Suspension concentrate acylhydrazone adenosine triphosphate diphosphatase inhibitor formulations

Abstract

The present disclosure relates to a formulation comprising an aqueous suspension of a first active compound having the following structure; and a dispersant, a freezing point inhibitor and a buffer or a partially neutralized base such that the pH of the formulation is from about 6 to about 11. The formulation comprises particles of the first active compound having a volume weighted median particle size of greater than 0.01 to 20 microns as measured by light scattering. The formulation may further comprise a viscosity modifier, a biocide, a defoamer, a surfactant and / or an agriculturally active compound such as an acaricide, an antimicrobial agent, a fungicide, a herbicide, an insecticide, a molluscicide or a nematicide or a combination thereof. Also disclosed are agricultural compositions comprising the formulations and methods of using the same. # imgabs0 #

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of the earlier filing date of U.S. Provisional Patent Application No. 63 / 417,917, filed on October 20, 2022, which is hereby incorporated by reference in its entirety. Technical Field

[0003] The present disclosure relates to suspensions concentrate adenosine triphosphate diphosphatase inhibitor formulations and methods of using the same, particularly methods of use in treating crops susceptible to pathogens. Background Art

[0004] Crops around the world are infected by various pathogens. Pathogens such as insects, mites, nematodes, weeds, and fungi have developed a series of mechanisms to survive under pesticides, such as by sequestering, exporting, or detoxifying pesticides. There is a need for formulations that enhance the efficacy of pesticides by blocking certain resistance mechanisms. Summary of the Invention

[0005] Embodiments of formulations are disclosed herein that include: an aqueous suspension of a first active compound having the following structure

[0006]

[0007] and a dispersant, a freezing - point depressant, and a buffer or a partially neutralized base such that the pH of the formulation is from about 6 to 11. The formulation includes particles of the first active compound, which, as measured by light scattering, have a volume - weighted median particle size greater than 0.01 to 20 microns. The formulation may also include a viscosity modifier, a biocide, an antifoaming agent, a surfactant, and / or an agro - active compound such as an acaricide, an antimicrobial agent, a fungicide, a herbicide, an insecticide, a molluscicide, or a nematicide or a combination thereof.

[0008] Embodiments of agricultural compositions suitable for agricultural applications are also disclosed herein. The agricultural composition includes water and the disclosed formulation and also contains an agro - active compound. The agro - active compound may be provided by the disclosed formulation, or in addition to being provided by the formulation, it may be added to the agricultural composition, or a combination thereof.

[0009] Methods of using the formulation or an agricultural composition comprising the formulation to control agricultural pathogens such as fungi are also disclosed.

[0010] The foregoing and other objects, features, and advantages of the present disclosure will become more apparent from the following detailed description Detailed Description

[0011] I. Terms

[0012] The following explanations of terms and methods are provided to better describe the present disclosure and guide one of ordinary skill in the art in practicing the present disclosure. Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” refer to one or more than one. Unless the context clearly indicates otherwise, the term “or” refers to a single one of the recited alternative elements or a combination of two or more elements. As used herein, “comprising” means “including.” Thus, “comprising A or B” means “including A, B, or A and B,” without excluding additional elements. All references (including patents and patent applications) cited herein are incorporated by reference in their entirety, unless otherwise indicated.

[0013] Unless otherwise indicated, all numerical values expressing quantities of ingredients, molecular weights, percentages, temperatures, times, etc., used in the specification or claims should be understood to be modified by the term “about.” Accordingly, unless otherwise implied or stated explicitly, the numerical parameters shown are approximations that may depend on the desired characteristics sought and / or the detection limits under standard test conditions / methods. When distinguishing embodiments directly and explicitly from the prior art being discussed, the embodiment numerical values are not approximations unless the word “about” is explicitly recited.

[0014] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, suitable methods and materials are described below. These materials, methods, and examples are illustrative only and not intended to be limiting.

[0015] “Application” means any suitable mode of application for controlling a pathogen such as a fungal pathogen, including treating an existing crop, agricultural product, seed, soil, or a combination thereof.

[0016] “In combination with” means applying the compounds simultaneously in a single application or sequentially in two or more different applications that may be separated in time, location, or method.

[0017] “Controlling” with respect to a pathogen such as a fungal pathogen means blocking, inhibiting, and / or eradicating the pathogen and / or preventing the pathogen from damaging the crop. In one embodiment, controlling means reducing one or more pathogens such as fungi to an undetectable level, or reducing or inhibiting a fungal pathogen to an acceptable level determined by one of ordinary skill in the art (e.g., a crop grower). The determination of an acceptable level of pathogen reduction is based on many factors, including the crop, the pathogen, the severity of the pathogen, use restrictions, economic thresholds, and other factors known to one of ordinary skill in the art.

[0018] As used herein, the terms "booster" and "synergist" refer to one or more compounds that enhance the effectiveness of pesticides as disclosed herein. Without being bound by theory, the booster compounds of the present invention disclosed herein may act by blocking one or more pathways of pathogens such as fungal pathogens such as by detoxifying, sequestering, or transporting pesticides away from toxicity. In certain embodiments, the compounds of the present invention inhibit the enzymatic activity of adenosine triphosphate diphosphatase, which results in the enhancement, potentiation, or synergism of the action of pesticides (such as acaricides, antimicrobials, fungicides, herbicides, insecticides, molluscicides, and / or nematicides). For example, when a booster or synergist is used in combination with a fungicide, the combination of the booster and the fungicide enhances the fungicidal effect of the fungicide and / or renders fungi resistant to the fungicide sensitive to the fungicide due to the activity of the booster. Most commonly, these boosters or synergists do not themselves inhibit pathogens such as fungi per se, nor do they have a harmful effect on living organisms that are (or may be) infected by the pathogens.

[0019] As used herein, the term "treatment" refers to a method for applying or administering an effective amount of the disclosed compound or its formulation to a target area of a field and / or a plant. The treatment method may be, but is not limited to, aerosol spraying, pressure spraying, direct watering, chemigation, atomization, and dipping. The target area of the plant may include, but is not limited to, the leaves, roots, stems, buds, flowers, fruits, seeds, and bulbs of the plant, including bulbs, corms, rhizomes, tubers, taproots, and rootstocks. The treatment may include methods in which one area of the plant (e.g., the root zone or the leaf surface) is treated and another area of the plant is protected (e.g., treating the leaf surface when the disclosed compound is applied to the root zone, or treating new growth when the disclosed compound is applied to the leaf surface).

[0020] As used herein, the term "suspension concentrate" or "SC" refers to a liquid formulation containing a stable suspension of an active ingredient in an aqueous fluid. The suspension concentrate can be stored as a formulation and can be provided to the market and / or the end user without further processing. In actual application, the suspension concentrate is prepared for application by the end user. Generally, the suspension concentrate is mixed with water in the end user's spray tank to an appropriate dilution for a particular application. The dilution may vary depending on factors such as the crop, the pathogen, the particular time of year, the geographical location, local regulations, and the intensity of the infection. After being appropriately diluted, the formulation can be applied, for example, by spraying.

[0021] II. Formulations

[0022] The common goal of formulators of agricultural products is to maximize the biological activity of the active ingredient. In aqueous suspension concentrates, this is particularly challenging because the solid active ingredient often limits bioavailability. However, when delivered as an aqueous suspension concentrate, it is generally not possible to predict whether a particular active ingredient will have good biological activity. Without being limited by theoretical understanding, factors that can determine biological activity include solubility in water (including how it varies with temperature, salinity, and pH at the application site), solubility in hydrophobic regions (including within the waxy leaf cuticle and any micellar surfactant domains), lattice energy, the density of the active ingredient crystals and thus their sedimentation tendency, the presence of crystal polymorphs and metastable states, diffusion rate in water, the ability of the active ingredient to diffuse through the plant cuticle, the location of the site where the active ingredient acts, and the concentration required of the active ingredient at that site of action. It is possible for formulators to discover a large number of modifications to overcome limitations in biological activity, and many of these modifications have interdependent effects (meaning that when each of them is varied simultaneously, testing each one individually does not fully inform the outcome), so it is not feasible to explore the entire experimental space.

[0023] Among the formulations tested during the work described in the present disclosure, the inventors have found that aqueous suspensions of (E)-3-methyl-N'-(1-(naphthalen-2-yl)ethylidene)benzohydrazide generally have poor biological activity. It has further been found that for formulations containing the desired components described below, by controlling the particle size within a specific size range, the biological activity is greatly enhanced.

[0024] A common requirement for formulators of agricultural products is to achieve acceptable stability both in terms of chemical stability (meaning that the active ingredient does not undergo significant chemical degradation) and in terms of physical stability (meaning that in the common product containers stored under the conditions typically encountered in the supply chain, the product remains similar to its state at the time of manufacture and the product is suitable and convenient for use by the end user). Whether a particular active ingredient is prone to chemical degradation is unpredictable because multiple factors can determine its behavior. These factors include the solubility of the active ingredient in any liquid phase present (including the hydrophobic phase of any surfactant micellar structure), the presence of chemicals in those liquid phases that may catalyze degradation, any tendency for the active ingredient to undergo autocatalysis and thus for the decomposition products to accelerate further reactions, the presence of chemical bonds within the active ingredient that are prone to cleavage, and the influence of adjacent groups on its susceptibility. Physical stability also has to be evaluated empirically, but it is known in the art that certain small-scale laboratory tests generally adequately represent the behavior at larger scales in commercial applications.

[0025] Among the formulations tested during the work described in the present disclosure, the inventors found that aqueous suspensions of (E)-3-methyl-N'-(1-(naphthalen-2-yl)ethylidene)benzohydrazide generally had unacceptable chemical stability. Further, it was found that for formulations containing the required components described below, acceptable chemical stability was obtained by controlling the pH within a specific range. Additionally, it was found that formulations containing the required components described below had sufficient physical stability and remained suitable for use even when subjected to stress testing at elevated temperatures (including those that commercial products may experience during transportation, storage, and use).

[0026] Disclosed herein is an aqueous suspension formulation comprising a first active compound having the following structure (also referred to herein as "Compound 1")

[0027]

[0028] (E)-3-methyl-N'-(1-(naphthalen-2-yl)ethylidene)benzohydrazide (Compound 1).

[0029] In some embodiments, the aqueous suspension formulation further comprises a dispersant, a freezing point inhibitor compound, a buffer, and / or a partially neutralized base and water.

[0030] In some embodiments, the aqueous suspension formulation is a suspension concentrate suitable for dilution by an end user, for example.

[0031] In some embodiments, at least a portion of the first active compound is present as a suspension in the aqueous suspension formulation. In some embodiments, the first active compound or a portion thereof is the only suspended material in the aqueous suspension formulation. In other embodiments, additional suspended components are present in the formulation in addition to the first active compound. In any embodiment, the total amount of suspended material is greater than 5 wt% of the total suspended solid material in the formulation, such as greater than 5 wt% to 70 wt%, 10 wt% to 70 wt%, 10 wt% to 60 wt%, 15 wt% to 60 wt%, 15 wt% to 50 wt%, or 15 wt% to 40 wt%. In some embodiments, the additional suspended components can include inert fillers. Suitable fillers are fine particulate solids that do not affect biological activity and include clays, minerals, salts, diatomaceous earth, silica, alumina, gelling materials, starches, wood flour, and other natural materials such as plant-based materials, animal-based materials, or microbe-based materials.

