Synergistic effects between mixtures of isothiocyanates and commercial fungicides.

Abstract

The present invention relates to fungicidal mixtures of isothiocyanate derivatives and commercial fungicides, and to compositions containing such mixtures and methods for using such mixtures as fungicides.

Description

[Technical field]

[0001] The present invention relates to fungicidal mixtures of isothiocyanate derivatives and commercial fungicides, and to compositions containing such mixtures and methods for using such mixtures as fungicides. [Background technology]

[0002] The human population is increasing year by year and will reach about 8.6 billion by 2030. To maintain a high level of food production, farmers must use external treatments such as: 1) chemical pesticides, which are highly efficient and affordable, but show negative effects on the environment and human health; 2) biological pesticides, which have no harmful effects on the environment but have low efficiency (less than 60% compared to existing chemical pesticides) and high cost. This makes biological pesticides unavailable for many countries, which opens the possibility of developing and introducing new organic treatments to the market that are highly efficient, affordable, and environmentally friendly.

[0003] In the past decades, several biological approaches have been developed to control B. cinerea in the field, such as the application of Bacillus subtilis and Trichoderma harzanium, but these are not widely used in agriculture due to their low efficiency.

[0004] In Western agriculture, the commonly used biological preventive fungicides are copper and sulfur. These fungicides are expensive to apply because they need to be reapplied after each rainfall. Furthermore, high concentrations of these metals in soil have negative environmental effects.

[0005] As a result, it is very important to provide alternatives to these techniques that are more environmentally respectful as well as highly efficient preventive treatments against fungal pathogens.

[0006] Plant fungal pathogens are one of the threats in agriculture, causing significant food losses every year. The efficiency of fungal pathogens is due to their easy spread in nature, rapid attachment on the host surface and rapid development of germ tubes that facilitate their penetration in plants.

[0007] Plants, on the other hand, have developed several defense mechanisms against fungal pathogens, e.g. necrotrophic ones: a) prevention of pathogen penetration; b) elevated levels of reactive oxygen species; c) induction of defense hormones such as jasmonates, ethylene, salicylic acid and abscisic acid. Furthermore, some plants synthesize antifungal toxic compounds that prevent fungal development on the plant surface and halt disease formation. The identification of plant compounds with strong antifungal activity could lead to the development of novel biological fungicides that could potentially replace currently existing chemical treatments.

[0008] The Brassicales order consists of economically important plants that are widely distributed and used as a source of food. This plant group has been shown to possess a unique set of secondary metabolites - glucosinolates. In the past decades, glucosinolate derivatives have been shown to have anti-cancer, anti-inflammatory and insecticidal properties.

[0009] CAROLINE MUELLER: “Role of glucosinolates in plant invasiveness”, PHYTOCHEMISTRY REVIEWS, KLUWER ACADEMIC PUBLISHERS,DO,vol.8,no.1,28 October 2008(2008-10-28),pp.227-242, XP019686442,ISSN:1572-980X discloses that many plants have been deliberately or accidentally introduced into new habitats, where some of them now pose major ecological and economic threats to natural and agricultural ecosystems. The potential to become invasive may depend on the characteristics of the plant and on specific interactions with other organisms, including other plants, microorganisms, herbivores or pollinators, acting as symbionts or antagonists. Invasiveness further depends on the abiotic conditions in the habitat. Several species of the Brassicaceae family, well known for their glucosinolate-myrosinase defense system, are invasive species. Various factors that may explain why these species have been able to colonize new areas so successfully are reviewed here. Particular emphasis is placed on the role of glucosinolates and their hydrolysis products in the invasive potential. This particular defense system is specifically involved in plant-plant, plant-microbe and plant-insect interactions. Most of the research has been carried out on the mechanisms underlying the invasive success of Alliaria petiolata and Brassica spp., followed by Bunias orientalis and Lepidium draba. Some examples are also given for plants that are not necessarily considered invasive but that have been well studied for their ability to disrupt their biotic environment. For each species, a combination of different plant characteristics probably promoted the competitive ability and resulted in diverse invasive phenotypes.

[0010] WO 2018 / 204435 A1 (DOW AGROSCIENCES LLC [US]) November 8, 2018 (2018-11-08) discloses a fungicidal composition containing a fungicidally effective amount of the compound (S)-1,1-bis(4-fluorophenyl)propan-2-yl(3-acetoxy-4-methoxypicolinoyl)-L-alaninate of formula I and at least one fungicide selected from the group consisting of tebuconazole, prothioconazole, difenconazole, epoxiconazole, mefentrifluconazole, benzovindiflupyr, penthiopyrad, fluxapyroxad, bixafen, fluopyram, picoxystrobin, pyraclostrobin, azoxystrobin, mancozeb and chlorothalonil, providing synergistic control of selected fungi.

[0011] WO 2020 / 011750 A1 (UNIV LAUSANNE [CH]) relates to the field of biological fungicides with broad-spectrum antifungal activity derived from plant extracts from the order Brassicaceae or molecules revealing a similar chemical structure. In particular, the applicants have surprisingly provided a new use of combinations of sulfonyl- and sulfinyl-containing aliphatic glucosinolates, their by-products and synthetic analogues as effective antifungal compounds with a broad spectrum of activity.

[0012] Control of plant diseases caused by fungal plant pathogens is very important in achieving high yield efficiency. Plant disease damage to ornamental plants, vegetables, fields, grains and fruit crops can cause significant loss of productivity, thereby causing increased costs to consumers. In addition to being often very destructive, plant diseases can be difficult to control and can lead to resistance to commercially available fungicides. Combinations of fungicides are often used to promote disease control, broaden the spectrum of control, and delay the development of resistance. Furthermore, certain rare combinations of fungicides exhibit greater than additive (i.e., synergistic) effects that provide commercially important levels of plant disease control. It is recognized in the art that the merits of a particular fungicide combination will vary depending on factors such as the particular plant species and plant disease being treated, and whether the plant is treated before or after infection by a fungal plant pathogen.

[0013] Therefore, new advantageous combinations are needed to provide a variety of options to best meet specific plant disease control needs. Summary of the Invention

[0014] Brief description of the invention In the present invention, applicants have identified fungicidal mixtures of glucosinolate derivatives, i.e. isothiocyanates (ITCs), and commercial fungicides, and synergistic compositions containing such mixtures, as well as methods for using such mixtures as fungicides. Potent fungitoxic effects against a broad range of fungal pathogens have been observed. This combination of products can be used as a new type of biological fungicide. One object of the present invention is to (a) at least one component which is a mixture of 1-isothiocyanato-8(methylsulfonyl)-octane (8MSOOH) and 1-isothiocyanato-8-(methylsulfinyl)-octane (8MSOH); (b) at least one further synthetic fungicidal component selected from mancozeb, dodine, chlorothalonil, tebuconazole, captan, cyprodinil, fludioxonil, fluxpiroxad and pyrimethanil, phosphorous acid and its salts or mixtures thereof; and (b) providing a synergistic fungicidal composition comprising:

[0015] Another object of the present invention is to provide a method for controlling plant diseases caused by fungal plant pathogens which comprises applying to a plant or part thereof, or to a plant seed, a fungicidally effective amount of the synergistic fungicidal composition of the present invention.

