Stable allyl sulfide compositions

Abstract

The present invention provides stable and storage-stable agricultural compositions, particularly storage-stable aqueous microemulsion compositions, comprising one or more allyl sulfide compounds and at least one acid wherein the composition is acidic as measured by pH in an aqueous environment, the composition is characterized by a pH of less than 6.5, preferably between pH 3.7 + / -5% and about 6. The one or more allyl sulfide compounds are typically those extracted from natural sources.

Description

Background Art

[0001] Essential oils have been used as pesticides and repellents since ancient times. Garlic has been used as an animal and insect repellent for many years and has been extensively studied for its microbicidal, pesticidal, and fungicidal properties.

[0002] Garlic essential oil is a natural repellent against sucking and tillage insects, it has a dissuading effect on the feeding habits of insect infestations, and it blocks the action of natural pheromones, causing disorientation towards insects during their reproductive stage.

[0003] The success of garlic essential oil as an agricultural pesticide and the like has apparently been limited by the low storage stability of its active ingredients, particularly the allyl sulfide compounds, which may account for its relatively low reported efficacy. Technical Field

[0004] The present invention relates to the field of pesticide control and to stable, and in particular storage-stable, compositions and methods useful for controlling pests (including without limitation insects, arthropods, mites, lepidopteran larvae, thrips etc.) and fungi, especially in agricultural environments. BRIEF DESCRIPTION OF THE DRAWINGS

[0005] Figure 1 Schematic diagram of the mechanism leading to coalescence of oil-in-water emulsions.

[0006] Figure 2 is a graph of the pH stability of the test compositions.

[0007] Figure 3 is pH relative to accelerated aging.

[0008] Figure 4 is a photograph of a sample showing the color change as a function of pH.

[0009] Figure 5 Here is a photo of the color changes in the diluted composition. Summary of the Invention

[0010] The present invention provides stable and storage-stable agricultural compositions comprising one or more allyl sulfide compounds and at least one acid, wherein the composition is acidic as measured by pH in an aqueous environment, the composition being characterized by a pH of less than 6.5.

[0011] The one or more allyl sulfide compounds are typically those extracted from natural sources, such as garlic extracts, a notable example being garlic essential oil.

[0012] The present invention provides stable agricultural compositions comprising one or more organosulfur compounds (OSCs), the compositions comprising at least one acid, wherein the composition is acidic as measured by pH in an aqueous environment, the composition being characterized by a pH of between 3.7±5% and about 6 measured in an aqueous environment, provided that the pH remains less than 6.5 upon compounding and during storage.

[0013] The organosulfur compound is preferably one or more allyl sulfide compounds.The organosulfur compounds are typically those extracted from natural sources, such as garlic extract.

[0014] The present invention provides stable aqueous compositions comprising organosulfur compounds (OSCs), these compositions comprising at least one acid, wherein the composition is characterized by a pH of less than 6.5. In notable embodiments, the composition is an emulsion, microemulsion, or nanoemulsion.

[0015] The present invention provides stable agricultural compositions comprising diallyl disulfide, the compositions comprising at least one acid, wherein the composition is acidic as measured by pH in an aqueous environment, the composition being characterized by a pH of less than 6.5.

[0016] The present invention provides storage-stable agricultural compositions comprising diallyl disulfide, the compositions comprising at least one acid, wherein the composition is acidic, measured in an aqueous environment, between 3.7±5% and 6, provided that the pH is maintained below 6.5 upon compounding and during storage. The present invention provides storage-stable agricultural compositions comprising organosulfur compounds (OSC) and at least one acid, the organosulfur compounds including at least one allyl sulfide compound selected from the group of diallyl sulfide (DAS), diallyl disulfide (DAS2), and combinations thereof, wherein the composition comprises greater than or equal to 90%, preferably 95%, of undegraded organosulfur compounds (OSC) after storage under so-called "accelerated storage" conditions (such as, for example, storage at 54°C for 14 days or at 40°C for 80 days, or any comparable accelerated storage conditions) compared to the organosulfur compound (OSC) content after compounding (most typically measured immediately before storage).

[0017] The storage-stable agricultural composition containing an organosulfur compound (OSC) of the present invention is characterized in that it contains a garlic extract, and the organosulfur compound includes one or more of diallyl sulfide (DAS), diallyl disulfide (DAS2), diallyl trisulfide (DAS3) and diallyl tetrasulfide (DAS4).

[0018] The present invention provides a stable agricultural composition comprising an organosulfur compound (OSC) and at least one acid, the organosulfur compound including at least one of diallyl sulfide (DAS) and diallyl disulfide (DAS2), wherein the composition is more chemically stable to degradation processes than a similar water-based composition characterized by a pH ≥ 6.5. The term similar water-based composition refers to a composition having equivalent ingredients but lacking the acid or containing an acid in an amount insufficient to provide a pH below 6.5.

[0019] The present invention provides a storage-stable agricultural composition comprising an organosulfur compound (OSC) and at least one acid, the organosulfur compounds including at least one of diallyl sulfide (DAS) and diallyl disulfide (DAS2), wherein the composition comprises greater than or equal to 90%, preferably 95%, of undegraded organosulfur compound (OSC) after storage at 54°C for 14 days or at 40°C for 80 days, or any comparable accelerated storage condition, compared to the organosulfur compound (OSC) content after compounding (most typically measured immediately before storage).

[0020] The present invention particularly provides compositions wherein the pH (measured in an aqueous system) is below 6.5 and preferably between 3.7 ± 5% and about 6%, provided that the pH of the composition remains below 6.5 during storage. As detailed below, unless otherwise clear based on the context or if otherwise specifically defined, numbers prefixed with the term "about" in this disclosure will generally be understood to include ± 10% of their value. Thus, "about 6" will include values ​​greater than 6 but less than 6.5, even if it is slightly less than + 10% based on the context.