[0032] In any embodiment, the suspended particles such as particles of the first active compound, as measured by light scattering, have a volume-weighted median particle size of from 0.01 microns to 40 microns such as from 0.01 microns to 30 microns, from 0.01 microns to 25 microns, from 0.01 microns to 20 microns, from 0.01 microns to 15 microns, from 0.01 microns to 10 microns, from 0.01 microns to 5 microns or from 0.01 microns to 2 microns, or from 1 micron to 20 microns such as from 1 micron to 15 microns such as from 2 microns to 10 microns or from 4 microns to 8 microns. Additionally, if the formulation contains additional suspending materials such as the materials disclosed herein, any such additional suspending materials may also have a particle size as measured by light scattering as disclosed above for the first active compound.

[0033] A. First active compound

[0034] The aqueous suspension formulation contains the first active compound (E)-3-methyl-N'-(1-(naphthalen-2-yl)ethylidene)benzohydrazide in an amount sufficient such that when used diluted, the first active compound is present in an amount sufficient to enhance the efficacy of one or more agroactive compounds that can be applied in combination with the first active compound. In some embodiments, the aqueous suspension formulation contains from 0.5 wt% to 60 wt% or more of the first active compound, such as from 1 wt% to 60 wt%, from 5 wt% to 55 wt%, from 10 wt% to 50 wt%, from 10 wt% to 45 wt% or from 15 wt% to 40 wt% of the first active compound.

[0035] In certain embodiments, the aqueous suspension formulation contains at least 15 wt% of the first active compound, such as from 15 wt% to 60 wt%, from 15 wt% to 50 wt% or from 15 wt% to 40 wt% of the first active compound.

[0036] In other embodiments, the aqueous suspension formulation contains less than 15 wt% of the first active compound, such as from 0.5 wt% to less than 15 wt%, from 1 wt% to less than 15 wt%, from 5 wt% to less than 15 wt% or from 10 wt% to less than 15 wt% of the first active compound. In such embodiments, the formulation may additionally contain additional suspending materials such as inert fillers so that the total amount of suspending materials reaches at least 10 wt%, as disclosed herein.

[0037] B. Dispersant

[0038] In some embodiments, the dispersant is a high molecular weight dispersant, such as having a molecular weight of 400 Daltons or greater, such as 400 Daltons to 2,000,000 Daltons, or 500 Daltons to 1,000,000 Daltons, 750 Daltons to 750,000 Daltons, 750 Daltons to 500,000 Daltons, 1,000 Daltons to 250,000 Daltons or 1,000 Daltons to 100,000 Daltons.

[0039] In some embodiments, the composition comprises 0.1 wt% to 15 wt% or more of the dispersant, such as 0.5 wt% to 15 wt%, 0.5 wt% to 12 wt% or 1 wt% to 10 wt% of the dispersant.

[0040] In any embodiment, the dispersant can be selected from anionic dispersants, cationic dispersants, non-ionic dispersants or combinations thereof. In some embodiments, the dispersant is or comprises an anionic dispersant. In other embodiments, the dispersant is or comprises a non-ionic dispersant. In any embodiment, the dispersant can be a low metal content dispersant, such as a low sodium dispersant, a low calcium dispersant, a low potassium dispersant or combinations thereof, and can be a low metal content non-ionic dispersant, such as a low sodium non-ionic dispersant, a low calcium non-ionic dispersant, a low potassium non-ionic dispersant or combinations thereof.

[0041] In any embodiment, the dispersant can be selected from one or more of the following:

[0042] Homopolymer dispersants, such as but not limited to polyacrylic acid, polyvinyl alcohol, polyvinylpyrrolidone, polystyrene sulfonate, polyethylene sulfonate, polyethyleneimine or combinations thereof;

[0043] Random or statistical copolymers, such as but not limited to polyethylene glycol / polyisobutylene succinic acid, vinylpyrrolidone / vinylcaprolactam or combinations thereof;

[0044] Block copolymers, such as but not limited to polyethylene oxide / polypropylene oxide, fatty acid / polyethylene oxide, polyethoxylated alcohol, polyethoxylated diamine or combinations thereof;

[0045] Naphthalene sulfonate formaldehyde condensates;

[0046] Lignin sulfonates;

[0047] Ethoxylated lignin sulfonates;

[0048] Or any combination thereof.

[0049] C. Freezing point inhibitor compounds

[0050] A cryoprotectant compound is a compound that lowers the freezing point of a formulation relative to a similar formulation that does not contain the cryoprotectant compound. Lowering the freezing point can increase the utility of the formulation by allowing use at lower temperatures and / or by increasing the physical stability of the formulation when subjected to temperature changes or freeze-thaw cycles. In certain embodiments, the cryoprotectant supports the maintenance of viscosity by providing increased stability under freeze-thaw conditions. In some embodiments, the cryoprotectant is a diol, a sugar, a water-soluble salt, or a combination thereof. The diol can be ethylene glycol, propylene glycol, glycerol, dipropylene glycol, tripropylene glycol, or a combination thereof. In certain embodiments, the cryoprotectant is or comprises propylene glycol.

[0051] The sugar can be a water-soluble sugar or a polysaccharide. In some embodiments, the sugar has a molecular weight of 1,000 daltons or less, such as from 180 daltons to 1,000 daltons. The sugar can be selected from ribose, xylose, glucose, fructose, mannose, sucrose, maltose, isomaltose, trehalose, xylitol, mannitol, sorbitol, dextrose, galactose, lactose, maltodextrin, sucrose, or a combination thereof.

[0052] The water-soluble salt can be any water-soluble salt suitable for an agricultural formulation, typically a non-toxic water-soluble salt. In some embodiments, the water-soluble salt is a halide, nitrate, sulfate, or phosphate. In some embodiments, the water-soluble salt is a lithium salt, sodium salt, potassium salt, magnesium salt, calcium salt, ammonium salt, or aluminum salt. And in certain embodiments, the water-soluble salt can be selected from fluorides, chlorides, iodides, nitrates, sulfates, or phosphates of lithium, sodium, potassium, magnesium, calcium, ammonium, or aluminum.

[0053] In any embodiment, the cryoprotectant and its amount are selected to lower the freezing point of the aqueous suspension formulation to below the freezing point of water, i.e., to below 0 °C. In some embodiments, the amount of cryoprotectant is sufficient to provide a freezing point of the aqueous suspension formulation of below -1 °C, such as below -2 °C, below -3 °C, below -4 °C, or below -5 °C, as measured by rheology and known to those of ordinary skill in the art, such as by using a rheometer. In some embodiments, the freezing point of the formulation is from 0 °C to -1 °C, 0 °C to -2 °C, -1 °C to -3 °C, -2 °C to -4 °C, -3 °C to -5 °C, -4 °C to -6 °C, -5 °C to -7 °C, -5 °C to -8 °C, -5 °C to -9 °C, or -5 °C to -10 °C.

[0054] In some embodiments, the aqueous suspension formulation comprises greater than 0 wt% to 25 wt% or more of the cryoprotectant compound, such as 1 wt% to 25 wt% or 5 wt% to 20 wt% of the cryoprotectant compound.

[0055] D. Buffer and / or Partially Neutralized Base

[0056] A buffer and / or a partially neutralized base is selected to provide a desired pH for the aqueous suspension formulation. In some embodiments, the pH is 6 or below to 11 or above, such as 7 to 11, 7 to 10.5, 6 to 10, 6 to 9, or 6 to 8.

[0057] The buffer and / or the partially neutralized base is any buffer and / or base suitable for agricultural applications. In some embodiments, the buffer is a phosphate, phthalate, CHES, phosphonate, sulfonate, or borate buffer or a combination thereof. In some embodiments, the buffer is a phosphate buffer, and in other embodiments, the buffer is a borate buffer. In one embodiment, the buffer comprises phthalate.

[0058] In other embodiments, the buffer and / or the partially neutralized base includes an amino alcohol, such as ethanolamine, diethanolamine, triethanolamine, or a combination thereof. However, in alternative embodiments, the buffer and / or the partially neutralized base does not include an amino alcohol.

[0059] E. Optional additional components

[0060] In some embodiments, the formulation may further comprise one or more additional components, such as a viscosity modifier, a biocide, an antifoaming agent, a low molecular weight surfactant, an agricultural active compound, or a combination thereof.

[0061] In some embodiments, the formulation comprises no more than 0.1 wt% of a compound including a primary amine, a secondary amine, and / or a tertiary amine, such as 0 wt% to 0.1 wt% of such a compound, or 0 wt% of such a compound.

[0062] In some embodiments, the formulation comprises no more than 0.1 wt% of a quaternary ammonium compound, such as 0 wt% to 0.1 wt% or 0 wt% of such a compound.

[0063] In some embodiments, the formulation comprises a total of no more than 0.1 wt% of any metal, metal ion, or a combination thereof, such as 0 wt% to 0.1 wt%, 0 wt% to 0.05 wt%, 0 wt% to 0.02 wt%, 0 wt% to 0.005 wt%, or 0 wt% to 0.002 wt% of the total metal and / or metal ion. In some embodiments, the formulation comprises a total of no more than 0.002 wt%, such as 0 wt% to 0.002 wt% of any metal, metal ion, or a combination thereof selected from Group 1 or Group 2 of the periodic table.

[0064] i. Viscosity modifier

[0065] In some embodiments, the formulation comprises a viscosity modifier. In some embodiments, the viscosity modifier is selected from polysaccharides or clays or combinations thereof. The polysaccharide can be xanthan gum, gellan gum, agar, guar gum, cellulose or a chemically modified form of the polysaccharide or combinations thereof. The clay can be kaolin, palygorskite, bentonite, laponite or combinations thereof. In some embodiments, the viscosity modifier is or comprises xanthan gum. And in some embodiments, the viscosity modifier is a combination of xanthan gum and clay, such as xanthan gum and palygorskite and / or kaolin.

[0066] The viscosity modifier can be present in an amount of 0.01 wt% to 15 wt%. In certain embodiments, the viscosity modifier is a polysaccharide or a chemically modified polysaccharide, such as xanthan gum, gellan gum, agar, guar gum or cellulose or combinations thereof, in an amount of 0.01 wt% to 0.5 wt%. In certain embodiments, the viscosity modifier is a clay, such as kaolin, palygorskite, bentonite, laponite or combinations thereof, and is present in an amount of 0.1 wt% to 15 wt%.

