BR122024009701A2 - POLYMORPHS, AGRICULTURAL COMPOSITIONS COMPRISING THE SAME AND METHOD OF PREVENTING OR CONTROLLING INSECT INFECTION IN PLANTS OR PLANT PROPAGATION MATERIAL - Google Patents

Abstract

POLYMORPHS, AGRICULTURAL COMPOSITIONS COMPRISING THE SAME AND METHOD OF PREVENTING OR CONTROLLING INSECT INFECTION IN PLANTS OR PLANT PROPAGATION MATERIAL The present invention relates to solid forms of the insecticide of formula I: I, compositions comprising the solid forms and methods of their use as insecticides.

Description

[0001] This invention relates to solid forms of an isoxazoline derivative, compositions comprising the solid forms and methods of using them as insecticides.

[0002] Document WO 2011/067272 discloses that certain isoxazoline derivatives have pesticide activity, in particular, insecticidal, acaricidal, molluscicidal and nematicidal activity. In particular, a compound of formula I is disclosed:

[0003] Mixtures of this compound with other insecticides are disclosed in document WO 2012/163960 and with fungicides in document WO 2012/163945.

[0004] New solid forms of this compound and its isomers, their compositions and methods for their preparation and use have now been discovered.

[0005] There are four isomers of the compound of formula I: A, B, C and D, as shown below. The present invention relates to polymorphic forms of all these isomers, in combination or in isolated form.

[0006] Accordingly, the present invention relates to new crystalline forms of the compound of formula IA, designated as Form A(a). This crystalline polymorph, Form A(a), can be characterized by the single-cell parameters of its single crystal as shown in Table 1. The polymorph was obtained using the method described in Example 1. TABLE 1

[0007] In the table, a, b, c = Length of the ends of the single cell; α, β, Y = Single cell angles; and Z = molecules per cell.

[0008] Therefore, in one embodiment of the present invention, the crystalline polymorph designated Form A(a) has the following lattice parameters: a = 5.06 Â ± 0.01 Â, b = 18.92 Â ± 0, 01 Â, c = 24.17 Â ± 0.01 Â, α = 90° ± 0.01°, β = 90° ± 0.01°, Y = 90° ± 0.01° and volume = 2315 Â3± 1 Â3.

[0009] The crystalline polymorph, designated Form A(a), can also be characterized by a powder X-ray diffraction pattern expressed in terms of 2θ angles or d spacings. Thus, in another embodiment of the invention, the crystalline polymorph has a powder X-ray diffraction pattern comprising at least three, at least six or all angle 2θ values selected from the group consisting of 6.0 ± 0.2, 8.8 ± 0.2, 9.4 ± 0.2, 10.1 ± 0.2, 11.9 ± 0.2, 14.5 ± 0.2, 15.9 ± 0.2, 20, 2 ± 0.2, 20.7 ± 0.2, 21.2 ± 0.2, 21.7 ± 0.2, 22.1 ± 0.2 and 22.7 ± 0.2. These peak values, along with the corresponding d-spacing values are shown in Table 2 below: TABLE 2

[0010] These 2θ angle values are derived from a powder X-ray diffraction pattern of the polymorph obtained using the method of Example 1. The values are generated using an average wavelength of 1.54056Â with a 2θ step size of 0.02°.

[0011] In another embodiment, the crystalline polymorph designated as Form A(a) has a melting point of 141 °C ± 2 °C. This melting point is obtained using Differential Scanning Calorimetry (DSC) with a heating rate of 10 °C/minute.

[0012] The crystalline polymorph, designated as Form A(a), can also be characterized by a Raman spectrum expressed in terms of Raman shift (cm-1). Thus, in another embodiment of the invention, the crystalline polymorph has a Raman spectrum comprising at least three, at least six, at least nine, at least twelve, at least fifteen or all Raman shift values selected from the group consisting of 1698 ± 2, 1640 ± 2, 1603 ± 2, 1564 ± 2, 1458 ± 2, 1364 ± 2, 1293 ± 2, 1272 ± 2, 1201 ± 2, 1178 ± 2, 1092 ± 2, 1069 ± 2, 1011 ± 2, 926 ± 2, 906 ± 2, 876 ± 2, 833 ± 2, 795 ± 2, 752 ± 2, 721 ± 2, 691 ± 2, 658 ± 2 and 631 ± 2.

[0013] The invention also relates to an additional new crystalline form of the compound of formula IA, designated Form A (b), which can be characterized by an X-ray powder diffraction pattern expressed in terms of 2θ angles or d spacings. . This crystalline polymorph has an X-ray powder diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 15.3 ± 0.2, 16.3 ± 0.2, 17.6 ± 0.2 , 19.3 ± 0.2, 19.8 ± 0.2, 22.0 ± 0.2, 22.9 ± 0.2, 24.9 ± 0.2 and 25.3 ± 0.2. These peak values, along with the corresponding d-spacing values are shown in Table 3 below:

[0014] These 2θ angle values are derived from a powder X-ray diffraction pattern of the polymorph obtained using the

Example 1. Values are generated using an average wavelength of 1.54056Å with a 2θ step size of 0.02°.

[0015] The crystalline polymorph designated Form A(b) has a melting point of 152 °C ± 2 °C. This melting point is obtained using Differential Scanning Calorimetry (DSC) with a heating rate of 10 °C/minute.

[0016] The invention also relates to an additional crystalline form of the compound of formula IA, designated Form A (h), which is a hydrate. This crystalline polymorph, Form A(h), can be characterized by the single-cell parameters of its single crystal as shown in Table 4. The polymorph was obtained using the method described in Example 1. TABLE 4

[0017] In the table, a, b, c = Length of the ends of the single cell; α, β, Y = Single cell angles; and Z = molecules per cell.

[0018] Therefore, in one embodiment of the present invention, the crystalline polymorph designated Form A(h) has the following lattice parameters: a = 8.03 Â ± 0.01 Â, b = 16.10 Â ± 0, 01 Â, c = 20.37 Â ± 0.01 Â, α = 90° ± 0.01°, β = 97.02° ± 0.01°, Y = 90° ± 0.01° and volume = 2615 Â3± 1 Â3.

[0019] The crystalline polymorph, designated Form A(h), can also be characterized by a powder X-ray diffraction pattern expressed in terms of 2θ angles or d spacings. Thus, in another embodiment of the invention, the crystalline polymorph has a powder X-ray diffraction pattern comprising at least three, at least six or all angle 2θ values selected from the group consisting of 4.4 ± 0.2, 7.0 ± 0.2, 8.7 ± 0.2, 10.3 ± 0.2, 11.0 ± 0.2, 12.4 ± 0.2, 12.7 ± 0.2, 13, 3 ± 0.2, 14.1 ± 0.2, 15.9 ± 0.2, 17.1 ± 0.2, 18.6 ± 0.2, 19.0 ± 0.2 and 19.6 ± 0.2. These peak values, along with the corresponding d-spacing values are shown in Table 5 below:

[0020] These angle 2θ values are derived from a powder X-ray diffraction pattern predicted using the single crystal intensity data of the polymorph obtained using the method of Example 1. The values are generated using an average wavelength of 1 .54056Â with a 2θ step size of 0.02°.

[0021] A crystalline form of the compound of formula IA, designated Form A(c) is also described, which can be characterized by a melting point of 127 °C ± 2 °C. This melting point is obtained using Differential Scanning Calorimetry (DSC) with a heating rate of 10 °C/minute. It is noted that the crystalline forms of the compound of formula ID will have identical parameters to those of the compound of formula IA. Thus, the present invention also relates to new crystalline forms of the compound of formula ID, which have the physical parameters listed above for the compound of formula IA.

[0022] The invention also relates to a new crystalline form of the compound of formula IB, which can be characterized by an X-ray powder diffraction pattern expressed in terms of 2θ angles or d spacings. This crystalline polymorph has an X-ray powder diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 4.1 ± 0.2, 8.3 ± 0.2, 10.2 ± 0.2 , 12.4 ± 0.2, 15.5 ± 0.2, 16.5 ± 0.2, 18.2 ± 0.2, 18.4 ± 0.2, 18.7 ± 0.2, 19 .0 ± 0.2, 20.5 ± 0.2, 21.0 ± 0.2 and 21.4 ± 0.2. These peak values, along with the corresponding d-spacing values are shown in Table 6 below: TABLE 6

[0023] These 2θ angle values are derived from a powder X-ray diffraction pattern predicted using the single crystal intensity data of the polymorph obtained using the method of Example 1. The values are generated using an average wavelength of 1.54056Â with a 2θ step size of 0.02°.

[0024] The crystalline polymorph of the compound of formula IB has a melting point of 206 °C ± 2 °C. This melting point is obtained using Differential Scanning Calorimetry (DSC) with a heating rate of 10 °C/minute.

[0025] The invention also relates to a new crystalline form of the compound of formula IC, which can be characterized by a powder X-ray diffraction pattern expressed in terms of 2θ angles or d spacings. This crystalline polymorph has an X-ray powder diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 4.1 ± 0.2, 8.3 ± 0.2, 10.2 ± 0.2 , 12.4 ± 0.2, 15.5 ± 0.2, 16.5 ± 0.2, 18.2 ± 0.2, 18.4 ± 0.2, 18.7 ± 0.2, 19 .0 ± 0.2, 20.5 ± 0.2, 21.0 ± 0.2 and 21.4 ± 0.2. These peak values along with the corresponding d-spacing values are shown in Table 7 below. Note that the powder X-ray diffraction profile of the compound of formula IC is identical to that of the compound of formula IB. TABLE 7

[0026] These 2θ angle values are derived from a powder X-ray diffraction pattern predicted using the single crystal intensity data of the polymorph obtained using the method of Example 1. The values are generated using an average wavelength of 1.54056Â with a 2θ step size of 0.02°.

[0027] The crystalline polymorph of the compound of formula IC has a melting point of 206 °C ± 2 °C. This melting point is obtained using Differential Scanning Calorimetry (DSC) with a heating rate of 10 °C/minute.

[0028] The invention also relates to an additional new crystalline form of the racemate of compounds of formula IA and formula ID, which can be characterized by a powder X-ray diffraction pattern expressed in terms of 2θ angles or d spacings. This crystalline polymorph has an X-ray powder diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 4.0 ± 0.2, 8.1 ± 0.2, 9.7 ± 0.2 , 11.1 ± 0.2, 12.7 ± 0.2, 15.3 ± 0.2, 15.9 ± 0.2, 16.2 ± 0.2, 16.7 ± 0.2, 18 .4 ± 0.2, 19.5 ± 0.2, 19.8 ± 0.2, 20.3 ± 0.2, 21.8 ± 0.2 and 23.9 ± 0.2. These peak values, along with the corresponding d-spacing values are shown in Table 8 below:

[0029] These 2θ angle values are derived from a powder X-ray diffraction pattern of the polymorph obtained using the

Example 1. Values are generated using an average wavelength of 1.54056Å with a 2θ step size of 0.02°.