[0016] A further object of the present invention is to (a) at least one component which is a mixture of 1-isothiocyanatomethylsulfinyl-octane (8MSOH) and 1-isothiocyanatomethylsulfonyl-octane (8MSOOH); (b) at least one further synthetic fungicidal component selected from mancozeb, dodine, chlorothalonil, tebuconazole, captan, cyprodinil, fludioxonil, fluxipyroxad and pyrimethanil, phosphorous acid and its salts or mixtures thereof in the prevention or treatment of fungal pathogens in plants; The present invention provides for the use of a synergistic composition comprising a combination of

[0017] Other objects and advantages of the present invention will become apparent to those skilled in the art from a consideration of the ensuing detailed description, which proceeds with reference to the following illustrative drawings and the appended claims. [Brief description of the drawings]

[0018] [Figure 1]Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (dodine, tebuconazole and chlorothalonil) alone and in combination against Penicillium digitatum, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data and the bold line represents the fit of the combo (fungicide + ITC) data. [Diagram 2] Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (pyrimethanil, chlorothalonil and tebuconazole) against Rhizoctonia solani, including the lowest combination index alone and in combination for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data and the bold line represents the fit of the combo (fungicide + ITC) data. [Diagram 3] Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) alone and in combination with synthetic fungicides (dodine, pyrimethanil and tebuconazole) against Alternaria radicina, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data and the bold line represents the fit of the combo (fungicide + ITC) data. [Figure 4]Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (tebuconazole and dodine) alone and in combination against Geotrichum candidum and Botrytis cinerea, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combo (fungicide + ITC) data. [Diagram 5] Results of in vitro fungitoxic activity (preventative) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (tebuconazole and chlorothalonil) alone and in combination against Geotrichum candidum and Rhizoctonia solani, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combination (fungicide + ITC) data. [Figure 6] Results of in vitro fungal toxicity activity (therapeutic) of ITC (8MSOH / 8MSOOH) alone and in combination with synthetic fungicides (fluxipyroxad, dodine and tebuconazole) against Lasiodiplodia pseudotheobromae, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data and the bold line represents the fit of the combo (fungicide + ITC) data. [Figure 7]Results of in vitro fungal toxicity activity (therapeutic) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (cyprodinil and fludioxonil) alone and in combination against Lasiodiplodia pseudotheobromae, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combo (fungicide + ITC) data. [Figure 8] Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (captan and tebuconazole) alone and in combination against Fusarium verticilloides, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combo (fungicide + ITC) data. [Figure 9] Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) alone and in combination with a synthetic fungicide (chlorothalonil) against Colletotrichum acutatum, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combo (fungicide + ITC) data. [Figure 10]Results of in vitro fungal toxicity activity (therapeutic) of ITC (8MSOH / 8MSOOH) alone and in combination with a synthetic fungicide (tebuconazole) against Penicillium commune, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combo (fungicide + ITC) data. [Figure 11] Results of in vitro fungitoxic activity (therapeutic) of ITC (8MSOH / 8MSOOH) and synthetic fungicides (mancozeb and dodine) alone and in combination against Plectosphaerella cucumerina, including the lowest combination index for synergy. The normal line represents the fit of the ITC data, the dotted line represents the fit of the fungicide data, and the bold line represents the fit of the combo (fungicide + ITC) data. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The publications and applications discussed herein are provided solely for their disclosure prior to the filing date of this application. Nothing herein should be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. Further, the materials, methods, and examples are illustrative only and not limiting.

[0020] In case of conflict, the present application, including definitions, will control.

[0021] 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 the subject matter herein belongs. As used herein, the following definitions are provided to facilitate the understanding of the present invention.

[0022] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains," or "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion and are used in the sense of including, i.e., permitting the presence of one or more features or components. For example, a composition, process, method that includes a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent in such composition, process, method.

[0023] Furthermore, unless clearly stated to the contrary, "or" refers to an inclusive "or" and not an exclusive "or." For example, condition A or B is satisfied by one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), or both A and B are true (or exist).

[0024] Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be open-ended regarding the number of instances (i.e., occurrences) of that element or component. Thus, "a" or "an" should be read to include one or at least one, and the singular form of an element or component also includes the plural, unless the number is clearly intended to be singular.

[0025] The presence in some instances of broadening words and phrases such as "one or more," "at least," "but not limited to," or other similar phrases should not be read to imply that a narrower case is intended or required in instances that may lack such broadening phrase.

[0026] "Fungi" are eukaryotic organisms that digest external food and absorb nutrients directly through the cell walls. Most fungi reproduce by spores and have a body (thallus) composed of microscopic tubular cells called hyphae. Fungi, like animals, are heterotrophs, obtaining their carbon and energy from other organisms. Some fungi obtain their nutrients from a living host (plant or animal) and are called biotrophs; others obtain their nutrients from dead plants or animals and are called saprotrophs (saprophytes). Some fungi infect a living host but kill the host cells to obtain their nutrients; these are called necrotrophs.

[0027] A "pathogenic fungus," also referred to herein as a "fungal pathogen," is a fungus that causes disease in plants, humans, or other organisms. Approximately 300 species of fungi are known to be pathogenic to humans. The study of fungal pathogenicity to humans is called "medical mycology." Fungi are eukaryotic, but many pathogenic fungi are microbial. The study of fungal and other organism pathogenicity to plants is called phytopathology.

[0028] There are thousands of plant pathogenic fungi that together account for 70% of all known plant diseases. Plant pathogenic fungi are parasites, but not all plant parasitic fungi are pathogens. Plant parasitic fungi obtain nutrients from a living plant host, but the plant host does not necessarily exhibit any symptoms. Plant pathogenic fungi are parasites and cause diseases that are characterized by symptoms.

[0029] "Fungicides" are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores (defined herein as mycotoxic). Fungicidal agents inhibit their growth. Fungi can cause severe damage in agriculture, resulting in significant losses in yield, quality and profits. Fungicides are used in both agriculture and medicine to combat fungal infections in animals or humans. Chemicals used to control non-fungal oomycetes are also called fungicides, because oomycetes use the same mechanism as fungi to infect plants. Fungicides can be either contact, translaminar or systemic. Contact fungicides are not taken up into plant tissue and only protect the plant on which the spray is deposited. Translaminar fungicides redistribute the fungicide from the upper sprayed leaf surface to the lower unsprayed surface. Systemic fungicides are taken up and redistributed through the xylem. Few fungicides translocate to all parts of the plant; some are systemic locally and some translocate upwards.

[0030] A "fungistatic agent" is an antifungal agent that inhibits the growth of fungi (without killing the fungi). The term fungistatic agent can be used both as a noun and an adjective. Fungistatic agents have applications in agriculture, the food industry, the paint industry and medicine.