[0067] ii. Biocide

[0068] In some embodiments, the formulation comprises one or more biocides. The biocide can be selected to reduce or prevent spoilage of the formulation or one or more of its components. In some embodiments, the biocide is selected to reduce or prevent spoilage of the viscosity modifier and / or the freezing point depressant such as sugars and / or diols. In some embodiments, the biocide is selected from benzisothiazolin-3-one, benzoic acid, 2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methyl-phenol, 2-bromo-2-nitro-1,3-propanediol, butylated hydroxyanisole, butylated hydroxytoluene, potassium benzoate, propyl gallate, propyl hydroxybenzoate, sodium nitrite or combinations thereof. In certain embodiments, the biocide is present in an amount of 0.01 wt% to 0.1 wt%.

[0069] iii. Surfactant

[0070] In some embodiments, the formulation comprises a surfactant different from the dispersant. The surfactant can be a low molecular weight surfactant. The surfactant can have a molecular weight of 150 daltons to less than 1,200 daltons. And / or the surfactant can be present in the formulation in an amount of 0.1 wt% to 10 wt%.

[0071] The surfactant can be an anionic surfactant, a cationic surfactant, a nonionic surfactant, a quaternary ammonium surfactant, an amphoteric surfactant or combinations thereof. In some embodiments, the surfactant is an anionic surfactant, a cationic surfactant, a nonionic surfactant or combinations thereof.

[0072] In any embodiment, the anionic surfactant is citrate, carbonate, phosphate, phosphonate, sulfate or sulfonate. The anionic surfactant can be an ester of an alcohol, an alcohol alkoxylate (such as an alcohol ethoxylate and / or an alcohol propoxylate), a tristyrylphenol ethoxylate, a fatty acid, a natural oil or a combination thereof. In certain embodiments, the anionic surfactant is a citrate, carbonate, phosphate, phosphonate, sulfate or sulfonate ester of an alcohol, an alcohol alkoxylate, a tristyrylphenol ethoxylate, a fatty acid or a natural oil or any combination thereof.

[0073] The cationic surfactant can be an ethoxylated amine, such as an ethoxylated amine of a natural oil, an alcohol, a fatty acid or a combination thereof.

[0074] The non-ionic surfactant can be an alkoxylate of an alcohol, a natural oil or a combination thereof, such as an ethoxylate and / or a propoxylate of an alcohol, a natural oil or a combination thereof.

[0075] The quaternary ammonium salt surfactant can comprise at least one chain having at least 6 carbon atoms such as 6 to 20 carbon atoms or 6 to 12 carbon atoms attached to the quaternary ammonium head group.

[0076] And in some embodiments, the zwitterionic surfactant comprises a positively charged group such as a quaternary ammonium ion group, and a negatively charged group such as a carboxylic acid moiety, a sulfonic acid moiety or a phosphoric acid moiety. An example of a zwitterionic surfactant is cocoamidopropyl betaine.

[0077] In certain embodiments, the surfactant is an anionic surfactant and is selected from phosphate, phosphonate, sulfate or sulfonate esters of an alcohol, an alcohol ethoxylate, a tristyrylphenol ethoxylate, a fatty acid or a natural oil or any combination thereof.

[0078] In other embodiments, the surfactant is a non-ionic surfactant and is selected from alkoxylates of an alcohol, a natural oil or a combination thereof.

[0079] Particularly with respect to surfactants, one of ordinary skill in the art should understand that the alkoxylate group (e.g., an ethoxylate or a propoxylate) can contain one or more alkoxy moieties (i.e., can be polyalkoxylated), such as 1 to 200 or more alkoxy moieties. And in some embodiments, the alkoxylate group includes more than 1 to 200 alkoxy groups, such as 4 to 200 or 4 to 150 alkoxy groups.

[0080] iv. Antifoaming agent

[0081] In some embodiments, the formulation comprises one or more defoamers. The defoamer can be selected to reduce or prevent foaming during the manufacture, handling, and / or use of the formulation. In some embodiments, the defoamer is an emulsion of silicone oil. In some embodiments, the defoamer is present in an amount of 0.01 wt% to 1.0 wt%.

[0082] F. Agricultural active compounds

[0083] The disclosed formulations can also comprise agricultural active compounds. In addition or alternatively, the formulations can be used in combination with one or more agricultural active compounds, typically as part of an agricultural composition for application to crops, seeds that can be sown to produce crops, harvested agricultural products, and / or soil on which crops have been or may be grown or sown. The agricultural composition can be a dilution composition that is formed at least in part by diluting the disclosed formulation with a suitable solvent or solvent mixture (such as water).

[0084] Embodiments of the disclosed formulations can be used to enhance the effectiveness of a variety of agrochemicals, including fungicides, antivirals, bactericides, herbicides, insect / acaricides, molluscicides, nematicides, soil insecticides, plant protectants, synergists, fertilizers, and soil conditioners.

[0085] In one embodiment, the formulations disclosed herein can be used to enhance the fungicidal activity of a variety of fungicides. Fungicides that can be used in combination with the disclosed formulations are well known to those skilled in the art and include, but are not limited to, those listed by category in Table 1:

[0086]

[0087]

[0088]

[0089]

[0090]

[0091] Fungicides are more generally catalogued by the Fungicide Resistance Action Committee (FRAC) in the FRAC Coding List 2022 and reproduced in Appendix 1, the full text of which is incorporated herein by reference.

[0092] In one embodiment, the disclosed formulation is used in combination with one or more compounds from the categories or groups listed in Table 1, Appendix 1, or both. In certain embodiments, the formulation is used in combination with one or more fungicides listed in column 1 of Table 1.

[0093] In certain embodiments, the disclosed formulations are used in combination with a fungicide selected from one or more of the following: benzimidazoles, dicarboximides, phenylpyrroles, anilinopyrimidines, hydroxyanilines, formamides, phenylamides, phosphonates, cinnamic acids, oxysterol binding protein inhibitors (OSBPIs), triazole carboxamides, cymoxanil, carbamates, benzamides, demethylation inhibiting piperazines, demethylation inhibiting pyrimidines, demethylation inhibiting azoles (including imidazoles and triazoles such as cyproconazole, difenoconazole, myclobutanil, flutriafol, fludioxonil, metconazole, ipconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole), morpholines, cyflufenamid, metrafenone, picarbutrazox, strobilurins, copper ammonium complexes, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, lime sulfur, ethylenebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinam, and thiazolidines.

[0094] Particular fungicides enhanced by the method herein through the use of an apyrase inhibitor in combination with the disclosed formulations are copper (such as copper octanoate, copper hydroxide, copper sulfate, etc.), myclobutanil, propiconazole, tebuconazole, epoxiconazole, difenoconazole, triticonazole, and prothioconazole.

[0095] In one embodiment, treatment with a combination of a selected fungicide and the disclosed formulation provides synergistic fungicidal activity against phytopathogenic fungi.

[0096] In one embodiment, the present disclosure provides compositions and methods for treating plants or plant seeds infected or at risk of being infected with a fungal pathogen. In one embodiment, the compositions of the present disclosure comprise a formulation of a fungicide, the disclosed formulation, and a botanically acceptable carrier. In another embodiment, the fungicide and the formulation are applied in separate compositions. In additional embodiments, agricultural or horticultural fungicides are used in combination with other compounds in addition to the disclosed formulation. Such other compounds may be applied in the same or separate compositions as the fungicide and / or the formulation. Examples of other components include known carriers for formulation. Additional examples thereof include conventionally known herbicides, insecticide / acaricides, nematicides, soil insecticides, plant protectants, synergists, fertilizers, soil conditioners, and animal feeds. In one embodiment, the inclusion of such other components has a synergistic effect on crop growth.

[0097] In one embodiment, the disclosed formulation is used to enhance the action of herbicides. Exemplary herbicides for use in combination with the formulation are known to those skilled in the art and include, but are not limited to, those described in Appendix 2. By way of example, suitable herbicides for use in combination with the disclosed formulation include acetyl-CoA synthase inhibitors, acetolactate synthase inhibitors, microtubule assembly inhibitors, microtubule organizing inhibitors, auxin analogs, photosynthesis inhibitors, deoxy-D-xylulose phosphate synthase inhibitors, enolpyruvate shikimate phosphate synthase inhibitors, phytoene desaturase inhibitors, glutamine synthetase inhibitors, dihydropteroate synthase inhibitors, protoporphyrinogen oxidase inhibitors, cellulose synthesis inhibitors, uncouplers, hydroxyphenylpyruvate dioxygenase inhibitors, fatty acid thioesterase inhibitors, serine-threonine protein phosphatase inhibitors, solanesyl diphosphate synthase inhibitors, very long chain fatty acid synthesis inhibitors, homogentisate solanesyltransferase inhibitors, lycopene cyclase inhibitors,

[0098] In one embodiment, the disclosed formulation is used to enhance the action of insecticides. Exemplary insecticides for use in combination with the disclosed formulation are known to those skilled in the art and include, but are not limited to, those described in Appendix 3.

[0099] III. Methods of using the formulation.

[0100] Embodiments of the method of using the disclosed formulation include diluting the formulation in a suitable diluent such as water to form an agricultural composition suitable for application to plants, parts of plants, seeds, the soil in which the plants are growing or will grow, or the soil in which seeds have been or will be sown. The method may also include applying the agricultural composition to plants, parts of plants, seeds, the soil in which the plants are growing or will grow, or the soil in which seeds have been or will be sown.

[0101] In some embodiments, the disclosed formulation contains one or more agricultural active compounds, and the agricultural composition is formed by diluting the formulation with a suitable solvent such as water to a concentration suitable for agricultural application. Optionally, one or more additional agricultural active compounds may be added before, during, and / or after diluting the formulation.

[0102] In other embodiments, the formulation does not contain agricultural active compounds, and the agricultural composition is formed by diluting the formulation in a suitable solvent such as water to a concentration suitable for agricultural use. In such embodiments, forming the agricultural composition may also include adding one or more agricultural active compounds to the water, then adding the formulation while diluting the formulation with water, and / or subsequently adding one or more agricultural active compounds to the diluted mixture containing the formulation.

[0103] In certain non-limiting embodiments, the disclosed formulations are diluted to provide an amount of the first active compound sufficient for agricultural applications in an amount of from about 0.01 to about 80% weight / weight in the final composition, or from about 25% to about 55% in the final composition, such as from about 30% to about 50%, from about 35% to about 45%, such as about 0.01, 0.05, 0.1, 0.5, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.5, 3.0, 4.0, 5.0, 7.5, 10, 20, 30, 40, 50, 55, 60 or 80% weight / weight. In one embodiment, the first active compound is provided in an amount of from about 0.01 to about 50% in the final diluted composition, such as from about 15% to about 50%, from about 20% to about 45%, from about 25% to about 40%, such as about 0.01, 0.05, 0.1, 0.5, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.5, 3.0, 4.0, 5.0, 7.5, 10, 15, 20, 30, 40 or 50% volume / volume.

[0104] In some embodiments, the agroactive compound is present in the agricultural composition at a concentration less than the concentration of the agroactive compound recommended for use in the absence of the formulations disclosed herein, such as in the absence of (E)-3-methyl-N'-(1-(naphthalen-2-yl)ethylidene)benzohydrazide.