[0030] The crystalline racemate polymorph of compounds of formula IA and formula ID have a melting point of 173 °C ± 2 °C. This melting point is obtained using Differential Scanning Calorimetry (DSC) with a heating rate of 10 °C/minute.

[0031] In the context of the present invention, a polymorph is a particular crystal form of a chemical compound that can exist in more than one crystal form in the solid state. A crystal form of a compound contains the constituent molecules arranged in orderly repeating patterns if extended in all three spatial dimensions (in contrast, an amorphous solid form has no long-range order in the position of the molecules). Different polymorphs of a compound have different arrangements of atoms and/or molecules in their crystal structure. When the compound is a biologically active compound, such as an insecticide, the difference in crystal structure can lead to different polymorphs having different chemical, physical and biological properties. Properties that may be affected include crystal shape, density, hardness, color, chemical stability, melting point, hydroscopicity, suspensibility, dissolution rate, and biological availability. As such, a specific polymorph may have properties that make it more advantageous in a particular use over another polymorph of the same compound: in particular, the physical, chemical and biological properties listed above may have a significant effect on the development of production methods and formulations, the ease with which a compound can be combined in a formulation with other active ingredients and formulation components and the quality and effectiveness of plant treatment agents, such as insecticides. It is noted that predicting whether the solid state of a compound may be present as more than one polymorph is not possible nor is it possible to predict the properties of any of these crystal forms.

[0032] In particular, the use of a specific polymorph may allow the use of new formulations compared to existing polymorphic/amorphous forms of a compound. This could be advantageous for several reasons. For example, a suspension concentrate (SC) formulation may be preferred over an emulsion concentrate (EC) because the absence of solvent in the SC often means that the formulation is likely to be less phytotoxic than an equivalent EC formulation. - however, if the existing form of a compound is not stable in such a SC formulation, polymorphic conversion could occur leading to unwanted crystal growth. Such crystal growth is harmful as it leads to, for example, thickening and potentially solidification of the formulation which can lead to blockages in application equipment, e.g. in spray nozzles on agricultural application machinery. Using a stable polymorphic form would overcome these issues.

[0033] Assessment of the solid state for the presence of crystals can be carried out by conventional methods known in the art. For example, it is convenient and routine to use X-ray powder diffraction techniques. Other techniques that can be used include differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Raman or Infrared spectroscopy, NMR, gas chromatography or HPLC. Single-crystal X-ray diffraction is especially useful in identifying crystal structures.

[0034] The polymorphs of the invention can be applied in unchanged form, but are more preferably incorporated into agrochemical compositions by conventional means. Accordingly, in a further aspect, the invention provides an agrochemical composition comprising a polymorph of the invention as defined above and at least one agriculturally acceptable carrier or diluent.

[0035] Furthermore, the compositions of the invention may comprise more than one polymorph of the invention. In particular, the compound of formula IA is more biologically active than the compounds of formulas IB, IC and ID. As such, although the compositions of the invention may contain a mixture of the compounds of IA, IB, IC and ID in the polymorphic forms disclosed herein or otherwise in any amount, they may also be enriched for the compound of formula IA or a polymorph of the compound of formula IA. In particular, these may be enriched for the polymorph designated Form A(a). "Enriched" means that the molar proportion of the compound or polymorph of formula IA compared to the total amount of compounds of formula IA, IB, IC and ID is greater than 50%, for example at least 55, 60, 65, 70 , 75, 80, 85, 90, 95, 96, 97, 98 or at least 99%.

[0036] The agrochemical compositions comprising the polymorph or polymorphs of the present invention are valuable active ingredients in preventive and/or curative terms in the area of pest control, even at low application rates, have a favorable biocidal spectrum and are well tolerated by species warm-blooded, fish and plants. The compositions of the invention can act on all developmental stages or only on individual developmental stages of normally sensitive but also resistant animal pests, such as insects or representatives of the order Acarina. The insecticidal or acaricidal activity of the compositions can be manifested directly, that is, in the destruction of pests, which takes place immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example at a reduced rate of oviposition and/or hatching, with good activity corresponding to a destruction (mortality) rate of at least 50 to 60%.

[0037] Therefore, agrochemical compositions comprising the polymorph or polymorphs of the present invention can be used to control plant pathogenic insects in a number of plant species. Accordingly, the invention also provides a method of preventing or controlling insect infection in plants or plant propagation material comprising treating the plant or plant propagation material with an insecticidally effective amount of an agricultural composition of the invention.

[0038] The term "insecticide" as used herein means a compound or composition that controls or modifies the growth of insects. The term "insecticidally effective amount" means the amount of such a compound or composition or a combination of such compounds or compositions that is capable of killing, controlling, or infecting insects, retarding the growth or reproduction of insects, reducing a population of insects, and/or reduce damage to plants caused by insects.

[0039] By "plant propagation material" we mean seeds of all types (fruit, tubers, bulbs, grains, etc.), cuttings, cut shoots and the like.

[0040] Examples of the above-mentioned animal pests are:

[0041] of the order Acarina, for example, Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp., Chorioptes spp ., Dermanyssus gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemus spp, Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp. Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus spp.;

[0042] of the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.;

[0043] of the order Coleoptera, for example, Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp., Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa decemLineata, Lissorhoptrus spp., Liogenys Maecolaspis, spp, Maladera castanea, Megascelis spp, Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp, Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Sitophilus spp. ., Sitotroga spp., Somaticus spp., Sphenophorus spp., Sternechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp.;

[0044] of the order Diptera, for example, Aedes spp., Anopheles spp, Antherigona soccata, Bactrocea oleae, Bibio hortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp ., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp. , Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Rhagoletis spp, Rivelia quadrifasciata, Scatella spp, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.;

[0045] of the order Hemiptera, for example, Acanthocoris scabrator, Acrosternum spp, Adelphocoris lineolatus, Amblypelta nitida, Bathycoelia thalassina, Blissus spp, Cimex spp., Clavigralla tomentosicollis, Creontiades spp, Distantiella theobroma, Dichelops furcatus, Dysdercus spp., spp , Euchistus spp., Eurydema Pulchrum, Euryaster spp., Halomorpha Halys, Horcias Nobilellus, Leptocorisa spp. p. , Piezodorus spp, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp. , Thyanta spp., Triatoma spp., and Vatiga illudens;

[0046] of the order Homoptera, for example, Acyrthosium pisum, Adalges spp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., auranti, Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana spectra, myzus spp, Cicadulina spp, Coccus hesperidum, Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia, Dysaphis spp, Empoasca spp, Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp, Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp., Neotoxoptera sp, Nephotettix s pp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae, Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis, Perkinsiella spp, Phorodon humuli, Phylloxera spp, Planococcus spp., Pseudaulacaspis pp., Pseudococcus spp., Pseudatomoscelis seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp., Scaphoideus spp., Schizaphis spp., Sitobion spp., Sogatella furcifera, Spissistilus festinus, Tarophagus Proserpina, Toxoptera spp, Trialeurodes spp, Tridiscus sporoboli, Trionymus spp, Trioza erytreae, Unaspis citri, Zygina flammigera, and Zyginidia scutellaris;

[0047] of the order Hymenoptera, for example, Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Pogonomyrmex spp, Slenopsis invicta, Solenopsis spp. and Vespa spp.;

[0048] of the order Isoptera, for example, Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate;

[0049] of the order Lepidoptera, for example, Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp, Argyrotaenia spp., Autographa spp. , Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp, Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis, Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis castanea, Earias spp., Eldana saccharina, Ephestia spp., Epinotia spp, Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp., Hellula undalis, Herpetogramma spp., Hyphantria cunea, Keiferia lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp., Lobesia botrana , Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Mythimna spp, Noctua spp, Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis flammea, Papaipema nebris, Pectinophora gossypiela, Perileucoptera coffeella, Pseudaletia unipuncta, Phthorimaea operculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp., Pseudoplusia spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia spp., Sparganothis spp., Spodoptera spp. , Sylepta derogate, Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tuta absolute, and Yponomeuta spp.;

[0050] of the order Mallophaga, for example, Damalinea spp. and Trichodectes spp.;

[0051] of the order Orthoptera, for example, Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp.;

[0052] of the order Psocoptera, for example, Liposcelis spp.;

[0053] of the order Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis;

[0054] of the order Thysanoptera, for example, Calliothrips phaseoli, Frankliniella spp., Heliothrips spp, Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp; and/or

[0055] of the order Thysanura, for example, Lepisma saccharina.

[0056] Examples of soil-dwelling pests, which can damage a crop in the early stages of plant development, are:

[0057] of the order Lepidoptera, for example, Acleris spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Autographa spp., Busseola fusca, Cadra cautella, Chilo spp., Crocidolomia binotalis, Diatraea spp., Diparopsis castanea, Elasmopalpus spp., Heliothis spp., Mamestra brassicae, Phthorimaea operculella, Plutella xylostella, Scirpophaga spp., Sesamia spp., Spodoptera spp. and Tortrix spp.;

[0058] of the order Coleoptera, for example, Agriotes spp., Anthonomus spp., Atomaria linearis, Chaetocnema tibialis, Conotrachelus spp., Cosmopolites spp., Curculio spp., Dermestes spp., Diabrotica spp., Dilopoderus spp., Epilachna spp ., Eremnus spp., Heteronychus spp., Lissorhoptrus spp., Melolontha spp., Orycaephilus spp., Otiorhynchus spp., Phlyctinus spp., Popillia spp., Psylliodes spp., Rhizopertha spp., Scarabeidae, Sitotroga spp., Somaticus spp. ., Tanymecus spp., Tenebrio spp., Tribolium spp., Trogoderma spp. and Zabrus spp.;

[0059] of the order Orthoptera, for example, Gryllotalpa spp.;

[0060] of the order Isoptera, for example, Reticulitermes spp.;

[0061] of the order Psocoptera, for example, Liposcelis spp.;

[0062] of the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.;

[0063] of the order Homoptera, for example, Eriosoma larigerum;

[0064] of the order Hymenoptera, for example, Acromyrmex, Atta spp., Cephus spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Solenopsis spp. and Vespa spp.;

[0065] of the order Diptera, for example, Tipula spp.;

[0066] cruciferous flea beetles (Phyllotreta spp.), root maggots (Delia spp.), cabbage seed pod weevil (Ceutorhynchus spp.) and aphids.