[0031] "Plants" refers to all plants and plant populations, such as desirable and undesirable wild plants, cultivars and plant species (whether protected or not by plant species or plant breeder's rights). Cultivars and plant species may be plants obtained by conventional propagation and breeding methods, which may be assisted or supplemented by one or more biotechnological methods, such as doubling monads, protoplast fusion, random and directed mutagenesis, by the use of molecular or genetic markers or by biotechnological and genetic engineering methods. Plant parts refer to all above-ground and below-ground parts and organs of plants, such as shoots, leaves, buds and roots, thereby including, for example, leaves, needles, stems, branches, buds, fruiting bodies, fruits and seeds, as well as roots, corms and rhizomes. Grains and vegetative and reproductive propagation material, such as cuttings, corms, rhizomes, stolons and seeds, also belong to plant parts. As referred to in this disclosure and claims, "plants" include members of the kingdom Plantae, particularly seed plants (Spermatopsida) at all stages of their life cycle, including young plants (e.g., germinating seeds that develop into seedlings) and mature, reproductive stages (e.g., plants that produce flowers and seeds). Plant parts include gravitropic members that generally grow below the surface of the propagation medium (e.g., soil), such as roots, tubers, bulbs, and corms, and also members that grow above the propagation medium, such as leaves (including stems and leaves), flowers, fruits, and seeds.

[0032] As referred to herein, the term "seedling", used either alone or in combination with words, means a young plant that develops from the embryo of a seed or shoot of a vegetative propagation unit such as a tuber, corm or rhizome.

[0033] Phosphorous acid and its salts are not found in nature, but are closely related to common substances found throughout the environment. The active ingredients are directly toxic to the target fungi and also appear to increase the effectiveness of the plant's defense mechanisms.

[0034] Those skilled in the art will recognize that salts of chemical compounds are in equilibrium with their corresponding non-salt forms in the environment and under physiological conditions, and therefore salts share the biological utility of the non-salt forms. When the compounds forming the mixtures and compositions contain acidic or basic moieties, a wide variety of salts can be formed, which are useful in the mixtures and compositions for controlling plant diseases caused by fungal plant pathogens (i.e., agriculturally suitable). When the compound contains a basic moiety, such as an amine function, the salts include acid addition salts with inorganic or organic acids, such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid, or valeric acid. When the compound contains an acidic moiety, such as a carboxylic acid, or an alcohol, such as a phenol, the salts include those formed with organic or inorganic bases, such as pyridine, triethylamine, or ammonia, or amides, hydrides, hydroxides, or carbonates of sodium, potassium, lithium, calcium, magnesium, or barium.

[0035] The compositions of the invention are fungitoxic and / or fungistatic in plants and may be applied to plant cultivation in the field or for their in vitro implementation.

[0036] "Synergy" is generally accepted to occur when the combined effect of two or more drugs is greater than the sum of their individual effects. In other words, synergy is said to occur when the combined effect of two or more drugs is greater than would be expected based on the performance of the drugs when used alone.

[0037] An "isothiocyanate" is a chemical group -N=C=S, formed by replacing the oxygen in an isocyanate group with sulfur. Many natural isothiocyanates from plants are produced by the enzymatic conversion of metabolic products called glucosinolates. These natural isothiocyanates, such as allyl isothiocyanate, are also known as mustard oil. An artificial isothiocyanate, phenyl isothiocyanate, is used for amino acid sequencing in the Edman degradation. In the context of the present invention, the term isothiocyanate or ITC refers to a mixture of 1-isothiocyanatomethylsulfinyl-octane (8MSOH) and 1-isothiocyanatomethylsulfonyl-octane (8MSOOH).

[0038] One object of the present invention is to (a) at least one component which is a mixture of 1-isothiocyanatomethylsulfinyl-octane (8MSOH) and 1-isothiocyanatomethylsulfonyl-octane (8MSOOH); (b) at least one further synthetic fungicidal component selected from selected from mancozeb, dodine, chlorothalonil, tebuconazole, captan, cyprodinil, fludioxonil, fluxpiroxad and pyrimethanil, phosphorous acid and its salts or mixtures thereof; and (b) providing a synergistic fungicidal composition comprising:

[0039] Preferably, component (b) is selected from pyrimethanil, tebuconazole, chlorothalonil, dodine, cyprodinil, fluxapyroxad, captan, mancozeb and fludioxonil.

[0040] Even more preferably, component (b) is selected from tebuconazole, captan, cyprodinil and dodine.

[0041] According to an embodiment of the present invention, component (a) is present in a 1-isothiocyanatomethylsulfinyl-octane / 1-isothiocyanatomethylsulfonyl-octane ratio of 50-50 vol. / vol. Preferably, the ratio of 1-isothiocyanatomethylsulfinyl-octane / 1-isothiocyanatomethylsulfonyl-octane is 99 / 1 vol. / vol.

[0042] According to another embodiment, component (a), i.e. the mixture of 1-isothiocyanato-8-(methylsulfonyl)-octane (8MSOOH) and 1-isothiocyanato-8-(methylsulfinyl)-octane (8MSOH), represents 0.5-7% of the concentration of the combination of the two active compounds, preferably 1-4% of the concentration of the combination of the two active compounds, most preferably 1-2% of the concentration of the combination of the two active compounds.

[0043] According to an embodiment of the present invention, the synergistic fungicidal composition further comprises at least one further component selected from the group consisting of a surfactant, a solid diluent and / or a liquid diluent.

[0044] According to yet another embodiment, the weight ratio of component (a) to component (b) is from 1:5 to 3137:1.

[0045] In particular, the weight ratio of component (a) to pyrimethanil is from 6:1 to 980:1.

[0046] According to another embodiment, the weight ratio of component (a) to tebuconazole is from 2:1 to 2500:1.

[0047] According to a further embodiment, the weight ratio of component (a) to chlorothalonil is from 1:5 to 880:1.

[0048] According to another embodiment, the weight ratio of component (a) to dodine is from 1:1 to 103:1.

[0049] According to a further embodiment, the weight ratio of component (a) to mancozeb is from 1:1 to 10:1.

[0050] According to yet a further embodiment, the weight ratio of component (a) to captan is from 1:1 to 2:1.

[0051] According to yet another embodiment, the weight ratio of component (a) to cyprodinil is from 22:1 to 207:1.

[0052] According to a further embodiment, the weight ratio of component (a) to fludioxonil is from 398:1 to 3137:1.

[0053] According to yet another embodiment, the weight ratio of component (a) to fluxapyroxad is from 4:1 to 31:1.

[0054] Another object of the present invention is to provide a method for controlling plant diseases caused by fungal plant pathogens which comprises applying to a plant or a part thereof or to a plant seed a fungicidally effective amount of the synergistic fungicidal composition of the present invention as defined above.

[0055] Preferably, the fungal plant pathogen is selected from the group consisting of Fusarium spp., Geotrichum candidum, Botrytis cinerea, Rhizoctonia solani, Penicillium digitatum, Alternaria radicina, Fusarium verticilloides, Penicillium commune, Plectosphaerella cucumerina, Colletotrichum acutatum and Lasiodiplodia pseudotheobromae.

[0056] A further object of the present invention is to provide a method for the prevention or treatment of fungal pathogens in plants, comprising: (a) at least one component which is a mixture of 1-isothiocyanatomethylsulfinyl-octane (8MSOH) and 1-isothiocyanatomethylsulfonyl-octane (8MSOOH); (b) at least one further synthetic fungicidal component selected from mancozeb, dodine, chlorothalonil, tebuconazole, captan, cyprodinil, fludioxonil, fluxpiroxad and pyrimethanil, phosphorous acid and its salts or mixtures thereof; The present invention provides for the use of a synergistic composition comprising a combination of

[0057] According to an embodiment of the present invention, component (a) is present in a ratio of 1-isothiocyanatomethylsulfinyl-octane / 1-isothiocyanatomethylsulfonyl-octane of 50-50 vol. / vol. Preferably, the ratio of 1-isothiocyanatomethylsulfinyl-octane / 1-isothiocyanatomethylsulfonyl-octane is 99 / 1 vol. / vol.

