or 2, comprising

[0503] The total amount of component (a) is in the range of 5% to 35% by weight, preferably in the range of 6% to 33% by weight,

[0504] The total amount of component (b) is in the range of 50% to 90% by weight, preferably in the range of 60% to 85% by weight,

[0505] and

[0506] The total amount of component (c) is 3 wt% or more, preferably 4 wt% or more,

[0507] Therein, the amounts stated in each case are based on the total weight of the composition.

[0508] Embodiment 5. A composition according to any one of embodiments 1 to 4, comprising

[0509] The total amount of component (a) is in the range of 8 wt % to 35 wt % or in the range of 10 wt % to 33 wt %,

[0510] and / or

[0511] The total amount of component (b) is in the range of 55 wt % to 85 wt % or in the range of 60 wt % to 85 wt %,

[0512] Therein, the amounts stated in each case are based on the total weight of the composition.

[0513] Embodiment 6. The 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.

[0514] Embodiment 7. The 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.

[0515] Embodiment 8. A composition according to any one of embodiments 1 to 7, wherein the molecular weight of the active ingredient or ingredients of component (a) is less than 800 Daltons, preferably in the range of 200 Daltons to 800 Daltons, preferably in the range of 200 Daltons to 700 Daltons, more preferably in the range of 210 Daltons to 600 Daltons, typically in the range of 300 Daltons to 600 Daltons or in the range of 320 Daltons to 500 Daltons.

[0516] Embodiment 9. The 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.

[0517] Embodiment 10. The 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.

[0518] Embodiment 11. The 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.

[0519] Embodiment 12. The composition according to any one of embodiments 1 to 11, wherein the solubility of one or more active ingredients of component (a) in deionized water at a pH of about 7 at 25°C and 1013 mbar is 20 g / L or less.

[0520] Embodiment 13. The composition according to any one of embodiments 1 to 11, wherein the solubility of one or more active ingredients of component (a) in deionized water at a pH of about 7 at 25°C and 1013 mbar is 10 g / L or less.

[0521] Embodiment 14. The composition according to any one of embodiments 1 to 11, wherein the solubility of one or more active ingredients of component (a) in deionized water at a pH of about 7 at 25°C and 1013 mbar is 5 g / L or less.

[0522] Embodiment 15. The composition according to any one of embodiments 1 to 11, wherein the solubility of the one or more active ingredients of component (a) in deionized water at a pH of about 7 at 25°C and 1013 mbar is 2 g / L or less.

[0523] Embodiment 16. The composition according to any one of embodiments 1 to 11, wherein the solubility of one or more active ingredients of component (a) in deionized water at a pH of about 7 at 25°C and 1013 mbar is 1 g / L or less.

[0524] 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 weight percent, based on the total weight of the composition.

[0525] 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 weight percent, based on the total weight of the composition.

[0526] 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 weight percent, based on the total weight of the composition.

[0527] Embodiment 20. The composition according to any one of embodiments 1 to 19, wherein the composition comprises water.

[0528] Embodiment 21. The composition according to any one of embodiments 1 to 20, wherein the 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.

[0529] 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 weight percent, based on the total weight of the composition.

[0530] 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 weight percent, based on the total weight of the composition.

[0531] Embodiment 24. The composition according to any one of embodiments 1 to 23, wherein components (a) and (b) are present substantially in the same phase.

[0532] Embodiment 25. The composition according to any one of embodiments 1 to 24, wherein the melting point of the composition is at least 2°C lower than the melting point of pure urea as measured by differential scanning calorimetry.

[0533] Embodiment 26. The composition according to any one of embodiments 1 to 25, wherein the composition is an inclusion compound.

[0534] Embodiment 27. The composition according to any one of Embodiments 1 to 25, wherein the composition is a solid solution.

[0535] Embodiment 28. A composition according to any one of embodiments 1 to 27, wherein upon addition of the composition to at least 5 times the weight of the composition in water, the nanoparticles of one or more active ingredients of component (a) are formed. The pH of the water at 25°C and 1013 mbar is about 7.