[0067] The compositions of the invention may also be useful for controlling nematodes. Therefore, agrochemical compositions comprising the polymorph of the present invention can be used to control plant pathogenic nematodes in a number of plant species. Accordingly, the invention also provides a method of controlling damage to plants and their parts by plant parasitic nematodes (Endoparasitic, Semi-endoparasitic and Ectoparasitic nematodes), the method comprising treating the plant or plant propagation material with an effective amount in terms of nematicides of an agricultural composition of the invention.

[0068] The term "nematicide" as used herein means a compound or composition that controls or modifies the growth of nematodes. The term "nematocidal effective amount" means the amount of such compound or composition or a combination of such compounds or compositions that is capable of killing, controlling, or infecting nematodes, retarding the growth or reproduction of nematodes, reducing a nematode population , and/or reduce damage to plants caused by nematodes.

[0069] Examples of the above-mentioned plant parasitic nematodes are:

[0070] root nodule nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other species of Meloidogyne; cyst-forming nematodes, Globodera grossochiensis and other species of Globodera; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other species of Heterodera; Seed gall-forming nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Eelonolaimus longicaudatus and other species of Belonolaimus; Pine nematodes, Bursaphelenchus xylophilus and other species of Bursaphelenchus; Ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other species of Ditylenchus; Piercing nematodes, Dolichodorus species; Spiral nematodes, Heliocotylenchus multicinctus and other species of Helicotylenchus; Sheath and sheath-shaped nematodes, Hemicycliophora species and Hemicriconemoides species; Hirshmanniella species; Spear nematodes, Hoploaimus species; false root knot nematodes, Nacobbus species; Needle nematodes, Longidorus elongatus and other species of Longidorus; Pin nematodes, Pratylenchus species; Wound nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other species of Pratylenchus; Burrowing nematodes, Radopholus similis and other species of Radopholus; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis and other species of Rotylenchus; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; Stunting nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other species of Tylenchorhynchus; Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other species of plant parasitic nematodes, such as Subanguina. spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp..

[0071] In particular, the nematode species Meloidogyne spp., Heterodera spp., Rotylenchus spp. and Pratylenchus spp can be controlled by the compositions of the invention.

[0072] The compositions according to the invention can be used for control, that is, containment or destruction, of pests of the above-mentioned type that occur in particular on plants, especially on useful plants and ornamental plants in agriculture, horticulture and in forests, or in organs such as fruits, flowers, foliage, stems, tubers or roots of such plants, and in some cases even plant organs that are formed at a later time remain protected against these pests.

[0073] Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beetroot, such as sugar or fodder beet; fruits, for example pome fruits, stone fruits or soft fruits, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; legume crops such as beans, lentils, peas or soybeans; oil crops such as rapeseed, mustard, poppies, olives, sunflowers, coconut, castor beans, cocoa or peanuts; cucurbits, such as pumpkins, cucumbers or melons; fibrous plants such as cotton, flax, hemp or jute; citrus fruits, such as oranges, lemons, grapefruits or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, the Plantaginaceae family and latex plants.

[0074] The compositions and/or methods of the present invention can also be used on any ornamental and/or vegetable crops, including flowers, shrubs, broadleaf trees and evergreen trees.

[0075] For example, the invention can be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp., Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I. Walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp. (clove), Canna spp., Oxalis spp., Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp. (pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (pink), Rudbeckia spp., Saintpaulia spp., Salvia spp., Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other layering plants.

[0076] For example, the invention can be used on any of the following species of vegetables: Allium spp. (A. sativum, A. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Cichorium endivia, Cichorum spp. (C. intybus, C. endivia), Citrillus lanatus, Cucumis spp. (C. sativus, C. melo), Cucurbita spp. (C. pepo, C. maxima), Cyanara spp. (C. scolymus, C. cardunculus), Daucus carota, Foeniculum vulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L. esculentum, L. lycopersicum), Mentha spp., Ocimum basilicum, Petroselinum crispum, Phaseolus spp. (P. vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica, Solanum melongena, Spinacea oleracea, Valerianella spp. (V. locusta, V. eriocarpa) and Vicia faba.

[0077] Preferred ornamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. John's wort, mint, peppers, tomatoes and cucumbers.

[0078] The polymorphs according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetables, maize, rice and soybean crops. The polymorphs according to the invention are additionally especially suitable for controlling Mamestra (preferably in legumes and vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in legumes and vegetables, vineyards), Leptinotarsa (preferably in potatoes) and Chilo suppressalis (preferably in rice).

[0079] Crops are to be understood as those that occur naturally, obtained by conventional breeding methods or obtained by genetic engineering. These include crops that contain so-called resultant traits (e.g. improved storage stability, higher nutritional value and improved taste).

[0080] Crops are to be understood as also including those crops that have been made tolerant to herbicides such as bromoxynil or to classes of herbicides such as ALS, EPSPS, GS, HPPD and PPO inhibitors. An example of a crop that has been made tolerant to imidazolinones, eg imazamox, by conventional breeding methods is Clearfield® summer canola. Examples of crops that have been made tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant apple varieties, commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.

[0081] Crops are also to be understood as being those that are naturally or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesizing one or more toxins with selective action, such as are known, for example, from toxin-producing bacteria. Examples of toxins that may be expressed include δ-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins from nematode-colonizing bacteria, and toxins produced by scorpions, arachnids, wasps, and fungi.

[0082] An example of a culture that has been modified to express the Bacillus thuringiensis toxin is Bt KnockOut® maize (Syngenta Seeds). An example of a crop comprising more than one gene encoding insecticide resistance and thus expressing more than one toxin is VipCot® (Syngenta Seeds). Crops or seed material thereof may also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification). For example, a plant may have the ability to express an insecticidal protein, while at the same time being tolerant to herbicides, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).

[0083] Additional areas of use of the compositions according to the invention are the protection of stored goods and warehouses, and the protection of raw materials such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, in particular the protection of humans, domestic animals and productive livestock against pests of the type mentioned.

[0084] The present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, the method for controlling pests comprises applying the compositions of the invention to the target pests, their locus or a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, an application by IRS (indoor residual spraying) on a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention. In another embodiment it is contemplated applying such compositions to a substrate such as a non-woven or woven material in the form of (or which can be used in the manufacture of) knitwear, clothing, bedding, curtains and tents. A further object of the invention is therefore a substrate selected from non-woven or woven material comprising a composition containing a compound of formula (I).

[0085] In one embodiment, the method for controlling such pests comprises applying a pesticide-effective amount of the compositions of the invention to the target pests, their locus, or a surface or substrate so as to provide residual pesticidal activity effective in surface or substrate. Such application can be done by brushing, rolling, spraying, spreading or dipping the pesticide composition of the invention. By way of example, an application by IRS to a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention in order to impart an effective residual pesticidal activity on the surface. In another embodiment, the application of such compositions for residual pest control to a substrate such as a material woven in the form of (or that can be used in the manufacture of) knitwear, clothing, bedding, curtains and tents is contemplated.

[0086] The substrates including non-wovens, fabrics or knits to be treated may be made of natural fibers such as cotton, raffia, jute, linen, sisal, single warp, or wool, or of synthetic fibers such as polyamide, polyester, polypropylene , polyacrylonitrile or similar. Polyesters are particularly suitable. Textile treatment methods are known, P.EX. WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, WO 2006/128870, EP 1724392, WO200511386 or WO 2007/090739.

[0087] Additional areas of use of the compositions according to the invention are the area of tree injection/trunk treatment for all ornamental trees as well as all types of fruit and nut trees.

[0088] In the area of tree injection/trunk treatment, the polymorphs according to the present invention are especially suitable against wood-boring insects of the order Lepidoptera as mentioned above, and of the order Coleoptera, especially against wood-boring insects listed in the following tables A and B: Table A. Examples of exotic wood borers of economic importance. Table B. Examples of native wood borers of economic importance.

[0089] The present invention can also be used to control any insect pests that may be present in grass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, armadillos, mites, paquinhas, mealybugs, mealy bugs, leafhoppers, southern grass bugs and white grubs. The present invention can also be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults.

[0090] In particular, the present invention can be used to control insect pests that feed on lawn roots including corots (such as Cyclocephala spp. (e.g., masked beetle, C. lurida), Rhizotrogus spp. (e.g. , European beetle, R. majalis), Cotinus spp. (e.g., St. John's beetle, C. nitida), Popillia spp. (e.g., Japanese beetle, P. japonica), Phyllophaga spp. May/June beetle), Ataenius spp. (e.g., black lawn beetle, A. spretulus), Maladera spp. (e.g., Asian garden beetle, M. castanea), and Tomarus spp. terrestrial (Margarodes spp.), paquinhas (orange, southern and with short wings; Scapteriscus spp., Gryllotalpa africana) and tipulas (common European melga, Tipula spp.).

[0091] The present invention can also be used to control thatch-inhabiting lawn insect pests, including armyworms (such as fall armyworm Spodoptera frugiperda, and pasture armyworm Pseudaletia unipuncta), cutworms, weevils (Sphenophorus spp., such as S. venatus verstitus and S. parvulus) and lawn moths (such as Crambus spp. and the tropical lawn moth, Herpetogramma phaeopteralis).

[0092] The present invention can also be used to control grass insect pests that live above ground and feed on grass blades, including grass bugs (such as southern grass bugs, Blissus insularis), lawn mites Bermuda (Eriophyes cynodoniensis), Rhodes grass mealy bugs (Antonina graminis), two-lined planthopper (Propsapia bicincta), leafhoppers, screwworms (family Noctuidae), and green aphids.

[0093] The present invention can also be used to control other grass pests such as red imported fire ants (Solenopsis invicta) that create ant mounds in grass.

[0094] In the hygiene sector, the compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, scabies-causing mites, trombiculid mites, flies (biting and licking), larvae of parasitic flies, lice, lice hair, bird lice and fleas.

Examples of such parasites are:

[0095] From the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp..

[0096] From the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp. and Felicola spp.

[0097] From the order Diptera and the suborders Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp. , Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp. and Melophagus spp.

[0098] From the order Siphonapterida, for example, Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp..

[0099] From the order Heteropterida, for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp..

[0100] From the order Blattarida, for example Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp..

[0101] From the subclass Acaria (Acarida) and the orders Meta- and Mesostigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp. , Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp. and Varroa spp.

[0102] From the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp ., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.

[0103] The compositions according to the invention are also suitable for protection against insect infestations in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and cardboard, leather, floor coverings and buildings.

[0104] The compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus , Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec., Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec. and Dinoderus minutus and also hymenoptera such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus augur and termites such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus , and moths such as Lepisma saccharina.