[0021] Extracts from Allium spp. (garlic essential extract or garlic essential oil) contain organosulfur compounds (OSCs) including methyl methanethiosulfinate, S-methyl 2-propylene-1-thiosulfinate, allicin and its derivatives, alliin and its derivatives, diallyl trisulfide, ajoene, S-allyl-L-cysteine, diallyl disulfide, S-ethylcysteine, N-acetylcysteine, S-allylmercaptocysteine, captopril, and S-allyl-mercapto-captopril. These compounds have the following structures.

[0022]

[0023]

[0024] In particular, extracts from Allium species, sometimes referred to as garlic essential oil, contain organosulfur compounds (OSCs) including diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), tetrasulfide, and sulfur dioxide (SDO).

[0025] It is worth mentioning that organosulfur compounds (OSC) derived from allicin and alliin are produced as a result of enzymatic processes after crushing, such as other thiosulfinates that have important fungicide and bactericide effects. This disclosure should not be considered as limiting the scope of useful organosulfur compounds (OSC) derived from allicin and alliin.

[0026] The present invention provides stable agricultural compositions comprising garlic extract, the compositions comprising at least one acid, wherein the composition is acidic as measured by pH in an aqueous environment, the composition being characterized by a pH of less than 6.5.

[0027] In general, inorganic acids are preferred in the preparation of the products of the present invention simply due to their ease of use. Some non-limiting examples using phosphoric acid are usefully described, but no inference should be drawn from this choice other than convenience.

[0028] The organosulfur compounds in the stable and storage-stable compositions of the present invention are most typically components of garlic essential oil, which is reported to be a natural repellent against sucking and tillage insects, has a dissuading effect on the feeding habits of insect pests, and blocks the action of natural pheromones, thereby causing disorientation to insects during their reproductive stages.

[0029] Garlic essential oil has several modes of action, including but not limited to,

[0030] A) Garlic extract is absorbed by the plant through the vascular system, which changes the plant's enzymatic system, leading to changes in perspiration and thus changes in the intracellular juices.

[0031] B) Increased masking of pheromones produced by insects, thereby disrupting the insect life cycle.

[0032] C) Its feeding habits change due to ingestion and exposure to garlic.

[0033] D) The presence of sulfur substances called xenopheromones that attack the insect's central nervous system.

[0034] The compositions of the present invention are suitable for application to a wide variety of crops such as eggplant, onion, pepper, pea, cucurbit, cabbage, cauliflower, broccoli, beans, lettuce, corn, watermelon, tobacco, tomato, citrus, peach, apple, pear and ornamental plants, as well as many other crops.

[0035] Some useful preventative control indicators include: sorghum brown bug, lygus bug, small cereal bug, fast bug, conchuela green: applied every 7-14 days. It causes disruption of feeding habits in both the nymph and adult stages.

[0036] Leaf miners: Apply every 8-12 days. In the nymph stage, it causes disturbances in feeding habits, and in the adult stage, it causes hyperexcitement and reproductive disorientation.

[0037] Whitefly, cotton midge or white midge: applied every 7-14 days, it causes disturbance of feeding habits in the nymph stage and repulsion and reproductive disorientation in the adult stage.

[0038] Chili borer or cotton boll weevil: Apply every 6-10 days. In the adult stage, it causes repulsion and reproductive disorientation.

[0039] Thrips, bean thrips, black thrips, thrips: applied every 8-12 days, in the adult stage, it causes disturbances in feeding habits, hyperexcitement and reproductive disorientation.

[0040] Thus, in some embodiments, the present invention provides storage-stable compositions for use in controlling pests (including insects, arthropods, mites, lepidopteran larvae, thrips, etc.), microorganisms, fungi, etc., comprising:

[0041] A carrier comprising water; a surfactant; an emulsifier, a wetting agent or the like; and an acid, and the composition is characterized by having a pH in the range of 1 to less than 6.5; and an allyl sulfide compound.

[0042] A storage-stable composition for use in controlling harmful organisms (including insects, arthropods, mites, lepidopteran larvae, thrips, etc.), microorganisms, fungi, etc., comprising:

[0043] A composition comprising a carrier of water, a surfactant, an emulsifier, a wetting agent or the like, and an acid, and characterized by having a pH in the range of 1 to less than 6.5; and at least one organic sulfur compound selected from the group consisting of:

[0044] Methyl methanethiosulfinate, S-methyl 2-propylene-1-thiosulfinate, allicin and / or its derivatives, alliin and / or its derivatives, diallyl trisulfide, ajoene, S-allyl-L-cysteine, diallyl disulfide, S-ethylcysteine, N-acetylcysteine, S-allylmercaptocysteine, captopril and S-allyl-mercaptopril, and combinations thereof, with the proviso that the composition contains at least one allyl sulfide compound.

[0045] The present invention provides a stable aqueous garlic extract composition comprising at least one acid, wherein the composition is characterized by a pH of less than 6.5. In notable embodiments, the composition is a storage-stable emulsion, microemulsion, or nanoemulsion.

[0046] In some embodiments, the present invention provides a garlic extract composition comprising at least one acid, wherein the composition is useful for pesticidal or repellent applications after dilution in an aqueous medium, the composition being characterized by a pH of less than 6.5 after dilution. In some embodiments, the composition is an emulsifiable concentrate, and the diluted composition comprises a stable emulsion, microemulsion, or nanoemulsion.