[0536] Embodiment 29. A composition according to any one of embodiments 1 to 28, wherein the one or more active ingredients of component (a) are substantially in liquid form once the composition is added to at least 5 times the weight of the composition in water, the pH value of the water being about 7 at 25°C and 1013 mbar.

[0537] Embodiment 30. A composition according to any one of embodiments 1 to 28, wherein the one or more active ingredients of component (a) are substantially present in liquid form once the composition is added to an aqueous solution of at least 1% by weight of one or more emulsifying surfactants at 25° C. and 1013 mbar, which is at least 5 times the weight of the composition.

[0538] Embodiment 31. A composition according to embodiment 29 or 30, wherein the active ingredient(s) of component (a) is substantially present in (emulsified) liquid form for at least 30 minutes.

[0539] Embodiment 32. The composition according to any one of embodiments 1 to 31, wherein at least one surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 3 or higher.

[0540] Embodiment 33. The composition according to any one of embodiments 1 to 31, wherein at least one surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 4 or higher.

[0541] Embodiment 34. The composition according to any one of embodiments 1 to 31, wherein at least one surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 5 or higher.

[0542] Embodiment 35. The composition according to any one of embodiments 1 to 31, wherein at least one surfactant in component (c) has a hydrophile-lipophile balance (HLB) value of about 6 or higher.

[0543] Embodiment 36. The composition according to any one of embodiments 1 to 31, wherein component (c) has a hydrophile-lipophile balance (HLB) value of about 3 or higher.

[0544] Embodiment 37. The composition according to any one of embodiments 1 to 31, wherein component (c) has a hydrophile-lipophile balance (HLB) value of about 4 or higher.

[0545] Embodiment 38. The composition according to any one of embodiments 1 to 31, wherein component (c) has a hydrophile-lipophile balance (HLB) value of about 5 or higher.

[0546] Embodiment 39. The composition according to any one of embodiments 1 to 31, wherein component (c) has a hydrophile-lipophile balance (HLB) value of about 6 or higher.

[0547] Embodiment 40. A composition according to any one of embodiments 1 to 39, wherein component (c) comprises or consists of one or more nonionic surfactants selected from (poly)alkoxylated alcohols, (poly)alkoxylated phosphates and (poly)alkoxylated tristyrylphenols.

[0548] Embodiment 41. A composition according to any one of embodiments 1 to 40, wherein component (c) comprises or consists of one or more nonionic surfactants selected from (poly)alkoxylated linear saturated or monounsaturated C12-C18 alcohols and (poly)alkoxylated phosphate esters of linear saturated or monounsaturated C12-C18 alcohols.

[0549] Embodiment 42. The composition according to any one of embodiments 1 to 41, wherein 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.

[0550] Embodiment 43. The composition according to any one of embodiments 1 to 41, wherein 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.

[0551] Embodiment 44. A composition according to any one of embodiments 1 to 43, wherein component (c) comprises or consists of one or more nonionic surfactants selected from (poly)ethoxylated linear saturated or monounsaturated C12-C18 alcohols and (poly)ethoxylated phosphate esters of linear saturated or monounsaturated C12-C18 alcohols.

[0552] Embodiment 45. A composition according to any one of embodiments 1 to 44, wherein component (c) comprises or consists of one or more nonionic surfactants comprising from about 2 to about 14 ethylene glycol units (PEG-2 to PEG-14).

[0553] Embodiment 46. A composition according to any one of embodiments 1 to 45, wherein component (c) comprises or consists of one or more nonionic surfactants comprising from about 4 to about 10 ethylene glycol units (PEG-4 to PEG-10).

[0554] 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 tristyrylphenol ethoxylates.

[0555] Embodiment 48. A composition according to embodiment 47, wherein component (c) comprises or consists of one or more nonionic surfactants comprising from about 6 to about 80 ethylene glycol units (PEG-6 to PEG-80).