[0105] The rate at which the agrochemical compositions of the invention are applied will depend on the particular type of insect, etc. to be controlled, the degree of control required and the timing and method of application and can be readily determined by the person skilled in the art. In general, the compositions of the invention can be applied at an application rate of between 0.005 kilograms/hectare (kg/ha) and about 5.0 kg/ha, based on the total amount of active ingredient (wherein "active ingredient" means the polymorph or polymorphs of the invention) in the composition. An application rate of between about 0.1 kg/ha and about 1.5 kg/ha is preferred, with an application rate of between about 0.3 kg/ha and 0.8 kg/ha being especially preferred.

[0106] In practice, agrochemical compositions comprising the polymorph or polymorphs of the invention are applied as a formulation containing the various adjuvants and carriers known or used in industry.

[0107] These formulations can be in various physical forms, e.g., in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent granules, emulsifiable concentrates, microemulsifiable concentrates, oil emulsions -in-water, flowable oils, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other known forms, e.g., from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can be used directly or diluted before use. Dilutions can be made, for example, with water, liquid fertilizers, micronutrients, biological organisms, oil or solvents.

[0108] Formulations can be prepared, for example, by mixing the polymorph or polymorphs ("active ingredient") with formulation adjuvants to obtain formulations in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredient can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.

[0109] The active ingredient can also be contained in very fine microcapsules. The microcapsules contain the active ingredient in a porous carrier. This allows the active ingredient to be released into the environment in controlled amounts (e.g., slow release). Microcapsules usually have a diameter of 0.1 to 500 microns. They contain the active ingredient in an amount of approximately 25 to 95% by weight of the capsule weight. The active ingredient may be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. Encapsulation membranes may comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers which are known to the skilled artisan. in technique. Alternatively, very fine microcapsules may be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.

[0110] Formulation adjuvants that are suitable for preparing the formulations according to the invention are known per se. As liquid carriers can be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abiethate, diethylene glycol butyl ether, diethylene glycolethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene , d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane , isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methylisoamylketone, methylisobutylketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n- octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol and higher molecular weight alcohols such as amyl alcohol, tetra alcohol -hydrofurfuryl, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone and the like.

[0111] Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, flour wheat, soy flour, pumice, wood flour, crushed walnut shells, lignin and similar substances.

[0112] A large number of surface-active substances can be advantageously used in solid and liquid formulations, especially in those formulations that can be diluted with a carrier before use. Surface-active substances can be anionic, cationic, nonionic or polymeric, and can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, alkyl sulfate salts, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products such as tridecyl alcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide, and salts of mono- and di-alkylphosphate esters, and also additional substances described, e.g., in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey, 1981.

[0113] Additional adjuvants that can be used in pesticide formulations include crystallization inhibitors, viscosity modifiers, suspending agents, colorants, antioxidants, foaming agents, light absorbers, mixing aids, antifoams, complexing agents, substances neutralizers or pH modifiers and buffers, corrosion inhibitors, fragrances, wetting agents, adhesion enhancers, micronutrients, plasticizers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides and liquid and solid fertilizers.

[0114] The formulations according to the invention may include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the formulations according to the invention is generally 0.01 to 10%, based on the mixture to be applied. For example, the oil additive may be added to a spray tank at the desired concentration after a spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example, rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example, methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and oleate methyl, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010.

[0115] The inventive formulations generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of polymorphs of the present invention and from 1 to 99.9% by weight of a formulation adjuvant that preferably includes from 0 to 25% by weight of a surfactant substance. Whereas commercial products may preferably be formulated as concentrates, the end user will typically employ diluted formulations.

[0116] Application rates vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the moment of application and the target culture. As a general guideline, the polymorphs of the invention can be applied at a rate of 1 to 2000 L/ha, especially 10 to 1000 L/ha.

[0117] Preferred formulations may have the following compositions (% by weight): Emulsifiable concentrates: active ingredient: 1 to 95%, preferably 60 to 90% surfactant: 1 to 30%, preferably 5 to 20% liquid vehicle: 1 to 80%, preferably 1 to 35% Dusts: active ingredient: 0.1 to 10%, preferably 0.1 to 5% solid vehicle: 99.9 to 90%, preferably 99.9 to 99% Suspension concentrates: active ingredient : 5 to 75%, preferably 10 to 50% water: 94 to 24%, preferably 88 to 30% surfactant: 1 to 40%, preferably 2 to 30% Wettable powders: active ingredient: 0.5 to 90%, preferably 1 to 80% surfactant: 0.5 to 20%, preferably 1 to 15% solid carrier: 5 to 95%, preferably 15 to 90% Granules: active ingredient: 0.1 to 30%, preferably 0.1 to 15 % solid carrier: 99.5 to 70%, preferably 97 to 85% The following Examples further illustrate, but do not limit, the invention.

[0118] The combination is thoroughly mixed with the adjuvants and the mixture is carefully ground in a suitable mill, providing wettable powders that can be diluted with water to give suspensions of the desired concentration.

[0119] The combination is completely mixed with the adjuvants and the mixture is completely ground in a suitable mill, resulting in powders that can be used directly for seed treatment.

[0120] Emulsions of any required dilution, which can be used to protect plants, can be obtained from this concentrate by dilution with water.

[0121] Ready-to-use powders are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry coatings for seeds.

[0122] The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

[0123] The finely ground combination is uniformly applied, in a mixer, to kaolin moistened with polyethylene glycol. Dust-free coated granules are thus obtained. Suspension concentrate

[0124] The finely ground combination is intimately mixed with the adjuvants, providing a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, live plants as well as plant propagation material can be treated and protected against infestation by microorganisms by spraying, pouring or immersing. Flowable concentrate for seed treatment

[0125] The finely ground combination is intimately mixed with the adjuvants, providing a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, live plants as well as plant propagation material can be treated and protected against infestation by microorganisms by spraying, pouring or immersing.

Suspension of Slow Release Capsules

[0126] 28 parts of the active ingredient are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts polyvinyl alcohol, 0.05 parts defoamer and 51.6 parts water until the desired particle size is achieved. To this emulsion is added a mixture of 2.8 parts of 1,6-diaminohexane in 5.3 parts of water. The mixture is stirred until the polymerization reaction is complete. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% active ingredient. The average diameter of the capsule is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in a device suitable for that purpose.

[0127] Each of the above formulations can be prepared as a package containing the polymorph or polymorphs of the invention together with other ingredients of the formulation (diluents, emulsifiers, surfactants, etc.). Formulations can also be prepared by a tank mixing method, in which the ingredients are obtained separately and combined at the site of growth.

[0128] These formulations can be applied to areas where control by conventional methods is desired. Dust and liquid formulations, for example, can be applied by the use of motor sprinklers, boom and hand sprayers, and spray sprinklers. The formulations can also be applied from aircraft as a dust or spray or by rope wick applications. The formulations, both solid and liquid, can also be applied to the soil at the locus of the plant to be treated, allowing the active ingredient to penetrate the plant through the roots.

[0129] The polymorphs of the invention and their compositions are also suitable for the protection of plant propagation material, for example seeds, such as fruits, tubers or grains, or nursery plants, against pests of the aforementioned type. Propagation material can be treated with the polymorph before planting, for example a seed can be treated before sowing. Alternatively, the polymorph can be applied to the seed grains (coating), either by soaking the grains in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted at the application site, for example in the seed furrow during the row formation process. Such treatment methods for the plant propagation material and the plant propagation material so treated are additional subjects of the invention. Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 and 200 grams per 100 kg of seeds, preferably between 5 and 150 grams per 100 kg of seeds, such as between 10 and 100 grams per 100 kg of seeds.

[0130] The term seed encompasses seeds and propagules of plants of all types, including but not limited to true seeds, pieces of seeds, corms, calluses, bulbs, fruits, tubers, grains, rhizomes, cuttings, sprouts from cuttings and similar, and means in a preferred embodiment true seeds.

[0131] The present invention also comprises seeds coated or treated with or containing a polymorph of the invention. The term "coated or treated with and/or containing" generally means that the active ingredient is mostly on the surface of the seed at the time of application, although more or less of the ingredient may penetrate the seed material, depending on the method of application. When said seed product is (re)planted, it can absorb the active ingredient. In one embodiment, the present invention makes available a plant propagation material to which a compound of formula (I) is adhered. Additionally, a composition comprising a plant propagation material treated with a compound of formula (I) is thus made available.

[0132] Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed treatment, seed coating, seed dusting, seed soaking and seed pelleting. Application to seed treatment of the compound of formula (I) can be carried out by any known methods, such as spraying or dusting the seeds before sowing or during sowing/planting the seeds.

[0133] Suitably, the agrochemical compositions and formulations of the present invention are applied before the development of the disease. The rates and frequency of use of the formulations are those conventionally used in the art and will depend on the risk of infestation by the insect pathogen.

[0134] The activity of compositions comprising compounds and polymorphs according to the invention can be considerably expanded, and adapted to prevailing circumstances, by including other active substances. The active substances can be chemical or biological, and in the case of biological, they can be additionally modified from biological species derived in nature. Active substances include substances that control, repel or attract pests that damage or harm useful plants in general, but also substances that enhance the growth of a useful plant, such as plant growth regulators, and substances that improve the performance of the active substance, such as synergists. Examples are insecticides, acaricides, nematicides, molluscicides, algaecides, virucides, rodenticides, bactericides, fungicides, chemical sterilants, anthelmintics. Examples of a biologically active substance include baculovirus, plant extracts, and bacteria.

[0135] Thus, the present invention provides the use of a composition according to the present invention in conjunction with one or more pesticides, plant nutrients or plant fertilizers. The combination may also encompass specific plant traits incorporated into the plant using any means, for example conventional breeding or genetic modification.

[0136] Mixtures of the polymorphs of the invention with other active substances can also have other surprising advantages that can also be described, in a broader sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different stages of development, or better behavior in relation to production, for example crushing or mixing, storage or use.

[0137] Individual active substances may occur in more than one group or class and in more than one location within a group or class: information about the active substances, their spectrum, sources and classifications can be found in the "Compendium of Pesticide Common Names " (see http://www.alanwood.net/pesticides/index.html) or in the "Pesticide Manual" created by the British Crop Production Council (see http://bcpcdata.com/pesticide-manual.html).

[0138] Preferred mixtures are indicated below, where the polymorph or polymorphs of the invention are indicated as "I":

[0139] Compositions comprising an adjuvant include I + compounds selected from the group of substances consisting of petroleum oils.