[0047] In one aspect, the present invention relates to storage-stable garlic extract oil compositions comprising at least diallyl disulfide, diallyl sulfide, and combinations thereof.

[0048] In at least one aspect, the present invention relates to aqueous compositions of garlic extract oil comprising at least diallyl disulfide, diallyl sulfide, and combinations thereof, characterized by their stability mediated by the acidic character of the aqueous compositions.

[0049] In some aspects, the present invention relates to stable aqueous emulsion compositions of garlic extract oil comprising at least diallyl disulfide, diallyl sulfide, and combinations thereof, characterized in that the compositions have stability mediated by the acidic nature of the aqueous compositions.

[0050] The term stability is understood to include chemical stability, typically measured by a relatively low rate of degradation of any active ingredient, as well as physical stability of the composition including, but not limited to, color and emulsion stability, among others.

[0051] The process of emulsion coalescence (complete breakdown, i.e. separation of the system into a bulk oil phase and an aqueous phase) is generally considered to consist of four different droplets:

[0052] Loss mechanism control: Brownian flocculation, creaming, sedimentation flocculation and disproportionation, which are schematically shown in Figure 1, which is reproduced from “Emulsion Stability and Testing” found at https: / / lubrizolcdmo.com / technical-briefs / emulsion-stability-and-testing.

[0053] The first three are the primary methods of destabilizing an emulsion, but all four processes can occur simultaneously and in any order.

[0054] The processes of creaming, flocculation, and coalescence are best demonstrated by taking an emulsion of limited stability and centrifuging it at low speeds or for varying lengths of time. For oils that are less dense than water (which will be assumed unless otherwise stated), an initial "rise" of the cream is observed. Then, as larger droplets rise and converge, they begin to appear at the top. Finally, the droplets coalesce to form a single oil layer at the top.

[0055] Creaming, which gets its name from the most well-known example of the demulsification process - the separation of milk into its separate fat (curds) and skim milk (whey) components. Creaming is not an actual breaking, but rather the separation of an emulsion into two

[0056] An emulsion in which one (the milk fat) is more concentrated in the dispersed phase than the other. Creaming is the primary process by which the dispersed phase separates from the emulsion and is typically a precursor to actual coalescence.

[0057] Table 2 lists the properties typically used to evaluate the quality of emulsion formulations. Ideally, all of these tests would be performed on the final formulation, but it is neither practical nor necessary to perform a full battery of tests on all preliminary formulations. Typically, initial formulations are screened for changes in pH and physical separation at elevated temperatures. Of note is the stability of these emulsion characteristics.

[0058]

[0059] Table 2

[0060] The aqueous emulsion composition embodiments of the present invention exhibit emulsion storage stability with respect to at least creaming and / or sedimentation, and preferably also flocculation and coalescence, after storage for both 14 days at 54°C and 80 days at 40°C, as well as other comparable accelerated storage conditions.

[0061] The aqueous emulsion composition embodiments of the present invention exhibit emulsion storage stability as measured by a reduced creaming rate such that no more than 30 mm of creaming and / or sedimentation is measured after storage for 14 days at 54° C. or 80 days at 40° C. Preferably, the aqueous emulsion composition exhibits a creaming rate of less than 20 mm, more preferably less than 15 mm, and most preferably less than 10 mm after storage for 14 days at 54° C. or 80 days at 40° C.

[0062] Generally speaking, a "creaming rate" of less than 1 mm / day is considered negligible.

[0063] In an aspect of the present invention, there is provided a stable aqueous composition comprising garlic extract and acid, wherein the composition comprises greater than or equal to 90%, preferably 95%, of undegraded organosulfur compounds (OSC) after storage at 54°C for 14 days or at 40°C for 80 days, compared to the organosulfur compound (OSC) content measured immediately after compounding or at the beginning of storage.

[0064] The stable aqueous composition comprising garlic extract has a pH below 6.5, and notably between 3.7 ± 5% and about 6. The composition is typically an emulsion, microemulsion (or the like), or emulsifiable or microemulsifiable concentrate, wherein the pH is measured in the aqueous product.

[0065] In the examples noted, the stabilized aqueous compositions containing garlic essential oil had a pH below 6, and excellent results were obtained with stabilized aqueous compositions containing garlic essential oil that were formulated to exhibit a pH of 5.5 upon compounding by judicious use of the acid content to adjust the pH. Mineral acids are sometimes preferred for reasons of convenience, ease of use, etc. Excellent results were noted using phosphoric acid, but no inference should be drawn that this choice is in any way essential, except for practical purposes.

[0066] In one aspect of the present invention, a stable aqueous emulsion composition is provided comprising garlic extract and an acid, wherein the color hue of the composition does not significantly change or darken after storage at 54°C for 14 days or at 40°C for 80 days, as measured by visual inspection, compared to the color hue immediately after compounding. The stable aqueous composition comprising garlic extract has a pH below 6.5, and notably between 3.7±5% and about 6. The composition is typically an emulsion, microemulsion (or the like), or emulsifiable or microemulsifiable concentrate, wherein the pH is measured in the aqueous product. For ease of measurement, the pH of the concentrate is often usefully measured after dilution in water.

[0067] While typical emulsion compositions of the present invention are generally microemulsions, the inventors contemplate that stable nanoemulsions comprising garlic extract and acid are within the scope of the present invention as conceived.

[0068] Chemical stability, measured by the rate of degradation of the component diallyl disulfide (DADS), has proven convenient.

[0069] No inference should be drawn from the selection of this stability-indicating component, and it should not be assumed that the present invention is in any way limited by the active component measured. However, as will be readily apparent, the present invention will clearly encompass methods of reducing the degradation rate of diallyl disulfide in an aqueous environment containing it by adjusting the pH of the aqueous environment to less than 6.5, and preferably equal to or less than 6.