[0556] Embodiment 49. A composition according to embodiment 47, wherein component (c) comprises or consists of one or more nonionic surfactants comprising from about 10 to about 60 ethylene glycol units (PEG-10 to PEG-60), preferably

[0557] 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 wt % to about 20 wt %, based on the total weight of the composition.

[0558] Embodiment 51. A composition according to any one of embodiments 1 to 50, wherein component (c) comprises or consists of one or more nonionic surfactants selected from 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 from about 4 wt.% to about 20 wt.%, based on the total weight of the composition.

[0559] Embodiment 52. A composition according to any one of embodiments 1 to 51, wherein component (c) comprises or consists of one or more nonionic surfactants selected from ethoxylated phosphate esters of 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 from about 2 wt.% to about 10 wt.%, based on the total weight of the composition.

[0560] Embodiment 53. The composition according to any one of embodiments 1 to 52, further comprising as component (d) one or more polymeric dispersants different from component (c).

[0561] Embodiment 54. A composition according to any one of embodiments 1 to 53, further comprising as component (d) one or more polymer dispersants different from component (c), the dispersant being selected from 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, lignin sulfonates, and mixtures thereof.

[0562] Embodiment 55. A 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), wherein the total amount of component (d) is in the range of about 1 wt % to about 15 wt %, based on the total weight of the composition.

[0563] Embodiment 56. A 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), wherein the composition comprises as component (e) one or more wetting agents preferably having a non-linear structure, wherein component (e) is different from components (c) and (d).

[0564] Embodiment 57. A composition according to any one of embodiments 1 to 56, wherein the composition comprises as component (e) one or more wetting agents different from components (c) and (d), the wetting agent being selected from Guerbet alcohol ethoxylates, alkyl polyglucosides, sodium alkyl naphthalene sulfonate condensates, and mixtures thereof.

[0565] Embodiment 58. A composition according to any one of embodiments 1 to 56, wherein the composition comprises as component (e) one or more wetting agents different from components (c) and (d), said wetting agents being selected from ethoxylated branched alcohols.

[0566] Embodiment 59. The composition according to any one of embodiments 1 to 56, wherein the composition comprises as component (e) one or more wetting agents different from components (c) and (d), the wetting agents being selected from alkylnaphthalenesulfonic acid condensates.

[0567] Embodiment 60. A composition according to any one of embodiments 1 to 59, wherein the composition comprises as component (e) one or more wetting agents different from components (c) and (d), and the total amount of component (e) is in the range of about 5 wt % to about 30 wt %, based on the total weight of the composition.

[0568] Embodiment 61. A composition according to any one of embodiments 1 to 60, wherein the composition comprises as component (f) a water-soluble polymer binder different from components (c), (d) and (e).

[0569] Embodiment 62. A composition according to any one of embodiments 1 to 61, wherein the composition comprises as component (f) a water-soluble polymer binder different from components (c), (d) and (e), the binder being selected from cellulose ethers and their salts, preferably water-soluble methylcellulose polymers, water-soluble hydroxypropylmethylcellulose polymers, and mixtures thereof.

[0570] Embodiment 63. A composition according to any one of Embodiments 1 to 62, wherein the composition comprises as component (f) a water-soluble polymer binder different from components (c), (d) and (e), the total amount of which is in the range of about 0.5 weight % to about 3 weight %, based on the total weight of the composition.

[0571] Embodiment 64. The composition of any one of Embodiments 1 to 63, wherein the total amount of methanol in the composition is less than about 1 weight percent, based on the total weight of the composition.

[0572] Embodiment 65. The composition of any one of Embodiments 1 to 64, wherein the total amount of ethanol in the composition is less than about 1 weight percent, based on the total weight of the composition.

[0573] Embodiment 66. The composition of any one of Embodiments 1 to 63, wherein the total amount of C1-C6 alcohols in the composition is less than about 1 wt %, based on the total weight of the composition.