[0140] Compositions comprising an acaricide include I + 1,1-bis(4-chlorophenyl)-2-ethoxyethanol, I + 2,4-dichlorophenyl benzenesulfonate, I + 2-fluoro-N-methyl-N-1-naphthylacetamide , I + 4-chlorophenylphenylsulfone, I + abamectin, I + acequinocil, I + acetoprol, I + acrinathrine, I + aldicarb, I + aldoxycarb, I + alpha-cypermethrin, I + amidithion, I + amidoflumeth, I + amidothioate, I + amitone, I + amitone hydrogen oxalate, I + amitraz, I + aramite, I + arsenous oxide, I + AVI 382, I + AZ 60541, I + azinophos-ethyl, I + azinophos-methyl, I + azobenzene, I + azocyclotine, I + nitrogenate, I + benomyl, I + benoxaphos, I + benzoximate, I + benzyl benzoate, I + bifenazate, I + bifenthrin, I + binapacryl, I + brofenvalerate, I + bromocyclene, I + bromophos, I + bromophos-ethyl, I + bromopropylate, I + buprofezin, I + butocarboxim, I + butoxycarboxym, I + butylpyridabene, I + calcium polysulfide, I + camphechlor, I + carbanolate, I + carbaryl, I + carbofuran, I + I + chlorobenzylate, I + chloromebuform, I + chloromethiurone, I + chloropropylate, I + chlorpyrifos, I + chlorpyrifos-methyl, I + chlorthiophos, I + cinerin I, I + cinerin II, I + cinerins, I + clofentezine, I + closantel , I + coumafos, I + crotamiton, I + crotoxiphos, I + kofraneb, I + cyantoate, I + cyflumetofen, I + cyhalothrin, I + cyhexatin, I + cypermethrin, I + DCPM, I + DDT, I + demephione, I + demephione-O, I + demephione-S, I + demetone, I + demetone-methyl, I + demetone-O, I + demetone-O-methyl, I + demetone-S, I + demetone-S -methyl, I + demeton- S-methylsulfone, I + diafenthiuron, I + dialiphos, I + diazinone, I + dichlofluanid, I + dichlorvos, I + diclifos, I + dicofol, I + dicrotophos, I + dienochlor, I + dimefox , I + dimethoate, I + dynactin, I + dinex, I + dinex-diclexin, I + dinobutone, I + dinocape, I + dinocape-4, I + dinocape-6, I + dinoctone, I + dinopentone, I + dinosulfone , I + dinoterbon, I + dioxathione, I + diphenylsulfone, I + disulfiram, I + disulfotone, I + DNOC, I + dofenapine, I + doramectin, I + endosulfan, I + endothione, I + EPN, I + eprinomectin, I + ethion, I + methyl ethoate, I + etoxazole, I + etrinfos, I + fenazaflor, I + fenazaquine, I + fenbutatin oxide, I + phenothiocarb, I + fenpropathrin, I + fenpyrad, I + fenpyroximate, I + phensone , I + fentrifanil, I + fenvalerate, I + fipronil, I + fluacripyrim, I + fluazurone, I + flubenzimine, I + flucicloxurone, I + flucitrinate, I + fluethyl, I + flufenoxurone, I + flumethrin, I + fluorbenside, I + fluvalinate, I + FMC 1137, I + formetanate, I + formetanate hydrochloride, I + formotiona, I + formparanate, I + gamma-HCH, I + gliodine, I + halfenprox, I + heptenophos, I + hexadecyl cyclopropanicarboxylate, I + hexythiazox, I + iodomethane, I + isocarbophos, I + O-(methoxyaminothiophosphoryl) isopropyl salicylate, I + ivermectin, I + jasmolin I, I + jasmolin II, I + iodofenphos, I + lindane, I + lufenurone, I + malathion, I + malonobene, I + mecarbame, I + mephospholane, I + messulfene, I + metacryphos, I + methamidophos, I + methydathione, I + methiocarb, I + methomyl, I + methyl bromide, I + metolcarb, I + mevinphos, I + mexacarbate, I + milbemectin, I + milbemycin oxime, I + mipafox, I + monocrotophos, I + morphothione, I + moxidectin, I + nalede, I + NC-184, I + NC-512, I + nifluridide, I + nicomycins, I + nitrilacarb, I + 1:1 nitrilacarb:zinc chloride complex, I + NNI-0101, I + NNI-0250, I + omethoate, I + oxamyl, I + oxideprofos, I + oxydisulfotone , I + pp'-DDT, I + parathion, I + permethrin, I + petroleum oils, I + fencaptone, I + phentoate, I + phorate, I + phosalone, I + phospholane, I + phosmet, I + phosfamidone, I + phoxim, I + pirimifos- methyl, I + polychloroterpenes, I + pollinactins, I + proclonol, I + profenofos, I + promacil, I + propargite, I + propetanphos, I + propoxur, I + protidation, I + protoate, I + pyrethrin I, I + pyrethrin II, I + pyrethrins, I + pyridabene, I + pyridafenthion, I + pyrimidifen, I + pyrimitate, I + quinalphos, I + quinthiophos, I + R-1492, I + RA-17, I + rotenone, I + escradane, I + sebufos, I + selamectin, I + SI-0009, I + sofamide, I + spirodiclofen, I + spiromesifen, I + SSI-121, I + sulfiram, I + sulfluramide, I + sulfotepe, I + sulfur, I + SZI-121, I + tau-fluvalinate, I + tebufenpyrad, I + TEPP, I + terbame, I + tetrachlorvinphos, I + tetradifone, I + tetranactin, I + tetrasul, I + thiafenox, I + thiocarboxime, I + thiophanox, I + thiometone, I + thioquinox, I + thuringiensin, I + triamiphos, I + triaratene, I + triazophos, I + triazurone, I + trichlorophone, I + tripenophos, I + trinactin, I + vamidothione, I + vaniliprole and I + YI-5302.

[0141] Compositions comprising an anthelmintic include I + abamectin, I + crufomate, I + doramectin, I + emamectin, I + emamectin benzoate, I + eprinomectin, I + ivermectin, I + milbemycin oxime, I + moxidectin, I + piperazine, I + selamectin, I + spinosad and I + thiophanate.

[0142] Compositions comprising an avicide include I + chloralose, I + endrin, I + phenthion, I + pyridin-4-amine and I + strychnine.

[0143] Compositions comprising a biological control agent include I + Adoxophyes orana GV, I + Agrobacterium radiobacter, I + Amblyseius spp., I + Anagrapha falcifera NPV, I + Anagrus atomus, I + Aphelinus abdominalis, I + Aphidius colemani, I + Aphidoletes aphidimyza, I + Autographa californica NPV, I + Bacillus firmus, I + Bacillus sphaericus Neide, I + Bacillus thuringiensis Berliner, I + Bacillus thuringiensis subsp. aizawai, I + Bacillus thuringiensis subsp. israelensis, I + Bacillus thuringiensis subsp. japonensis, I + Bacillus thuringiensis subsp. kurstaki, I + Bacillus thuringiensis subsp. tenebrionis, I + Beauveria bassiana, I + Beauveria brongniartii, I + Chrysoperla carnea, I + Cryptolaemus montrouzieri, I + Cydia pomonella GV, I + Dacnusa sibirica, I + Diglyphus isaea, I + Encarsia formosa, I + Eretmocerus eremicus, I + Helicoverpa zea NPV, I + Heterorhabditis bacteriophora and H. megidis, I + Hippodamia convergens, I + Leptomastix dactylopii, I + Macrolophus caliginosus, I + Mamestra brassicae NPV, I + Metaphycus helvolus, I + Metarhizium anisopliae var. acridum, I + Metarhizium anisopliae var. anisopliae, I + Neodiprion sertifer NPV and N. lecontei NPV, I + Orius spp., I + Paecilomyces fumosoroseus, I + Phytoseiulus persimilis, I + Spodoptera exigua multicapsid nuclear polyhedrosis virus, I + Steinernema bibionis, I + Steinernema carpocapsae, I + Steinernema feltiae, I + Steinernema glaseri, I + Steinernema riobrave, I + Steinernema riobravis, I + Steinernema scapterisci, I + Steinernema spp., I + Trichogramma spp., I + Typhlodromus occidentalis and I + Verticillium lecanii.

[0144] Compositions comprising a soil sterilant include I + iodomethane and methyl bromide.

[0145] Compositions comprising a chemical sterilant include I + afolate, I + bisazir, I + busulfan, I + diflubenzurone, I + dimatife, I + hemel, I + hempa, I + metepa, I + methiotepa, I + methyl afolate , I + morzide, I + penflurone, I + tepa, I + thiohempa, I + thiotepa, I + tretamine and I + uredepa.

[0146] Compositions comprising an insect pheromone include I + (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol, I + (E)- tridec-4-en-1-yl, I + (E)-6-methylhept-2-en-4-ol, I + (E,Z)- tetradeca-4,10-dien-1- acetate yl, I + (Z)-dodec-7-en-1-yl acetate, I + (Z)-hexadec-11-enal, I + (Z)-hexadec-11-en-1-yl acetate, I + (Z)-hexadec-13-en-11-in-1-yl acetate, I + (Z)-icos-13-en-10-one, I + (Z)-tetradec-7-en- 1-al, I + (Z)-tetradec-9-en-1-ol, I + (Z)-tetradec-9-en-1-yl acetate, I + (7E,9Z)-dodeca- acetate 7,9-dien-1-yl, I + (9Z,11E)-tetradeca- 9,11-dien-1-yl acetate, I + (9Z,12E)-tetradeca-9,12-dien- acetate 1-yl, I + 14- methyloctadec-1-ene, I + 4-methylnonan-5-ol with 4-methylnonan-5-one, I + alpha- multistriatin, I + brevicomin, I + codlelure, I + codlemone, I + cuelure, I + disparlure, I + dodec-8-en-1-yl acetate, I + dodec-9-en-1-yl acetate, I + dodec-8, I + 10-dien-acetate 1-yl, I + dominicalure, I + 4- ethyl methyloctanoate, I + eugenol, I + frontalin, I + gossyplure, I + grandlure, I + grandlure I, I + grandlure II, I + grandlure III, I + grandlure IV, I + hexalure, I + ipsdienol, I + ipsenol, I + japonylure, I + lineatin, I + litlure, I + looplure, I + medlure, I + megatomoic acid, I + methyleugenol, I + muscalure, I + acetate octadeca-2,13-dien-1-yl, I + octadeca-3,13-dien-1-yl acetate, I + orfralure, I + orictalure, I + ostramon, I + siglure, I + sordidine, I + sulcatol, I + tetradec-11-en-1-yl acetate, I + trimedlure, I + trimedlure A, I + trimedlure B1, I + trimedlure B2, I + trimedlure C and I + trunc- call.