[0070] In aspects of the present invention, there is provided a stable water-based composition comprising diallyl disulfide and an acid, wherein the composition of the present invention is more chemically stable to degradation processes than a similar water-based composition characterized by a pH ≥ 6.5.

[0071] In an aspect of the present invention, a storage-stable aqueous composition is provided comprising diallyl disulfide and an acid, wherein the composition comprises not less than 90% undegraded diallyl disulfide after storage at 54° C. for 14 days or at 40° C. for 80 days, compared to the diallyl disulfide content immediately after compounding or at the beginning of the storage period. The stable aqueous composition comprising diallyl disulfide has a pH below 6.5, and notably between 3.7±5% and about 6, but even more preferably below pH 6.

[0072] In an aspect of the present invention, a storage-stable aqueous composition is provided comprising diallyl disulfide and an acid, wherein the composition comprises not less than 95% undegraded diallyl disulfide after storage at 54° C. for 14 days or at 40° C. for 80 days, compared to the diallyl disulfide content immediately after compounding or immediately before storage. The stable aqueous composition comprising diallyl disulfide has a pH below 6.5, and notably between 3.7±5% and about 6, but even more preferably below pH 6.

[0073] In an aspect of the present invention, a stable aqueous emulsion composition is provided comprising diallyl disulfide and an acid, wherein the color hue of the composition does not significantly change or darken after storage at 54° C. for 14 days or at 40° C. for 80 days as measured by visual inspection compared to the color hue immediately after compounding. The stable aqueous composition comprising diallyl disulfide has a pH below 6.5, and notably between 3.7±5% and about 6, but even more preferably below pH 6.

[0074] Formulating chemically and physically stable compositions comprising garlic extract oil (Allium sativum extract) is very challenging. This is true both from the perspective of the stability of the active ingredient to chemical degradation as well as the physical stability of the composition.

[0075] The stability of these compositions was found to be mediated by the acidity of the composition, and in particular, the acidic pH of the aqueous composition can determine the degree of stability of the composition.

[0076] It is well understood that the choice of composition ingredients can affect the stability of any composition, however, all things being equal, the acidity of the garlic extract oil composition will determine the relative stability of otherwise equivalent compositions. The acidity of the compositions of the present invention is most usefully defined by the pH measured when the composition is in an aqueous system.

[0077] Most notably, emulsion compositions, and in particular water-based microemulsion compositions, have been found to benefit from the practice of the present invention, whereby the garlic extract oil emulsion compositions of the present invention have been found to be not only more chemically stable to degradation processes during storage, but also to have improved stability of the physical parameters of the emulsion (emulsion stability) compared to similar emulsion compositions characterized by a pH ≥ 6.5.

[0078] Typical emulsion stability tests are conducted to observe what happens when a product is diluted in water. In these tests, it is common to dilute the concentrated product to the final use concentration (field application rate) and test its physical parameters, including creaming and sedimentation. In addition, it has been observed that as the acidity of the composition (as measured by pH) increases, the color of the emulsion becomes unacceptably degraded during storage, with clear visible discoloration.

[0079] Furthermore, the inventors have established that acidic compositions characterized by a pH below 6.5, and notably a pH of about 6 and preferably below 6, and notably aqueous compositions are significantly more stable than more basic or alkaline compositions.

[0080] As defined later, unless otherwise clear based on the context or if specifically defined otherwise, all numbers (numerals) in this disclosure, and especially numbers prefixed with the term "about" or "approximately", will most generally be understood to include ±10% of their value. As an example, because the stable pH of the composition is defined herein as "less than" 6.5, it is clear that it is not intended to include values ​​of 6.5 and greater, and thus a ±10% range for an upper limit of "about 6" is inappropriate and will be clearly understood as such, while including values ​​above 6 but less than 6.5 (e.g., a pH of 6.4), while it is clear from this disclosure that a limit of 6 is clearly preferred, and a pH below 6 is even more preferred.

[0081] Thus, a possible rephrasing of the present stability-related pH of a stable aqueous composition can be a stable composition of garlic extract that exhibits an aqueous pH of less than or equal to about 6, provided that the pH of the composition in the aqueous medium is less than 6.5.

[0082] It will be understood that pH is a characteristic that has any meaning only in aqueous systems, however the present invention clearly encompasses non-aqueous formulations intended for incorporation into aqueous systems. These non-aqueous compositions may be water-dispersible solid particles or powders, or emulsifiable concentrates, etc.

[0083] Such incorporation of non-aqueous compositions into aqueous systems may involve simple dilution or dissolution of the non-aqueous composition in water, or emulsification, and the like. It appears that a potentially important stabilizing characteristic of such non-aqueous systems is "acidity," while it is recognized that measuring and providing a useful range of values ​​is more practical in terms of pH for those systems dispersed in water.

[0084] In all cases, the compositions of the invention are characterized by their pH measured when they are in an aqueous system.

[0085] It is convenient in experiments to evaluate stability using so-called accelerated stability storage conditions, such as a 14-day storage regime at a temperature of 54° C. These accelerated regimes generally predict the stability of the test sample over a longer period of time under milder conditions, such as storage under ambient conditions.

[0086] The agriculturally useful activity of garlic extracts, including their repellent qualities (eg for insects) or pesticidal qualities, is largely due to the high content of bioactive compounds found therein and in particular organosulfur compounds (OSCs).

[0087] Therefore, maintaining the amount of those OSCs by reducing their degradation rate will clearly have a positive impact on maintaining the efficacy of the composition, especially over an extended storage period.