[0105] In some embodiments, a method of preparing an agricultural composition comprises adding the formulations disclosed herein to water in an amount sufficient to enhance the agroactive compound, and adding an agroactive compound in an amount sufficient to provide a concentration in the agricultural composition that is less than the concentration recommended for use in the absence of the disclosed formulations, such as in the absence of (E)-3-methyl-N'-(1-(naphthalen-2-yl)ethylidene)benzohydrazide. One of ordinary skill in the art will understand that the disclosed formulations and the agroactive compound can be added to water in any order, sequentially or substantially simultaneously, to form the agricultural composition.

[0106] In any embodiment, the one or more agroactive compounds can be agricultural or horticultural pesticides as disclosed herein, such as acaricides, antimicrobials, fungicides, herbicides, insecticides, molluscicides or nematicides or combinations thereof. In some embodiments, the method is a method for controlling or preventing fungal growth.

[0107] As is known to those of ordinary skill in the agricultural arts, treatable crops include crops infected with various pathogens, including but not limited to bacteria, viruses, fungal pathogens, mites, nematodes, mollusks, weeds, or other pests. By way of example, such agricultural and horticultural crops that can be treated in accordance with the present disclosure include plants, whether genetically modified or not, including their harvested products, such as: grains; vegetables; root crops; potatoes; trees such as fruit trees, for example banana trees, tea trees, coffee trees, or cocoa trees; grasses; turfgrasses; or cotton.

[0108] An agricultural composition comprising the disclosed formulation can be applied to each part of a plant, such as leaves, stems, patterns, flowers, flower buds, fruits, seeds, seedlings, roots, tubers, rhizomes, sprouts, or cuttings. The formulation can also be applied to improved varieties, cultivars, and mutants, hybrids, and genetically modified embodiments of these plants.

[0109] An agricultural composition comprising the disclosed formulation can be used for seed treatment, foliar application, soil application, or water application in order to control various diseases occurring in agricultural or horticultural crops (including flowers, turf, and forage).

[0110] An agricultural composition comprising the disclosed formulation can be used to enhance the action of antimicrobials. For example, the disclosed formulation can be used in combination with antimicrobials to combat bacterial and viral infections.

[0111] Embodiments of the disclosed formulation can be used to enhance the action of herbicides. For example, the disclosed formulation can be used in combination with one or more herbicides to control weeds or other unwanted vegetation.

[0112] Embodiments of the disclosed formulation can be used to enhance the action of insecticides. For example, the disclosed formulation can be used in combination with one or more insecticides to control insect pests.

[0113] Embodiments of the disclosed formulation can be used to enhance the action of acaricides or miticides. For example, the disclosed formulation can be used in combination with one or more acaricides to control mites.

[0114] Embodiments of the disclosed formulation can be used to enhance the action of molluscicides. For example, the disclosed formulation can be used in combination with one or more molluscicides to prevent slugs or snails from disturbing crops.

[0115] Embodiments of the disclosed formulation can be used to enhance the action of nematicides. For example, the disclosed formulation can be used in combination with one or more nematicides to prevent nematodes from disturbing crops.

[0116] Embodiments of the disclosed formulations can be particularly useful for enhancing the action of fungicides against plant fungal pathogens. Examples of pathogens treated according to the present disclosure include, but are not limited to, Botrytis cinerea, Colletotrichum graminicola, Fusarium oxysporum, Sclerotiana sclerotiorum, Verticillium dahlia, Mycospharella gramincola, and Sphacelotheca reliana.

[0117] Botrytis cinerea is an airborne plant pathogen with a necrotrophic lifestyle that attacks over 200 crop hosts worldwide. It mainly attacks dicotyledonous plant species (including important protein, oil, fiber, and horticultural crops, grapes, and strawberries), and Botrytis also causes secondary soft rot of fruits and vegetables during storage, transportation, and in the market. Many types of fungicides cannot control Botrytis cinerea due to its genetic plasticity.

[0118] The genus Colletotrichum includes approximately 600 species that attack over 3,200 monocotyledonous and dicotyledonous plant species. Colletotrichum graminicola mainly infects maize (Zea mays) and causes losses of approximately $1 billion per year in the United States alone (Connell et al., 2012).

[0119] Banana wilt, caused by the soil-borne fungus Fusarium oxysporum f.sp. cubense, is a major threat to banana production worldwide. Currently, there are no fungicides available to effectively control the disease after the plant is infected (Peng J et al., 2014).

[0120] The white mold Sclerotiana sclerotiorum is known to attack over 400 host species and is considered one of the most prolific plant pathogens. Most infected crop species are dicotyledons, as well as some agriculturally important monocotyledons. Some important crops infected by Sclerotiana include legumes (soybeans), most vegetables, stone fruits, and tobacco.

[0121] The ascomycete Verticillium dahlia is a soil-borne fungal plant pathogen that causes vascular wilt in a wide range of dicotyledonous host species. Verticillium dahlia can cause severe yield and quality losses in cotton and other important crops such as vegetables, fiber, fruits, nut trees, forest trees, and ornamental plants.

[0122] The ascomycete fungus Septoria tritici (anamorph: Septoria tritici) is one of the most important foliar diseases of wheat, occurring wherever wheat is grown. Yield losses due to this disease range from 25% to 50%, and are particularly high in Europe, the Mediterranean region, and East Africa. Infection by Septoria tritici is initiated by airborne ascospores produced on crop residues from the previous season. Primary infection usually occurs after emergence in spring or autumn. The mature disease is characterized by necrotic lesions on the leaves and stems of infected plants.

[0123] The basidiomycete fungus Sphacelotheca reiliana systemically infects maize (Zea mays), causing smut. Yield losses due to this disease are variable and depend directly on the incidence of the disease. The fungus overwinters in crop debris or soil in the form of diploid teliospores. The flower structure is transformed into a sorus containing large amounts of powdery teliospores, similar to the mature galls of common smut.

[0124] Examples of crops and plant diseases (pathogens) controlled by treating with the compounds and compositions disclosed by the present invention include, but are not limited to:

[0125] Beet: Cercospora leaf spot (Cercospora beticola), black root rot (Aphanomyces cochlioides), root rot (Thanatephorus cucumeris), leaf rot (Thanatephorus cucumeris), etc.

[0126] Peanut: Brown leaf spot (Mycosphaerella arachidis), leaf mold (Ascochyta sp.), rust (Puccinia arachidis), damping-off (Pythium debaryanum), rust spot (Alternaria alternata), stem rot (Sclerotium rolfsii), black rust (Mycosphaerella berkeleyi), etc.

[0127] Cucumber: Powdery mildew (Sphaerotheca fuliginea), downy mildew (Pseudoperonospora cubensis), gummy stem blight (Mycosp haerella melonis), fusarium wilt (Fusarium oxysporum), sclerotinia rot (Sclerotinia sclerotiorum), gray mold (Botrytis cinerea), anthracnose (Colletotrichum orbiculare), angular leaf spot (Cladosporium cucumerinum), brown spot (Coryn espora cassiicola), damping-off (Pythium debaryanum, Rhizoctonia solani Kuhn), Phomopsis root rot of cucumber (Phomopsis sp.), bacterial leaf spot (Pseudomonas syringae pv. Lechrymans), etc.

[0128] Tomato: Gray mold (Botrytis cinerea), leaf mold (Cladosporium fulvum), late blight (Phytophthora infestans), Verticillium wilt (Verticillium albo-atrum, Verticillium dahliae), powdery mildew (Oidium neolycopersici), early blight (Alternaria solani), leaf mold (Pseudocercospora fuligena), etc.

[0129] Eggplant: Gray mold (Botrytis cinerea), black rot (Corynespora melo ngenae), powdery mildew (Erysiphe cichoracearum), leaf mold (Mycovellosiella nattrassii), sclerotinia rot (Sclerotinia sclerotiorum), Verticillium wilt (Verticillium dahliae), Phomopsis blight (Phomopsis vexans), etc.

[0130] Strawberries: Gray mold (Botrytis cinerea), powdery mildew (Sphaerotheca humuli), anthracnose (Colletotrichum acutatum, Colletotrichum fragariae), Phytophthora rot (Phytophthora cactorum), soft rot (Rhizopus stolonifer), fusarium wilt (Fusarium oxysporum), Verticillium wilt (Verticillium dahliae), etc.

[0131] Onions: Neck rot (Botrytis allii), gray mold (Botrytis cinerea), leaf blight (Botrytis squamosa), downy mildew (Peronospora destructor), Phytophthora porn disease (Phytophthora porn), etc.

[0132] Cabbages: Clubroot (Plasmodiophora brassicae), soft rot (Erwinia carotovora), black rot (Xanthomonas campestris pv. campestris), bacterial black spot (Pseudomonas syringae pv. Maculicola, P. s. pv. alisalensis), downy mildew (Peronospora parasitica), sclerotinia rot (Sclerotinia sclerotiorum), black spot (Alternaria brassicicola), gray mold (Botrytis cinerea), etc.

[0133] Common beans: Sclerotinia rot (Sclerotinia sclerotiorum), gray mold (Botrytis cinerea), anthracnose (Colletotrichum lindemuthianum), angular leaf spot (Phaeoisariopsis griseola), etc.

[0134] Apple: Powdery mildew (Podosphaera leucotricha), Scab (Venturia inaequalis), Brown rot (Monilia mali), Black spot (Mycosphaerella pomi), Canker (Valsa mali), Alternaria blotch (Alternaria mali), Rust (Gymnosporangium yamadae), Ring rot (Botryosphaeria berengeriana), Anthracnose (Glomerella cingulata, Colletotrichum acutatum), Leaf rot (Diplocarpon mali), Flyspeck (Zygophiala jamaicensis), Sooty blotch (Gloeodes pomigena), Violet root rot (Helicobasidium mompa), Gray mold (Botrytis cinerea), etc.

[0135] Japanese apricot: Scab (Cladosporium carpophilum), Gray mold (Botrytis cinerea), Brown rot (Monilinia mumecola), etc.

[0136] Persimmon: Powdery mildew (Phyllactinia kakicola), Anthracnose (Gloeosporium kaki), Angular leaf spot (Cercospora kaki), etc.

[0137] Peach: Brown rot (Monilinia fructicola), Scab (Cladosporium carpophilum), Phomopsis rot (Phomopsis sp.), Bacterial shot hole (Xanthomonas campestris pv. pruni), etc.

[0138] Almond: Brown rot (Monilinia taxa), Spot disease (Stigminacarpophila), Scab (Cladosporium carpophilum), Red leaf spot (Polystigma rubrum), Target spot (Alternaria alternata), Anthracnose (Colletotrichum gloeospoides), etc.

[0139] Yellow peach: Brown rot (Monilinia fructicola), Anthracnose (Colletotrichum acutatum), Black spot (Alternaria sp.), Sclerotinia of young fruit (Monilinia kusanoi), etc.