[0147] Compositions comprising an insect repellent include I + 2-(octylthio)ethanol, I + butopyronoxyl, I + butoxy(polypropylene glycol), I + dibutyl adipate, I + dibutyl phthalate, I + dibutyl succinate, I + diethyltoluamide, I + dimethyl carbate, I + dimethyl phthalate, I + ethyl hexanediol, I + hexamide, I + methochin-butyl, I + methylneodecanamide, I + oxamate and I + picaridin.

[0148] Compositions comprising an insecticide include I + 1-dichloro-1-nitroethane, I + 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane, I +, I + 1,2-dichloropropane, I + 1,2-dichloropropane with 1,3-dichloropropene, I + 1-bromo-2-chloroethane, I + 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate, I + 2- 2,2-dichlorovinyl ethylsulfinylethylmethylphosphate, I + 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate, I + 2-(2-butoxyethoxy)ethyl thiocyanate, I + 2-(4,5) methylcarbamate -dimethyl-1,3-dioxolan-2-yl)phenyl, I + 2-(4-chloro-3,5-xylyloxy)ethanol, I + 2-chlorovinyl diethylphosphate, I + 2-imidazolidone, I + 2- isovalerylindane-1,3-dione, I + 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate, I + 2-thiocyanatoethyl laurate, I + 3-bromo-1-chloroprop-1-ene, I + dimethylcarbamate 3-methyl-1-phenylpyrazol-5-yl, I + 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate, I + 5,5-dimethyl-3-oxocyclohex-dimethylcarbamate 1-enyl, I + abamectin, I + acephate, I + acetamiprid, I + acethione, I + acetoprol, I + acrinathrin, I + acrylonitrile, I + alanicarb, I + aldicarb, I + aldoxycarb, I + aldrin, I + allethrin, I + alosamidine, I + alixicarb, I + alpha-cypermethrin, I + alpha-ecdysone, I + aluminum phosphide, I + amidithion, I + amidothioate, I + aminocarb, I + amitone, I + hydrogen oxalate amitone, I + amitraz, I + anabasine, I + atidathione, I + AVI 382, I + AZ 60541, I + azadirachtin, I + azamethiphos, I + azinophos-ethyl, I + azinophos-methyl, I + nitrogenate, I + delta-endotoxins from Bacillus thuringiensis, I + barium hexafluorosilicate, I + barium polysulfide, I + barthrin, I + Bayer 22/190, I + Bayer 22408, I + bendiocarb, I + benfuracarb, I + bensultape, I + beta -cyfluthrin, I + beta-cypermethrin, I + bifenthrin, I + bioalethrin, I + S-cyclopentenyl isomer of bioalethrin, I + bioethanometrin, I + biopermethrin, I + bioresmethrin, I + bis(2-chloroethyl) ether, I + bistriflurone, I + borax, I + brofenvalerate, I + bromofenvinphos, I + bromocyclene, I + bromo-DDT, I + bromophos, I + bromophos-ethyl, I + bufencarb, I + buprofezin, I + butacarb, I + butathiofos, I + butocarboxym, I + butonate, I + butoxycarboxym, I + butylpyridabene, I + cadusafos, I + calcium arsenate, I + calcium cyanide, I + calcium polysulfide, I + camphechlor, I + carbanolate, I + carbaryl, I + carbofuran, I + carbon disulfide, I + carbon tetrachloride, I + carbophenothione, I + carbosulfan, I + Cartape, I + Cartape hydrochloride, I + cevadine, I + chlorobicyclene, I + chlorodane, I + chlorodecone, I + chlordimeform, I + chlordimeform hydrochloride, I + chlorethoxyphos, I + chlorofenapyr, I + chlorofenvinphos, I + chlorofluazurone, I + chloromephos, I + chloroform, I + chloropicrin, I + chlorofoxim, I + chloroprazophos, I + chlorpyrifos, I + chlorpyrifos-methyl, I + chlorthiophos, I + chromafenozide, I + cinerin I, I + cinerin II, I + cinerins, I + cis-resmethrin, I + cysmethrin, I + clocitrin, I + chloretocarb, I + closantel, I + clothianidin, I + copper acetoarsenite, I + copper arsenate, I + copper oleate, I + coumafos, I + coumitoate, I + crotamitone, I + crotoxiphos, I + crufomate, I + cryolite, I + CS 708, I + cyanofenphos, I + cyanophos, I + cyantoate, I + cyclethrin, I + cycloprothrin, I + cyfluthrin, I + cyhalothrin, I + cypermethrin, I + cyphenothrin, I + cyromazine, I + cythioate, I + d-limonene, I + d-tetramethrin, I + DAEP, I + dazomet, I + DDT, I + decarbofuran, I + deltamethrin, I + demefion, I + demefion-O, I + demefion-S, I + demethone , I + demetone-methyl, I + demetone-O, I + demetone-O-methyl, I + demetone-S, I + demetone-S-methyl, I + demetone-S-methylsulfone, I + diafentiurone, I + dialyphos , I + diamidaphos, I + diazinone, I + dicaptone, I + diclofenthion, I + dichlorvos, I + dicliphos, I + dicresyl, I + dicrotophos, I + dicyclanyl, I + dieldrin, I + 5-methylpyrazol-3-ylphosphate diethyl, I + diflubenzurone, I + dilor, I + dimefluthrin, I + dimefox, I + dimethane, I + dimethoate, I + dimethrin, I + dimethylvinphos, I + dimethylane, I + dinex, I + dinex-diclexin, I + dinoprope, I + dinosam, I + dinoseb, I + dinotefuran, I + diophenolan, I + dioxabenzofos, I + dioxacarb, I + dioxathione, I + disulfotone, I + diticrophos, I + DNOC, I + doramectin, I + DSP , I + ecdysterone, I + EI 1642, I + emamectin, I + emamectin benzoate, I + EMPC, I + empentrin, I + endosulfan, I + endothione, I + endrin, I + EPBP, I + EPN, I + epofenonan, I + eprinomectin, I + esfenvalerate, I + etaphos, I + ethiofencarb, I + ethion, I + etiprol, I + methyl ethoate, I + etoprophos, I + ethyl formate, I + ethyl-DDD, I + ethylene dibromide, I + ethylene dichloride, I + ethylene oxide, I + etofenprox, I + ethrinphos, I + EXD, I + fanfur, I + fenamiphos, I + fenazaflor, I + fenchlorophos, I + fenetacarb, I + fenfluthrin, I + fenitrothion, I + fenobucarb, I + fenoxacrim, I + fenoxycarb, I + fenpyrithrin, I + fenpropathrin, I + fenpyrad, I + fensulfothione, I + fenthion, I + fenthion-ethyl, I + fenvalerate, I + fipronil, I + flonicamide, I + flubendiamide, I + flucofurone, I + flucicloxurone, I + flucitrinate, I + fluenethyl, I + flufenerim, I + flufenoxurone, I + flufenprox, I + flumethrin, I + fluvalinate, I + FMC 1137 , I + fonofos, I + formetanate, I + formetanate hydrochloride, I + formotiona, I + formparanate, I + phosmethylane, I + fospirate, I + fosthiazate, I + fosthiethane, I + furathiocarb, I + furethrin, I + gamma -cyhalothrin, I + gamma-HCH, I + guazatine, I + guazatine acetates, I + GY-81, I + halfenprox, I + halofenozide, I + HCH, I + HEOD, I + heptachlor, I + heptenophos , I + heterophos, I + hexaflumurone, I + HHDN, I + hydramethylnone, I + hydrogen cyanide, I + hydroprene, I + hyquincarb, I + imidacloprid, I + imiprothrin, I + indoxacarb, I + iodomethane, I + IPSP , I + isazophos, I + isobenzane, I + isocarbophos, I + isodrine, I + isofenphos, I + isolane, I + isoprocarb, I + O-(methoxyaminothiophosphoryl) isopropyl salicylate, I + isoprothiolane, I + isothioate, I + isoxathione, I + ivermectin, I + jasmolin I, I + jasmolin II, I + iodofenphos, I + juvenile hormone I, I + juvenile hormone II, I + juvenile hormone III, I + celevan, I + quinoprene, I + lambda- cyhalothrin, I + lead arsenate, I + lepimectin, I + leptophos, I + lindane, I + lyrinphos, I + lufenurone, I + lithidathione, I + m-cumenyl methylcarbamate, I + magnesium phosphide, I + malathion, I + malonobene, I + mazidox, I + mecarbame, I + mecarphone, I + menazone, I + mephospholane, I + mercurous chloride, I + mesulfenphos, I + metaflumizone, I + metam, I + metam-potassium, I I + methoxychlor, I + methoxyfenozide, I + methyl bromide, I + methyl isothiocyanate, I + methylchloroform, I + methylene chloride, I + metofluthrin, I + metolcarb, I + methoxydiazone, I + mevinphos, I + mexacarbate, I + milbemectin, I + milbemycin oxime, I + mipafox, I + mirex, I + monocrotophos, I + morphothione, I + moxidectin, I + naphthalophos, I + nalede, I + naphthalene, I + NC-170, I + NC- 184, I + nicotine, I + nicotine sulfate, I + nifluridide, I + nitenpyram, I + nithiazine, I + nitrilacarb, I + 1:1 nitrilacarb:zinc chloride complex, I + NNI-0101, I + NNI -0250, I + nornicotine, I + novalurone, I + noviflumurone, I + O-5-dichloro-4-iodophenyl O-ethyl-ethylphosphonothioate, I + O,O-dietol-O-4-methyl-2 phosphorothioate - oxo-2H-chromen-7-yl, I + O,O-diethyl-O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate, I + O,O,O',O'-tetrapropyl dithiopyrophosphate , I + oleic acid, I + omethoate, I + oxamyl, I + oxidemeton-methyl, I + oxideprophos, I + oxydisulfotone, I + pp'-DDT, I + para-dichlorobenzene, I + parathion, I + parathion-methyl , I + penflurone, I + pentachlorophenol, I + pentachlorophenyl laurate, I + permethrin, I + petroleum oils, I + PH 60-38, I + phencaptone, I + phenothrin, I + phentoate, I + phorate + TX, I + phosalone, I + phospholane, I + phosmet, I + phosnichlor, I + phosfamidone, I + phosphine, I + phoxim, I + phoxim-methyl, I + pyrimetaphos, I + pirimicarb, I + pirimiphos-ethyl, I + pirimiphos-methyl, I + polychlorodicyclopentadiene isomers, I + polychloroterpenes, I + potassium arsenite, I + potassium thiocyanate, I + pralethrin, I + precone I, I + precono II, I + precono III, I + primidone, I + profenofos, I + proflutrin, I + promacil, I + promecarb, I + propaphos, I + propetanphos, I + propoxur, I + protidation, I + prothiophos, I + protoate, I + protrifenbut, I + pymetrozine, I + pyraclophos , I + pyrazophos, I + pyresmethrin, I + pyrethrin I, I + pyrethrin II, I + pyrethrins, I + pyridabene, I + pyridalyl, I + pyridafenthion, I + pyrimidifen, I + pyrimitate, I + pyriproxyfen, I + quassia , I + quinalphos, I + quinalphos-methyl, I + quinothione, I + quinthiophos, I + R-1492, I + rafoxanide, I + resmethrin, I + rotenone, I + RU 15525, I + RU 25,475, I + ryania , I + ryanodine, I + sabadilha, I + escradane, I + sebufos, I + selamectin, I + SI-0009, I + SI-0205, I + SI-0404, I + SI-0405, I + silafluofen, I + SN 72129, I + sodium arsenite, I + sodium cyanide, I + sodium fluoride, I + sodium hexfluorosilicate, I + sodium pentachlorophenoxide, I + sodium selenate, I + sodium thiocyanate, I + sofamide, I + spinosad, I + spiromesifene, I + spirotetramate, I + sulcofurone, I + sulcofurone-sodium, I + sulfluramide, I + sulfotepe, I + sulfuryl fluoride, I + sulprophos, I + tar oils, I + tau- fluvalinate, I + tazincarb, I + TDE, I + tebufenozide, I + tebufenpyrad, I + tebupirinphos, I + teflubenzurone, I + tefluthrin, I + temephos, I + TEPP, I + teralethrin, I + terbame, I + terbufos, I + tetrachloroethane, I + tetrachlorvinphos, I + tetramethrin, I + theta-cypermethrin, I + thiacloprid, I + thiafenox, I + thiamethoxam, I + ticrophos, I + thiocarboxime, I + thiocyclam, I + thiocyclam hydrogen oxalate, I + thiodicarb, I + thiophanox, I + thiometone, I + thionazine, I + thiosultape, I + thiosultape-sodium, I + thuringiensin, I + tolfenpyrad, I + tralomethrin, I + transfluthrin, I + transpermethrin, I + triamifos, I + triazamate, I + triazophos, I + triazurone, I + trichlorophone, I + trichlorometaphos-3, I + trichloronate, I + tripenophos, I + triflumurone, I + trimetacarb, I + triprene, I + vamidothione, I + vaniliprole, I + veratridine, I + veratrin, I + + chlorantraniliprol, I + cyenopirafen, I + cyflumetofen, I + pyrifluquinazone, I + spinetoram, I + spirotetramate, I + sulfoxaflor, I + flufiprol, I + meperfluthrin, I + tetramethylfluthrin, I + triflumezopyrime.

