Pest management

Abstract

The present invention relates to a method of controlling pests, the method comprising exposing the pests to a pest-controlling amount of a triketone compound in combination with at least one second insecticide. Formulations and kits comprising the combination are also described.

Description

Invention Field

[0001] This invention relates to a method for controlling pests, comprising exposing the pests to a combination of a pest-controlling amount of a triketone compound and at least one second insecticide. Formulations and kits comprising this combination are also described. Background of the Invention

[0003] Synthetic insecticides and arachnids, with different modes of action, have been used for decades to control insect and arachnid pests, respectively. Numerous problems exist associated with synthetic insecticides and arachnids, including toxicity to other beneficial insects, arachnids, and animals or humans; non-biodegradability; environmental persistence; waterway pollution; and the development of resistance in target pest populations.

[0004] Resistance within target pest populations and toxicity to other populations or the environment have led to many pesticides being used little or not at all. This has reduced the number of pesticides available for controlling pests such as insects and arachnids.

[0005] There is a continued need for new and alternative pest management methods that address at least some of the problems mentioned above and provide users with additional pest management options.

[0006] Pest management systems may include combinations of insecticides or arachnids, particularly combinations of insecticides or arachnids with different modes of action. Such combinations may allow the use of reduced amounts of one or more insecticides or arachnids, providing effective pest control while reducing at least some of the aforementioned problems.

[0007] WO 2002 / 089587 discloses naturally occurring β-diketones and β-triketones such as flamesone and their derivatives as effective insecticides (including insecticides and arachnids). However, it is advantageous to use the minimum possible amount of insecticide or to use a combination of insecticides in the minimum permissible amount.

[0008] This invention is based, at least in part, on the discovery that flavorone has a unique mode of action as a potassium channel activator, and is therefore surprisingly useful in insecticide combinations. This invention is also based, at least in part, on the discovery that the combination of flavorone and another insecticide, permethrin, is effective in controlling insects. Invention Overview

[0010] In one aspect, the present invention provides a method for controlling pests, the method comprising exposing pests to a combination of a compound of formula (I) or a tautomer thereof and at least one second insecticide:

[0011]

[0012] R1 is selected from –C(=O)R7, -OR8, -SR8, -C 1-10 Hydroxyalkyl, -NR9R 10 , -C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7 and –OSO3R8;

[0013] R2 is selected from hydrogen, -C 1-10 Alkyl, -C 2-10 alkenyl, aryl, and heteroaryl;

[0014] R3, R4, R5, and R6 are each independently selected from hydrogen, -C 1-10 Alkyl, -C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl, -OR8, -SR8, -NR9R 10 , -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C 1-10 Alkyl aryl and –C(=O)R7;

[0015] R7 is selected from hydrogen, -C 1-10 Alkyl, -C 2-10 alkylaryl, C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Alkyl heteroaryl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl, -C 1-10 Halogenated alkoxy groups, -C 1-10 Hydroxyalkyl, -C 1-10 Thioalkyl, -C 1-10 Nitroalkyl, -C 1-3 Alkyl OC 1-3 Alkyl, -C 1-3 Alkyl OC 1-3 Halogenated alkyl, -C 1-3 Alkyl OC 1-3 Dihaloalkyl, -C 1-3 Alkyl OC 1-3Trihaloalkyl, -OR8, -SR8 and –NR9R 10 ;

[0016] R8 is selected from hydrogen, -C 1-10 Alkyl, -C 2-10 Alkyl aryl, -C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Alkyl heteroaryl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl, -C 1-10 Halogenated alkoxy groups, -C 1-10 Hydroxyalkyl, -C 1-10 Thioalkyl and -C 1-10 Nitroalkyl;

[0017] R9 and R 10 Independently selected from hydrogen, -C 1-10 Alkyl, -C 2-10 Alkyl aryl, -C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Alkyl heteroaryl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl

[0018] In another aspect of the invention, an insecticide composition is provided comprising a compound of formula (I) as described above and at least one second insecticide.

[0019] In another aspect of the invention, a kit is provided comprising a compound of formula (I) as described above and at least one second insecticide. Invention Details

[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 this invention pertains. While any methods and materials similar to or equivalent to those described herein may be used for the implementation or testing of this invention, preferred methods and materials are described. For the purposes of this invention, the following terms are defined.

[0022] This article uses the articles “a” and “an”, which refer to one or more (i.e., at least one) grammatical object of the article. For example, “element” means one or more elements.

[0023] As used herein, the term “about” refers to a quantity, level, value, dimension, size, or amount that varies by as much as 30%, 25%, 20%, 15%, or 10% relative to a reference quantity, level, value, dimension, size, or amount.

[0024] In the appended claims and the preceding description of the invention, unless the context otherwise requires it due to the language of expression or necessary implication, the words “comprise” or variations such as “comprises” or “comprising” are used in an inclusive sense, that is, specifying the presence of the stated features in various embodiments of the invention, but not excluding the presence or addition of other features.

[0025] It should be understood that if any prior art publications are cited in this document, such citation does not constitute an acknowledgment that such publications form part of the general knowledge in the art in Australia or any other country.

[0026] As used herein, the term "combination" refers to a compound of formula (I) and at least one second insecticide, wherein the compound of formula (I) and at least one second insecticide are used simultaneously in a single composition or in different compositions or sequentially in different compositions, such that the biological activities of each compound in the pest overlap or occur simultaneously.

[0027] As used herein, the term “prevention” refers to preventing the infestation of pests (such as insects and arachnids), removing pests from the environment, fighting against pests, eradicating or eliminating pests, including increasing the mortality rate of pests or inhibiting the growth and / or development of pests.

[0028] As used herein, the term "environment" refers to the environment in which a combination of compounds can be applied to ensure that pests are exposed to the combination of compounds. An environment can be an agricultural environment, a domestic environment, an industrial environment, or another environment that hosts or may host pests. An agricultural environment includes the environment in which crops, trees, and other commercially important plants that may be susceptible to infestation are grown. An agricultural environment includes not only the plants themselves, but also the soil and area surrounding the plants as they grow, and areas where plant parts (e.g., seeds, grains, leaves, roots, or fruits) can be stored. A domestic environment includes the environment in which humans or animals live, and may include indoor environments such as carpets, curtains, closets, and indoor air. A domestic environment may also include a home garden. An industrial environment includes environments used for industrial purposes (e.g., the manufacture, storage, or sale of products). Industrial environments include warehouses, manufacturing plants, shops, storage facilities, etc. Other environments may include recreational areas such as parks and stadiums, or bodies of water such as rivers, lakes, ponds, or places where water may accumulate, move slowly, or remain stagnant.

[0029] As used herein, the term "alkyl" refers to a straight-chain or branched saturated hydrocarbon group having 1 to 10 carbon atoms. Where appropriate, the alkyl group may have a specified number of carbon atoms, for example, C1. 1-6 Alkyl groups include alkyl groups having 1, 2, 3, 4, 5, or 6 carbon atoms arranged linearly or branchedly. Examples of suitable alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 4-methylbutyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 5-methylpentyl, 2-ethylbutyl, 3-ethylbutyl, heptyl, octyl, nonyl, and decyl.

[0030] As used herein, the term "alkenyl" refers to a straight-chain or branched hydrocarbon group having one or more double bonds between carbon atoms and having 2 to 10 carbon atoms. Where appropriate, an alkenyl group may have a specified number of carbon atoms. For example, C2-C6 as in "C2-C6 alkenyl," C2-C6 alkenyl includes groups having 2, 3, 4, 5, or 6 carbon atoms arranged linearly or branchedly. Examples of suitable alkenyl groups include, but are not limited to, vinyl, propenyl, isopropenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl, hexadienyl, heptenyl, octenyl, nonenyl, and decenyl.

[0031] As used herein, the term "cycloalkyl" refers to a saturated cycloalkyl ring. A cycloalkyl ring may include a specified number of carbon atoms. For example, 3- to 6-membered cycloalkyl groups include 3, 4, 5, or 6 carbon atoms. Examples of suitable cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0032] As used herein, the term "aryl" is intended to refer to any stable monocyclic, bicyclic, or tricyclic carbocyclic system with up to seven atoms per ring, wherein at least one ring is aromatic. Examples of such aryl groups include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, fluorenyl, phenanthrenyl, biphenyl, and binaphthalene.

[0033] As used herein, the term "heteroaryl" refers to a stable monocyclic, bicyclic, or tricyclic ring with up to seven atoms per ring, wherein at least one ring is aromatic and at least one ring contains one to four heteroatoms selected from the group consisting of O, N, and S. Heteroaryl groups within this definition include, but are not limited to, acridine, carbazolyl, cinnolinyl, quinoxalinyl, quinazolinyl, pyrazolyl, indole, isoindole, 1H,3H-1-oxoisoindole, benzotriazolyl, furanyl, thienyl, thiophenyl, benzothienyl, benzofuranyl, benzodioxane, and benzene. And dioxin, quinolinyl, isoquinolinyl, oxazolyl, isoxazolyl, imidazole, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrroleyl, tetrahydroquinolinyl, thiazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,4,5-tetraazinyl and tetrazolyl. Specific heteroaryl groups have 5 or 6-membered rings, such as pyrazolyl, furanyl, thiophene, oxazolyl, indole, isoindole, 1H,3H-1-oxoisoindole, isoxazolyl, imidazolyl, pyrazinyl, pyridinyl, pyrimidinyl, pyrrole, thiazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, and 1,2,4-oxadiazolyl and 1,2,4-thiadiazolyl.

[0034] As used herein, the term "haloalkyl" refers to an alkyl group in which one or more hydrogen atoms of the alkyl group are replaced by halogen atoms. Where appropriate, the alkyl group may have a specified number of carbon atoms, for example, C2. 1-6Haloalkyl groups include alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms arranged in a linear or branched manner. Examples of haloalkyl groups include fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-fluoroethyl, 1,1,2-trifluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 4-fluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, 5-fluoropentyl, 5,5-difluoropentyl, 5,5,5-trifluoropentyl, 6-fluorohexyl, 6,6-difluorohexyl or 6,6,6-trifluorohexyl, chloromethyl, dichloromethyl, trichloromethyl, 1-chloroethyl, 2-chloroethyl, 1,1-dichloroethyl, 2,2-chloroethyl, 1,1,2-trichloroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 3,3-dichloropropyl, 3 3,3-Trichloropropyl, 4-Chlorobutyl, 4,4-Dichlorobutyl, 4,4,4-Trichlorobutyl, 5-Chloropentyl, 5,5-Dichloropentyl, 5,5,5-Trichloropentyl, 6-Chlorohexyl, 6,6-Dichlorohexyl or 6,6,6-Trichlorohexyl, Bromomethyl, Dibromomethyl, Tribromomethyl, 1-Bromoethyl, 2-Bromoethyl, 1,1-Dibromoethyl, 2,2-Dibromoethyl Ethyl, 1,1,2-tribromoethyl, 2,2,2-tribromoethyl, 3-bromopropyl, 3,3-dibromopropyl, 3,3,3-tribromopropyl, 4-bromobutyl, 4,4-dibromobutyl, 4,4,4-tribromobutyl, 5-bromopentyl, 5,5-dibromopentyl, 5,5,5-tribromopentyl, 6-bromohexyl, 6,6-dibromohexyl or 6,6,6-tribromohexyl, etc.