[0088] Since agricultural compositions are most frequently applied by end users (e.g., farmers), the acidic agricultural garlic extract compositions according to the present invention will generally exhibit a higher level of efficacy in the field after a substantial storage period than a more basic or alkaline equivalent composition.

[0089] Without wishing to be bound by any theory, the inventors speculate that, in addition to any efficacy enhancement that may be related to the acidity of the composition, the fact that more of the active ingredient remains undegraded after the storage period will undoubtedly be reflected in a higher relative efficacy.

[0090] Since it was found that due to the increased stability of the compositions of the present invention there is a concomitant increase in efficacy as explained above, it is in principle possible to reduce the amount of active ingredient while maintaining the efficacy levels achieved in previous non-storage stable compositions of garlic extract.

[0091] While it is generally believed that unlikely and creative solutions to known problems with known causes are most surprising, in noteworthy cases such as here, it is the elucidation of the cause of the problem that is most surprising, after which the solution to the problem may appear trivial to a novice, which is far from the truth. If the root cause of the problem is unknown (or even if the problem exists at all), then the solution to the problem is surprising—a question that can only be raised in hindsight.

[0092] In some embodiments, the compositions of the present invention are formulated to exhibit increased storage stability by including components that will lower the pH of the composition in aqueous media. These components are typically acids. The inventors have no doubt that other ingredients that are not typically referred to as "acids" themselves that reduce the acidity of such compositions are useful and fully consider these compounds to be within the scope of the protection sought, providing sufficient guidance to those skilled in the art of compounding to suggest a range of stabilizing additives.

[0093] In some embodiments, the acid component of the composition may typically or usefully include, but is certainly not limited to, a mineral acid or an inorganic acid.

[0094] Other examples of acids can be organic acids, such as citric acid, acetic acid, alpha-hydroxy acids, beta-hydroxy acids, salicylic acid, lactic acid, glycolic acid, natural fruit acids, or combinations thereof. Generally, formulation considerations will dictate the choice of acid, as it is contemplated that while many garlic extract oil compositions are more readily formulated with mineral acids (e.g., phosphoric acid), some, such as completely oily or solid formulations, may be more readily prepared with organic components.

[0095] In addition, inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, sulfamic acid, phosphoric acid, and combinations thereof can be used to lower the pH of the composition and stabilize the composition. The inventors have noted the ease and / or speed with which a desired pH can be achieved using mineral acids, making them convenient for some compositions.

[0096] Mention is made of formic acid, acetic acid, oxalic acid, tartaric acid, phosphoric acid, phthalic acid, benzoic acid, boric acid, ethylenediaminetetraacetic acid, gluconic acid, glutamic acid, glutaric acid, lactic acid, malic acid, succinic acid, hydrochloric acid, sulfuric acid, acetic acid, citric acid, ascorbic acid, sorbic acid, propionic acid, butyric acid, oxalic acid, succinic acid, malic acid, tartaric acid, fumaric acid, aconitic acid, dipicolinic acid and mixtures thereof.

[0097] Given the disclosed compounding and testing methods and the most useful acidity ranges, any researcher will be able to readily select their most preferred embodiment that best suits a proposed formulation.

[0098] In some embodiments, the acid is phosphoric acid (orthophosphoric acid).

[0099] In some embodiments, the compositions of the present invention are emulsions or microemulsions.

[0100] In some embodiments, the compositions of the present invention are concentrates that form emulsions or microemulsions when combined with water, also referred to as emulsifiable or microemulsifiable concentrates. In some embodiments, the emulsion formed when combined with water is a microemulsion. Of course, nanoemulsions and nanoemulsifiable concentrates are expressly contemplated.

[0101] The compositions of the present invention will typically include non-biologically active ingredients or excipients, and / or auxiliary ingredients useful in compounding agricultural compositions. For emulsions or EC compositions, an emulsifier (e.g., ethoxylated vegetable oil) is typically included, which is usually accompanied by a surfactant. The surfactant (if present) can be, for example, an ethoxylated sorbitan ester, an ethoxylated oil or fatty acid, an ethoxylated fatty acid alcohol, an arylsulfosuccinate, an arylbenzenesulfonate, or an ethoxylated arylalkyl phosphate. However, the inventors emphasize that the present invention is independent of the choice of surfactant, which is well within the skill of those skilled in the art of formulating these agricultural compositions, provided that it does not adversely affect the acidity and, importantly, the stability of the composition. It must be noted (although it goes without saying) that emulsifiers and surfactants that destabilize the active ingredient, the organosulfur component, are generally not selected as ingredients.

[0102] However, the inventors can envision situations where the inclusion of one or more destabilizing non-biologically active components, excipients, compatibilizing or auxiliary components is necessary for formulation purposes, and therefore in these situations, the present invention should be understood to provide composition components that can ameliorate the deleterious effects of including these necessary but destabilizing components. In these aforementioned situations, it is the reduction in degradation rather than a specific target degradation rate that indicates increased stabilization.

[0103] In some embodiments, the present invention provides a combination comprising:

[0104] (1) a certain amount of garlic extract oil,

[0105] (2) Water, and

[0106] (3) A certain amount of acid.

[0107] In some typical embodiments, the present invention provides a composition comprising:

[0108] (1) a certain amount of garlic extract oil,

[0109] (2) Water,

[0110] (3) emulsifiers, and

[0111] (4) A certain amount of acid.

[0112] Therefore, in an embodiment of the present invention, the stable aqueous emulsion composition of the present invention may contain the following ingredients.