[0149] Compositions comprising a molluscicide include I + bis(tributyltin oxide), I + bromoacetamide, I + calcium arsenate, I + chlorethocarb, I + copper acetoarsenite, I + copper sulfate, I + fentin, I + phosphate ferric, I + metaldehyde, I + methiocarb, I + niclosamide, I + niclosamide-olamine, I + pentachlorophenol, I + sodium pentachlorophenoxide, I + tazincarb, I + thiodicarb, I + tributyltin oxide, I + tripenomorph, I + trimetacarb , I + triphenyltin acetate and triphenyltin hydroxide, I + pyriprole.

[0150] Compositions comprising a nematicide include I + AKD- 3088, I + 1,2-dibromo-3-chloropropane, I + 1,2-dichloropropane, I + 1,2-dichloropropane with 1,3-dichloropropene, I + 1,3-dichloropropene, I + 1,1- 3,4-dichlorotetrahydrothiophene dioxide, I + 3-(4-chlorophenyl)-5-methylrhodanine, I + 5-methyl-6-thioxo-1,3,5 acid -thiadiazinan-3-ylacetic, I + 6- isopentenylaminopurine, I + abamectin, I + acetoprol, I + alanicarb, I + aldicarb, I + aldoxycarb, I + AZ 60541, I + benclothiaz, I + benomyl, I + butylpyridabene, I + cadusafos, I + carbofuran, I + carbon disulfide, I + carbosulfan, I + chloropicrin, I + chlorpyrifos, I + chloretocarb, I + cytokinins, I + dazomet, I + DBCP, I + DCIP, I + diamidaphos, I + diclofenthion, I + diclifos, I + dimethoate, I + doramectin, I + emamectin, I + emamectin benzoate, I + eprinomectin, I + etoprophos, I + ethylene dibromide, I + fenamiphos, I + fenpyrad, I + fensulfothione, I + fosthiazate, I + fosthiethane, I + furfural, I + GY-81, I + heterophos, I + iodomethane, I + isamidophos, I + isazophos, I + ivermectin, I + kinetin, I + mecarphone, I + metam, I + metam-potassium, I + metam-sodium, I + methyl bromide, I + methyl isothiocyanate, I + milbemycin oxime, I + moxidectin, I + Myrothecium verrucaria composition, I + NC-184, I + oxamyl, I + phorate, I + phosfamidone, I + phosphocarb, I + sebufos, I + selamectin, I + spinosad, I + terbame, I + terbufos, I + tetrachlorothiophene, I + thiafenox, I + thionazine, I + triazophos, I + triazuron, I + xylenols, I + YI-5302 and zeatin, I + fluensulfone.

[0151] Compositions comprising a synergist include I + 2-(2-butoxyethoxy)ethyl piperonylate, I + 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone, I + farnesol with nerolidol, I + MB-599, I + MGK 264, I + piperonyl butoxide, I + piprotal, I + propyl isomer, I + S421, I + sesamex, I + sesasmolin and I + sulfoxide.

[0152] Compositions comprising an animal repellent include I + anthraquinone, I + chloralose, I + copper naphthenate, I + copper oxychloride, I + diazinone, I + dicyclopentadiene, I + guazatine, I + guazatine acetates, I + methiocarb , I + pyridin-4-amine, I + thiram, I + trimetacarb, I + zinc naphthenate and I + zyram.

[0153] Other compositions include I + Broflutrinate, I + Cycloxapride, I + Diflovidazine, I + Flometoquine, I + Fluhexafone, I + Guadipyr, I + Plutella xylostella granulosis virus, I + Cydia pomonella granulosis virus, I + Harpina, I + Imiciafos, I + Heliothis virescens nuclear polyhedrosis virus, I + Heliothis punctigera nuclear polyhedrosis virus, I + Helicoverpa armigera nuclear polyhedrosis virus, I + Helicoverpa zea nuclear polyhedrosis virus, I + Helicoverpa zea nuclear polyhedrosis virus Spodoptera frugiperda nuclear polyhedrosis, I + Plutella xylostella nuclear polyhedrosis virus, I + Pasteuria nishizawae, I + p-cymene, I + Piflubumide, I + Pirafluprol, I + pyrethrum, I + QRD 420, I + QRD 452, I + QRD 460, I + Terpenoid Combinations, I + Terpenoids, I + Tetraniliprol, and I + α-terpinene.

[0154] The composition also includes mixtures of the polymorph or polymorphs of the invention and an active substance referenced by a code, such as I + AE code 1887196 (BSC-BX60309), I + code NNI-0745 GR, I + code IKI-3106 , I + code JT-L001, I + code ZNQ-08056, I + code IPPA152201, I + code HNPC-A9908 (CAS: [660411-21-2]), I + code HNPC-A2005 (CAS: [860028- 12-2]), I + code JS118, I + code ZJ0967, I + code ZJ2242, I + code JS7119 (CAS: [929.545-74-4]), I + code SN-1172, I + code HNPC-A9835 , I + code HNPC-A9955, I + code HNPC-A3061, I + code Chuanhua 89-1, I + code IPP-10, I + code ZJ3265, I + code JS9117, I + code SYP-9080, I + code ZJ3757, I+code ZJ4042, I+code ZJ4014, I+code ITM-121, I+code DPX-RAB55 (DKI-2301), I+code Me5382, I+code NC-515, I+code NA-89, I + code MIE-1209, I + code MCI-8007, I + code BCS-CL73507, I + code S-1871, I + code DPX-RDS63, and I + code AKD-1193.

[0155] Although compositions comprising the polymorph or polymorphs of the invention and another insecticide, etc., are explicitly disclosed above, the skilled person will appreciate that the invention extends to additional three-way and multiple combinations comprising the above two-way mixtures.

[0156] The weight ratio of the polymorph or polymorphs of the invention to another insecticide is generally between 1000:1 and 1:100, more preferably between 500:1 and 1:100, for example between 250:1 and 1:66, between 125:1 and 1:33, between 100:1 and 1:25, between 66:1 and 1:10, between 33:1 and 1:5 and between 8:1 and 1:3.

[0157] The polymorphs of the invention are also useful in the field of animal health, e.g., they can be used against parasitic invertebrate pests, more preferably against parasitic invertebrate pests in or on an animal. Examples of pests include nematodes, trematodes, cestodes, flies, mites, ticks, lice, fleas, bedbugs and chiggers. The animal may be a non-human animal, e.g., an animal associated with agriculture, e.g., a cow, a pig, a sheep, a goat, a horse, or a donkey, or a pet, e.g. a dog or a cat.

[0158] In a further aspect, the invention provides a polymorph of the invention for use in a therapeutic treatment method.

[0159] In a further aspect, the invention relates to a method of controlling parasitic invertebrate pests in or on an animal comprising administering a pesticide-effective amount of a polymorph of the invention. Administration may be for example oral administration, parenteral administration or external administration, e.g. to the surface of the animal's body. In a further aspect, the invention relates to a polymorph of the invention for controlling parasitic invertebrate pests in or on an animal. In a further aspect, the invention relates to the use of a polymorph of the invention in the manufacture of a medicament for controlling parasitic invertebrate pests in or on an animal.

[0160] In a further aspect, the invention relates to a method of controlling parasitic invertebrate pests comprising administering a pesticide-effective amount of a polymorph of the invention into the environment in which an animal resides.

[0161] In a further aspect, the invention relates to a method of protecting an animal from a parasitic invertebrate pest comprising administering to the animal a pesticide-effective amount of a polymorph of the invention. In a further aspect, the invention relates to a polymorph of the invention for use in protecting an animal from a parasitic invertebrate pest. In a further aspect, the invention relates to the use of a polymorph of the invention in the manufacture of a medicament for protecting an animal from a parasitic invertebrate pest.