[0035] As used in this article, "halogenated" refers to fluorinated, chlorinated, brominated, and iodinated substances.

[0036] The terms “hydroxyalkyl”, “thioalkyl” and “nitroalkyl” each refer to an alkyl group as defined above in which one of its hydrogen atoms is replaced by a hydroxyl group, a thiol group or a nitro group, respectively.

[0037] As used herein, the term "alkoxy" refers to an oxygen substituent that is replaced by an alkyl group as defined above. Examples of suitable alkoxy groups include, but are not limited to, -OCH3, -OCH2CH3, -O(CH2)2CH3, -OCH(CH3)2, -O(CH2)3CH3, -OCH2CH(CH3)2, -OC(CH3)3, -O(CH2)4CH3, and -O(CH2)5(CH3).

[0038] Compounds of formula (I) can exist in a variety of tautomeric forms. For example, tautomerism is shown in the figure below:

[0039]

[0040] The intention is to include all these tautomer structures within the scope of equation (I).

[0041] It is also possible that the compounds of formula (I) exist in stereoisomers. The compounds can be enantiomers or diastereomers, and can exist as individual isomers or as mixtures (including racemic mixtures).

[0042] The method of the present invention

[0043] In one aspect, the present invention provides a method for controlling pests, the method comprising exposing pests to a combination of a compound of formula (I) or a tautomer thereof and at least one second insecticide:

[0044]

[0045] R1 is selected from –C(=O)R7, -OR8, -SR8, -C 1-10 Hydroxyalkyl, -NR9R 10 , -C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7 and –OSO3R8;

[0046] R2 is selected from hydrogen, -C 1-10 Alkyl, -C 2-10 alkenyl, aryl, and heteroaryl;

[0047] R3, R4, R5, and R6 are each independently selected from hydrogen, -C 1-10 Alkyl, -C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl, -OR8, -SR8, -NR9R 10 , -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C 1-10 Alkyl aryl and –C(=O)R7;

[0048] R7 is selected from hydrogen, -C 1-10 Alkyl, -C 2-10 alkylaryl, C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Alkyl heteroaryl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl, -C 1-10 Halogenated alkoxy groups, -C 1-10 Hydroxyalkyl, -C 1-10Thioalkyl, -C 1-10 Nitroalkyl, -C 1-3 Alkyl OC 1-3 Alkyl, -C 1-3 Alkyl OC 1-3 Halogenated alkyl, -C 1-3 Alkyl OC 1-3 Dihaloalkyl, -C 1-3 Alkyl OC 1-3 Trihaloalkyl, -OR8, -SR8 and –NR9R 10 ;

[0049] R8 is selected from hydrogen, -C 1-10 Alkyl, -C 2-10 Alkyl aryl, -C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Alkyl heteroaryl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl, -C 1-10 Halogenated alkoxy groups, -C 1-10 Hydroxyalkyl, -C 1-10 Thioalkyl and -C 1-10 Nitroalkyl;

[0050] R9 and R 10 Independently selected from hydrogen, -C 1-10 Alkyl, -C 2-10 Alkyl aryl, -C 3-6 cycloalkyl, -C 2-10 alkenyl, -C 1-10 Alkyl heteroaryl, -C 1-10 Halogenated alkyl, -C 1-10 Dihaloalkyl, -C 1-10 Trihaloalkyl

[0051] In some embodiments, the compound of formula (I) is the compound of formula (II) or a tautomer thereof:

[0052]

[0053] Where R 11 Selected from –CR 12 R 13 R 14 Or –NR 15 R 16 ;

[0054] R 12 and R 13 One is hydrogen, and the other is a hydroxyl group or –OCR 17 R 18 R19 , or R 12 and R 13 Together they form an oxo group (=O) or an N-OH group;

[0055] R 14 It is –CH(CH3)CR 20 R 21 R 22 -CH2CH(CH3)CR 20 R 21 R 22 Or –CH(CH3)CH2CR 20 R 21 R 22 ;

[0056] R 15 and R 16 Independently selected from hydrogen and C 1-10 alkyl;

[0057] R 17 R 18 and R 19 Independently selected from hydrogen or halogen; and

[0058] R 20 R 21 and R 22 Independently selected from hydrogen, hydroxyl, halogen, NO2 and –OCR 17 R 18 R 19 .

[0059] In some embodiments, the compound of formula (I) is a compound of formula (III) or a tautomer thereof:

[0060]

[0061] Where R 23 and R 24 One is hydrogen, and the other is a hydroxyl group or –OCR 27 R 28 R 29 , or R 23 and R 24 Together they form an oxo group (=O);

[0062] R 25 Yes – CR 30 R 31 R 32 -CH2CR 30 R 31 R 32 Or –CH(CH3)CR 30 R 31 R32 ;

[0063] R 26 For H or –CH3; where, in R 26 In the case of H, R 25 -CH(CH3)CR 30 R 31 R 32 ;

[0064] R 27 R 28 and R 29 Independently selected from hydrogen or halogen; and

[0065] R 30 R 31 and R 32 Independently selected from hydrogen, hydroxyl, halogen, NO2 and –OCR 27 R 28 R 29 .

[0066] In some embodiments, the compounds of formula (I) are selected from:

[0067]

[0068]

[0069]

[0070] Or its tautomers.

[0071] In a particular embodiment, the compound of formula (I) is flamesone, 1-isobutyryl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione:

[0072]

[0073] Cellulone (1-pentanoyl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione):

[0074]

[0075] Or isocelluloseone (1-isovaleroyl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione):

[0076]

[0077] The combination of the present invention suitably comprises a compound of formula (I) and at least one second insecticide having a different mode of action than the compound of formula (I). As shown in Example 2, the compound of formula (I) is an activator of potassium ion channels. Suitable second insecticides include insecticides and arachnid-killing substances having different modes of action.

[0078] In some implementations, the pests to be controlled are selected from insects and arachnids. In some implementations, the pests are insects. In other implementations, the pests are arachnids, especially ticks or mites.

[0079] In some embodiments, at least one secondary insecticide is at least one insecticide. In some embodiments, at least one secondary insecticide includes sodium channel modifiers, such as pyrethroids and methoxychlor. Suitable pyrethroids include flufenacet, allethrin, bifenthrin, bioallethrin, bioallethrin-S-cyclopentyl, biobenzylfuran, cypermethrin, cyfluthrin, β-cypermethrin, cyhalothrin, γ-cypermethrin, λ-cypermethrin, cypermethrin, α-cypermethrin, β-cypermethrin, θ-cypermethrin, ζ-cypermethrin, deltamethrin, dimefluthrin, empenthrin, and esfenvalerate. Etofenprox, cypermethrin, fenvalerate, flucythrinate, cypermethrin, tau-cypermethrin, fenvalerate, methoxyfenozide, permethrin, fenvalerate, prallethrin, profluthrin, pyrethrin, benzalkonium chloride, RU15525, flusilylpyrethrin, tetramethrin, tetramethrin, transfluthrin, and ZX18901.

[0080] In some embodiments, at least one secondary insecticide includes an acetylcholinesterase (AChE) inhibitor, such as a carbamate or organophosphate. Suitable carbamates include alanycarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, and xylylcarb.Suitable organophosphates include acephate, azamethiphos, azinphos, methyl glutathione, ethyl glutathione, cadusafos, chlorethoxyfos, chlorfenvinfos, chlormephos, chlorpyrifos, methyl chlorpyrifos, coumaphos, cyanophos, demeton-S-methyl, diazinon, and dichlorvos. dichlorvos, didrotophos, dimethoate, dimethylvinphos, disulfoton, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, isofenphos, oxadixyl Isoxathion, malathion, mecarbam, methidathion, mevinphos, naled, oxydemeton-methyl, methyl parathion, phenthoate, phosalone, phosmet, phoxim, pirimiphos, methyl pyrimiphos, profenfos, propeta The following are listed: mphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, triclofon, and vamidothion.

[0081] In some embodiments, at least one secondary insecticide includes a GABA-gated chlorine channel antagonist, such as an organochlorine or fiprole. Suitable organochlorines include chlordane and α-endodane. Suitable fiproles include ethiprole, fipronil, pyrafluprole, and pyriprole.

[0082] In some embodiments, at least one secondary insecticide includes a nicotinic acetylcholine receptor agonist, such as nicotine or a chloronicotinic compound. Suitable chloronicotinic compounds include acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiocloprid, and thiamethoxam.

[0083] In some embodiments, at least one secondary insecticide includes an allosteric acetylcholine receptor modulator, such as spinosad or spintocin.

[0084] In some embodiments, at least one secondary insecticide includes an actuator, such as abamectin, emamectin benzoate, lepimectin, or milkemectin.

[0085] In some embodiments, at least one secondary insecticide includes a juvenile hormone mimic selected from hydroprene, kinoprene, methomyl, S-methoxyprine, fenoxycarb, or pyriproxyfen.

[0086] In some embodiments, at least one secondary insecticide includes a homoptera feeding inhibitor, such as pymetrozine or flonicamid.

[0087] In some embodiments, at least one secondary insecticide includes a mitochondrial ATP synthase inhibitor, such as diafenthiuron or tetradifon.

[0088] In some embodiments, at least one second insecticide includes an oxidatively phosphorylated uncoupling agent, such as chlorfenapyr or DNOC.

[0089] In some embodiments, at least one second insecticide includes a nicotinic acetylcholine receptor channel blocker, such as bensultap, cartap hydrochloride, thiocyclam, or thiosultap-sodium.

[0090] In some embodiments, at least one secondary insecticide includes a chitin biosynthesis inhibitor, such as benzoylurea or thiamethoxam. Suitable benzoylureas include bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, or triflumuron.

[0091] In some implementations, at least one secondary insecticide includes a molting disruptor, such as cyromazine.

[0092] In some embodiments, at least one secondary insecticide includes a ecdysone receptor agonist or interferon, such as diazinon. Suitable diazinons include chromafenozide, halofenozide, methoxyfenozide, or tebufenozide.

[0093] In some implementations, at least one secondary insecticide includes an octopamine receptor agonist, such as amitraz.

[0094] In some embodiments, at least one secondary insecticide includes an inhibitor of mitochondrial complex I electron transport, such as hydramethylnon, acequinocyl, and fluacrypryrim.

[0095] In some embodiments, at least one secondary insecticide includes an acetyl-CoA carboxylase inhibitor, such as a tetronic acid derivative or a tetramic acid derivative. Suitable tetronic acid derivatives include spirodiclofen and spiromesifen, and suitable tetramic acid derivatives are spirotetramat.

[0096] In some embodiments, at least one secondary insecticide includes a voltage-dependent sodium channel blocker, such as indoxacarb or metaflumizone.