[0113] Garlic oil (garlic extract),

[0114] Emulsifier (e.g., ethoxylated castor oil),

[0115] Antifreeze (for example, propylene glycol)

[0116] Acid (e.g., phosphoric acid)

[0117] Defoamers (e.g., emulsions of siloxanes, polyorganosiloxanes, silicones, silica, etc.), and

[0118] water

[0119] In an exemplary embodiment, the acid is orthophosphoric acid and is conveniently introduced into the composition as phosphoric acid 85% to adjust the pH and may comprise 0.05% of the composition. Similarly, in certain instances, the composition is adjusted to a pH of 5.5 during manufacture.

[0120] As must be very clear, the acid component is a very important component of the composition of the present invention, while the ingredients in the composition other than the organosulfur compound are selected from a wide range of both inactive and biologically active components having their own acidity and / or alkalinity, and therefore, the precise amount of acid that the formulator uses to adjust the pH of the formulated composition is not as important as the pH achieved by adjusting the acid.

[0121] In an exemplary manufacturing method, a composition is compounded and the pH is adjusted by including an acid. In a specific embodiment, the pH is adjusted to about 5.5. While stability has been demonstrated over the entire pH range of about 6 and below, it is sometimes reported that pH values ​​may change during storage. For this and other reasons, the inventors have illustrated that a pH of 5.5 is a useful value for compositions at the time of their manufacture. Similarly, while compositions having a pH greater than 6 but less than 6.5 at the time of compounding are well within the values ​​contemplated by the inventors, it is useful to monitor the pH during storage to ensure that the pH does not reach 6.5 or greater.

[0122] It should be noted that pH measurements typically vary at least slightly between measurements and between instruments, and it is not uncommon to find that a particular sample can have a pH reading that is ±0.2 of the reading of the same sample using different devices, or between devices calibrated at different times by different technicians.

[0123] The compositions of the present invention encompass a wide range of formulation types, including concentrates, emulsions (including microemulsions, nanoemulsions, etc.), and diluted, ready-to-use compositions. Thus, the garlic essential oil content can be up to 25%, more typically up to 20%, often up to 15%, and in some cases up to 10% of the composition. Useful emulsifiable concentrates may contain 12.5% ​​± 10% garlic essential oil.

[0124] In the case of an aqueous microemulsion, the garlic oil extract (garlic essential oil) may be present in an amount of less than 5% of the composition and typically about 2% w / w, and in exemplary embodiments, about 1.8% w / w or 1.75% w / w (18 g / L) of the composition. In diluted embodiments, the composition may contain 1.8 g / L garlic essential oil (which translates to 0.18% by weight of the composition), although further dilution will obviously reduce this value.

[0125] When addressing chemical degradation processes, it is often noted that chemical degradation problems are more pronounced in dilute systems.

[0126] The exemplified components and detailed examples relate to dilution systems and no inference should be drawn from this choice of % content of garlic essential oil in the examples of the present compositions, except that the inventors used the most challenging dilution system which at the same time had concentrations well within levels that would be practical for its real-world application.

[0127] Garlic essential oil has a typical diallyl disulfide content of about 30%-45%, but has been reported to contain between 30% and 55%. It is preferred to use garlic essential oil having a diallyl disulfide concentration of about 35%-40%.

[0128] Generally speaking, those skilled in the art of agricultural compounding, e.g., formulation technicians, will be fully aware of other useful components of aqueous agricultural compositions and methods of producing them, and the compositions of the present invention are not limited by the identity or percentage content of these components, except that the pH of the compounded composition is less than 6.5 and preferably between 3.7±5% and about 6 (provided that the pH remains less than 6.5 during storage).

[0129] It should be readily apparent that compositions containing components which accelerate the chemical degradation of the active ingredient or which destabilize the physical form of the composition are highly unfavorable, however the inventors have noted that in extenuating circumstances where the inclusion of such ingredients is necessary for compounding reasons, the addition of acidifying components (particularly acids) can at least to some extent compensate for the deleterious effects of these unfavorable ingredients.

[0130] In some embodiments, the stabilized agricultural composition comprising an organosulfur compound (OSC) comprising at least one acid further comprises ingredients that improve its efficacy. One example of many such ingredients includes incorporating a penetration enhancer into the composition. These ingredients are well known to those skilled in the art of agricultural formulation and will be selected based on common compounding principles, including selecting such ingredients that will not adversely affect the biological activity of the composition (e.g., by accelerating the degradation of the organosulfur compound (OSC)).

[0131] In some embodiments, stable compositions comprising garlic extract oil (garlic extract) can realize advantages over compositions that also contain one or more additional agriculturally active ingredients. In certain embodiments, the additional active ingredients would adversely interact with the garlic extract oil without the stabilization provided by adjusting the pH of the composition. These multi-component compositions comprising garlic extract oil (garlic extract) are clearly within the scope of the present invention as contemplated by the inventors.

[0132] While the inventors have found that adding specific amounts of specific acids is particularly useful, the inventors do not wish to limit the invention by the amount or content of the acidic component, as long as a stabilized pH is achieved. Therefore, the inventors have exemplified phosphoric acid (orthophosphoric acid) as a stabilizing acid, and while no specific preference for this acid has been expressed, the amount of phosphoric acid is more fully optimized. The inventors' choice of acid was based on ease of use rather than preference for a more stabilizing species.

[0133] In some embodiments where the acidifying ingredient is an acid, the amount of acid in the composition is defined as that amount of acid that will ensure that the pH of the composition in an aqueous environment is less than 6.5, and preferably about equal to or less than 6.

[0134] While it is often useful to provide numerical ranges for the amounts of the ingredients of the present invention, in this case, limiting the stabilizing component by its percentage or weight content may exclude some acceptably stable compositions from being covered, which the inventors do not intend. However, some non-limiting examples are provided as guidance, but no inference should be drawn as to acceptable ranges for the selection of ingredients or their amounts.