[0574] Embodiment 67. The composition according to any one of embodiments 1 to 66, wherein the total amount of oleic acid in the composition is less than about 1 weight percent, based on the total weight of the composition.

[0575] Embodiment 68. A composition according to any one of embodiments 1 to 67, wherein the total amount of components in salt form is about 10 wt% or less, preferably about 5 wt% or less, in each case based on the total weight of the composition.

[0576] Embodiment 69. The composition according to any one of embodiments 1 to 68, wherein the composition comprises phosphoric acid or methanesulfonic acid.

[0577] Embodiment 70. The composition according to embodiment 69, wherein the total amount of phosphoric acid and methanesulfonic acid is in the range of about 0.3 wt. % to 1.5 wt. %, preferably about 0.6 wt. % to 1.2 wt. %, in each case based on the total weight of the composition.

[0578] Embodiment 71. A composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of one or more pesticidal active ingredients.

[0579] Embodiment 72. The composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of a pesticidal active ingredient selected from the group consisting of fungicides, herbicides, insecticides and safeners.

[0580] Embodiment 73. A composition according to any one of embodiments 1 to 70, wherein component (a) is selected from chlorotriazine herbicides, pyridine fungicides, aromatic cyclohexanedione herbicides, carbamate herbicides, conazole fungicides, pyridylpyrazole insecticides, and mixtures thereof.

[0581] Embodiment 74. The composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of a pesticide active ingredient selected from atrazine, cyproconazole, fluopyram, isoxathiapiprolin, mesotrione, betaine, prothioconazole, cyproconazole, tetrazopyram and mixtures thereof.

[0582] Embodiment 75. The composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of a pesticide active ingredient selected from atrazine, fluopyram, mesotrione, betaine, prothioconazole, tampoxadone, tetrazopyram and mixtures thereof.

[0583] Embodiment 76. The composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of tembotrione, mesotrione, betaine or a combination thereof.

[0584] Embodiment 77. The composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of fluopyram.

[0585] Embodiment 78. The composition according to any one of embodiments 1 to 70, wherein component (a) comprises or consists of tetrazobactam.

[0586] Embodiment 79. A product obtainable or obtained by extruding a composition as defined in any one of embodiments 1 to 78.

[0587] 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 the molten composition is subsequently cooled to a temperature below 55°C.

[0588] Embodiment 81. The product obtainable or obtained by melting a composition as defined in any one of embodiments 1 to 78, and subsequently cooling the molten composition to a temperature below 55°C.

[0589] Embodiment 82. The product according to embodiment 81, wherein the melting of the composition is carried out at a temperature of the molten composition in the range of about 75°C to about 110°C.

[0590] Embodiment 83. The product of any one of Embodiments 79 to 82, wherein the total amount of methanol and / or ethanol in the product is less than about 1 weight percent, based on the total weight of the product.

[0591] Embodiment 84. The product of any one of Embodiments 79 to 82, wherein the total amount of C1-C6 alcohol in the product is less than about 1 wt %, based on the total weight of the product.

[0592] Embodiment 85. The product of any one of Embodiments 79 to 84, wherein the total amount of oleic acid in the product is less than about 1 wt %, based on the total weight of the product.

[0593] Embodiment 86. A method for preparing a composition according to any one of embodiments 1 to 78, characterized by the following steps:

[0594] 1. Combining components (a), (b), (c) according to embodiments 1 to 78 and optionally one or more further components selected from water and components (d), (e) and (f);

[0595] 2. mixing the combination obtained in step 1 at a temperature ranging from about 60°C to about 140°C, preferably at a temperature ranging from about 75°C to about 125°C, more preferably at a temperature ranging from about 80°C to about 110°C,

[0596] 3. Cool the composition obtained in step 2.

[0597] Embodiment 87. The method according to Embodiment 86, wherein step 3 comprises extrusion, spray drying, spray cooling, granulation, spheronization, or a combination thereof.