[0097] In some embodiments, at least one secondary insecticide includes a mitochondrial complex IV electron inhibitor, such as a phosphine or cyanide. Suitable phosphides include zinc phosphide, aluminum phosphide, calcium phosphide, or phosphine.

[0098] In some embodiments, at least one secondary insecticide includes a mitochondrial complex IV electron transport inhibitor, such as cyenopyrafen.

[0099] In some embodiments, at least one secondary insecticide includes a ryanodine receptor modulator, such as chlorantraniliprole, cyantraniliprole, and flubendiamide.

[0100] In a particular embodiment, at least one second insecticide includes a sodium channel modulator, more particularly pyrethroids, even more particularly pyrethroids, permethrin, bifenthrin, cyhalothrin, deltamethrin, or tetrafluorobenzyl, most particularly permethrin.

[0101] In other embodiments, at least one secondary insecticide is an arachnid-killing substance, particularly an acaricide. In some embodiments, the at least one secondary arachnid-killing substance is selected from: abamectin, acequinocyl, flufenoxuron, cypermethrin, amiditin, amiton, amitraz, aramite, ethyl phosphonate, methyl phosphonate, azobenzene, azocyclotin, azophos, benomyl, benzoximate, benzyl benzoate, bifenazate, bifenthrin, binapacryl, bromocyclen, bromoxynil, ethyl bromide, etc. Phosphate, bromopropylate, methyl ethyl ketone, carbanolate, carbophenothion, carvacrol, chinomethionat, chlorbenside, brofenol, chlorfenethol, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorobenzilate, chloromebufo rm, chloromethiuron, chloropropylate, chlorpyrifos, chlorthiophos, clofentezine, closantel, coumaphos, crotamiton, crotoxyphos, cypermethrin, cycloprate, cyenopyrafren, cyflumetofen, deltamethrin, tricyclic tin, cypermethrin, cyromazine, demeton-methyl, systemic methamidophos Phosphorus, Methionol-O, Methionol-O-methyl, Methionol-S, Methionol-S-methyl, Diethyl ether urea, Dialifos, Diazinon, Dichlofluanid, Dichlorvos, Dienochlor, Diflovidazin, Dimefox, Dimethoate, Dinex, Dinobuton, Dinocap, Dinoocton, Dinopenton, Dinosulfon, DinoterbonDioxathion, diphenyl sulfone, ethion, DNOC, endothion, ethion, ethoate-methyl, etoxazole, fenazaflor, fenazaquin, fenbutatin oxide, fenothiocarb, cypermethrin, fenpyroximate, fenson, fentrifanil, cypermethrin, fipronil, fluacrypyrim, fluazuron, flubenzimine, flucycloxuron, fluenetil, flufenoxuron, flubenside, fluoramine Cypermethrin, amitraz, formothion, formoparanate, genit, halfenprox, heptachlorophene, hexythiazox, isocarbophos, lindane, malathion, pymetrozine, methomyl, chlorpyrifos, fenpropathrin, fenpropathrin, fenpropathrin, mipafox, dibromophos, nifluridide , oxydeprofos, oxydisulfoton, permethrin, fenthion, fenthion, fenthion, fenthion, fenthion, fenthion, fenthion, fenthion, fenthion, propargite, propargite, prothidathion, prothoate, pyridaben, pyrimidifen, quinalphos, quintiofos, schradan, sophamid e) Spirodiclofen, sulfluramid, sulfotep, sulfur, tau-flufenoxamyl, tebufenpyrad, TEPP, carbendazim, tetrasul, thiocarboxime, thiofanox, methamidophos, thuringiensin, triarathene, triazophos,Trichlorfon and vamidothion.

[0102] In some embodiments, a second insecticide, such as an insecticide or arachnidicide, is used. In other embodiments, more than one second insecticide is used, such as two second insecticides or arachnidicides, such that the combination comprises three insecticides.

[0103] The compounds of formula (I) can be isolated from oil-bearing trees such as those from the Myrtaceae family, such as the Manuka tree (Leptospermum scoparium), the giant eucalyptus (Eucalyptus grandis), and the large-flowered eucalyptus (Eucalyptus cloeziana), especially the Manuka tree.

[0104] In other embodiments, the compound of formula (I) can be prepared synthetically, for example, as described in WO 2002 / 089587. For example, 1,3,5-trihydroxybenzene can be reacted with RCN in the presence of zinc chloride (Blatt, Org. Synth. Col 11, 1943, 522-523), as shown in Scheme 1:

[0105]

[0106] Option 1

[0107] As shown in Scheme 2, anhydrous methyl iodine (6 equivalents) is slowly added to 1-acyl-2,4,6-trihydroxybenzene (1 equivalent) and sodium ethoxide (6 equivalents) in anhydrous methanol to obtain 1-acyl-3,3,5,5-tetramethyl-2,4,6-cyclohexanetrione (US4,202,840).

[0108]

[0109] Option 2

[0110] At least one secondary insecticide is commercially available.

[0111] The effective amount of the combination can be readily determined by those skilled in the art, and can depend on the combination, the environment in which the combination is used, and the species of insect to be controlled.

[0112] The effective amount of each compound in the combination can be the amount used as is known in the art. For example, the second insecticide can be used in the amount specified on its label. The amount of the compound of formula (I) can be in the range of 0.1 to 500,000 ppm, particularly 1 to 200,000 ppm or 1 to 100,000 ppm, or in the range of 0.01 to 500 g / L.

[0113] However, in some embodiments, one, two, or all of the components in the combination are present in reduced amounts than normally used, particularly at least one of the second insecticides is used in a reduced amount. Advantageously, the reduced amount can reduce toxicity and / or environmental impact.

[0114] In some embodiments, the amount of one, two, or all components is reduced to such a degree that if the component were used alone, it would be ineffective or incapable of achieving complete control of insect pests. In some embodiments, one, two, or all of the compounds in the combination are used in synergistic amounts to achieve a synergistic effect. For example, in some embodiments, the compound of formula (I) is used in a sub-effective amount, such as LC. 10 LC 15 LC 20 LC 25 LC 30 LC 35 LC 40 LC 45 LC 50 LC 55 LC 60 LC 65 LC 70 LC 75 LC 80 LC 85 LC 90 or LC 95 The first insecticide is used in the recommended dosage, and the second insecticide is used at its recommended dosage. In other embodiments, the compound of formula (I) and the second insecticide are used in a sub-effective amount.

[0115] In some embodiments, the effective amount is an effective insecticide or arachnidicide intended to cause death in populations of insects or arachnids exposed to the combination. In other embodiments, the effective amount is an insecticide or arachnid repellent amount intended to repel insects or arachnids from a specific environment at risk of insect or arachnid infestation.

[0116] The compositions and methods of the present invention can be applied to control insects, for example:

[0117] (a) Insects from the order Lepidoptera, such as the brown-banded cotton leafroller (Adoxophyes orana), small cutworm (Agrotis ipsilon), yellow cutworm (Agrotis segetum), cotton leafroller (Alabamaargillacea), soybean cutworm (Anticarsia gemmatalis), Argyresthia conjugella, gamma cutworm (Autographa gamma), Cacoecla murinana, tobacco leafroller (Capua reticulana), spruce leafroller (Choristoneura fumiferana), spotted grass moth (Chilo partellus), western spruce leafroller (Choristoneura occidentalis), armyworm (Cirphis unipuncta), rice leaf roller (Cnaphalocrocis medinalis), pan-African hairy moth (Crocidolomia binotalis), codling moth (Cydiapomonella), and European pine caterpillar (Dendrolimus). The following are listed: pini, cucumber silkworm moth (Diaphania nitidalis), southwestern corn borer (Diatraea grandiosella), cotton fruit moth (Earias insulana), South American corn seedling moth (Elasmopalpus lignosellus), privet leaf roller (Eupoecilia ambiguella), Feltia subterranea, plum fruit moth (Grapholitha funebrana), pear fruit moth (Grapholithamolesta), Heliocoverpa armigera, Heliocoverpa virescens, American cotton bollworm (Heliocoverpazea), Chinese cabbage moth (Hellula undalis), Hibernia defoliaria, Hypliantria cunea, apple leafminer moth (Hyponomeuta malinellus), tomato stem moth (Keiferia lycopersicella), hemlock looper (Lambdina fiscellaria), beet armyworm (Laphygma). exigua), spiral leaf miner (Leucopterascitella), Lithocolletis blancardella, European grape moth (Lobesia botrana), meadow moth (Loxostege)sticticalis, gypsy moth (Lymantria dispar), tussock moth (Lymantria monacha), peach leafminer (Lyonetia clerkella), tobacco hawk moth (Manduca sexta), tent caterpillar (Malacosomaneustria), cabbage cutworm (Mamestra brassicae), Mocis repanda, Operaphthera brumata, yellow cedar tussock moth (Oryyia pseudotsugata), corn borer (Ostrinia nubilalis), apple brown leafroller (Pandemisheparana), Panolis flamnea, cotton bollworm (Pectinophora gossypiella), potato tuber moth (Phthorimaea operculella), citrus leafminer (Phyllocnistis citrella), European white butterfly (Pieris brassicae), alfalfa green armyworm (Plathypena scabra), Dutch carnation leafroller (Platynota) stultana, diamondback moth (Plutella xylostella), orange leafroller (Prays citri), olive leafroller (Prays oleae), Prodenia sunia, Prodenia ornithogalli, soybean cutworm (Pseudoplusia includens), pine shoot roller (Rhyacionia frustran), scrobipalpula absoluta, Chinese twig borer (Sesamia inferens), grape long-bearded leafroller (Sparganothis pilleriana), fall armyworm (Spodoptera frugiperda), cotton fall armyworm (Spodoptera littoralis), beet armyworm (Spodoptera litura), Syllepta derogata, Synanthedon myopaeforinis, Thaumatopoea pityocampa, oak green leafroller (Tortrix viridana), pink leafroller (Trichoplusia ni), rice stem borer (Tryporyza) *Incertulas* and *Zeirapheracanadensis*, as well as the large wax moth (Galleria mellonella), the wheat moth (Sitotroga cerealella), and the powdery meal moth (Ephestia).cautella and Tineola bisselliella;