[0135] Non-limiting examples

[0136] Example 1 Microemulsion composition of garlic extract oil (essential oil)

[0137]

[0138] Density is approximately 1.03

[0139] Seven batches of composition were prepared, and the pH of each batch was adjusted with more or less acid to achieve compositions showing a pH of 4, 5, 5.5, 6, 6.5, 7, and 8, respectively.

[0140] Example 2 Stability

[0141] 1. Chemical stability

[0142] Garlic extract microemulsions contain garlic extract. The main active ingredients are diallyl disulfide and diallyl sulfide. The results presented below demonstrate a strong correlation between the chemical stability of the active ingredients and the acidity level in the microemulsion system.

[0143] As presented in the following tables and figures, the active substance degrades with increasing pH, and degradation can begin immediately after production and continue during storage at 54°C. As a useful indicator of chemical stability, the amount of diallyl disulfide was measured immediately before and at the end of the storage period. As presented in the table and see Figure ( Figure 2 and Figure 3 ), diallyl disulfide degrades immediately after production and continues to degrade during storage at 54° C. as pH increases. As with all naturally derived multi-component compounds, the % content of one component (e.g., diallyl disulfide) in garlic extracts may vary, and therefore to compare the stability of different batches or lots, it is convenient to look at the % of diallyl disulfide that has not degraded after the storage period compared to the percentage content at the beginning of storage.

[0144] Table 3 - Diallyl disulfide content of compositions stored at 54°C

[0145]

[0146]

[0147]

[0148] 2. Physical stability of the composition

[0149] The stability of the composition can also be assessed by visual inspection.

[0150] Color Test

[0151] Specific observations were made after the compositions were stored at 54°C for 14 days. In stability samples, a color change was observed that varied with the pH of the product composition. There may be a direct correlation between color and the amount of degradants, providing a visual indicator of active ingredient degradation.

[0152] exist Figure 4 In the photographs, it is apparent that compositions with a pH of 7 and above are significantly darker than compositions with a pH of ≤ 6.

[0153] The lighter colored samples were a very pale yellow and the higher pH compositions turned to a dark brown color.

[0154] 3. Physical stability test-emulsion stability .

[0155] This emulsion stability test was conducted to evaluate what happens when the product is diluted in water at the concentration used for end-use application (field).

[0156] Product samples were diluted according to the field application rate and evaluated for "creaming" and settling.

[0157] From the results obtained from the emulsion stability tests conducted, it was observed that as the pH of the composition increased above 6, the emulsion quality deteriorated significantly after storage at 54°C for 14 days.

[0158] Incidentally, the color change seen in the concentrated composition above is also reflected in the diluted composition, although it is difficult to see in the black and white image, see Figure 5 .

Claims

1. A storage-stable agricultural organosulfur composition comprising one or more allyl sulfide compounds and at least one acid, wherein the composition is acidic as measured by pH in an aqueous environment, wherein the composition is characterized by a pH of less than 6.

5.

2. The composition according to claim 1, wherein The one or more allyl sulfide compounds is garlic extract.

3. The composition according to claim 1, wherein The composition is a water-based composition.

4. The composition according to claim 1, wherein The compositions are concentrates suitable for dilution with an aqueous medium before use.

5. The composition according to claim 1, wherein The composition is any, some or all of an aqueous emulsion, microemulsion, nanoemulsion and / or an emulsifiable concentrate that forms an aqueous emulsion, microemulsion or nanoemulsion upon dilution with an aqueous medium.

6. The storage-stable agricultural composition according to any one of claims 1 to 5, wherein The composition contains greater than or equal to 90% undegraded organosulfur compounds (OSC) after storage at 54°C for 14 days, compared to the organosulfur compound (OSC) content after compounding measured immediately before storage.

7. The storage-stable agricultural composition according to any one of claims 1 to 6, wherein The allyl sulfide compound is one or more garlic extracts, and the one or more garlic extracts contain at least one, some or all of diallyl sulfide (DAS), diallyl disulfide (DAS2), diallyl trisulfide (DAS3) and diallyl tetrasulfide (DAS4).

8. The storage-stable agricultural composition according to any one of claims 1 to 7, wherein The allyl sulfide compound includes diallyl disulfide.

9. The storage-stable agricultural composition according to any one of claims 1 to 8, wherein The composition contains greater than or equal to 90%, preferably 95%, of undegraded diallyl disulfide after storage under conditions selected from the group consisting of: a. 54°C for 14 days; and b. 40℃ for 80 days.

10. The storage-stable agricultural composition of any one of claims 1 to 9, comprising one or more garlic extracts, wherein the composition contains greater than or equal to 95% undegraded diallyl disulfide after storage under conditions selected from the group consisting of: a. 54°C for 14 days; and b. 40℃ for 80 days.

11. The storage-stable agricultural composition of any one of claims 1 to 9 comprising one or more garlic extracts, wherein the composition is an aqueous emulsion and the composition exhibits emulsion stability as measured by a creaming rate resulting from no more than 30 mm creaming and / or sedimentation, preferably less than 20 mm creaming and / or sedimentation after storage at 54°C for 14 days or at 40°C for 80 days.

12. The storage-stable agricultural composition of claim 1 , comprising an organosulfur compound (OSC) and at least one acid, wherein the organosulfur compound comprises at least one allyl sulfide compound selected from the group consisting of diallyl sulfide (DAS), diallyl disulfide (DAS2), and combinations thereof, wherein the composition comprises greater than or equal to 90%, preferably 95%, of undegraded organosulfur compound (OSC) after storage under conditions selected from the group consisting of: a. 54°C for 14 days; and b. 40℃ for 80 days.