[0598] Embodiment 88. A product obtainable or obtained according to the method of embodiment 86 or 87, wherein when the product is added to an amount of water sufficient to dissolve urea at 25°C, the one or more active ingredients of component (a) are essentially present as nanoparticles having a diameter significantly below 100 nm, as measured by dynamic light scattering.

[0599] Embodiment 89. A product obtainable or obtained according to the method of embodiment 86 or 87, wherein when the product is added to an aqueous emulsifier diluent sufficient to dissolve urea at 25°C, a liquid emulsion of one or more active ingredients of component (a) is obtained, which emulsion is stable and prevents crystallization of the one or more active ingredients of component (a) for at least 30 minutes at 25°C.

[0600] Embodiment 90. An application mixture comprising

[0601] - a composition or product as defined in any one of embodiments 1 to 85, 88 or 89,

[0602] - water in an amount (by weight) of at least 10 times, preferably at least 25 times, more preferably at least 50 times the amount of the composition or product,

[0603] and

[0604] - One or more components selected from other adjuvants, other diluents and other active ingredients.

[0605] Embodiment 91. The application mixture according to embodiment 90, wherein the application mixture is a spray application mixture.

[0606] Embodiment 92. A formulation comprising a composition or product as defined in any one of embodiments 1 to 85, 88 or 89, and one or more other components selected from adjuvants, liquid components at 25°C and 1013 mbar, solid active ingredients at 25°C and 1013 mbar, and mixtures thereof.

[0607] Embodiment 93. The formulation according to embodiment 92, wherein the formulation is selected from wettable granules (WG), wettable powders (WP) and oil dispersions (OD).

[0608] Embodiment 94. The formulation according to embodiment 92 or 93, wherein the formulation is an oil dispersion (OD) formulation, and the one or more formulation adjuvants are selected from the group consisting of oily active ingredients, vegetable oils, oily solvents, and mixtures thereof.

[0609] Embodiment 95. The formulation of embodiment 94, comprising an oily herbicide, wherein the oily herbicide comprises or is acetochlor.

[0610] Embodiment 96. The formulation according to embodiment 94 or 95, comprising an oily solvent, wherein the oily solvent comprises or is a long-chain fatty acid methyl ester, preferably soybean oil methyl ester.

[0611] Embodiment 97. A formulation according to embodiment 92 or 93, wherein the formulation is a wettable granule (WG) formulation or a wettable powder (WP) formulation, wherein the adjuvant comprises or is a dry emulsifier powder or a dry dispersant powder.

[0612] Embodiment 98. A composition, product, application mixture or formulation according to any one of embodiments 1 to 85, 88 to 91 or 92 to 97 comprising a pesticide active ingredient for use in a method of controlling unwanted vegetation, plant pests, (phytopathogenic) fungi or (phytopathogenic) nematodes.

[0613] Embodiment 99. A method for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes, 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 pesticide active ingredient to said unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

[0614] Embodiment 100. Use of a composition, product, application mixture or formulation comprising a pesticidal active ingredient as defined in any one of embodiments 1 to 85, 88 to 91 or 92 to 97 for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

[0615] Embodiment 101. A composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of embodiments 1 to 85 or 88 to 91 for use as a medicament.

[0616] Embodiment 102. A composition, product or administration mixture comprising a pharmaceutically active ingredient according to any one of embodiments 1 to 85 or 88 to 91 for use in a method of treatment of an animal or human.

[0617] Embodiment 103. A method of treating a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of Embodiments 1 to 85 or 88 to 91.

[0618] Embodiment 104. Use of a composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of embodiments 1 to 85 or 88 to 91 for treating an animal or a human, wherein the composition, product or administration mixture is preferably administered orally to the animal or a human.

[0619] Exemplary embodiments have been provided to make the present disclosure complete and fully convey the scope to those skilled in the art. Many specific details, such as examples of specific components, combinations and methods, are set forth to provide a full understanding of the embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be used, and exemplary embodiments may be embodied in many different forms, and neither should be construed as limiting the scope of the present disclosure. In some exemplary embodiments, known methods, known device structures and known technologies are not described in detail.