[0140] Grape: Gray mold (Botrytis cinerea), Powdery mildew (Uncinula necator), Ripe rot (Glomerella cingulata, Colletotrichum acutatum), Downy mildew (Plasmopara viticola), Anthracnose (Elsinoe ampelina), Brown leaf spot (Pseudocercospora vitis), Black rot (Guignardia bidwellii), White rot (Coniella castaneicola), Rust (Phakopsora ampelopsidis), etc.

[0141] Pear: Scab (Venturia nashicola), Rust (Gymnosporangium asiaticum), Black spot (Alternaria kikuchiana), Ring rot (Botryosphaeria berengeriana), Powdery mildew (Phyllactinia mali), Spruce canker (Phomopsis fukushii), Brown spot (Stemphylium vesicarium), Anthracnose (Glomerella cingulata), etc.

[0142] Tea: Target spot (Pestalotiopsis longiseta, Pestalotiopsis theae), Anthracnose (Colletotrichum theae-sinensis), Net blight (Exobasidium reticulatum), etc.

[0143] Citrus fruits: black spot (Elsinoe fawcettii), blue mold (Penicillium italicum), common green mold (Penicillium digitatum), gray mold (Botrytis cinerea), melanose (Diaporthe citri), canker (Xanthomonas campestris pv. Citri), powdery mildew (Oidium sp.), etc.

[0144] Wheat: powdery mildew (Blumeria graminis f.sp. tritici), red mold (Gibberella zeae), red rust (Puccinia recondita), brown snow mold (Pythium iwayamai), pink snow mold (Monographella nivalis), eyespot (Pseudocercosporella herpotrichoides), leaf scorch (Septoria tritici), glume blotch (Leptosphaeria nodorum), patchy snow blight (Typhula incarnata), sclerotial snow blight (Myriosclerotinia borealis), damping-off (Gaeumannomyces graminis), ergot (Claviceps purpurea), bunt (Tilletia caries), loose smut (Ustilago nuda), etc.

[0145] Barley: leaf spot (Pyrenophora graminea), net blotch (Pyrenophora teres), leaf spot (Rhynchosporium secalis), loose smut (Ustilago tritici, U. nuda), etc.

[0146] Rice: Blast (Pyricularia oryzae), Sheath Rot (Rhizoctonia solani), Bakanae Disease (Gibberella fujikuroi), Brown Spot (Cochliobolus miyabeanus), Damping-off (Pythium graminicola), Bacterial Blight (Xanthomonas oryzae), Bacterial Seedling Blight (Burkholderia plantarii), Brown Stripe (Acidovorax avenae), Bacterial Grain Rot (Burkholderia glumae), Cercospora Leaf Spot (Cercospora oryzae), False Smut (Ustilaginoidea virens), Brown Spot of Rice (Alternaria, Curvularia intermedia), Discoloration of Rice Grains (Alternaria padwickii), Powdering of Rice Grains (Epicoccum purpurascens), etc.

[0147] Tobacco: Sclerotinia Rot (Sclerotinia sclerotiorum), Powdery Mildew (Erysiphe cichoracearum), Phytophthora Rot (Phytophthora nicotianae), etc.

[0148] Tulip: Gray Mold (Botrytis cinerea), etc.

[0149] Sunflower: Downy Mildew (Plasmopara halstedii), Sclerotinia Rot (Sclerotinia sclerotiorum), etc.

[0150] Evergreen Grass: Sclerotinia Snow Blight (Sclerotinia borealis), Giant Leaf Spot (Rhizoctonia solani), Brown Spot (Rhizoctonia solani), Dollar Spot (Sclerotinia homoeocarpa), Blast (Pyricularia sp.), Pythium Blight (Pythium aphanidermatum), Anthracnose (Colletotrichum graminicola), etc.

[0151] Orchard Grass: Powdery Mildew (Erysiphe graminis), etc.

[0152] Soybeans: Purple spot (Cercospora kikuchii), downy mildew (Peronospora manshurica), Phytophthora rot (Phytophthora sojae), rust (Phakopsora pachyrhizi), sclerotinia rot (Sclerotinia sclerotiorum), anthracnose (Colletotrichum truncatum), gray mold (Botrytis cinerea), citrus scab (Elsinoe glycines), black mold (Diaporthe phaseolorum var. sojae), etc.

[0153] Potatoes: Phytophthora rot (Phytophthora infestans), early blight (Alternaria solani), scurf (Rhizoctonia solani), Verticillium wilt (Verticillium albo - atrum, Verticillium dahliae, Verticillium nigrescens, etc.

[0154] Bananas: Panama disease (Fusarium oxysporum), banana leaf spot (Mycosphaerella fijiensis, Mycosphaerella musicola), etc.

[0155] Rapeseed: Sclerotinia rot (Sclerotinia sclerotiorum), root rot (Phoma lingam), black leaf spot (Alternaria brassicae), etc.

[0156] Coffee: Rust (Hemileia vastatrix), anthracnose (Colletotrichum coffeanum), leaf spot (Cercospora coffeicola), etc.

[0157] Sugarcane: Brown rust (Puccinia melanocephala), etc.

[0158] Maize: Banded leaf spot (Gloeocercospora sorghi), rust (Puccinia sorghi), southern rust (Puccinia polysora), smut (Ustilago maydis), brown spot (Cochliobolus heterostrophus), northern leaf blight (Setosphaeria turcica), etc.

[0159] Cotton: Seedling blight (Pythium sp.), rust (Phakopso ragossypii), sour rot (Mycosphaerella areola), anthracnose (Glomerella gossypii), etc.

[0160] IV. Method for preparing the preparation

[0161] The disclosed preparation can be prepared by methods known to those of ordinary skill in the art. In some embodiments, the method includes providing a first active compound, a dispersant, a freezing point inhibitor, a buffer and / or a partially neutralized base, and water, and forming the preparation. Optionally, a viscosity modifier, a surfactant, a biocide, an antifoaming agent, and / or an agricultural active compound can also be added. In some embodiments, the solid material in the mixture is optionally mixed with a first portion of water in the presence of a dispersant, a freezing point inhibitor, a buffer and / or a partially neutralized base and crushed, such as by stirring with beads, until the solid particles have the desired size for the preparation. In other embodiments, the solid material, such as the first active compound, can be ground to a suitable size or provided in such a size and then added to water or the preparation.

[0162] Additional components (including additional water and / or buffer and / or partially neutralized base) can be added to provide the desired pH and concentration. Those of ordinary skill in the art understand that the dispersant, the freezing point inhibitor, the buffer and / or the partially neutralized base, and any optional components such as the viscosity modifier, the surfactant, the biocide, the antifoaming agent, and / or the agricultural active compound can be added in any suitable or convenient order.

[0163] In one embodiment, the order of addition of components is the first portion of water, a freezing point inhibitor, a dispersant, a small molecule surfactant (if present), an antifoaming agent (if present), a buffer and / or a partially neutralized base, a first active compound, a viscosity modifier (if present), a biocide (if present), and the balance of water to provide a formulation of desired concentration. Typically, the mixture is milled after addition of the first active compound, e.g., to reduce the particle size of the first active compound to a desired size. In some embodiments, the mixture is milled after addition of the first active compound and before addition of any additional components. In one embodiment, the order of addition of components can be the first portion of water, followed by addition of the freezing point inhibitor, dispersant, small molecule surfactant (if present), and antifoaming agent (if present) in any order. Then a pH modifier, such as a buffer and / or a partially neutralized base, is added, followed by the first active compound. Then the mixture can be milled. Subsequently, a viscosity modifier (if present) and / or a biocide (if present) can be added, followed by addition of the balance of water.

[0164] In any embodiment, additional buffer, acid, base, and / or partially neutralized base can be added to adjust the final pH of the formulation.

[0165] V. Examples

[0166] Example 1

[0167] Preparation of a Stable Aqueous Suspension Concentrate

[0168]

[0169] First Active Compound

[0170] 2.5 g of the first active compound was placed in a 100 mL glass beaker together with 0.5 g of the dispersant Tamol SN, 1 g of propylene glycol, 0.006 g (10 mM) of boric acid powder buffer, 5 g of water, optionally 0.05 g of the low molecular weight surfactant Surfonic L24-7, and optionally 0.01 g of the antifoam SAG1572. 30 g of glass beads with a diameter of 2 mm were added, and the suspension was milled using a mechanical stirrer to a median diameter below 1.5 microns as measured on a Malvern Mastersizer 3000. 0.5 g of a pre-gel containing 2% xanthan gum polysaccharide and 2% of the biocide Acticide B20 was added to the suspension concentrate, and the mechanical stirrer was run for an additional 10 minutes. The pH was adjusted to 9.0 using 2% phosphoric acid or 1 M sodium hydroxide as needed. Water was added as needed to bring the final concentration of Compound B to 25 wt%. The suspension concentrate was collected by sieving out the glass beads.

[0171] Example 2

[0172] Enhanced biological efficacy

[0173] Samples were prepared according to the methods described herein such as in Example 1 above, except that the grinding conditions were adjusted to obtain different particle sizes in the various samples. The biological activity of the combination of the test samples with a commercial fungicide was tested. The degree of pathogen control was expected to depend on the particle size.

[0174] Example 3

[0175] Acceptable chemical stability

[0176] Samples were prepared according to the methods described herein such as in Example 1 above, except that the pH was adjusted so that each sample had a different pH. The chemical stability of the samples was evaluated by storing the samples at high temperature and periodically measuring the remaining concentration of the active ingredient by HPLC. A reference sample was stored at low temperature and also tested at the same time points. The expected results were to show that within a specific pH range, the chemical stability was acceptable.

[0177] Example 4

[0178] Acceptable chemical stability

[0179] Samples were prepared according to the methods described herein such as in Example 1 above, except that low concentrations of certain components (including primary amines, secondary amines, tertiary amines, quaternary amines or alkali metals) were added to specific sub - samples. The chemical stability was evaluated as described in Example 3 above. The expected results were to show that certain components accelerated chemical degradation and had to be excluded from the formulations of the present invention.

[0180] Example 5

[0181] Acceptable physical stability

[0182] Several liters of formulation were prepared according to the methods described herein such as in Example 1 above, except that some formulation components were replaced by other components such that the components of the composition still fell within the compositional ranges described in Part II above. Sub - samples were stored at several different temperatures and the pH, viscosity, appearance, sedimentation and syneresis were evaluated periodically. The formulations were expected to have excellent physical stability.

[0183] Example 6

[0184] Chemical stability as a function of pH

[0185] Prepare a working solution of Compound 1 at a concentration of 500 μM in dimethyl sulfoxide. Add 2 μL of the working solution and 198 μL of PBS pH 4.5 or PBS pH 7.4 to a glass vial to achieve a final concentration of 5 μM. Set up in duplicate. Incubate the vials at 37 °C with 60 rpm in a water bath and sample at the designated time points of 0, 2, 4, 6, and 24 hours. For each time point, terminate the incubation with 1000 μL of cold acetonitrile containing an internal analytical reference standard. Vortex the samples for 1 minute and then centrifuge at 2500 g for 10 minutes at RT. Take an aliquot of 200 μL of the supernatant for LC-MS / MS analysis.