13. The storage-stable agricultural composition comprising an organosulfur compound (OSC) according to any one of claims 1 to 12, characterized in that it comprises a garlic extract, and wherein the organosulfur compound comprises one or more of diallyl sulfide (DAS), diallyl disulfide (DAS2), diallyl trisulfide (DAS3) and diallyl tetrasulfide (DAS4).

14. The storage-stable agricultural composition of claim 13, comprising at least one of diallyl sulfide (DAS) and diallyl disulfide (DAS2), and at least one acid, wherein the composition comprises greater than or equal to 90%, preferably 95%, of undegraded organosulfur compounds (OSC) after storage at 54°C for 14 days or at 40°C for 80 days, compared to the organosulfur compound (OSC) content after compounding before storage.

15. The storage-stable agricultural composition of claim 1 , comprising diallyl disulfide, wherein the composition comprises greater than or equal to 95% undegraded diallyl disulfide after storage at 54° C. for 14 days or at 40° C. for 80 days, compared to the diallyl disulfide content after compounding prior to storage.

16. The storage-stable agricultural composition of claim 1 comprising diallyl disulfide, wherein the composition is an aqueous emulsion or microemulsion, wherein the storage stability is emulsion stability as measured by a creaming rate of no more than 30 mm creaming and / or sedimentation, preferably less than 20 mm creaming and / or sedimentation, after storage at 54°C for 14 days or at 40°C for 80 days.

17. The storage-stable agricultural organosulfur composition of claim 1, comprising: a. Garlic extract oil (garlic essential oil), b. Water, c. emulsifiers and / or surfactants, and d. Acid wherein the composition is characterized by a pH of less than 6.

5.

18. The storage-stable agricultural organosulfur composition of claim 17, when the composition is an aqueous emulsion composition, comprising: a. Garlic extract oil (Garlic essential oil, Allium species), b. an emulsifier and optionally a surfactant, c. Antifreeze, d. Defoaming agent e. Acid, and f. Water wherein the composition is characterized by a pH of less than 6.

5.

19. The storage-stable agricultural organosulfur composition of claim 17, wherein The composition is an aqueous emulsion composition comprising, a. 1.75% w / w garlic extract oil (Garlic essential oil, Allium species), b. 28% w / w ethoxylated castor oil, c.0.01% w / w active silicone emulsion (30%) d. 5% w / w propylene glycol e. Phosphoric acid 85%, and f. Water, make up to 100% wherein the amount of phosphoric acid is adjusted to adjust the pH of the composition to a pH of less than 6.5 upon compounding.

20. The storage-stable agricultural organosulfur composition according to any one of claims 17 to 19, wherein The % content of acid added to adjust the pH was about 0.05% w / w.

21. The storage-stable agricultural organosulfur composition according to any one of claims 17 to 19, wherein The % content w / w of garlic essential oil (Allium species) in the composition is selected from the group consisting of: a. Up to 25%; b. Up to 20%; c. Up to 15% d. Up to 10%; e.12.5％±10％； f.2％±10％； g. 1.8% ± 10%; and h.0.18％±10％， Based on the total weight of the composition.

22. The storage-stable agricultural organosulfur composition according to any one of claims 1 to 21, wherein The pH of the composition measured in an aqueous environment is between 3.7 ± 5% and about 6, provided that the pH remains less than 6.5 upon compounding and during storage.

23. The storage-stable agricultural organosulfur composition according to any one of claims 1 to 22, wherein The pH of the composition measured in an aqueous environment was adjusted to a pH of 5.5 during manufacture by adjusting the acid content.

24. A stable water-based composition comprising diallyl disulfide and an acid, wherein the composition is more chemically stable to degradation processes than a similar water-based composition characterized by a pH > 6.

5.

25. The storage-stable agricultural organosulfur composition of claim 1 for use in controlling pests including insects, arthropods, mites, lepidopteran larvae, thrips, microorganisms, and fungi, the agricultural organosulfur composition comprising: a. a carrier comprising water, b. surfactants, c. Emulsifier d. Wetting agents, and e. acid, The agricultural organosulfur composition is characterized by a pH between 1 and less than 6.5 as measured in an aqueous environment, and at least one organosulfur compound selected from the group consisting of methyl methanethiosulfinate, S-methyl 2-propylene-1-thiosulfinate, allicin, allicin derivatives, alliin, alliin derivatives, diallyl trisulfide, ajoene, S-allyl-L-cysteine, diallyl disulfide, diallyl sulfide, S-ethylcysteine, N-acetylcysteine, S-allylmercapto-cysteine, captopril and S-allyl-mercapto-captopril, and combinations thereof, with the proviso that the composition contains at least one allyl sulfide compound.

26. The storage-stable agricultural organosulfur composition of claim 1, for use selected from the group consisting of: a. As a natural repellent against sucking and tillage insects; b. Resulting in a dissuading effect on the feeding habits of insects that infest; and c. Hindering the action of natural pheromones, causing disorientation to insects during their reproductive stages; The agricultural organosulfur composition is characterized by a pH between 1 and less than 6.5 as measured in an aqueous environment, comprises at least one compound selected from diallyl disulfide, diallyl sulfide, and combinations thereof, wherein the composition comprises greater than or equal to 95% of undegraded organosulfur compounds after storage at 54°C for 14 days or at 40°C for 80 days, compared to the content of the same organosulfur compound after compounding prior to storage.

27. A storage-stable agricultural organosulfur composition comprising one or more allyl sulfide compounds and at least one acid, wherein the composition is acidic as measured by pH in an aqueous environment, wherein the composition is characterized by a pH of less than 6.5.

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