[0058] According to another embodiment of the present invention, the synergistic composition further comprises at least one additional component selected from the group consisting of a surfactant, a solid diluent and / or a liquid diluent.

[0059] According to one embodiment, the weight ratio of component (a) to component (b) is from 1:5 to 3137:1.

[0060] In particular, the weight ratio of component (a) to pyrimethanil is from 6:1 to 980:1.

[0061] According to another embodiment, the weight ratio of component (a) to tebuconazole is from 2:1 to 2500:1.

[0062] According to a further embodiment, the weight ratio of component (a) to chlorothalonil is from 1:5 to 880:1.

[0063] According to another embodiment, the weight ratio of component (a) to dodine is from 1:1 to 103:1.

[0064] According to a further embodiment, the weight ratio of component (a) to mancozeb is from 1:1 to 10:1.

[0065] According to yet a further embodiment, the weight ratio of component (a) to captan is from 1:1 to 2:1.

[0066] According to yet another embodiment, the weight ratio of component (a) to cyprodinil is from 22:1 to 207:1.

[0067] According to a further embodiment, the weight ratio of component (a) to fludioxonil is from 398:1 to 3137:1.

[0068] According to yet another embodiment, the weight ratio of component (a) to fluxapyroxad is from 4:1 to 31:1.

[0069] Synergistic fungicidal compositions include those in which components (a) and (b) are present in fungicidally effective amounts and the weight ratio of component (a) to component (b) is from 1:5 to 3137:1. These compositions are particularly effective for controlling plant diseases caused by Fusarium spp., Geotrichum candidum, Botrytis cinerea, Rhizoctonia solani, Penicillium digitatum, Alternaria radicina, Fusarium verticilloides, Penicillium commune, Plectosphaerella cucumerina, Colletotrichum acutatum and Lasiodiplodia pseudotheobromae fungal plant pathogens.

[0070] The mixture of components of the present invention is generally used to provide the fungicidal active ingredient in a composition, i.e., formulation, with at least one additional ingredient selected from the group consisting of surfactants, solid and liquid diluents, formulating agents, excipients, which act as carriers. The formulation or composition ingredients are selected to match the physical properties of the active ingredient, the mode of application, and environmental factors such as soil type, moisture, and temperature.

[0071] According to one embodiment, components (a) and (b) and one or more other biologically active compounds or agents may be formulated separately and applied separately in an appropriate weight ratio, for example as a tank mix, or may be applied simultaneously; or (ii) components (a) and (b) and / or one or more other biologically active compounds or agents may be formulated together in a proper weight ratio.

[0072] Preferably, the carrier or diluent to be used in the present invention is phytologically acceptable.

[0073] As used herein, the term "phytologically acceptable" formulation refers to a composition, diluent, excipient and / or carrier generally applicable for use with any part of a plant during any part of its life cycle, including but not limited to seeds, seedlings, plant cells, plants or flowers. The formulations may be prepared according to procedures, methods and recipes standard in the agricultural arts. Following the teachings of the present invention, a person skilled in the agricultural and / or chemical arts can easily prepare the desired composition. Most generally, the fungicidal compositions of the present invention may be formulated to be stored and / or applied as such or as an aqueous or non-aqueous suspension or emulsion prepared from a concentrated formulation of the composition. The water-soluble, aqueous-suspendable or emulsifiable formulations may also be converted to or formulated as solids (e.g. wettable powders), which may then be diluted into the final formulation. In certain formulations, the synergistic fungicidal compositions of the present invention may also be provided in growth media, such as in vitro media for the growth of plants or other types of cells, in laboratory plant growth media, in soil, or for spraying on seeds, seedlings, roots, stems, stalks, leaves, flowers or whole plants.

[0074] These phytologically acceptable formulations are prepared in a known manner, for example by mixing the synergistic fungicidal composition of the invention with extenders which are liquid solvents, liquefied gases under pressure and / or solid carriers, optionally with the use of surfactants which are emulsifiers and / or dispersants and / or foam-forming agents. If the extender used is water, it is also possible to use, for example, organic solvents as auxiliary solvents. Essentially, suitable liquid solvents include aromatics, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic compounds, or chlorinated aliphatic hydrocarbons, such as chlorobenzene, chloroethylene or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, such as petroleum fractions, alcohols, such as butanol or glycols, and their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide and dimethylsulfoxide, or water. Liquefied gas extenders or carriers are to be understood as meaning liquids that are gaseous at ambient temperature and under atmospheric pressure, such as aerosol propellants, for example butane, propane, nitrogen and carbon dioxide. Suitable solid carriers are: for example ground natural minerals, such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as micronized silica, alumina and silicates. Suitable solid carriers for granules are: for example crushed and divided natural rocks, such as calcite, marble, pumice, sepiolite and dolomite, or else synthetic granules of inorganic and organic meal, and granules of organic substances, such as sawdust, coconut shells, corn cobs and tobacco stalks. Suitable emulsifiers and / or foam formers are: for example nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, such as alkylaryl polyglycol ethers, alkyl-sulfonates, alkyl sulfates, aryl sulfonates, or protein hydrolysates. Suitable dispersants are: for example lignin-sulfite waste liquor, methylcellulose, ethylcellulose and hydroxypropylmethylcellulose.

[0075] The synergistic fungicidal compositions according to the present invention may be used in various forms such as aerosol dispensers, capsule suspensions, cold fogging concentrates, dusts, emulsifiable concentrates, oil in water emulsions, water in oil emulsions, encapsulated granules, fine granules, seed treatment flowables, gases (under pressure), gas generators, granules, hot fogging concentrates, macrogranules, microgranules, oil dispersible powders, oil miscible flowables, oil miscible liquids, pastes, vegetable rodlets, dry seed treatment powders, pesticide coated seeds, liquids, soluble powders, seed treatment solutions, suspension concentrates (flowables), ultra-trace volume (ULV) liquids, ultra-trace volume (ULV) suspensions, water dispersible granules or tablets, water dispersible powders for slurry treatment, water soluble granules or tablets, water soluble powders for seed treatment and wettable powders. These compositions include compositions which are ready to be applied to the plants or seeds to be treated by suitable equipment, such as spraying or dusting equipment, but also concentrated commercially available compositions which must be diluted before application to the crop.

[0076] In a preferred embodiment of the present invention, the synergistic fungicidal composition can be specifically applied to fruits and vegetables in storage facilities by ultrasonic sprayers. Ultrasonic sprayers are devices that use ultrasonic sound waves to break water into very small droplets (<10um) and spray it into the air as a dense, cold mist (i.e., not resulting from boiling water). Examples of ultrasonic sprayers and systems are described in the following US patents: US 4,042,016; US 4,058,253; US 4,118,945; US 4,564,375; US 4,667,465; US 4,702,074; US 4,731,990; US 4,731,998; US 4,773,846; US 5,454,518; US 6,854,661. Typically, an ultrasonic atomizer includes: a generally cylindrical body having an axial bore with an outlet at the front of the body; a gas supply and a liquid supply connected to the bore; a front face having at least a portion of the front face having a curved convex surface, a flat central annular area surrounding the bore outlet; and a resonator on an opposite side spaced from the bore outlet end. Such devices are commonly used to control humidity levels in greenhouses, to deliver nutrients to plants in aeroponics, or to generate optimal humidity levels in greenhouses.