[0186] For samples incubated in PBS buffer at pH 4.5 for 0, 2, 4, 6, 24 hours, the remaining amounts of Compound 1 were 100%, 62.3%, 33.7%, 29.2%, 3.1% respectively. For samples incubated in PBS buffer at pH 7.4 for 0, 2, 4, 6, 24 hours, the remaining amounts of Compound 1 were 100%, 112.4%, 96.2%, 97.8%, 91.1% respectively.

[0187] These results indicate rapid degradation under weakly acidic conditions and an apparent half-life slightly longer than 2 hours at 37 °C. In this experiment, the solubility of Compound 1 in water was lower than the total concentration of 5 μM, so the actual degradation rate in solution was very fast, with an estimated half-life of less than one hour. Relative to acidic conditions, the stability at pH 7.4 was excellent.

[0188] Example 7

[0189] Long-term chemical stability as a function of pH

[0190] Method: Prepare an aqueous suspension concentrate with the following composition: 30 wt% Compound 1, 2.5 wt% tri-styrylphenol polyoxyethylene ether surfactant, 2.0 wt% ethylene oxide-propylene oxide block copolymer dispersant, 5.0 wt% propylene glycol antifreeze protector, 0.1 wt% silicone oil defoamer, 52.4% distilled water, and add 8.0 wt% viscosity modifier gel after grinding for 2 hours. The viscosity modifier gel contains 2.0% xanthan gum and 1.0% biocide aqueous solution. Take aliquots of the suspension and adjust to pH 6, 7, and 8 with 10 wt% sulfuric acid, pH 10 borate buffer, and 10 wt% sodium hydroxide respectively. Subdivide the three samples and store at room temperature (RT, about 25 °C) and 38 °C. Store the control sample at 0 °C for reference. Regularly take aliquots and dilute in acetonitrile for analysis by HPLC.

[0191] Results: After 1 month and 9 months at RT, the amounts of Compound 1 remaining in the pH 6 sample were 99% and 86%, respectively. After 1 month and 9 months at 38 °C, the amounts of Compound 1 remaining in the pH 6 sample were 103% and 94%, respectively. After 1 month and 9 months at RT, the amounts of Compound 1 remaining in the pH 7 sample were 103% and 76%, respectively. After 1 month and 9 months at 38 °C, the amounts of Compound 1 remaining in the pH 7 sample were 104% and 89%, respectively. After 1 month and 9 months at RT, the amounts of Compound 1 remaining in the pH 8 sample were 99% and 102%, respectively. After 1 month and 9 months at 38 °C, the amounts of Compound 1 remaining in the pH 6 sample were 99% and 103%, respectively.

[0192] These results indicate that the aqueous suspension of Compound 1 is chemically unstable at neutral or acidic pH, but stable at pH 8. Additionally, there is a trend of slightly faster degradation at RT than at 38 °C. Without being limited to any particular theory, this may be the result of the complex relationship between the apparent solubility and temperature in this formulation. Since Compound 1 has a much higher solubility in the hydrophobic inner phase of the surfactant micelles than in the aqueous phase and the surfactant micelles undergo a phase transition as a function of temperature, as the temperature rises, due to micelle instability, the amount of Compound 1 in the solution may decrease with increasing temperature, and the overall degradation rate decreases. Nevertheless, pH remains an important factor for the aqueous solution stability of Compound 1.

[0193] Example 8

[0194] Physical and Chemical Stability as a Function of Buffer

[0195] Method: An aqueous suspension was prepared as described in Example 7 and subdivided into 3 aliquots, which were adjusted to pH 6, 7, and 8, respectively. Each aliquot was further divided into 3 groups, and each group of materials was stored at 0 °C, 25 °C, and 38 °C. After six months of storage, the pH of all aliquots was measured.

[0196] Results: When stored at 0 °C, 25 °C, and 38 °C, the formulations initially at pH 6 dropped to pH 3.64, 2.86, and 2.84, respectively. When stored at 0 °C, 25 °C, and 38 °C, the formulations initially at pH 7 dropped to pH 5.06, 4.35, and 3.90, respectively. When stored at 0 °C, 25 °C, and 38 °C, the formulations initially at pH 8 dropped to pH 7.55, 6.95, and 5.80, respectively.

[0197] These results indicate that, in the absence of a buffer to stabilize the pH, the aqueous suspension of Compound 1 becomes more acidic over time due to the chemical degradation of Compound 1. Example 7 above shows that the degradation rate is greater at neutral or low pH, and thus the degradation is autocatalytic, i.e., the more Compound 1 degrades, the lower the pH drops and the faster the degradation. A buffer can be used to maintain a stable pH (which supports the function of the viscosity modifier to prevent sedimentation) and to minimize chemical degradation. As will be understood by those skilled in the formulation art, the amount of buffer will depend on the details of the amount of Compound 1 and other components present in the formulation and can be routinely determined by those skilled in the art.

[0198] Example 9

[0199] Physical stability at low temperature as a function of antifreeze protectant

[0200] Method: Two aqueous suspensions were prepared substantially as described in Example 7, except that one sample contained 5 wt% propylene glycol antifreeze protectant and the other sample did not contain propylene glycol antifreeze protectant, with the balance consisting of water. The samples were subjected to two freeze-thaw cycles by alternating storage in a freezer below -4 °C and at room temperature. Viscosity was measured using a Brookfield spindle viscometer.

[0201] Results: Both samples remained homogeneous in appearance, with no significant sedimentation or syneresis during the short duration of this experiment. The viscosity of the sample without propylene glycol was 480 mPa before the freeze-thaw challenge and 1100 mPa afterwards; and the viscosity of the sample containing propylene glycol was 420 mPa both before and after the freeze-thaw challenge.

[0202] The antifreeze protectant propylene glycol inhibits the formation of structures (where the structures are molecular aggregates of the substances present in the aqueous solution) in the liquid phase, which would otherwise result in unacceptably high viscosities, rendering the formulation unsuitable for pumping and inconvenient for the end user.

[0203] Example 10

[0204] Efficacy as a function of particle size

[0205] Method: An aqueous suspension concentrate containing 30 wt% of Compound 1 was prepared as described in Example 7, except that the grinding conditions were controlled to achieve a certain range of particle sizes. Specifically, grinding was carried out using ceramic grinding media in a water-jacketed stirred vessel, and the duration of grinding was varied. The samples were diluted in water and bioassayed in pairs with commercial fungicides Amistar (0.03 L / ha), Imtrex (0.35 L / ha), Proline (0.125 L / ha), or Balaya (0.2 L / ha) at a rate of 20 ppm of Compound 1 in a greenhouse. Each pair combination was used to attack each of four commercially important pathogenic fungi: Botrytis cinerea (on tomato plants), Septoria tritici (on wheat plants), Puccinia triticina (on wheat plants), and Phakopsora pachyrhizi (on soybean cultivar Siverka). Seeds were sown in 9 cm diameter pots to a depth of 1 - 2 cm using Petersfield potting compost (75% medium grade peat, 12% screened sterilized loam, 3% medium grade vermiculite, 10% coarse sand (5 mm screened, lime-free), 1.5 kg PG mixture / m^3, lime to pH 5.5 - 6.0, and wetting agent (Vitax Ultrawet 200 ml / m^3) and germinated / grown under a 16-hour day / 8-hour night light regime at 23°C. When the plants were at the BBCH 11 growth stage (when the first pair of true leaves (single leaves) had unfolded, two to three weeks after sowing), the plants were treated. Using a tracked sprayer, the plants were treated with the commercial fungicides and Compound 1 using a water volume of 200 L / ha. Twenty-four hours after treatment, the plants were inoculated with the appropriate fungus (pathogen). Each combination of fungicide, pathogen, and formulation was used with four replicates. After the disease symptoms had fully developed between seven and twenty days (depending on the pathogen), the percent disease control of each plant was evaluated. Appropriate controls were used for all experiments, including the inoculated 'checks' where plants were inoculated with the specific pathogen of the plant to evaluate the disease level. Additionally, each commercial fungicide was tested separately as part of each treatment, which was the 'control' benchmark for evaluating the experimental compound. The percent disease control of each treated plant was calculated as the average disease severity of the inoculated but untreated plants ('check') minus the average disease severity of the treated plants, divided by the 'check'. The percent synergy of each combination of formulation plus fungicide (test combination) was calculated as the disease control of the plants treated with only the fungicide ('control') minus the disease control of the test combination, divided by 100% minus the 'control'.Synergy represents the amount of benefit achieved by adding the formulation of Compound 1 to the fungicide, expressed as a percentage of the maximum possible benefit. Thus, 100% would mean complete disease control, and 0% would mean no benefit from the combination.

[0206] Results:

[0207] The particle size of the ground samples was measured using a laser scattering instrument, and the median volume-weighted particle diameters were 1.0, 7.0, and 15 microns, respectively, as the grinding duration decreased. For simplicity in the following discussion, these samples were designated as A1, B7, and C15.

[0208] Septoria tritici: There was no consistent synergy with Amistar. The synergy with Imtrex was 28%, 28%, and 4.6% for A1, B7, and C15, respectively. The synergy with Proline was 26%, 25%, and 61% for A1, B7, and C15, respectively. The synergy with Balaya was 51%, 40%, and 36% for A1, B7, and C15, respectively.

[0209] Phakopsora pachyrhizi: The synergy with Amistar was 30% for A1 and there was no synergy for B7 or C15. There was no significant synergy with Imtrex and Proline. The synergy with Balaya was 40%, 33%, and 20% for A1, B7, and C15, respectively.

[0210] Puccinia triticina: There was no significant synergy with Amistar. The synergy with Imtrex was 29%, 3%, and no synergy for A1, B7, and C15, respectively. There was no significant synergy with Proline or Balaya.

[0211] Botrytis cinerea: There was no significant synergy with Amistar. The synergy with Imtrex was 18%, 6%, and no synergy for A1, B7, and C15, respectively. The synergy with Proline was 33%, 14%, and 10% for A1, B7, and C15, respectively. There was no significant synergy with Balaya.

[0212] Conclusion: In these greenhouse assays, it was clear that in some cases, no synergistic effect between Compound 1 and fungicides was observed in controlling some pathogens. This may be because, for example, in this particular test, the application rate of the commercial fungicide was too low or too high relative to the degree of plant disease caused by the inoculated pathogen, such that adding Compound 1 may not produce any measurable benefit or may not have the opportunity to further improve the already high level of disease control. In some cases, it may also be that in the specific test, the mode of action and detoxification of the fungicide against the pathogen may not involve the enzymes regulated by Compound 1, and thus it cannot act synergistically with the adenosine triphosphate diphosphatase inhibitor. These results without synergistic effect can be ignored in order to evaluate the impact of particle size on efficacy.

[0213] In cases where there is a synergistic effect, if we group the results by fungicide, the following results can be highlighted:

[0214] a) In combination with Imtrex, B7 was always superior to C15, and A1 was essentially the same as B7 (1 case) or superior to B7 (3 cases), i.e., A1 > B7 > C15.