[0118] (b) Insects from the order Coleoptera, such as the cotton boll weevil (Anthonomus grandis), apple blossom weevil (Anthonomus pomorum), bean weevil (Apion vorax), beet gnater (Atomaria linearis), pine pit beetle (Blastophagus piniperda), beet beetle (Cassidanebulosa), bean leaf beetle (Cerotoma trifurcata), beetle leaf beetle (Ceuthorhynchus assimilis), beetle flea beetle (Chaetocnema tibialis), tobacco wireworm (Conoderus vespertinus), asparagus beetle (Crioceris asparagi), rusty flour beetle (Cryptolestes ferrugineus), red-winged bark beetle (Dendroctonus rufipennis), and long-horned leaf beetle (Diabrotica). The following species are listed: longicornis, Diabrotica punctata, corn root leaf beetle (Diabrotica virgifera), Mexican bean ladybug (Epilachna varivestis), tobacco flea beetle (Epitrix hirtipennis), weevil variant (Eutinobothrus brasiliensis), pine bark weevil (Hylobius abietis), Hypera brunneipennis, alfalfa leaf weevil (Hypera postica), spruce bark beetle (Ips typographus), Lema bilineata, Lema melanopus, potato leaf beetle (Leptinotarsadecemlineata), beet beetle (Limonius californicus), rice water weevil (Lissorhoptrusoryzophilus), Melanotus communis, rapeseed flower beetle (Meligethes aeneus), Melolonthahippocastani, Melolontha melolontha, rice mud beetle (Oulema). Oryzae, Grape Black-eared Beetle (Otiorhynchus sulcatus), Otiorhynchus ovatus, Horseradish Ape Leaf Beetle (Phaedon cochleariae), Garden Leaf Beetle (Phyllopertha horticola), Species of the genus Phyllophorasp.), Phyllotretachrysocephala, Phyllotreta nemorum, Phyllotreta striolata, Japanese golden beetle (Popillia japonica), Psylliodes napi, tufted bark beetle (Scolytus intricatus) and Sitonalineatus, as well as bean weevil (Bruchus rufimanus), pea weevil (Bruchus pisorum), Bruchuslentis, grain weevil (Sitophilus granarius), tobacco beetle (Lasioderma serricorne), saw grain beetle (Oryzaephilus surinamensis), grain beetle (Rhyzopertha dominica), rice weevil (Sitophilus oryzae), red flour beetle (Tribolium castaneum), spotted grain beetle (Trogoderma granarium), and Brazilian bean weevil (Zabrotes subfasciatus);

[0119] (c) Insects from the order Diptera,Examples include the Mexican fruit fly (Anastrepha ludens), the Mediterranean fruit fly (Ceratitis capitata), the sorghum gall fly (Contarinia sorghicola), the melon fruit fly (Dacus cucurbitae), the olive fruit fly (Dacus oleae), the rapeseed leaf gall fly (Dasineura brassicae), the wheat seed fly (Delia coarctata), the cabbage seed fly (Delia radicum), the leaf miner (Hydrellia griseola), Hyleniyia platura, the American serpentine leafminer (Liriomyza sativae), the trifoliate serpentine leafminer (Liriomyza trifolii), the Hessian gall fly (Mayetiola destructor), the Asian rice gall fly (Orseolia oryzae), the Swedish wheat stem fly (Oscinella frit), the beet leaf miner (Pegomya hyoscyami), Phorbia antiqua, Phorbia brassicae, Phorbia coarctata, and the cherry fruit fly (Rhagoletis). The species *Cerasi* and *Rhagoletis pomonella*, as well as *Aedes aegypti*, *Aedes vexans*, *Aedes albopictus*, *Anopheles maculipennis*, *Chrysomya bezziana*, *Cochliomyia hominivorax*, *Chrysamya macellaria*, *Cordylobia anthropophaga*, *Culex pipiens*, *Fannia canicularis*, *Gasterophilus intestinalis*, *Glossina morsitans*, *Haematobiairritans*, *Haplodiplosis equestris*, *Hypoderma lineata*, *Luciliacuprina*, *Lucilia sericata*, and *Musca* are also mentioned. Domestica, stable carrion fly (Muscinastabulans), sheep mad fly (Oestrus ovis), horsefly (Tabanus bovinus), and black fly (Simulium damnosum);

[0120] (d) Insects from the order Thysanoptera, such as Frankliniella fusca, Frankliniella occidentalis, Frankliniella tritici, Haplothrips tritici, Heliothrips shaemorrhoidalis, Scirtothrips citri, Thrips oryzae, Thrips palmi, and Thrips tabaci;

[0121] (e) Insects from the order Hymenoptera, such as turnip sawfly (Athalia rosae), big-headed leafcutter ant (Atta cephalotes), Atta sexdens leafcutter ant (Atta sexdens), Texas leafcutter ant (Atta texana), Hoplocampa minuta, Hoplocampa testudinea, Argentine rainbow stink ant (Iridomyrmex humilis), purple rainbow stink ant (Iridomyrmex purpureus), small yellow house ant (Monomorium pharaonis), tropical fire ant (Solenopsis geminata), red fire ant (Solenopsis invicta), black fire ant (Solenopsis richteri), and white-legged stink ant (Technomyrmex albipes);

[0122] (f) Insects from the order Heteroptera, such as the green bug (Acrosternum hilare), American long-haired stalk bug (Blissus leucopterus), Cyrtopeltis notatus, red bug (Dysdercus cingulatus), Dysdercus intermedius, wheat bug (Eurygaster integriceps), Euschistus ictericus, Leptoglossus phyllopus, bean grass bug (Lygus hesperus), American pasture bug (Lygus lineolaris), pasture bug (Lygus pratensis), Mormidea pictiventris, rice green bug (Nezara viridula), Piesma quadrata, Solubea insularis, and Thyanta perditor;

[0123] (g) Insects from the order Homoptera, such as *Acyrthosiphon onobrychis*, pea aphid (*Acyrthosiphon pisum*), larch ball aphid (*Adelges laricis*), red scale insect (*Aonidiella aurantii*), *Aphidula nasturtii*, bean euonymus aphid (*Aphis fabae*), cotton aphid (*Aphis gossypii*), apple aphid (*Aphis pomi*), eggplant weevil aphid (*Aulacorthum solani*), whitefly (*Bemisia tabaci*), *Brachycaudus cardui*, cabbage aphid (*Brevicoryne brassicae*), corn yellow-winged leafhopper (*Dalbulusmaidis*), *Dreyfusia nordmannianae*, spruce ball aphid (*Dreyfusia piceae*), *Dysaphis radicola*, broad bean leafhopper (*Empoasca fabae*), *Eriosorna*. lanigerum, gray planthopper (Laodelphaxstriatella), Macrosiphum avenae, Macrosiphun euphorbiae, Macrosiphon rosae, vegetable aphid (Megoura viciae), wheat aphid (Metopolophium dirhodum), peach aphid (Myzus persicae), myzus cerasi, black-tailed leafhopper (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), sugarcane flat-horned planthopper (Perkinsiella saccharicida), hopacust aphid (Phorodon humuli), apple psyllid (Psylla mali), pear psyllid (Psylla pyri), pear yellow psyllid (Psylla pyricola), corn aphid (Rhopalosiphum maidis), wheat aphid (Schizaphis graminum), Sitobion avenae, white-backed planthopper (Sogatella furcifera), citrus aphid (Toxoptera) citricida, Trialeurodes abutilonea, greenhouse whitefly (Trialeurodes vaporariorum), and grape phylloxera (Viteus vitifoliae);

[0124] (h) Insects from the order Isoptera, such as the yellow-necked wood termite (Kalotermes flavicollis), species of the genus Coptotermes spp., Leucotermes flavipes, Macrotermes subhyalinus, Macrotermes darwiniensis, Mastotermes spp., species of the genus Microtermes spp., species of the genus Nasutitermes spp. such as Nasutitermes walkeri, Odontotermes formosanus, Reticulitermes lucifugus, and Termes natalensis;

[0125] (i) Insects from the order Orthoptera, such as the European mole cricket (Gryllotalpagryllotalpa), the Oriental migratory locust (Locusta migratoria), the two-banded black locust (Melanoplus bivittatus), the red-legged black locust (Melanoplus femurrubrum), the mexicanus, the blood locust (Melanoplus sanguinipes), the Rocky Mountain locust (Melanoplus spretus), the red-winged locust (Nomadacris septemfasciata), the South American desert locust (Schistocerca americana), the Schistocerca peregrina, the Stauronotus maroccanus, and the desert locust (Schistocerca gregaria), as well as the domestic cricket (Acheta domesticus), the oriental cockroach (Blatta orientalis), the German cockroach (Blattella germanica), and the American cockroach (Periplaneta americana);

[0126] (j) Insects from the order Phthiraptera, such as Mallophaga, including Damalinaspp., and species from the suborder Anoplura, including the genera Linognathus and Haematopinus spp.;

[0127] (k) Insects from the order Hemiptera, such as aphids, whiteflies, warty aphids, Aeneolamia, leafhoppers, leafhoppers, planthoppers, pyrilla, Aonidiella, scale insects, mealybugs, thorny mirid bugs, and grass mirid bugs. s), species of the genera *Dysdercus*, *Oxycarenus*, *Nezara*, *Aleyrodes*, *Triatoma*, *Psylla*, *Myzus*, *Megoura*, *Phylloxera*, *Adelges*, *Nilaparvata*, *Nephotettix*, or *Cimex spp.*;

[0128] (l) Insects from the order Siphonaptera, such as species of the genus Ctenocephalides or Pulex spp.;

[0129] (m) Insects from the order Thysanura, such as Lepisina spp.;

[0130] (n) Insects from the order Dermaptera, such as species of the genus Forficula spp.;

[0131] and

[0132] (o) Insects from the order Psocoptera, such as Peripsocus spp.

[0133] In certain implementations, the insects are dipterans, particularly species of the genus *Musca*, such as the housefly (*Musca domestica*); species of the genus *Aedes*, such as *Aedes aegypti*, *Aedes vexans*, and *Aedes albopictus*; and species of the genus *Culex*, such as *Culex pipiens* and *Culex quinquefasciatus*.

[0134] The compositions and methods of the present invention can be used to control arachnids, especially ticks and mites, for example:

[0135] i) Mites, such as *Aculops lycopersicae*, *Aculops pelekassi*, *Aculus Schlechtendali*, *Brevipalpus phoenicis*, *Brevipalpus californicus*, *Bryobia praetiosa*, *Bryobia rubrioculus*, *Dermanyssus gallinae*, *Eotetranychus carpini*, *Eotetranichus lewisi*, *Eutetranychus banksia*, *Eutetranychus orientalis*, *Eriophyes sheldoni*, *Eryophyes tiliae*, *Eriophyes inangulis*, *Eriophyes vitis*, *Oligonychus pratensis*, and *Oligonychus pratensis*. coffeae, Olignitis oryzae, Olignychus milleri, Panonychus ulmi, Panonychus citri, Phyllocoptrutaoleivora, Polyphagotarsonemus latus, Psoroptes ovis, Sarcoptes scabiei, Tarsonemus pallidus, Tetranychus cinnabarinus, Tetranychus kanzawai, Tetranychus pacificus, and Tetranychus urticae.

[0136] ii) Ticks, such as Amblyomma americanum, Amblyomma variegatum, Argas persicus, Boophilus annulatus, Boophilus decoloratus, Boophilus microplus, Dermacentorsilvarum, Hyalomma truncatum, Ixodes ricinus, Ixodes rubicundus, Ornithodorus moubata, Otobius megnini, Rhipicephalus apendiculatus, Rhipicephalus evertsi, and Rhipicephalus microplus.