[0620] When introducing elements of the present disclosure or one or more preferred embodiments thereof, the articles "a," "an," "the," and "said" are intended to mean that one or more elements are present. The terms "comprising," "including," and "having" are intended to be inclusive, and mean that other elements may be present in addition to the listed elements. The method steps, processes, and operations described herein should not be construed as necessarily requiring that they be performed in the particular order discussed or described, unless expressly indicated as an order of performance. It should also be understood that additional or alternative steps may be used.

[0621] Although the term first, second, third etc. can be used to describe various elements, components, seeds, members and / or parts in this article, these elements, components, seeds, members and / or parts should not be limited by these terms.These terms can only be used to distinguish a kind of element, component, seed, member or part from another kind of element, component, seed, member or part.Unless the context clearly indicates, otherwise the terms used in this article such as "first", "second" and other numerical terms do not imply order or sequence.Therefore, without departing from the teaching of exemplary embodiments, the first element, component, seed, member or part described below can be referred to as the second element, component, seed, member or part.

[0622] In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

[0623] As various changes could be made in the above products and processes without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

Claims

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

2. The composition according to claim 1, comprising The total amount of component (a) is 5 wt% or more, 6 wt% or more, 7 wt% or more, preferably 8 wt% or more, more preferably 10 wt% or more, typically in the range of 5 wt% to 35 wt%, preferably in the range of 6 wt% to 33 wt%, preferably in the range of 7 wt% to 32 wt%, preferably in the range of 8 wt% to 31 wt%, more preferably in the range of 10 wt% to 30 wt%; The total amount of component (b) is 50 wt% or more, 60 wt% or more, typically in the range of 50 wt% to 90 wt%, preferably in the range of 60 wt% to 85 wt%, usually in the range of 65 wt% to 80 wt%; and / or The total amount of component (c) is 2 wt% or more, 3 wt% or more, 4 wt% or more, preferably 5 wt% or more, more preferably 8 wt% or more, usually 10 wt% or more.

3. The composition of claim 1 or 2, 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 of claim 1 or 2, 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 any one of claims 1 to 4, wherein the 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, and / or The 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.

6. A composition according to any one of claims 1 to 5, wherein components (a) and (b) are present in substantially the same phase.

7. The composition according to any one of claims 1 to 6, wherein The melting point of the composition is at least 2°C lower than the melting point of pure urea, as measured by differential scanning calorimetry.

8. The composition according to any one of claims 1 to 7, wherein the composition is an inclusion compound or wherein the composition is a solid solution.

9. A composition according to any one of claims 1 to 8, wherein the nanoparticles of one or more active ingredients of component (a) are formed by adding the composition to water having a pH of about 7 at 25°C and 1013 mbar, the amount of water being at least about 5 times the weight of the composition.

10. The composition according to any one of claims 1 to 9, wherein the one or more active ingredients of component (a) are substantially in liquid form when the composition is added to deionized water having a pH of about 7 at 25° C. and 1013 mbar, and the amount of water is at least 5 times the weight of the composition; or The one or more active ingredients of component (a) are substantially in liquid form when added to a 1 wt% aqueous solution of one or more emulsifying surfactants at 25°C and 1013 mbar, and the amount of the aqueous solution is at least 5 times the weight of the composition.

11. A composition according to any one of claims 1 to 10, wherein the at least one surfactant of component (c) has a hydrophile-lipophile balance (HLB) value of about 3 or greater.

12. The composition according to any one of claims 1 to 11, wherein component (c) comprises or consists of one or more nonionic surfactants selected from the group consisting of (poly)alkoxylated alcohols, (poly)alkoxylated phosphates and (poly)alkoxylated tristyrylphenols, wherein component (c) preferably 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 linear saturated or monounsaturated C 12 -C 18 (Poly)ethoxylated phosphoric acid esters of alcohols.