[0215] b) In combination with Balaya, B7 > C15.

[0216] c) In combination with Amistar, there was only a synergistic effect and an obvious trend against Phakopsora pachyrhizi, where again A1 > B7 > C15.

[0217] d) In combination with Proline, in one case A1 > B7 > C15, while in another case C15 > A1 = B7.

[0218] However, in cases where there is a synergistic effect, if we group the results by pathogen, the following results can be highlighted:

[0219] a) Against Septoria tritici, in combination with Imtrex, A1 = B7 > C15; in combination with Proline, C15 > A1 = B7; in combination with Balaya, A1 > B7 > C15.

[0220] b) Against Phakopsora pachyrhizi, in combination with Amistar, only A1 had a synergistic effect; in combination with Balaya, A1 > B7 > C15.

[0221] c) Against Puccinia triticina, in combination with Imtrex, A1 > B7 > C15.

[0222] d) Against Botrytis cinerea, in both combinations with Imtrex and with Proline, A1 > B7 > C15

[0223] In this series of experiments, there was one clear counterexample of proline against Septoria tritici (a possible outlier based on C15), while the other seven examples established the pattern. Overall, the suspension concentrate with a median particle size of 1 micron was more biologically effective than the suspension concentrate with a median particle size of 7 microns, and the suspension concentrate with a median particle size of 7 microns was more biologically effective than the suspension concentrate with a median particle size of 15 microns. This pattern was effective against all the pathogens tested in this article. Among the fungicides tested in this article, this effect was most consistent with Imtrex and Balaya, but there were also examples of two other fungicides.

[0224] According to many possible embodiments in which the principles of the disclosed invention can be applied, it should be recognized that the illustrated embodiments are merely preferred examples of the present invention and should not be considered as limiting the scope of the present invention. On the contrary, the scope of the present invention is defined by the following claims. We therefore claim as our invention all that falls within the scope and spirit of these claims.

[0225] Appendix 1

[0226]

[0227]

[0228]

[0229]

[0230]

[0231]

[0232]

[0233]

[0234]

[0235]

[0236]

[0237]

[0238]

[0239] Appendix 2

[0240]

[0241]

[0242]

[0243]

[0244]

[0245]

[0246]

[0247]

[0248]

[0249]

[0250]

[0251]

[0252] Appendix 3

[0253]

[0254]

[0255]

[0256]

[0257]

[0258]

[0259]

[0260]

[0261]

[0262]

[0263]

Claims

1. A preparation, the preparation comprising: an aqueous suspension of a first active compound having the following structure a dispersant; a freezing point inhibitor; and a buffer or a partially neutralized base such that the pH of the preparation is from about 6 to 11; wherein as measured by light scattering, the particles of the first active compound have a volume weighted median particle size greater than 0.01 to 20 microns.

2. The preparation according to claim 1, wherein the preparation comprises from 0.5 wt% to about 60 wt% of the first active compound.

3. The preparation according to claim 1 or claim 2, wherein the preparation comprises from 15 wt% to 40 wt% of the first active compound.

4. The preparation according to claim 1 or claim 2, wherein the preparation comprises less than 15 wt% of the first active compound, and the preparation further comprises an inert filler such that the total amount of suspended material in the preparation is at least 10 wt%.

5. The preparation according to any one of claims 1 to 4, wherein the preparation comprises from 0.1 wt% to 15 wt% of the dispersant.

6. The preparation according to any one of claims 1 to 5, wherein the preparation comprises from 1 wt% to 10 wt% of the dispersant.

7. The preparation according to any one of claims 1 to 6, wherein the dispersant has a molecular weight of from 400 daltons to 2,000,000 daltons.

8. The preparation according to any one of claims 1 to 7, wherein the dispersant has a molecular weight of from 1,000 daltons to 100,000 daltons.

9. The preparation according to any one of claims 1 to 8, wherein the dispersant is an anionic dispersant, a cationic dispersant, a non-ionic dispersant or a combination thereof.

10. The preparation according to claim 9, wherein the dispersant is an anionic dispersant.

11. The preparation according to claim 9, wherein the dispersant is a non-ionic dispersant.

12. The preparation according to any one of claims 1 to 9, wherein the dispersant is selected from homopolymer dispersants, random or statistical copolymers, block copolymers or combinations thereof.

13. The preparation according to any one of claims 1 to 9, wherein the dispersant is selected from polyacrylic acid, polyvinyl alcohol, polyvinylpyrrolidone, polystyrene sulfonate, polyethylene sulfonate, polyethyleneimine, polyethylene glycol / polyisobutylene succinic acid, vinylpyrrolidone / vinylcaprolactam, polyethylene oxide / polypropylene oxide, fatty acid / polyethylene oxide, polyethoxylated alcohol, polyethoxylated diamine, naphthalene sulfonate formaldehyde condensate, lignin sulfonate, ethoxylated lignin sulfonate or combinations thereof.

14. The preparation according to any one of claims 1 to 13, wherein the preparation comprises greater than 0 wt% to 25 wt% of the freezing point inhibitor.

15. The preparation according to any one of claims 1 to 14, wherein the preparation comprises from 5 wt% to 20 wt% of the freezing point inhibitor.

16. The preparation according to any one of claims 1 to 15, wherein the freezing point inhibitor is a diol, a sugar, a water-soluble salt or a combination thereof.

17. The preparation according to claim 16, wherein the sugar has a molecular weight of from 180 Daltons to 1,000 Daltons.

18. The preparation according to claim 16 or claim 17, wherein: the diol is ethylene glycol, propylene glycol, glycerol, dipropylene glycol, tripropylene glycol, or a combination thereof; the sugar is ribose, xylose, glucose, fructose, mannose, sucrose, maltose, isomaltose, trehalose, xylitol, mannitol, sorbitol, dextrose, galactose, lactose, maltodextrin, sucrose, or a combination thereof; the water-soluble salt is a fluoride, chloride, iodide, nitrate, sulfate, or phosphate of ammonium, lithium, sodium, potassium, magnesium, calcium, or aluminum; or a combination thereof.

19. The preparation according to claim 18, wherein the freezing point depressant is propylene glycol.

20. The preparation according to any one of claims 1 to 19, wherein the freezing point depressant is selected to lower the freezing point of the preparation to below 0 °C.

21. The preparation according to any one of claims 1 to 20, wherein the freezing point depressant is selected to lower the freezing point of the preparation to below -5 °C.

22. The preparation according to any one of claims 1 to 21, wherein the buffer or partially neutralized base provides a pH of 7 to 10.5 for the preparation.

23. The preparation according to any one of claims 1 to 22, wherein the buffer or partially neutralized base provides a pH of about 6 to about 8 for the preparation.

24. The preparation according to any one of claims 1 to 23, wherein the buffer and / or partially neutralized base is any buffer and / or base suitable for agricultural applications.

25. The preparation according to any one of claims 1 to 24, wherein the buffer is a phosphate, phthalate, CHES, phosphonate, sulfonate, or borate buffer, or a combination thereof.

26. The preparation according to claim 25, wherein the buffer is a phosphate buffer or a borate buffer.

27. The preparation according to any one of claims 1 to 26, wherein the volume-weighted median particle size of the first active compound is less than about 15 microns as measured by light scattering.

28. The preparation according to claim 27, wherein the volume-weighted median particle size of the first active compound is less than about 7 microns as measured by light scattering.

29. The preparation according to claim 27, wherein the volume-weighted median particle size of the first active compound is from greater than 0.01 microns to 10 microns as measured by light scattering.

30. The preparation according to claim 27, wherein the volume-weighted median particle size of the first active compound is from greater than 0.01 microns to 5 microns as measured by light scattering.

31. The preparation according to claim 27, wherein the volume-weighted median particle size of the first active compound is from greater than 0.01 microns to 2 microns as measured by light scattering.

32. The preparation according to claim 27, wherein the volume-weighted median particle size of the first active compound is about 1 micron or less as measured by light scattering.

33. The preparation according to claim 27, wherein the volume - weighted median particle size of the first active compound, as measured by light scattering, is about 1 micron.

34. The preparation according to claim 27, wherein the volume - weighted median particle size of the first active compound, as measured by light scattering, is less than about 1 micron.

35. The preparation according to any one of claims 1 to 34, wherein the preparation further comprises a viscosity modifier.

36. The preparation according to claim 35, wherein the viscosity modifier is selected from polysaccharides, chemically modified polysaccharides, and / or clays.

37. The preparation according to claim 36, wherein: the polysaccharide is xanthan gum, gellan gum, agar, guar gum, cellulose, or a combination thereof; the clay is kaolin, palygorskite, bentonite, hectorite; or a combination thereof.

38. The preparation according to any one of claims 35 to 37, wherein the viscosity modifier is present in an amount of 0.01 wt% to 15 wt%.

39. The preparation according to claim 38, wherein: the viscosity modifier is a polysaccharide or a chemically modified polysaccharide in an amount of 0.01 wt% to 0.5 wt%; or the viscosity modifier is a clay and is present in an amount of 0.1 wt% to 15 wt%.

40. The preparation according to any one of claims 1 to 39, wherein the preparation further comprises a biocide.

41. The preparation according to claim 40, wherein the biocide is selected from benzisothiazolin - 3 - one, benzoic acid, 2 - (2H - benzotriazol - 2 - yl) - 6 - dodecyl - 4 - methyl - phenol, 2 - bromo - 2 - nitro - 1,3 - propanediol, butylated hydroxyanisole, butylated hydroxytoluene, potassium benzoate, propyl gallate, propyl hydroxybenzoate, sodium nitrite, or a combination thereof.

42. The preparation according to any one of claims 1 to 41, wherein the preparation further comprises 0.1 wt% to 10 wt% of a surfactant.

43. The preparation according to claim 42, wherein the surfactant has a molecular weight of 150 daltons to less than 1,200 daltons.

44. The preparation according to claim 42 or claim 43, wherein the surfactant is an anionic surfactant, a cationic surfactant, a non - ionic surfactant, a quaternary ammonium salt surfactant, an amphoteric surfactant, or a combination thereof.

45. The preparation according to claim 44, wherein: the anionic surfactant is a citrate, carbonate, phosphate, phosphonate, sulfate, or sulfonate ester of an alcohol, an alcohol ethoxylate, a triphenylvinylphenol ethoxylate, a fatty acid, or a natural oil, or any combination thereof; the cationic surfactant is an ethoxylated amine of a natural oil, an alcohol, a fatty acid, or a combination thereof; or the non - ionic surfactant is a polyethoxylated and / or polypropoxylated product of an alcohol, a natural oil, or a combination thereof.

46. The preparation according to any one of claims 1 to 45, wherein the preparation further comprises an antifoaming agent.

47. The preparation according to claim 46, wherein the antifoaming agent is an emulsion of silicone oil.

48. The preparation according to claim 46 or claim 47, wherein the antifoaming agent is present in an amount of 0.01 wt% to 1 wt%.