[0077] Applicants have demonstrated that this technology can be used to apply products, such as fungicides, used to extend the freshness of fruits and vegetables in storage facilities. This technology makes it possible to effectively treat fruits and vegetables that, due to their packaging, are inaccessible to treatments applied by spraying or other applications (i.e., they cannot be easily sprayed directly because they are stored, for example, in containers, or because spraying may damage the fruits and vegetables).

[0078] Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspoemulsions), etc., which can be optionally thickened into gels. Common types of aqueous liquid compositions are solutions, flowables, capsule suspensions, concentrated emulsions, microemulsions, and suspoemulsions. Common types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsions, dispersible concentrates, and oil dispersions.

[0079] Common types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings), etc., which may be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient may be (micro)encapsulated and further formed into a suspension or solid formulation; or the entire formulation of the active ingredient may be encapsulated (or overcoated). Encapsulation may control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsion and dry granule formulations. High strength compositions are used initially as intermediates for further formulation.

[0080] Sprayable formulations are generally expanded in a suitable medium before spraying. Such liquid and solid formulations are formulated to be easily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more commonly from about 10 to several hundred liters per hectare. Sprayable formulations can be tank-mixed with water or another suitable medium for foliar treatment by aerial or ground spraying or for application to the plant growth medium. Liquid and dry formulations can be metered directly into drip irrigation systems or into furrows during planting. Liquid and solid formulations can be applied onto the seeds of crops and other desired plants as seed treatments prior to planting to protect the growing roots and other subsurface plant parts and / or foliage through systemic uptake.

[0081] The formulations generally contain effective amounts of active ingredients, diluents and surfactants within the following approximate ranges known to those of skill in the art, which may be multiplied up to 100 weight percent:

[0082] The synergistic fungicidal compositions of the present invention exhibit several advantages; they demonstrate fungitoxic and / or fungistatic activity against environmental, plant, storage and medical fungal pathogens.

[0083] The synergistic fungicidal composition used in the present invention has been shown to extend the useful life of fruits, vegetables and cut flowers infected with fungal pathogens in storage facilities by at least one week. The compounds used (i.e., the mixture of ITCs) have been shown to be non-toxic to insects and humans. The composition of the present invention is easy to apply with specific effectiveness on ripening perishable foods and requires no additional installation costs. The synergistic fungicidal composition of the present invention is of interest to storage companies (i.e., reducing packaging costs), forestry, landscapers and farmers.

[0084] Therefore, the synergistic fungicidal composition of the present invention is used as a fungus toxic agent and / or a fungistatic agent in plants. The synergistic fungicidal composition of the present invention to be used as a fungicide has shown great effectiveness in treating various plants or plant families (hosts). In fact, the synergistic fungicidal composition of the present invention can be used in treating more than 1400 agriculturally important crops or plants, including orders such as Solanales, Rosales, Vitaliales, and Oryzales.

[0085] The synergistic fungicidal compositions of the present invention may be used on any part of the plant during any part of its life cycle including, but not limited to, the seed, the seedling, the plant cell, the plant or the flower.

[0086] According to the invention, all plants and plant parts can be treated.

[0087] Among the plants which may be protected by the synergistic fungicidal composition of the invention, mention may be made in particular of the main agricultural crops, such as corn, soybean, cotton, cruciferous oilseeds, such as Brassica napus (e.g. canola), Brassica rapa, B. juncea (e.g. mustard) and Brassica carinata, rice, wheat, sugar beet, sugar cane, oats, rye, barley, foxtail millet, triticale, flax, kudzu and various fruits and vegetables of various plant taxa, such as Rosaceae sp. (e.g. pip fruits such as apple and pear). fruit), as well as stone fruits such as apricots, cherries, almonds and peaches, and berries such as strawberries), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp. (e.g. banana trees and plantations), Rubiaceae sp. (e.g. coffee), Theaceae sp., Sterculiceae sp., Rutaceae sp. (e.g. lemon, orange and grapefruit); Solanaceae sp. (e.g. tomato, potato, pepper, eggplant), Liliaceae sp., Compositiae sp. (e.g. lettuce, artichoke and chicory including chicory root, endive or common chicory), Umbelliferae sp. (e.g. carrot, parsley, celery and celeriac), Cucurbitaceae sp.(e.g. cucumber, including pickling cucumber, squash, watermelon, gourd and melon), Alliaceae sp. (e.g. onion and leek), Cruciferae sp. (e.g. white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, bok choy, kohlrabi, radish, horseradish, watercress, Chinese cabbage), Leguminosae sp. (e.g. peanuts, peas and beans), beans (such as kidney beans and broad beans), Chenopodiaceae sp. (e.g. mangold, spinach beet, spinach, beetroot), Malvaceae (e.g. okra), Asparagaceae (e.g. asparagus); horticultural and forest crops; flowers, including ornamental plants and cut flowers; grasses, i.e. golf courses, turf, and genetically modified homologues of these crops.

[0088] For example, the synergistic fungicidal compositions of the present invention may be used to control common fungal diseases such as powdery mildew, rust, downy mildew and anthracnose in field crops, fruit trees and vegetables.

[0089] In addition, the synergistic fungicidal composition of the present invention can be used for the treatment of resistant diseases, mainly for the control of wheat powdery mildew, rice blast, rice koji disease, melon powdery mildew, tomato powdery mildew, apple rust, watermelon anthracnose and flower powdery mildew. Moreover, the synergistic fungicidal composition has very good control effect on cucumber downy mildew, grape downy mildew, scab, anthracnose and spotted defoliation.

[0090] In a particular embodiment of the invention the synergistic fungicidal compositions of the invention are used in the treatment or prevention of tree diseases caused by fungal pathogens, such as Panama disease of bananas, ash dieback.

[0091] Furthermore, the synergistic fungicidal compositions of the invention can be used directly in the field in plant culture and also in vitro, for example for practice in plant culture.

[0092] The composition of component (a) in combination with component (b) may be further mixed with one or more other biologically active compounds or agents, including insecticides, nematicides, fungicides, acaricides, herbicides, herbicide antidotes, growth regulators such as insect molting inhibitors and rooting stimulants, sterilizers, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or insect pathogenic bacteria, viruses or fungi, to form a multi-component pesticide that provides an even broader spectrum of agricultural protection. Thus, the present invention also relates to a composition comprising a fungicidally effective amount of the mixture of component (a) in combination with component (b) and a biologically effective amount of at least one additional biologically active compound or agent, and which may further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compound or agent may also be formulated separately in a composition that comprises at least one of a surfactant, a solid or liquid diluent. For the compositions of the present invention, one or more other biologically active compounds or agents may be formulated together with both components (a) and (b) to form a premix, or one or more other biologically active compounds or agents may be formulated separately from components (a) and (b) and the formulations combined together prior to application (e.g. in a spray tank), or alternatively applied sequentially.