[0137] preparation

[0138] In some embodiments, the compound of formula (I) and at least one second insecticide are formulated separately for simultaneous or sequential application. In other embodiments, the compound of formula (I) and at least one second insecticide (optionally together with an acceptable carrier, diluent, and / or excipient) are formulated into a single composition.

[0139] In another aspect of the invention, a composition is provided comprising a compound of formula (I) and at least one second insecticide, the composition optionally further comprising a carrier, a diluent and / or an excipient.

[0140] The composition can be formulated into any suitable formulation, such as spray, aerosol, oil, emulsifiable concentrate, wettable powder, flowable formulation, granular formulation, powder, dust, solution, suspension, emulsion, or controlled-release formulation. The composition may be formulated with a solid or liquid carrier, as appropriate. The choice of formulation and method of application will depend on the combination to be used, the pest to be controlled, and the environment in which control is carried out, and will be appropriately selected taking into account the combination, the pest, and the environment.

[0141] In some embodiments, the formulation may contain naturally occurring additives, such as antioxidants and stabilizers. For example, antioxidants may include α-tocopherol, and suitable stabilizers may include gum arabic, guar gum, locust bean gum, xanthan gum, kelgum, polyvinyl alcohol, sodium caseinate, and mixtures thereof.

[0142] Examples of solid carriers useful in the preparation of formulations are clays, including kaolin, diatomaceous earth, water-containing synthetic silicon oxide, bentonite, Fubasami clay, and acid clay; talc; ceramics; and inorganic minerals such as Celite™, quartz, sulfur, activated carbon, calcium carbonate, and hydrated silica; these solid carriers are finely crushed or granular. Examples of useful liquid carriers include water, alcohols such as methanol and ethanol, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, and methylnaphthalene, aliphatic hydrocarbons such as hexane, cyclohexane, kerosene, and light oil, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and isobutyronitrile, ethers such as diisopropyl ether and dioxane, acid amides such as N,N-dimethylformamide and N,N-dimethylacetamide, halogenated hydrocarbons such as dichloromethane, trichloroethane, and carbon tetrachloride, dimethyl sulfoxide and fish oil, mineral oil, plant-derived oils such as canola oil, olive oil, cottonseed oil, soybean oil, and sesame oil, and essential oils such as lavender oil, eucalyptus oil, tea tree oil, and citrus oil. Solid or liquid carriers can be used alone or in combination. Examples of gas carriers (gas carriers for propellants) are butane gas, isobutene, pentane, LPG (liquefied petroleum gas), dimethyl ether, fluorocarbons, and carbon dioxide gas.

[0143] Examples of surfactants include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and their polyoxyethylene adducts, polyethylene glycol ethers, polyol esters, sugar alcohol derivatives, sorbitan monolaurates, alkyl allyl sorbitan monolaurates, alkylbenzene sulfonates, alkylnaphthalene sulfonates, lignin sulfonates, and sulfate salts of higher alcohols. These surfactants can be used alone or in combination.

[0144] Examples of adjuvants (such as binders and dispersants) used in formulations include casein, gelatin, polysaccharides such as starch, gum arabic, cellulose derivatives and alginic acid, lignin derivatives, bentonite, sugars, and water-soluble synthetic high molecular weight substances such as polyvinyl alcohol, polyvinylpyrrolidone, and polyacrylic acid. Examples of stabilizers include PAP (acid isopropyl phosphate), BHT (2,6-di-tert-butyl-4-cresol), BHA (a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), synergists such as piperonyl butoxide, vegetable oils, mineral oils, fish oils, surfactants, and fatty acids or their esters.

[0145] Suitable emulsifiers for use are one or more selected from nonionic or anionic emulsifiers. Examples of nonionic emulsifiers include, but are not limited to, polyoxyethylene alkylphenyl ethers, polyoxyethylene alkyl ethers, polyethylene glycol fatty esters, sorbitan fatty esters, polyoxyethylene sorbitan fatty esters, polyoxyethylene sorbitan fatty esters, and polyoxyethylene polyoxypropylene alkyl ethers. Examples of anionic emulsifiers include alkyl sulfates, polyoxyethylene alkyl ether sulfates, sulfosuccinates, taurine derivatives, sarcosine derivatives, phosphate esters, alkylbenzene sulfonates, etc. A mixture of polyoxyethylene styrene phenyl ether and calcium allylbenzene sulfonate is preferred. These emulsifiers can be used in amounts of 1 to 20 parts by weight per 100 parts by weight of the composition of the present invention.

[0146] In a particular embodiment, the composition is formulated as a spray composition comprising a compound of formula (I) and a second insecticide, wherein the compound of formula (I) is a flamesone and wherein at least one of the second insecticides is an insecticide, including pyrethroids such as permethrin, deltamethrin, or cypermethrin.

[0147] The spray can be formulated as a liquid for use in atomizers or sprayers. In some embodiments, the liquid solubilizes the compound of formula (I) and the second insecticide, for example, where the liquid or solvent is an oil or hydrocarbon solvent. In other embodiments, the liquid is an aqueous liquid, and the formulation is in the form of a suspension or emulsion.

[0148] In some embodiments, the composition may contain a propellant such as butane, isobutene, pentane, carbon dioxide, or nitrogen.

[0149] Spray formulations can be used as insecticides, especially insecticidal aerosols, which are deployed into the air in environments (such as home or industrial settings) to control airborne insects such as flies and mosquitoes. Optionally, the spray formulation can be applied to surfaces on which insects or arachnids may land, such as windowsills, floor surfaces, benches or work surfaces, shelves, steps, etc. When the insects or arachnid pests come into contact with the treated surface, they are exposed to the composition.

[0150] In a particular embodiment of the invention, a composition is provided comprising flamesone and a pyrethroid compound and a liquid carrier, wherein the composition is formulated as a spray composition.

[0151] In some embodiments, the spray composition is a sprayer or atomizer composition.

[0152] In certain embodiments, a method for controlling insects in domestic, industrial, or indoor agricultural environments is provided, the method comprising exposing insects to a combination comprising a flamesone and a pyrethroid compound.

[0153] In some embodiments, the combination is in the form of a single composition. In some embodiments, the composition is a spray composition, such as a sprayer or atomizer composition.

[0154] In some embodiments, the insects targeted are flying insects, such as flies or mosquitoes. In some embodiments, the composition is deployed into the ambient air. In other embodiments, the composition is deployed on one or more surfaces in the environment.

[0155] Advantageously, the combination of flamesone and pyrethroid compounds not only provides a "knockdown" effect on flying insects but also increases mortality. "Knockdown" refers to the rapid loss of ability in insects upon contact with the composition, preventing them from crawling or flying away. Knockdown can be permanent, leading to death; it can also occur over a period of time after which the insect regains its ability to fly and crawl. Rapid knockdown allows insects to remain exposed to the lethal insecticide for a longer period, resulting in higher mortality.

[0156] Reagent test kit

[0157] In another aspect of the invention, a kit is provided comprising a compound of formula (I) or a tautomer thereof and at least one second insecticide.

[0158] Each compound can be formulated into different compositions for individual application. Alternatively, each compound can be formulated into a single composition for combined application.

[0159] In some implementations, the kit includes instructions for use. These instructions may include the appropriate application ratio for a specific insect or arachnid pest or environment, or for mixing the active compounds together.

[0160] In some implementations, the kit may also include a dispensing device, such as a spray bottle or device.

[0161] In order to make the present invention readily understood and put into practice, specific preferred embodiments will now be described by way of the following non-limiting examples. Brief description of the attached diagram

[0163] Figure 1 illustrates the chemical dose-response curves of the peach aphid (M. persicae) 96 hours after exposure to a) flamesone, b) pirimicarb, c) dimethoate and d) α-cypermethrin.

[0164] Figure 2 A graph (black circles) shows the mean aphid mortality rates (for different mixtures of imidacloprid and flamesone) after 96 hours of exposure. The mortality rates of imidacloprid alone at equivalent concentrations are shown in black squares. Error bars indicate standard errors. An asterisk indicates a statistically significant synergistic effect based on a logistic regression model.

[0165] Figure 3 A graph (black circles) shows the average aphid mortality rates (indicating mortality rates) of different mixtures of dimethoate and flamesone after 96 hours of exposure. Mortality rates of dimethoate alone at equivalent concentrations are shown in black squares. Error bars indicate the standard error.

[0166] Figure 4 A graph (black circles) shows the mean aphid mortality rates (indicated by different mixtures of α-cypermethrin and flamesone) after 96 hours of exposure. Mortality rates of α-cypermethrin alone at equivalent concentrations are shown by black squares. Error bars indicate standard errors. An asterisk indicates a statistically significant synergistic effect based on a logistic regression model.

[0167] Figure 5 illustrates the dose-mortality assays, evaluating the effects of synthetic pyrethroid (SP) permethrin alone (5 dose points, circles) and synthetic pyrethroid (SP) permethrin versus single LC at (A) 24 hours and (B) 48 hours post-treatment. 10 Synergistic interactions of combined flavesone doses at dose points (squares) on susceptible strains of Aedes aegypti L3 Liverpool (LVP) SP. Figure 5(c) shows the LC50 interactions at 24 and 48 hours. 10 and LC 90A single-dose point-administered positive control of flamesone. Data represent n = 3 biological replicates.

[0168] Figure 6 provides a diagram of dose-mortality determination, which evaluated the effects of synthetic pyrethroid (SP) permethrin alone (5 dose points, circles) and synthetic pyrethroid (SP) permethrin versus single LC at (A) 24 hours and (B) 48 hours post-treatment. 10 Synergistic interactions of combined flavesone doses at dose points (squares) against the Aedes aegypti L3 Puerto Rican (PRS) SP resistant strain. Figure 5(c) shows the LC50-24 hour and LC50-28 hour doses. 10 and LC 90 A single-dose point-administered positive control of flamesone. Data represent n = 3 biological replicates. Example

[0169] Example 1

[0170] A spray composition was prepared by mixing 100g of permethrin and 500g of flamesone in 1L of hydrocarbon solvent. The formulation was then placed in a pump-spray container for application.

[0171] Example 2

[0172] The following formulations were prepared:

[0173] 1. Flavesone in hydrocarbon liquids: 200 mg / mL

[0174] 2. Flavesone in hydrocarbon liquids: 100 mg / mL

[0175] 3. Permethrin in the hydrocarbon liquid: 2.5 mg / mL

[0176] 4. Permethrin in the hydrocarbon liquid: 1.25 mg / mL

[0177] 5. Combinations in hydrocarbon liquids 1

[0178] flavesone 200mg / mL

[0179] Permethrin 2.5 mg / mL

[0180] 6. Combinations 2 in hydrocarbon liquids

[0181] flavesone 200mg / mL

[0182] Permethrin 1.25 mg / mL

[0183] 7. Combinations 3 in hydrocarbon liquids

[0184] flavesone 100mg / mL

[0185] Permethrin 2.5 mg / mL

[0186] 8. Combinations in liquid hydrocarbons (4)

[0187] flavesone 100mg / mL

[0188] Permethrin 1.25 mg / mL

[0189] Fill each formulation into a handheld pump sprayer. Apply the treatment to the tile at a distance of 20 cm. Place the tile 0.5 m away. 2 On the grid, and at 50 mL / m 2 The spraying rate covers the entire 0.5m area, including the ceramic tile. 2 To ensure the correct volume is applied, the pump sprayer is weighed before and after spraying.