49. The preparation according to any one of claims 1 to 48, the preparation further comprising an agroactive compound.

50. The preparation according to claim 49, wherein the agroactive compound is an acaricide, an antimicrobial agent, a fungicide, a herbicide, an insecticide, a molluscicide or a nematicide or a combination thereof.

51. The preparation according to claim 49, wherein the agroactive compound is a fungicide.

52. The preparation according to claim 51, wherein the agroactive compound is a fungicide selected from the group consisting of: benzimidazole fungicides, dicarboximide fungicides, phenylpyrrole fungicides, anilinopyrimidine fungicides, hydroxyaniline fungicides, formamide fungicides, phenylamide fungicides, phosphonate fungicides, cinnamic acid fungicides, OSBPI fungicides, triazoleformamide fungicides, Group 27 fungicides, carbamate fungicides, benzamide fungicides, demethylation-inhibiting fungicides, piperazine fungicides, pyrimidine fungicides, imidazole fungicides, triazole fungicides, morpholine fungicides, Group U6 fungicides, Group 50 fungicides, QoI methoxyacrylate fungicides, quinoline fungicides, inorganic fungicides, copper fungicides, sulfur fungicides, lime sulfur fungicides, ethylene bisdithiocarbamate (EBDC) fungicides, EBDC-like fungicides, aromatic hydrocarbon fungicides, chloronitrile fungicides, phthalimide fungicides, guanidine fungicides, Qil fungicides, polyoxin fungicides, Group 29 fungicides, thiazolidine fungicides or a combination thereof.

53. The preparation according to claim 51, wherein the agroactive compound is a fungicide selected from the following: benomyl, thiabendazole, thiophanate-methyl, iprodione, vinclozolin, fludioxonil, cyprodinil, pyrimethanil, fenhexamid, amisulbrom, boscalid, carboxin, fluxapyroxad, flutolanil, fluopyram, indoxacarb, isofetamid, oxycarboxin, pirifenox, pyraclostrobin, solatenol (benzovindiflupyr), metalaxyl-M, metalaxyl, oxadixyl, tribasic aluminum salts, phosphoric acid, dimethomorph, mandipropamid, fluopyram, azoxystrobin, cyazofamid, amisulbrom, cymoxanil, propamocarb, fluopicolide, zineb, chlorothalonil, captan, dodine, cyazofamid, polyoxin, fluazinam, fluopyram, or a combination thereof.

54. An agricultural composition, the agricultural composition comprising water and a preparation according to any one of claims 1 to 53.

55. The agricultural composition according to claim 54, wherein the composition comprises 0.01 wt% to 10 wt% of a preparation according to any one of claims 1 to 54.

56. The agricultural composition according to claim 54, wherein the preparation is a preparation according to any one of claims 1 to 55, and the agricultural composition further comprises an agroactive compound.

57. The agricultural composition according to claim 56, wherein the preparation according to any one of claims 1 to 51 is present in the agricultural composition in an amount sufficient to enhance the biological effect of the agroactive compound, such that the total amount of the agroactive compound in the agricultural composition applied to the crop or agricultural product is lower than the amount usually required and / or recommended to provide the same biological effect in a composition that does not comprise a compound according to any one of claims 1 to 51.

58. The agricultural composition according to claim 56 or claim 57, wherein the agroactive compound is a miticide, an antimicrobial agent, a fungicide, a herbicide, an insecticide, a molluscicide or a nematicide or a combination thereof.

59. The agricultural composition according to claim 58, wherein the agroactive compound is a fungicide.

60. The agricultural composition according to claim 58, wherein the agricultural active compound is a fungicide selected from the group consisting of: benzimidazole fungicides, dicarboximide fungicides, phenylpyrrole fungicides, anilinopyrimidine fungicides, hydroxyaniline fungicides, formamide fungicides, phenylamide fungicides, phosphonate fungicides, cinnamic acid fungicides, OSBPI fungicides, triazole carboxamide fungicides, Group 27 fungicides, carbamate fungicides, benzamide fungicides, demethylation inhibitor fungicides, piperazine fungicides, pyrimidine fungicides, imidazole fungicides, triazole fungicides, morpholine fungicides, Group U6 fungicides, Group 50 fungicides, QoI methoxyacrylate fungicides, quinoline fungicides, inorganic fungicides, copper fungicides, sulfur fungicides, lime sulfur fungicides, ethylene bisdithiocarbamate (EBDC) fungicides, EBDC-like fungicides, aromatic hydrocarbon fungicides, chloronitrile fungicides, phthalimide fungicides, guanidine fungicides, Qil fungicides, polyoxin fungicides, Group 29 fungicides, thiazolidine fungicides, or combinations thereof.

61. The agricultural composition according to claim 58, wherein the agricultural active compound is a fungicide selected from the group consisting of: benomyl, thiabendazole, thiophanate-methyl, iprodione, vinclozolin, fludioxonil, cyprodinil, pyrimethanil, fenhexamid, amisulbrom, boscalid, carboxin, fluxapyroxad, flutolanil, flutriafol, indoxacarb, isofetamid, oxycarboxin, pythiocarb, penflufen, solatenol (benzovindiflupyr), metalaxyl-M, metalaxyl, oxadixyl, tribasic aluminum salts, phosphoric acid, dimethomorph, mandipropamid, fluopyram, dimethomorph, azoxystrobin, cyazofamid, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, fenarimol, spiroxamine, cyflufenamid, metrafenone, picoxystrobin, oxpoconazole, imazalil, fluoxastrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, orysastrobin, quinoxyfen, Bordeaux, copper ammonium complex, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, calcium polysulfide, mancozeb, maneb, metiram, ferbam, thiram, ziram, dichloran (DCNA), chloroneb, quintozene, chlorothalonil, captan, dodine, cyazofamid, polyoxin, fluazinam, fluopicolide, or combinations thereof.

62. A method of using the agricultural composition according to any one of claims 54 to 61, the method comprising applying the agricultural composition to a plant, a part of a plant, a seed, soil in which a plant is growing or will grow, or soil in which a seed has been or will be sown.

63. A method for controlling or preventing fungal growth, the method comprising applying an agricultural composition as claimed in any one of claims 59 to 61 to a site where fungal growth has occurred or is at risk of occurring.

64. A method for controlling or preventing fungal growth, the method comprising: diluting a formulation as claimed in any one of claims 1 to 53 with water to form a diluted mixture; and applying the diluted mixture to a site where fungal growth has occurred or is at risk of occurring.

65. The method according to claim 64, wherein the formulation is a formulation as claimed in any one of claims 1 to 53, and diluting the formulation further comprises adding an agroactive compound.

66. The method according to claim 65, wherein adding the agroactive compound comprises adding an amount of the agroactive compound that is less than the amount of the agroactive compound recommended for use in the absence of a formulation as claimed in any one of claims 1 to 51.

67. The method according to claim 65 or claim 66, wherein the agroactive compound is a fungicide selected from the group consisting of: benzimidazole fungicides, dicarboximide fungicides, phenylpyrrole fungicides, anilinopyrimidine fungicides, hydroxyaniline fungicides, formamide fungicides, phenylamide fungicides, phosphonate fungicides, cinnamic acid fungicides, OSBPI fungicides, triazoleformamide fungicides, Group 27 fungicides, carbamate fungicides, benzamide fungicides, demethylation-inhibiting fungicides, piperazine fungicides, pyrimidine fungicides, imidazole fungicides, triazole fungicides, morpholine fungicides, Group U6 fungicides, Group 50 fungicides, QoI methoxyacrylate fungicides, quinoline fungicides, inorganic fungicides, copper fungicides, sulfur fungicides, lime sulfur fungicides, ethylene bisdithiocarbamate (EBDC) fungicides, EBDC-like fungicides, aromatic hydrocarbon fungicides, chloronitrile fungicides, phthalimide fungicides, guanidine fungicides, Qil fungicides, polyoxin fungicides, Group 29 fungicides, thiazolidine fungicides, or combinations thereof.

68. The method according to claim 65 or claim 66, wherein the agroactive compound is a fungicide selected from the group consisting of: benomyl, thiabendazole, thiophanate-methyl, iprodione, vinclozolin, fludioxonil, cyprodinil, pyrimethanil, fenhexamid, amisulbrom, boscalid, carboxin, fluxapyroxad, flutolanil, fluopyram, isopyrazam, metrafenone, oxycarboxin, penflufen, prothioconazole, pyraclostrobin, sedaxane, solatenol, metalaxyl-M, metalaxyl, oxadixyl, tribasic aluminum salts, phosphoric acid, dimethomorph, mandipropamid, flupyradifurone, thifluzamide, cymoxanil, propamocarb, fluopicolide, azoxystrobin, chlorothalonil, captan, dodine, cyazofamid, polyoxin, fluazinam, fluopyram, or a combination thereof.

69. Use of an agricultural composition according to any one of claims 54 to 61 for application to plants, parts of plants, seeds, soil in which plants are growing or are to be grown, or soil in which seeds have been or are to be sown.

70. Use of an agricultural composition according to any one of claims 54 to 61 for controlling or preventing fungal growth at sites where fungal growth is occurring or at risk of occurring.

71. The preparation according to claim 1, wherein the particles of the first active compound have a volume-weighted median particle size of less than about 15 microns as measured by light scattering.

72. The preparation according to claim 1, wherein the particles of the first active compound have a volume-weighted median particle size of less than about 7 microns as measured by light scattering.

73. The preparation according to claim 1, wherein the particles of the first active compound have a volume-weighted median particle size of about 1 micron or less as measured by light scattering.

74. The preparation according to claim 1, wherein the pH of the preparation is greater than about 7.

75. The preparation according to claim 1, wherein the pH of the preparation is greater than about 7.

4.

76. The preparation according to claim 1, wherein the pH of the preparation is greater than about 8.

77. A method for protecting crops from pests, the method comprising applying the preparation according to any one of claims 1 to 53 or the agricultural composition according to any one of claims 54 to 61 to a plant, a part of a plant, a seed, the soil in which the plant is growing or will grow, or the soil in which the seed has been or will be sown, or a combination thereof.

78. The method according to claim 77, the method further comprising applying a pesticide to the following parts: the plant, a part of the plant, a seed, the soil in which the plant is growing or will grow, or the soil in which the seed has been or will be sown, or a combination thereof.

79. The method according to claim 78, wherein the action of the pesticide is enhanced by the preparation or the agricultural composition.

80. The method according to claim 78, wherein the combination of the preparation or the agricultural composition and the pesticide has a synergistic effect.

81. The method according to any one of claims 77 to 80, wherein the preparation or the composition is applied to a part where fungal growth has occurred or is at risk of occurring.

82. The method according to any one of claims 78 to 81, wherein the pesticide comprises a fungicide.

83. The method according to claim 82, wherein the fungicide comprises Imtrex, Balaya, Amistar, Proline or a combination thereof.

84. The method according to claim 82, wherein the fungicide is used to treat tomato plants.

85. The method according to claim 82, wherein the fungicide is used to treat wheat.

86. The method according to claim 82, wherein the fungicide is used to treat soybean plants.

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