[0093] Examples of such biologically active compounds or agents with which the compositions of component (a) may be formulated together with component (b) are insecticides such as abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, quinomethionate, chlorfenapyr, chlorfluazuron, chlorantraniliprole, 3-bromo-1-(3-chloro-2-pyridinyl) -N-[4-cyano-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1H-pyrazole-5-carboxamide, 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide, 3-chloro-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide, 3-chloro-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide (1-methylethyl)-N-[4-cyano-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1H-pyrazole-5-carboxamide, Chlorpyrifos, Chlorpyrifos-methyl, Chlorobenzilate, Chromafenozide, Clothianidin, Cyflumetofen, Cyfluthrin, Beta-cyfluthrin, Cyhalothrin, Gamma-cyhalothrin, Lambda-cyhalothrin, Cyhexatin, Cypermethrin, Cyromazine, Deltamethrin, Diafenthiuron, Diazinon, Dicofol, Dieldrin, Dienochlor, Diflubenzuron, Dimef Lutrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonofos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyaphos,Imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrins, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulprofos, nematicides, such as aldicarb, imicyaphos, oxamyl and fenamiphos; fungicides, such as streptomycin; acaricides, such as amitraz, quinomethionate, chlorobenzilate, cyenopyrafen, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents, including entomopathogenic bacteria, such as Bacillus thuringiensis (Bacillus aizawai, Bacillus thuringiensis subsp. kurstaki and encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungi; and baculoviruses, nuclear polyhedrosis viruses (NPVs), such as HzNPV,insect pathogenic viruses, including AfNPV; and granulosis viruses (GV), such as CpGV.

[0094] The mixtures and compositions of the present invention may be applied to plants that have been genetically transformed to express a protein toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxin). The effect of the exogenously applied fungicidal mixtures of the present invention may be synergistic with the toxic protein expressed.

[0095] General references for agricultural protectants (i.e. insecticides, fungicides, nematicides, acaricides, herbicides and biologicals) include The Pesticide Manual, 13th Edition, CDS Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, UK, 2003 and The BioPesticide Manual, 2nd Edition, LG Copping, Ed., British Crop Protection Council, Farnham, Surrey, UK, 2001.

[0096] For embodiments in which one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the mixture of components (a) and (b) is generally 1:100 to 3000:1. Of note are weight ratios of 1:30 to 300:1 (e.g., in the range of 1:1 to 30:1). It is clear that the inclusion of these additional components may expand the spectrum of diseases controlled beyond that controlled by the mixture of components (a) and (b).

[0097] The compositions of the present invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens, comprising applying an effective amount of the mixture of the present invention or a fungicidal composition comprising said mixture to the plant or its parts to be protected, or to the plant seeds or vegetative propagation units to be protected.

[0098] Plant disease control is usually accomplished by applying an effective amount of the mixture of the present invention, generally as a formulated composition, either pre- or post-infection to the parts of the plant to be protected, such as roots, stems, leaves, fruits, seeds, tubers or bulbs, or to the medium (soil or sand) in which the plant to be protected is growing. The mixture can also be applied to seeds to protect the seeds and seedlings that develop from the seeds. The mixture can also be applied through irrigation water to treat the plants.

[0099] The application rate of these mixtures and compositions of the present invention may be affected by many environmental factors and should be determined under actual use conditions. Leaves can usually be protected when treated with a rate of active ingredient of less than about 1 g / ha to about 5,000 g / ha. Seeds and seedlings can usually be protected when the seeds are treated with a rate of about 0.1 to about 10 g / kilogram of seed; vegetative propagation units (e.g., cuttings and tubers) can usually be protected when the propagation units are treated with a rate of about 0.1 to about 10 g / kilogram of propagation unit.

[0100] The mixtures and / or compositions of the present invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the classes of Basidiomycetes, Ascomycetes, Oomycetes and Imperfect Fungi. They are effective in controlling a broad spectrum of plant diseases and foliar pathogens of crops including: cereal crops such as wheat, barley, oats, rye, triticale, rice, corn, sorghum and foxtail millet; vine crops such as table and wine grapes; field crops such as rapeseed (canola), sunflower; sugar beet, sugarcane, soybean, peanut, tobacco, alfafa, clover, bush clover, trefoil and crowfoot. peas; pome fruits such as apples, pears, crabapples, loquats, mayhaws and quince; stone fruits such as peaches, cherries, plums, apricots, nectarines and almonds; citrus fruits such as lemons, limes, oranges, grapefruit, mandarins (tangerines) and kumquats; root and tuberous plants and crops (and their leaves) such as artichokes, red beets and sugar beets, carrots, cassava, peppers and other fruits. cabbage, ginseng, horseradish, parsnip, potato, radish, rutabaga, sweet potato, turnip and yams; bulb vegetables, such as garlic, leeks, onions and shallots; leafy vegetables, such as arugula (rocket), celery, celery, cress, endive (escarole), fennel, head and leaf lettuce, parsley, radicchio (red chicory), rhubarb, spinach and Swiss chard; Brassica (cole) leafy vegetables, such as bromelain, cucumber, onion, lettuce, radish, lettuce, cucumber, lettuce, radish, rhubarb, spinach and Swiss chard. Roccoli, broccoli rabe (rapini), Brussels sprouts, cabbage, bok choy, cauliflower, collards, kale, kohlrabi, mustard and leafy vegetables; legume vegetables (succulent or dried) such as lupins, beans (Phaseolus spp.) (including field beans, kidney beans, lima beans, white beans, pinto beans, green beans, snap beans, tepary beans and wax beans), beans (Vigna spp.)) (including adzuki bean, asparagus bean, cowpea, pigeon pea, yearling pea, cowpea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean and yardlong bean), fava beans, chickpeas (garbanzo beans), guar, jack beans, rab-rab beans, lentils and peas (Pisum spp.) (dwarf pea, edible-podded snow pea, pea, chick ... pea), English pea, field pea, garden pea, green pea, snow pea, snap pea, pigeon pea and soybean; fruiting vegetables such as eggplant, ground cherry (Physalis spp.), pepino and mustard (including paprika, chili pepper, cooking pepper, pimento, sweet pepper; tomatillo and tomato); cucurbit vegetables such as chayote (fruit), winter melon (winter melon), citron melon, cucumber, gherkin, edible gourd (including bottle gourd, cucuzza, loofah and Chinese okra), Momordica spp.(including bitter melon, bitter gourd, bitter melon and Chinese cucumber), muskmelon (including cantaloupe and pumpkin), summer and winter squash (including butternut squash, bottle gourd, hubbard squash, acorn squash, somen squash) and watermelon; berries, such as blackberries (bingle berries, boysenberries, dewberries, lowberries, berries), marionberries, olallieberries and youngberries, blueberries, cranberries, currants, elderberries, gooseberries, huckleberries, loganberries, raspberries and strawberries; nuts, such as almonds, beech nuts, Brazil nuts, butternuts, cashews, chestnuts, chinquapin, hazelnuts (hazelnuts), hickory nuts, macadamia nuts, pecans and walnuts; tropical fruits and other crops, such as bananas, plantains, mangoes, coconuts, papayas, guavas, avocados, lychees, agave, coffee, cocoa, sugar cane, oil palm, sesame, rubber and spices; fiber crops, such as cotton, flax and hemp fiber; turfgrasses (including warm and cool season turfgrasses), such as bentgrass, Kentucky bluegrass, St. Augustine grass, tall fescue and Bermuda grass.