[0190] Before the evaluation begins, leave the tiles for two hours after treatment to allow the preparation to dry on the tiles.

[0191] A control tile that was not treated with any formulation (untreated) was also used.

[0192] Using a powered suction device, ten mixed-sex houseflies (Musca domestica) were placed in a plastic petri dish. The dish was then placed on either a treated ceramic tile surface or a control ceramic tile surface. The petri dish had perforations for ventilation, and cotton plugs soaked in a sugar solution provided moisture and blocked the insect introduction holes in the dish.

[0193] Houseflies were continuously exposed to treated or untreated tile surfaces. Exposure was conducted at a temperature of 22±2°C and a relative humidity (RH) of approximately 50%.

[0194] After 30 minutes of exposure, place a piece of paper on the tile surface to prevent houseflies from coming into contact with the treated or untreated tiles. Expose the houseflies to the tiles for 24 hours at 22±2°C and approximately 50% RH.

[0195] Housefly knockdowns were recorded 15 and 30 minutes after exposure, and 1, 2, 3, and 4 hours after initial exposure. Deaths were recorded 24 hours after initial exposure.

[0196] The experiment was repeated four times to give five replicates. No statistical analysis was performed. The results are shown in Table 1:

[0197] Table 1: Housefly mortality at different exposure times

[0198]

[0199]

[0200] Table 1: Housefly Mortality at Different Exposure Times (Continued)

[0201]

[0202] Table 1: Housefly Mortality at Different Exposure Times (Continued)

[0203]

[0204]

[0205] Individually formulated flamesone

[0206] Flavesone alone, formulated at ratios of 200 mg / mL and 100 mg / mL, achieved 100% housefly knockdown after 15 minutes of exposure. For both formulations of flamesone, mortality was 100% at 24 hours post-initial exposure.

[0207] Permethrin alone

[0208] At both the 2.5 mg / mL label ratio and 50% of the 1.25 mg / mL label ratio, permethrin alone did not achieve 100% housefly knockdown at any evaluation time. One hour after initial exposure, both ratios achieved 94%; however, some recovery was observed. At 24 hours after initial exposure, housefly mortality was 72% at the 2.5 mg / mL ratio and 62% at the 1.25 mg / mL ratio.

[0209] The combination of flavesone and permethrin

[0210] All four combinations of the formulated flavorone and permethrin achieved 100% knockdown after 15 minutes of exposure. The mortality rate was 100% at 24 hours after initial exposure.

[0211] Comparison

[0212] The mortality rate in controls 24 hours after initial exposure was 4%.

[0213] Example 2: Effects of flavesone on the electrophysiological activity of dorsal root ganglia

[0214] Dorsal root ganglion (DRG) cells were obtained from adult male Sprague-Dawley rats weighing 220-250g. The rats were housed in groups of four in an air-conditioned room with a 12-hour light / dark cycle and were provided with food and water at will.

[0215] Cell separation

[0216] Animals were humanely euthanized, and DRGs from the lower thoracic and upper lumbar regions were removed and stored in frozen phosphate-buffered saline (PBS). The DRGs were carefully trimmed and then digested in a 37°C shaking water bath for 45–60 min with freshly prepared 2 mg / mL trypsin (XII-S type) and 2 mg / mL collagenase (XI type) in PBS. Subsequently, after thorough washing with PBS and then with plating medium (PM; a 50:50 mixture of DMEM / Hams F12 supplemented with 10% fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin), the DRGs were carefully prepared using sterile, flame-polished glass pipettes with decreasing diameters. Cells were then plated onto coated glass coverslips (BD Biosciences, BD Biocoat, poly-D-Lysine) included in 35 mm tissue culture dishes for easy transfer to the recording chamber mounted on an Olympus IX51 vertical microscope for electrophysiological recording. Cells were incubated under standard tissue culture conditions (36°C, in a humid atmosphere of 5% CO2 and 95% air) and used within 48–72 hours after plating.

[0217] Electrophysiological recording

[0218] Whole-cell patch-clamp recordings were performed at room temperature (-21°C) using an Axopatch 200B amplifier (Axon Instruments Inc., USA) with 3–7 MΩ electrodes (depending on patch success rate and recording quality). Data were filtered and appropriately digitized. Current-clamp recordings were performed using a pipette solution containing 140 mM KCl, 0.5 mM EGTA, 5 mM HEPES, 3 mM Mg-ATP, and 3 mM Na-GTP (pH 7.3), adjusted to 310 mOsm / L with glucose. The bathing solution contained 140 mM NaCl, 3 mM KCl, 2 mM MgCl2, 2 mM CaCl2, and 10 mM HEPES (pH 7.3), adjusted to 315 mOsm / L with glucose. During the first few minutes after establishing whole-cell configuration, passive membrane properties (e.g., resting membrane potential (Vm)) were monitored periodically during recording. Evoked potential recording began 3–5 minutes after establishing whole-cell configuration.

[0219] On the day of recording, a flamesone test solution was freshly prepared from the stock solution (96.7% w / w). 100 μL of the flamesone composition was mixed with 100 μL of Tween 80 and diluted to 10 mL in artificial cerebrospinal fluid (aCSF) to provide a final flamesone concentration of 1%. Immediately before use, the pH of the 1% solution was adjusted to 7.3 with 1M NaOH and diluted to 0.5% and 0.25% flamesone concentrations with aCSF containing 1% Tween 80. The test compound was applied using a DAD-16VC rapid perfusion system (ALAS Scientific Instruments, USA) and compared with results collected using a control procedure. The control was aCSF containing 1% Tween 80.

[0220] Comparative samples of permethrin were prepared as 100 μM benzylpermethrin in dimethoxysulfuron (DMSO).

[0221] analyze

[0222] All analyses were performed using Clampfit (MDS Analytical Technologies) and Excel (Microsoft) software. Student's t-test was used for statistical comparisons between groups, and a p-value < 0.05 was used to determine statistical significance.

[0223] Table 2 shows the effect of different concentrations of flamesone on membrane potential.

[0224] Table 2

[0225]

[0226] Table 3 shows the effects of 100 μM permethrin in the same experiment, compared with 0.5% flamesone.

[0227] Table 3

[0228]

[0229] Flavesone reduced the average resting potential (Vm) in cells from approximately -62 mV to approximately -84 mV. This result indicates that flamesone activates one or more potassium channels.

[0230] In contrast, permethrin (100 μM) had no effect on the mean resting potential (Vm).

[0231] The effects of flamesone and permethrin on the action potential discharge characteristics of DRG were examined. The results are shown in Tables 4 to 9.

[0232] Table 4

[0233]

[0234]

[0235] Table 5

[0236]

[0237] Table 6

[0238]

[0239] Flavesone slightly reduced the action potential number (Table 4) and the amplitude of the action potential (Table 5). However, flamesone had no significant effect on the action potential threshold (Table 6).

[0240] Table 7

[0241]

[0242] Table 8

[0243]

[0244]

[0245] Table 9

[0246]

[0247] In contrast, permethrin (100 μM) significantly reduced action potential (Table 7), but had no effect on action amplitude (Table 8) or action potential threshold (Table 9).

[0248] Pyrethroids, such as permethrin, are known sodium channel modulators. The effects of flamesone and permethrin on sodium conductance in DRG were examined. Results are shown in Tables 10 to 12.

[0249] Flavesone had no significant effect on sodium conductivity amplitude (Table 10), and there were no significant differences in the area under the curve (AUC) between the control, 0.5% flamesone, 1% flamesone, and washing with Tween 80.

[0250] Although permethrin has a small effect on the amplitude of sodium conductivity (Table 11), the area under the curve (AUC) is significantly increased (Table 12).

[0251] Table 10

[0252]

[0253] Table 11

[0254]

[0255] Table 12

[0256]

[0257] In summary, flamesone induces significant membrane hyperpolarization in DRG neurons, which rapidly recovers upon washing. Permethrin has no effect on the membrane potential of DRG neurons. Flavesone also reduces the input resistance in DRG neurons, indicating the opening of ion channels in the membrane. The resting potential derived from the current-voltage relationship is approximately -84 mV, indicating the activation of one or more potassium channels in the presence of flamesone. In contrast, permethrin has no effect on the input resistance of DRG neurons.

[0258] Flavesone reduced action potential and action potential amplitude in DRG neurons, although these effects are likely due to a direct membrane shunt caused by potassium conductance activation rather than a direct effect on the action potential itself. Permethrin also significantly reduced action potential in DRG neurons but had no effect on their mean amplitude. The reduction in action potential reflects slowed channel inactivation and deactivation, leading to prolonged channel opening time. The threshold of action potential discharge was largely unaffected by either flamesone or permethrin. When evaluated in a voltage-clamp recording configuration, flamesone reduced sodium channel conductance by approximately 20%, although this difference was not significant compared to control and had no effect on channel inactivation / deactivation. Permethrin had a small effect on the peak sodium channel conductance but significantly prolonged channel inactivation.

[0259] These results indicate that flamesone activates potassium channels but has no effect on sodium channels, while permethrin (a known sodium channel modulator) affects sodium channels but has no effect on potassium channels.

[0260] Example 3: Evaluation of the combination of flamesone and methyl chlorpyrifos (Reldan) against major stored grain pests resistant to commonly used insecticides.

[0261] For this experiment, laboratory-established strains (both susceptible and resistant) of five species were considered. The resistant strains listed below represent cereal protectant-resistant genotypes commonly encountered in cereal storage in Australia, particularly in the Eastern Grain Belt:

[0262] • The grain beetle strain QRD1440 is resistant to OP protectant and pyrethroids.

[0263] • The red prawn bark cultivar QTC279 exhibits resistance to malathion and bio-benzylfuran.

[0264] • Rusty Red Flat Valley Stealth Series QCF73 is resistant to phosphides

[0265] • Sawmill looter strain QOS302 is resistant to fenitrothion and methyl chlorpyrifos.

[0266] The rice weevil strain QSO393 is resistant to fenitrothion.

[0267] Test program

[0268] Grain processing and bioassay

[0269] This study used organically produced wheat that was free of residues and insects. The moisture content of the wheat was maintained at 11% before treatment. The chemicals used in these experiments, flamesone and Reldan (500 g / L methyl chlorpyrifos), were obtained from Bio-Gene Technology and Dow AgroSciences, respectively. For the independent flamesone experiments, two ratios (25 and 60 ppm) were considered.