13. The composition according to any one of claims 1 to 12, further comprising as component (d) one or more polymeric dispersants different from component (c), preferably selected from 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, lignin sulfonates, and mixtures thereof.

14. The composition according to any one of claims 1 to 13, wherein the composition comprises as component (e) one or more wetting agents different from components (c) and (d), wherein preferably the composition comprises as component (e) one or more wetting agents having a non-linear structure, wherein component (e) is different from components (c) and (d), wherein the total amount of component (e) is preferably in the range of about 5 wt. % to about 30 wt. %, based on the total weight of the composition.

15. The composition according to any one of claims 1 to 14, wherein the composition comprises as component (f) a water-soluble polymer binder different from components (c), (d) and (e), preferably selected from cellulose ethers and salts thereof, more preferably water-soluble methylcellulose polymers, water-soluble hydroxypropylmethylcellulose polymers, and mixtures thereof.

16. A product obtainable or obtained by extruding a composition as defined in any one of claims 1 to 15.

17. A product obtainable or obtained by melting a composition as defined in any one of claims 1 to 15 and subsequently cooling the molten composition to below 55°C.

18. A method for preparing a composition as defined in any one of claims 1 to 15, characterized in that Follow these steps:

1. Combining components (a), (b), (c) as defined in any one of claims 1 to 15 and optionally one or more further components selected from water and components (d), (e) and (f); 2. mixing the combination obtained in step 1 at a temperature ranging from about 60°C to about 140°C, preferably at a temperature ranging from about 75°C to about 125°C, and more preferably at a temperature ranging from about 80°C to about 110°C; 3. Cool the composition obtained in step 2.

19. A product obtainable or obtained by the method according to claim 18, wherein When the product is added to water sufficient to dissolve urea at 25°C, the one or more active ingredients of component (a) are substantially in the form of nanoparticles having a diameter substantially below 100 nm as determined by dynamic light scattering.

20. A product obtainable or obtained by the method according to claim 18, wherein When this product is added to an aqueous emulsifier diluent sufficient to dissolve urea at 25°C, a liquid emulsion of one or more active ingredients of component (a) is obtained, which is stable and can prevent crystallization of one or more active ingredients of component (a) for at least 30 minutes at 25°C.

21. An application mixture comprising - A composition or product according to any one of claims 1 to 17, 19 or 20, - water in an amount at least 10 times, preferably at least 25 times, more preferably at least 50 times the amount of the composition or product, and - One or more components selected from other adjuvants, other diluents and other active ingredients.

22. A formulation comprising a composition or product as defined in any one of claims 1 to 17, 19 or 20, 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 ingredient at 25°C and 1013 mbar, and mixtures thereof.

23. A composition, product, application mixture or formulation comprising a pesticidal active ingredient as defined in any one of claims 1 to 17 or 19 to 22, for use in a method of controlling unwanted vegetation, plant pests, (phytopathogenic) fungi or (phytopathogenic) nematodes.

24. A method for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes, which comprises applying to the unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes a composition, product, application mixture or formulation comprising a pesticidal active ingredient as defined in any one of claims 1 to 17 or 19 to 22.

25. Use of a composition, product, application mixture or formulation comprising a pesticidal active ingredient as defined in any one of claims 1 to 17 or 19 to 22 for controlling unwanted vegetation, plant pests, phytopathogenic fungi or phytopathogenic nematodes.

26. A composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of claims 1 to 17 or 19 to 21 for use as a medicament.

27. A composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of claims 1 to 17 or 19 to 21 for use in a method of treatment of an animal or human.

28. A method of treating a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of claims 1 to 17 or 19 to 21.

29. Use of a composition, product or administration mixture comprising a pharmaceutically active ingredient as defined in any one of claims 1 to 17 or 19 to 21 for treating an animal or human being, wherein the composition, product or administration mixture is preferably administered orally to the animal or human being.

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