[0101] These pathogens include: oomycetes, Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomiand Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and Downy Mildews such as Plasmopara viticola, Peronospora spp. (Peronospora tabacina and Peronospora parasitica). parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes including Alternaria blight, e.g. Alternaria solani and Alternaria brassicae, Guignardia blight, e.g. Guignardia bidwelli, Venturia blight, e.g. Venturia inaequalis, Septoria blight, e.g. Septoria nodorum and Septoria tritici, Powdery mildew, e.g. Erysiphe spp.(including Erysiphe graminis and Erysiphe polygoni), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botulism such as Botrytis cinerea, Monilinia fructicola, Sclerotinia disease such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola viticola, Helminthosporium diseases, e.g. Helminthosporium tritici repentis, Pyrenophora teres, Anthracnose, e.g. Glomerellaor Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare) and Gaeumannomyces graminis; Basidiomycetes, including Puccinia spp.Rust diseases caused by (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rhizoctonia spp. (such as Rhizoctonia solani and Rhizoctonia oryzae); Fusarium diseases, e.g. Fusarium roseum, Fusarium graminearum, graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; Rutstroemia floccosum (also known as Sclerontina homoeocarpa); and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae and other related species.

[0102] Mixtures of fungicides can provide significantly better disease protection than would be expected based on the activity of the individual components. This synergy has been described as "the cooperative action of two components of a mixture such that the overall effect is greater or longer lasting than the sum of the effects of the two (or more) taken independently" (see Tames, PML, Neth. J. Plant Pathology, (1964), 70, 73-80).

[0103] The synergistic fungal toxicity activity was then estimated using CompuSyn software (Chou et al. 2005; Chou 2006), which was used to determine the Combination Index (CI) for the fungicide combination and hence the presence of synergy (CI<1; values ​​of 0.1-0.3 are considered strong synergy and values ​​<0.1 are considered very strong synergy; Chou 2008).

[0104] Compositions are provided in accordance with the present invention that include ratios of component (a) and component (b) that are particularly useful for combating specific fungal diseases. These compositions are deemed to be particularly useful for controlling Fusarium spp., Geotrichum candidum, Botrytis cinerea, Rhizoctonia solani, Penicillium digitatum, Alternaria radicina, Fusarium verticilloides, Penicillium commune, Plectosphaerella cucumerina, Colletotrichum acutatum and Lasiodiplodia pseudotheobromae.

[0105] The doses of the synergistic fungicidal composition usually applied in the treatment according to the invention are generally and advantageously between 10 and 800 g / ha for application in foliar treatment, preferably between 50 and 300 g / ha. The doses of the fungicidal composition applied are generally and advantageously between 2 and 200 g / 100 kg of seed, preferably between 3 and 150 g / 100 kg of seed, in the case of seed treatment.

[0106] It is clearly understood that the doses indicated herein are given as illustrative examples of the treatment method according to the invention. A person skilled in the art will know how to adapt the application doses in particular according to the nature of the plants or crops to be treated.

[0107] Those skilled in the art will recognize that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications without departing from its spirit or essential characteristics. The invention also includes all of the steps, properties, compositions and compounds referred to or shown in this application, individually or collectively, and any and all combinations or any two or more of the above steps or properties. The present disclosure is therefore to be considered in all its embodiments as illustrative and not limiting, the scope of the invention being indicated by the appended claims, and all changes that come within the meaning and range of equivalence are intended to be embraced therein.

[0108] The foregoing description will be more fully understood with reference to the following examples. In the following examples, all percentages are by weight. Without further elaboration, it is believed that one skilled in the art can utilize the present invention to its fullest extent using the preceding description. The following examples are therefore to be construed as merely illustrative in any manner and not limiting of the present disclosure, whatever the case may be. Percentages are by weight unless otherwise indicated.

[0109] Example 1: Applicant tested the synergy between (i) a mixture of two isothiocyanate molecules (i.e., 1-isothiocyanatomethylsulfinyl-octane (8MSOH) and 1-isothiocyanatomethylsulfonyl-octane (8MSOOH), with a ratio of 8MSOH / 8MSOOH of 99 / 1 vol. / vol.; this mixture is referred to as "ITC") and (ii) a mixture of various commercial fungicides (referred to as "fungicides"; chlorothalonil, dodine, pyrimethanil, tebuconazole) that are widely used in agriculture. The mixture of (i) and (ii) is referred to as "Combo."

[0110] The Applicants selected five different fungal pathogens (see Table 1), which are responsible for important losses in agriculture and are genetically distant, i.e. from different orders and genera, to highlight the versatility of their approach, which consists of a synthetic fungicide mixed with a natural active ingredient (8MSOH / 8MSOOH). [Table 1]

[0111] All experiments were performed in the same way, with minor differences between therapeutic and preventive cases. In a 48-well plate, each well was filled with various concentrations of ITC, fungicide or a combination of both in a volume of 180 μL and topped with 180 μL of potato dextrose agar (PDA). Three wells were used per concentration for better precision. After solidification of the wells, either a 2x2 mm plug of grown fungus (therapeutic case) or 20 μL of spore solution (~1E5 spores / mL, preventive case) was placed in each well and the 48-well plate was sealed with parafilm. After 7 days of incubation at 20°C in a controlled growth chamber, fungal growth was measured and EC50 was calculated by 4-parameter logistic regression in XLSTAT.

[0112] Afterwards, the concentration of fungicide at which there was no fungal growth (i.e. below EC50) was determined. Applicants repeated the 48-well experiment by filling wells with a mixture of ITC and fungicide; the fungicide concentration was kept constant at the determined concentration mentioned above, and the ITC concentration was varied. As before, fungal growth was measured after 7 days of incubation. To calculate the synergistic properties of the combo ITC + fungicide, the combination index (CI) described by Chou (2006) was calculated using CompuSyn software.