[0270] For each strain of borer (internal feeder), grain beetle, and rice weevil, three batches of 160g wheat were weighed into glass jars (500mL capacity), i.e., one jar for each treatment and one for the control (distilled water only). The solution for each treatment (prepared individually and in combination at predetermined dilution ratios) was aspirated separately into the glass jar immediately above the grain surface at a ratio equivalent to 10mL solution / kg wheat. Distilled water was applied to the control grain at the same ratio as the treatment. All jars were sealed, briefly shaken and inverted by hand, and then mechanically agitated for 1 hour. The moisture content after treatment was 12%, reflecting the upper limit accepted by Australian bulk cargo handling companies. On the first day after treatment, each 240g batch of wheat was divided into three replicates of 80g each, which were placed in separate glass jars (250mL capacity). For red flour beetle, rusty red flour beetle, and sawtooth flour beetle, the procedure remained unchanged except that three batches of 600g wheat were treated for each strain. On the first day after treatment, each 600g batch of wheat was divided into three replicates of 190g each, which were then placed in glass jars (500mL capacity). The remaining 30g of wheat was ground into flour, divided into three batches of 10g each, and added to the relevant whole wheat replicates, so that each replicate weighed a total of 200g. Grinding 5% of each replicate into flour was intended to improve the reproduction of the three pest species (who are external breeders). The above activities were repeated twice over the next two days, resulting in a total of three replicates for each treatment.

[0271] Bioassays were initiated by adding 50 adults (1–3 weeks post-emergence) to each container of treated or control wheat. Each container was covered with a filter paper lid and stored in a constant-environment chamber at 25°C and 55% RH for 2 weeks, after which adults were sieved from the wheat and mortality was recorded. Subsequently, all adults (dead and surviving) were discarded and the wheat containers were incubated for an additional 6 weeks, during which the number of adult offspring was recorded. To ensure synchronized emergence of offspring, containers containing rice weevils and sawtooth beetles were incubated at 25°C and 55% RH, while containers containing other species were incubated at 30°C and 55% RH.

[0272] Data Analysis

[0273] Each dataset is presented in a simple table containing the percentage of adult mortality and the number of surviving adult F1 offspring for each species (mean ± standard error of 3 replicates), as well as the percentage reduction in offspring calculated based on the mean number of F1 offspring in treated wheat and untreated controls.

[0274] In all treatment combinations, the control mortality rates in both susceptible and resistant strains of all five species were negligible (0–3%) (Tables 13–17). In the controls, the number of adult offspring produced was 186 for both the susceptible (QRD14) and resistant (QRD1440) strains of *Carex spp.* (Table 13); 59 (QTC4) and 480 (QTC279) for *Triticum aestivum* (Table 14); 467 (QCF31) and 188 (QCF73) for *Triticum aestivum* (Table 15); 526 (VOS48) and 429 (QOS302) for *Triticum aestivum* (Table 16); and 720 (LS2) and 565 (QSO393) for the susceptible and resistant strains of *Rhizoctonia solani* (Table 17).

[0275] All experimental combinations of flamesone and methyl chlorpyrifos applied at both high and low ratios were highly successful for all susceptible lines of the five tested species, achieving 100% adult mortality and offspring reduction (Tables 13–17). The efficacy of all these combinations was greatest for resistant lines of *Russula fruticosa*, where complete control of adults and offspring was achieved (Table 16). Furthermore, except for a few combinations with offspring reduction of 99%, all these treatments achieved 100% offspring control in resistant lines of *Russula fruticosa* (QTC279), *Russula fruticosa* (QOS302), and *Rhizoctonia solani* (QSO393) (Tables 14, 16, and 17). However, for the resistant strain of cereal beetle (QRD1440), complete adult mortality was only achieved when using the combination of flamesone 60 + methyl chlorpyrifos 5, and complete offspring reduction was achieved in cereals treated with the combination of flamesone 30 + methyl chlorpyrifos 10, flamesone 60 + methyl chlorpyrifos 5, and flamesone 60 + methyl chlorpyrifos 10 (Table 13).

[0276] Table 13. Efficacy of the combination of Flavesone and methyl chlorpyrifos (OP) against adult and progeny grain borers in treated wheat.

[0277]

[0278]

[0279] *Mean ± Standard Error

[0280] Table 14. Efficacy of the combination of Flavesone and methyl chlorpyrifos (OP) against adult and progeny red flour beetles in treated wheat.

[0281]

[0282] *Mean ± Standard Error

[0283] Table 15. Efficacy of the combination of Flavesone and methyl chlorpyrifos (OP) against adult and progeny of the rusty flat flour beetle in treated wheat.

[0284]

[0285]

[0286] *Mean ± Standard Error

[0287] Table 16. Efficacy of the combination of Flavesone and methyl chlorpyrifos (OP) against adult and progeny sawtooth beetles in treated wheat.

[0288]

[0289] *Mean ± Standard Error

[0290] Table 17. Efficacy of the combination of Flavesone and methyl chlorpyrifos (OP) against adult and progeny rice weevils in treated wheat.

[0291]

[0292]

[0293] *Mean ± Standard Error

[0294] Table 18 provides an overview of the efficacy of the combination of methyl chlorpyrifos and flamesone.

[0295] Table 18. Overview of the efficacy of Flavesone combined with methyl chlorpyrifos (CM) in different ratios against five major stored grain pests.

[0296]

[0297]

[0298] Example 4: Evaluation of the combination of flamesone and deltamethrin (K-Obiol) on susceptible and resistant strains of cereal beetle.

[0299] The experiments of Example 3 were repeated using a combination of flamesone and deltamethrin, as well as the susceptible strain QRD14 and the resistant strain QRD1440.

[0300] In these experiments, control mortality rates remained below 1% in both the susceptible and resistant strains of the species, with similar numbers of live adult offspring (126 and 125) (Table 19). Complete control of adults and offspring was achieved in all combinations for the susceptible strain (QRD14), while a high level of control was achieved for the resistant strain (QRD1440) (Table 19). For adults in the resistant strain, the mortality rate was 93–100% in all combinations. Similarly, all combinations resulted in a 99–100% reduction in offspring for the resistant strain QRD1440 (Table 19).

[0301] The results are shown in Table 19.

[0302] Table 19. Efficacy of the combination of Flavesone and deltamethrin against adult and progeny grain borers in treated wheat.

[0303]

[0304] *Mean ± Standard Error

[0305] Example 5: Combination of Flavesone with one of pirimicarb, dimethoate, or α-cypermethrin and its activity against susceptible green peach aphid populations.

[0306] Research nature

[0307] The green peach aphid (Myzus persicae) is a significant pest of many crops, particularly due to its ability to transmit plant viruses. Control of this pest largely relies on the application of broad-spectrum insecticides. However, in Australia, resistance to multiple chemical classes, including pyrethroids, organophosphates, carbamates, and neonicotinoids, is widespread among peach aphids. This study aimed to examine the potential synergistic effects of flavorone in combination with three standard commercial products—Pirimor, Astound Duo, and dimethoate 400—on insecticide-sensitive peach aphid populations.

[0308] method

[0309] Following the method of Belden & Lydy (2000, Environmental Toxicology and Chemistry, 19(9):2266-2274), two bioassays were used to determine whether there was a synergistic effect between flamesone and different concentrations of pirimicarb, dimethoate, or α-cypermethrin on peach aphids. The first bioassay was performed to generate dose-response curves for each individual insecticide against peach aphids (Figure 1(ad)). The concentration range for each insecticide was 1 x 10⁻⁶ of the field ratio. -4 Up to 10 times (Table 20). LC values ​​for each insecticide were calculated from the dose-response curves of 96-hour exposure using a logistic regression model with random effects (Robertson & Preisler 1992, Pesticide Bioassays with Arthropods. CRC: Boca Ratan; Venables & Ripley 2002, Modern Applied Statistic with S, Spring: New York (http: / / www.stats.ox.ac.uk / pub / MASS4)). Logistic regression was suitable for the analysis of binary response data (i.e., death / survival), and the random effects component of the model controlled for the non-independence of aphid mortality scores in replicate samples.

[0310] The second bioassay evaluated the toxicity of low concentrations of flamesone against three standard insecticides. Four concentrations of each insecticide were selected, each expected to provide approximately 10-60% mortality. These were assessed individually and in conjunction with their corresponding LC values. 15 and LC 30 The values ​​were tested in combination with two concentrations of flavesone (1200 and 1800 mg ai / L flavesone, respectively).

[0311] Table 20: Field ratios of insecticides with synergistic effects against peach aphids tested using laboratory bioassays

[0312]

[0313]

[0314] Bioassays were performed following the leaf dip method described by Moores et al. (1994, Pesticide Biochemistry and Physiology, 49, 114-120). Leaf discs (25 mm in diameter) cut from cabbage leaves (Brassica napuschinensis) were immersed in an insecticide solution or water (control) for 1 second and then placed adaxially upward on 10 g / L agar in 35 mm petri dishes. Seven to eight replicate leaf discs were prepared for each treatment. After the leaves were air-dried, eight peach aphid nymphs from a known insecticide-susceptible population (originally collected from Shepparton, VIC and maintained in the laboratory since 2002) were transferred to each insecticide-dipped leaf disc using a fine-bristled brush. Each petri dish was inverted over a lid containing 25 mm diameter filter paper to control humidity and sealed with parafilm to prevent aphid escape. All petri dishes were then placed in an incubator maintained at 18℃±2℃ with a photoperiod of 16:8LD cycles. At 48 and 96 hours, aphids were scored as alive (vibrant and freely moving), dead (no movement within a 5-second time interval), or incapacitated (inhibited movement). Incapacitated individuals were grouped together with dead individuals for analysis, as they were all dead and therefore would not contribute to the next generation.

[0315] Data Analysis

[0316] To determine whether synergistic effects exist when chemicals are mixed, the observed toxicity of the mixture is compared with the predicted co-toxicity derived from knowledge of the toxicity of each individual component (Cedergreen et al. 2013, Toxicity Prediction of Chemical Mixtures. In Encyclopaedia of Environmental Management. Taylor and Francis: New York. Published online: 3 May 2013: 2572-2581). The most widely established method for predicting the co-toxicity of chemical mixtures is concentration addition (CA) (Loewe 1926, Archive for Experimental Pathology and Pharmacology, 114: 313-326), which assumes no interaction between the components. To calculate the co-toxicity of chemicals using CA, the concentration of each chemical in each mixture is normalized to its individual toxicity, termed a toxicity unit (TU). The value of 1 TU is assigned to the 50% lethal concentration (LC) of the chemical. 50 The TU values ​​are then summed, as shown below, to provide a prediction of the toxicity of the insecticide mixture:

[0317]

[0318] Among them, Cw i It refers to the concentration of chemicals in the mixture, and the LC50. i The LC values ​​for the corresponding chemicals are from 1 to 5. 50 (Pape-Lindstrom & Lydy 1997, Environmental Toxicology and Chemistry, 16(11):2415-2420). After 96 hours of exposure, the LC of each standard chemical was recalculated based on aphid mortality data from treatments containing only the standard chemicals. 50 Values. LC was calculated using a logistic regression model and the Fieller method (Finney 1971, Probit analysis, Cambridge University Press, Cambridge, UK). 50 Values ​​and associated 95% confidence intervals (CIs). LC values ​​for flavesone were calculated based on previous bioassays. 50 The value is insufficient to calculate the LC value because two concentrations of the chemical are not enough. 50 value.

[0319] The empirically determined toxicity (and 95% CI) for each mixture was calculated by dividing the mortality rate by 50 to provide the observed toxicity (TU). 观察到的 ), and then compared it with the predicted toxicity (TU). 预测的 The comparison was performed. The null hypothesis for the synergistic effect test is that the toxicity of the insecticide mixture will demonstrate concentration summation (i.e., the observed peach aphid mortality rate upon exposure to the insecticide mixture will equal the mortality rate predicted by the toxicity unit model). An alternative hypothesis is that exposure to the insecticide mixture will result in either a greater-than-additive response (synergistic or combined toxicity of interactions) or a less-than-additive response (antagonistic effect) (i.e., the 95% CI of the observed TU for each mixture will not overlap with the predicted TU).

[0320] The CA method indicated that some mixtures exhibited greater than additive toxicity. To confirm the existence of synergistic effects in these cases, mortality data from eight replicate petri dishes of the mixture, as well as mortality data for individual flamesone and standard chemicals, were analyzed using a logistic regression model that included the interaction effects between the two insecticides.

[0321]

[0322] Where Cw1 is the concentration of the standard insecticide in the mixture, and Cw2 is the concentration of flamesone. The significant interaction effect (γ) is greater than the summative toxicity (Belden & Lydy 2000, as mentioned above).

[0323] All analyses were performed using R version 3.3.1 (R Development Core Team 2016).

[0324] result

[0325] Table 21 shows the mortality rates of peach aphids 96 hours after exposure to individual insecticides at the concentrations used in the synergistic effect test mixture. The LC ratios were calculated based on the mortality response at these concentrations. 50 The LC values ​​(and 95% CI) were: imidacloprid, 19.7 (17.3–22.4) mg ai / L; dimethoate, 526 (420–643) mg ai / L; α-cypermethrin, 44.6 (36.2–54.9) mg ai / L. The LC values ​​for Flavesone were... 50 The value was previously calculated to be 2,731 (2,259–3,303) mg ai / L.

[0326] The mortality rates following exposure to a combination of flamesone with imidacloprid, dimethoate, and α-cypermethrin were respectively... Figure 2-4 The graph is drawn in black. The mortality response to the same concentration of each standard insecticide applied alone is drawn in squares.

[0327] Table 21. Average aphid mortality rate when insecticides are applied alone at the concentrations used in the mixture. Standard error is included in parentheses.

[0328] Comparison - 11.2(3.9) Flavesone 1200 10.9(4.4) Flavesone 1800 25.7(12.4) Aphid-resistant 10 20.3(8.5) Aphid-resistant 18.5 36.1(10.6) Aphid-resistant 23 82.8(9.1) Aphid-resistant 30 76.2(14.4) Lego 300 38.4(13.8) Lego 430 41.4(13.6) Lego 800 66.5(13.4) Lego 1100 81.3(9.1) α-Cypermethrin 16 21.6(7.2) α-Cypermethrin 40 44.9(6.0) α-Cypermethrin 60 52.2(10.6) α-Cypermethrin 80 86.9(6.5)

[0329] The toxicity of each insecticide mixture predicted by the CA method, and the observed toxicity calculated from mortality data, are shown in Table 22. For insecticide mixtures, the 95% CI of the observed TU for each mixture does not overlap with the predicted TU, indicating evidence of synergy, and is indicated by an asterisk. For each of the three standard insecticides, the CA method identified at least one mixture combination for which the detected toxicity was greater than the sum of the toxicities. These synergies were only evident at low concentrations of the standard insecticides.

[0330] Further analysis using a logistic regression model showed that there was a difference between 10 mg ai / L of imidacloprid and 1800 mg ai / L of flamesone (x... 2 =4.23, p<0.05) and between 16 mg ai / L α-cypermethrin and 1200 mg ai / L flamesone (x 2 =12.5, p<0.001) indicates a statistically significant interaction.

[0331] Table 22. Response of peach aphids to exposure to flamesone and mixtures of three standard insecticides at different concentrations. Mortality was assessed 96 hours after exposure, and standard error is included in parentheses. Predicted toxicity (TU) was calculated according to Equation 1. 预测的 The observed toxicity (TU) was calculated by dividing the mortality rate by 50. 观察到的 According to the CA method, toxicity greater than additive (synergistic) (where the observed toxicity has a 95% CI greater than the predicted toxicity) is indicated by an asterisk, and in these mixtures, by logical...

[0332] Statistically significant synergistic effects detected by the regression model are indicated by two asterisks.

[0333]

[0334]

[0335] Conclusion: The results of this study demonstrate evidence of a synergistic effect of flamesone when combined with certain concentrations of pirimicarb and α-cypermethrin. When combined with standard insecticides, there was no clear pattern at which flamesone exhibited a synergistic effect, and in this study, the synergistic effect was only observed at low concentrations of the standard insecticides.

[0336] Although the CA method highlights several mixtures for which it detected toxicity greater than the sum of its toxicities (including one containing dimethoate), the model does not account for control mortality rates greater than 0%. Therefore, a logistic regression model is used to provide a more conservative statistical test for mixtures exhibiting synergistic effects.

[0337] Example 5: Local dose-mortality determination of mosquito larvae to study synergistic effects

[0338] The efficacy of the flamesone formulation against mosquito larvae was investigated, and the potential for synergistic effects between flamesone and one or more technical-grade insecticides was explored. Dose-mortality assays were performed to assess the toxicity of the technical-grade insecticides, with single application of synthetic pyrethroid (SP) permethrin at different concentrations (minimum 5 dose points) and co-application with a single dose of flamesone. Assays were performed using L3 larvae of the Liverpool strain (susceptible to SP) and the Puerto Rican strain (SP resistant) of *Aedes aegypti*, continuously cultured and maintained at Purdue University, USA. Larvae were transferred to 24-well tissue plates using a wide-mouth plastic transfer pipette, 5 larvae per well. Water was gently removed from the wells with a 1 mL pipette, and an equal volume of ddH₂O was added. An appropriate volume of the test compound was added to each well of the four replicates for each treatment, and the plate was gently vortexed to ensure homogeneous mixing. Plates were placed in a test or growth chamber under constant conditions of 22–25°C and approximately 75–85% relative humidity, with a 12-hour light / 12-hour dark cycle. Assays were scored at 24, 48, and 72 hours post-exposure to confirm the phenotypic endpoint of death / paralysis. Each assay included a positive control (flavesone) and a negative control (mediator only), and at least four technical replicates were performed for each dose of the test chemical. Data reported here represent three biological replicates.

[0339] First, experimental assays were used to determine the appropriate flavesone dose for synergistic assays (such as the LC determined in previous dose-mortality tests). 50 LC 25 or LC 10 (Dosage). Based on these studies, the LC50 of flamesone was determined. 10The dosage was optimal for synergistic capture effects (higher doses combined with SP could result in 100% mortality in the test mosquito population, thus masking any potential synergistic effects). Dose-response curves are provided (Figures 5 and 6), as well as lethal concentrations (LC50) of the insecticide ± flamesone. 50 Data and 95% CL values ​​(Table 23). The synergistic ratio (SR) of the insecticide + flamesone combination is also shown, and the synergistic effect is evaluated based on studies published by Ahmed and Matsumura (2012, Journal of Medical Entomology 49(6):1405-10) and Ahmed and Vogel (2015, Acta Tropica 155:1-5).

[0340] Table 1. Synthetic pyrethroids, permethrin, and flamesone (LC) at 24 and 48 hours post-exposure. 10 The toxicity of the drug to L3 larvae of the Liverpool strain (susceptible to SP) and the Puerto Rican strain (SP-resistant) after co-application (at the specified dosage) was assessed. Toxicity was reported as lethal concentration (LC50). 50 Values, 95% confidence intervals. Synergistic ratio (SR) and p-value are shown; n = 3 biological replicates.

[0341]

[0342] n a Total number of larvae per n = 3 biological replicates

[0343] SR, Synergy Ratio; LC 50 Permethrin / LC 50 Permethrin + Flavesone

[0344] P-value; calculated using t-test and SR value, **p<0.01

[0345] result

[0346] Unlike the application of permethrin alone, LC 10 Co-administration of the dose of flavesone with SP and permethrin reduced the LC at 24 and 48 hours after exposure to the test chemical. 50 Values ​​(Figs. 5 & 6; Table 23). In Figs. 5 and 6, the dose-response curves shift to the left (squares; permethrin + flamesone). This effect was observed in both SP-susceptible mosquito strains (Liverpool, LVP) and SP-resistant mosquito strains (Puerto Rico, PRS) treated with SP + flamesone, but was more pronounced in the Liverpool strain. The LC values ​​obtained for Puerto Rico strain larvae were significantly higher than those for Liverpool strain larvae.50 The dosage was also higher (Table 23), reflecting approximately 10 times the resistance to permethrin in this strain. In summary, these data suggest that low doses of flamesone can extend the utility of commercial SPs.

[0347] The data support the synergistic activity of permethrin and flamesone against the Liverpool (SP-susceptible) strain at 24 and 48 hours (p < 0.01). Under the conditions used here (LC... 10 The data (at the appropriate flavesone dose) support the combined effects against Puerto Rican (SP-resistant) strains. This observation may reflect a synergistic effect involving the low flavesone dose used in the experiments or pathways related to voltage-gated sodium channels and / or cytochrome P450 metabolism (both mechanisms previously reported in PRS strains). Further studies using higher doses of flavesone may reveal synergistic activity involved in PRS strains. These results suggest that low doses of flavesone can work synergistically with SP insecticides such as permethrin and extend the utility of this class against SP-sensitive insects.

[0348] As observed in previous studies, the addition of flamesone resulted in a distinct “lethal” larval phenotype (larvae that did not respond at the bottom of the wells on the plate), in contrast to permethrin-treated larvae, which could recover activity after exposure to sublethal doses.

Claims

1. A method for controlling peach aphids ( Myzus persicae The method comprises exposing the peach aphid to a combination of 1800 mg ai. / L of flamesone and 10 mg ai. / L of pirimicarb or a combination of 1200 mg ai. / L of flamesone and 16 mg ai. / L of α-cypermethrin.

2. A composition comprising: a) 1800 mg ai / L of flamesone and 10 mg ai / L of pirimicarb; or b) 1200 mg ai / L of flamesone and 16 mg ai / L of α-cypermethrin.

3. The composition according to claim 2, wherein the composition is formulated for spraying applications.

4. The composition according to claim 3, wherein the spraying application is performed by an atomizer or sprayer.

5. A kit comprising: a) 1800 mg ai / L of flamesone and 10 mg ai / L of pirimicarb; or b) 1200 mg ai / L of flamesone and 16 mg ai / L of α-cypermethrin.

Images