[0113] Conclusion: The results clearly demonstrated the synergistic effect between ITC (8MSOH / 8MSOOH) and synthetic fungicides when used in combination. Strong synergy is indicated by the combination index lower than 0.170 (Table 2 and Figures 1-5). [Table 2] TIFF2024523948000003.tif145159

[0114] [Table 3]

[0115] The minimum and maximum weight ratios for each combination ITC:fungicide were calculated as follows: The minimum concentration of ITC was chosen as the EC50 of the combo (ITC+fungicide) and the maximum concentration was chosen as the maximum concentration of ITC tested. Only the ITC concentration was varied while the fungicide concentration was kept fixed for a given fungus. These molar concentrations were multiplied by the molecular weight of the compound to obtain the mass concentration. Finally, the weight ratio ITC:fungicide was obtained by dividing the mass concentration of ITC by the mass concentration of fungicide for both the minimum and maximum ITC concentrations. [Table 4]

[0116] The minimum and maximum concentration ratios for ITC:fungicide for each combination were calculated as follows: The minimum concentration of ITC was chosen as the EC50 of the combo (ITC + fungicide) and the maximum concentration was chosen as the maximum concentration of ITC tested. Only the ITC concentration was varied while the fungicide concentration was kept fixed for a given fungus. The concentration ratio ITC:fungicide was obtained by dividing the molar concentration of ITC by the molar concentration of fungicide for both the minimum and maximum ITC concentrations. [Table 5]

[0117] Example 2: Applicants tested the synergy between (i) a mixture of two isothiocyanate molecules (i.e., 1-isothiocyanatomethylsulfinyl-octane (8MSOH) and 1-isothiocyanatomethylsulfonyl-octane (8MSOOH) in a 99 / 1 vol. / vol ratio of 8MSOH / 8MSOOH; this mixture is referred to as "ITC") and (ii) a variety of commercially available fungicides (referred to herein as "fungicides"; captan, cyprodinil, fludioxonil, fluxapyroxad, chlorothalonil, dodine, tebuconazole, mancozeb) that are widely used in agriculture. The mixture of (i) and (ii) was referred to as "Combo."

[0118] The Applicants selected five different fungal pathogens involved in important losses in agriculture and genetically distant, i.e. from different orders and genera, to highlight the versatility of their approach, which consists of a synthetic fungicide mixed with a natural active ingredient (8MSOH / 8MSOOH) (see Table 1). [Table 6]

[0119] All experiments were performed identically. In a 48-well plate, each well was filled with various concentrations of ITC, fungicide or a combination of both in a volume of 180 μL and topped with 180 μL of potato dextrose agar (PDA). Two or three wells were used per concentration for better precision. After solidification of the wells, a 2x2 mm plug of grown fungus was placed in each well and the 48-well plate was sealed with parafilm. After 7 days of incubation at room temperature, fungal growth was measured and EC50 was calculated by 4-parameter logistic regression in XLSTAT.

[0120] Afterwards, the concentration of fungicide at which there was no fungal growth (i.e. below EC50) was determined. Applicants repeated the 48-well experiment by filling wells with a mixture of ITC and fungicide; the fungicide concentration was kept constant at the determined concentration mentioned above, and the ITC concentration was varied. As before, fungal growth was measured after 7 days of incubation. To calculate the synergistic properties of the combo ITC + fungicide, the combination index (CI) described by Chou (2006) was calculated using CompuSyn software.

[0121] Conclusion: The results clearly demonstrated the synergistic effect between ITC (8MSOH / 8MSOOH) and synthetic fungicides when used in combination. Strong synergy is indicated by the combination index lower than 0.170 (Table 7 and Figures 6-11). [Table 7] Table 7: Fungal pathogens tested in the treatments, EC50 of ITCs (8MSOH / 8MSOOH) and synthetic fungicides alone and in combination, fixed synthetic fungicide concentrations used in combination, concentration range of ITCs used in combination and synergistic effect (minimum combination index; CI).

[0122] [Table 8]

[0123] The minimum and maximum weight ratios for each combination ITC:fungicide were calculated as follows: The minimum concentration of ITC was chosen as the EC50 of the combo (ITC+fungicide) and the maximum concentration was chosen as the maximum concentration of ITC tested. Only the ITC concentration was varied while the fungicide concentration was kept fixed for a given fungus. These molar concentrations were multiplied by the molecular weight of the compound to obtain the mass concentration. Finally, the weight ratio ITC:fungicide was obtained by dividing the mass concentration of ITC by the mass concentration of fungicide for both the minimum and maximum ITC concentrations. [Table 9]

[0124] The minimum and maximum concentration ratios for ITC:fungicide for each combination were calculated as follows: The minimum concentration of ITC was chosen as the EC50 of the combo (ITC + fungicide) and the maximum concentration was chosen as the maximum concentration of ITC tested. Only the ITC concentration was varied while the fungicide concentration was kept fixed for a given fungus. The concentration ratio ITC:fungicide was obtained by dividing the molar concentration of ITC by the molar concentration of fungicide for both the minimum and maximum ITC concentrations. [Table 10]

[0125] References Chou,T.C.,Martin,N.,2005.CompuSyn for drug combinations:PC software and user’s guide:A Computer Program for quantitation of synergism and antagonism in drug combinations,and the determination of IC50 and ED50 and LD50 values.ComboSyn Inc,Paramus,NJ.. Chou,T.C.,2006.Theoretical basis,experimental design,and computerized simulation of synergism and antagonism in drug combination studies.Pharmacol Rev.58,621-81. Chou,T.C.,2008.Preclinical versus clinical drug combination studies.Leuk Lymph.49,2059-2080.

Claims

1. (a)At least one constituent which is a mixture of 1-isothiocyanato-8-(methylsulfonyl)-octane (8MSOOH) and 1-isothiocyanato-8-(methylsulfinyl)-octane (8MSOH); (b)At least one further synthetic fungicidal constituent selected from mancozeb, dodine, chlorothalonil, tebuconazole, captan, cyprodinil, fluazinam, fluxapyroxad and pyrimethanil, its salts or mixtures thereof, A synergistic fungicidal composition comprising the same.

2. The synergistic fungicidal composition according to claim 1, wherein constituent (b) is selected from mancozeb, dodine, chlorothalonil, tebuconazole, captan, cyprodinil, fluazinam, fluxapyroxad and pyrimethanil.

3. The synergistic fungicidal composition according to claim 2, wherein constituent (b) is selected from tebuconazole, captan, cyprodinil and dodine.

4. The synergistic fungicidal composition according to claim 1, wherein constituent (a) is present in a 99 / 1 vol. / vol ratio of 1-isothiocyanatomethylsulfinyl-octane / 1-isothiocyanatomethylsulfonyl-octane.

5. The synergistic fungicidal composition according to claim 1, further comprising at least one further constituent selected from the group consisting of surfactants, solid diluents and / or liquid diluents.

6. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to constituent (b) is from 1:5 to 3137:

1.

7. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to pyrimethanil is from 6:1 to 980:

1.

8. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to tebuconazole is from 2:1 to 2500:

1.

9. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to dodine is from 1:1 to 103:

1.

10. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to mancozeb is from 1:1 to 10:

1.

11. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to captan is from 1:1 to 2:

1.

12. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of constituent (a) to cyprodinil is from 22:1 to 207:

1.

13. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of component (a) to fluoxydinyl is from 398:1 to 3137:

1.

14. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of component (a) to fluxapyroxad is from 4:1 to 31:

1.

15. The synergistic fungicidal composition according to claim 1, wherein the weight ratio of component (a) to chlorothalonil is from 1:5 to 880:

1.

16. A method for controlling a plant disease caused by a fungal plant pathogen, comprising applying a fungicidally effective amount of the synergistic fungicidal composition according to claim 1 to a plant or a part thereof, or to a plant seed.

17. The method according to claim 16, wherein the fungal plant pathogen is selected from the group consisting of Fusarium spp., Geotrichum candidum, Botrytis cinerea, Rhizoctonia solani, Penicillium digitatum, Alternaria radicina, Fusarium verticillioides, Penicillium commune, Plectosphaerella cucumerina, Colletotrichum acutatum, and Lasiodiplodia pseudotheobromae.

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