[0162] In a further aspect, the invention provides a method of treating an animal suffering from a parasitic invertebrate pest comprising administering to the animal a pesticide-effective amount of a polymorph of the invention. In a further aspect, the invention relates to a polymorph of the invention for use in treating an animal suffering from a parasitic invertebrate pest. In a further aspect, the invention relates to the use of a polymorph of the invention in the manufacture of a medicament for treating an animal suffering from a parasitic invertebrate pest.

[0163] In a further aspect, the invention provides a pharmaceutical composition comprising a polymorph of the invention and a pharmaceutically suitable excipient.

[0164] The polymorph of the invention can be used alone or in combination with one or more other biologically active ingredients.

[0165] In one aspect, the invention provides a combination product comprising a pesticide-effective amount of component A and a pesticide-effective amount of component B wherein component A is a polymorph of the invention and component B is a compound as described below.

[0166] The polymorph of the invention can be used in combination with anthelmintic agents. Such anthelmintic agents include compounds selected from the class of macrocyclic lactone compounds such as derivatives of ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin as described in EP-357460, EP-444964 and EP-594291. Additional anthelmintic agents include semi-synthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO-9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxybendazole, parbendazole and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levadamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides such as triclabendazole and clorsulon, and cestocides such as praziquantel and epsiprantel.

[0167] The polymorphs of the invention can be used in combination with derivatives and analogues of the paraherquamide/marcfortin class of anthelmintic agents, as well as antiparasitic oxazolines such as those disclosed in US-5478855, US-4639771 and DE-19520936 .

[0168] The polymorphs of the invention can be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO-9615121 and also with anthelmintically active cyclic depsipeptides such as those described in WO-9611945, WO -9319053, WO-9325543, EP626375, EP-382173, WO-9419334, EP-382173, and EP-503538.

[0169] The polymorphs of the invention can be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenurone; ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.

[0170] The polymorphs of the invention can be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers WO95/19363 or WO04/72086, particularly the compounds disclosed therein.

[0171] Other examples of such biologically active compounds with which the compounds of the invention can be used in combination include the following, but are not restricted to the following:

[0172] Organophosphates: acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, bromophos, bromophos-ethyl, cadusaphos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demetone, demetone-S-methyl, demetone-S-methylsulfone, dialiphos, diazinone , dichlorvos, dicrotophos, dimethoate, disulfotone, ethione, etoprophos, etrymphos, famfur, fenamiphos, fenitrothion, fensulfothione, fenthion, flupyrazophos, phonofos, formotiona, fosthiazate, heptenophos, isazophos, isothioate, isoxathione, malathione, metacryphos, methamidophos, methidathione, methyl -parathion, mevinfos, monocrotophos, nalede, omethoate, oxidemeton-methyl, paraoxone, parathion, parathion-methyl, phentoate, phosalone, phospholane, phosphocarb, phosmet, phosfamidone, phorate, phoxim, pirimiphos, pirimiphos-methyl, profenofos, propaphos, proetamphos , prothiophos, pyraclophos, pyridapenthion, quinalphos, sulprophos, temephos, terbufos, tebupirimphos, tetrachlorvinphos, thymtone, triazophos, trichlorphone, vamidothione.

[0173] Carbamates: alanicarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, chloretocarb, ethiofencarb, fenoxycarb, fenthiocarb, furatiocarb, HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl -m- cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiophanox, triazamate, UC-51717.

[0174] Pyrethroids: acrinatin, allethrin, alphamethrin, (E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl) 5-benzyl-3-furylmethyl cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, cyfluthrin, a-cypermethrin, beta-cypermethrin, bioalethrin, bioalethrin ((S)-cyclopentyl isomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cytithrin, cyfenothrin, deltamethrin, empenthrin, esfenvalerate, etofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucitrinate, flumethrin, fluvalinate (D-isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin, permethrin, phenothrin, pralethrin, pyrethrins (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, t- fluvalinate, tefluthrin, tralomethrin, Zeta-cypermethrin.

[0175] Arthropod growth regulators: a) inhibitors of chitin synthesis: benzoylureas: chlorfluazurone, diflubenzurone, fluazurone, flucicloxurone, flufenoxurone, hexaflumurone, lufenurone, novalurone, teflubenzurone, triflumurone, buprofezin, diophenolan, hexithiazox, etoxazole, chlorphentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.

[0176] Other antiparasitics: acequinocil, amitraz, AKD-1022, ANS-118, azadirachtin, Baciilus turingiensis, bensultape, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, campeflor, cartape, chlorobenzylate, chlordimeform, chlorfenapyr, chromafenozide , clothianidin, cyromazine, diaclodene, diafenthiuron, DBI-3204, dynactin, dihydroxymethyldihydroxypyrrolidine, dinobutone, dinocape, endosulfan, etiprol, etofenprox, fenazaquin, flumite, MTI-800, fenpyroximate, fluacripyrime, flubenzimine, flubrocitrinate, flufenzine, next , fluproxifen, halofenprox, hydramethylnone, IKI-220, canemite, NC-196, neem protectant, nidinorterfuran, nitanpyram, SD-35651, WL-108477, pyridaryl, propargite, protrifenbut, pymetrozine, pyridabem, pyrimidifeme, NC-1111, R -195,RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomadine, spinosad, tebufenpyrad, tetradifone, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosin , trinactin, verbutin, vertalec, YI-5301.

[0177] Fungicides: acibenzolar, aldimorph, ampropilphos, andoprim, azaconazole, azoxystrobin, benalaxyl, benomyl, bialaphos, blasticidin-S, Bordeaux mixture, bromuconazole, bupirimate, carpropamide, Captafol, Captan, carbendazim, chlorphenazole, chloroneb, chloropicrin, chlorothalonil , clozolinate, copper oxychloride, copper salts, cyflufenamide, cymoxanil, cyproconazole, cyprodinil, ciprofuram, RH-7281, diclocimet, diclobutrazol, diclomezine, dichlorane, difenoconazole, RP-407213, dimethomorph, domoxystrobin, diniconazole, diniconazole-M, dodina , edifenfos, epoxiconazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramide, fenpiclonil, fenpropidine, fenpropimorph, fentin acetate, fluazinam, fludioxonil, flumetover, flumorph/flumorlin, fentin hydroxide, fluoxastrobin, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet , fosetyl-aluminum, furalaxyl, furametapyr, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, cresoxim-methyl, mancozeb, maneb, mefenoxam, mepronil, metalaxyl, metconazole, metominostrobin/phenominostrobin, metrafenone, myclobutanil, neo-asozin, nicobifen , orisastrobin, oxadixil, penconazole, pencicurone, probenazole, prochloraz, propamocarb, propioconazole, proquinazid, prothioconazole, pyrifenox, pyraclostrobin, pyrimethanil, pyroquilone, quinoxifene, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil , triadimephone, triadimenol, tricyclazole, trifloxystrobin, triticonazole, validamycin, vinclozine.

[0178] Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, viruses and fungi.

[0179] Bactericides: chlortetracycline, oxytetracycline, streptomycin.

[0180] Other biological agents: enrofloxacin, febantel, penethamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, carprofen, metaflumizone, praziquarantel, triclabendazole .

[0181] When used in combination with other active ingredients, the compounds of the invention are preferably used in combination with imidacloprid, enrofloxacin, praziquantel, pyrantel embonate, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, fipronil, ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine, thiamethoxam, pyriprol, deltamethrin, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, metaflumizone, moxidectin, methoprene (including S-methoprene), clorsulone, pyrantel, amitraz, triclabendazole, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxybendazole, parbendazole, tetramisole, levadamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, , lufenurone, ecdysone or tebufenozide; more preferably, enrofloxacin, praziquantel, pyrantel embonate, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprol, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin, clorsulone, pyrantel, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxybendazole, parbendazole, tetramisole, levadamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, lufenurone or ecdysone; even more preferably, enrofloxacin, praziquantel, pyrantel embonate, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, piriprol, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen , moxidectin, clorsulone or pyrantel.

[0182] Of particular note is a combination in which the added active ingredient has a site of action different from the polymorph of the invention. In certain cases, a combination with at least one other parasitic invertebrate pest control active ingredient having a similar control spectrum but with a different site of action will be particularly advantageous for resistance management. Thus, a combination product of the invention may comprise a pesticide-effective amount of a polymorph of the invention and a pesticide-effective amount of at least one additional parasitic invertebrate pest control active ingredient having a similar control spectrum but a different place of action.

[0183] One skilled in the art recognizes that, since in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding non-salt forms, salts share the biological utility of the non-salt forms.

[0184] Thus, a wide variety of polymorph salts of the invention (and active ingredients used in combination with the active ingredients of the invention) may be useful for controlling invertebrate pests and animal parasites. Salts include acid addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. . The polymorphs of the invention also include N-oxides. Accordingly, the invention comprises combinations of polymorphs of the invention including their N-oxides and salts and an additional active ingredient including their N-oxides and salts.

[0185] Compositions for use in animal health may also contain formulation aids and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation aids and additives can control: pH (buffers), foaming during processing (antifoams such as polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), microbial growth within the container (antimicrobials). ), product freezing (antifreezes), color (dye/pigment dispersions), washing removal (film formers or binders), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation aids and additives include those listed in McCutcheon's Volume 2: "Functional Materials", annual international and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.

[0186] The polymorphs of the invention can be applied without other adjuvants, but more frequently the application will be a formulation comprising one or more active ingredients with suitable carriers, diluents, and surfactants and possibly in combination with a food, depending on the end use contemplated. . One method of application involves spraying an aqueous dispersion or refined oily solution of the combination products. Compositions with spray oils, spray oil concentrations, spreaders-adhesives, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance the effectiveness of the compounds. Such sprays may be applied from spray containers such as a can, bottle or other container, by means of a pump or by releasing them from a pressurized container, e.g. a pressurized aerosol spray can. . Such spray compositions may take various forms, for example, sprays, mists, foams, fumes or fog. Such spray compositions may thus additionally comprise propellants, foaming agents, etc., as appropriate. Of note is a spray composition comprising a pesticide-effective amount of a compound of the invention and a carrier. One embodiment of such a spray composition comprises a pesticide-effective amount of a compound of the invention and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the above. Of note is a spray composition (and a method utilizing such a spray composition dispensed from a spray container) used to control at least one parasitic invertebrate pest selected from the group consisting of mosquitoes, midges, stable flies, horse flies, deer, horseflies, wasps, yellow jackets, hornets, ticks, spiders, ants, gnats, and the like, including individually or in combinations.

[0187] Animal parasite control includes control of external parasites that are parasitic on the surface of the host animal's body (e.g., forequarters, armpits, abdomen, inner thighs) and internal parasites that are parasitic on the inside of the host animal's body (e.g., stomach, intestine, lung, veins, under the skin, lymphatic tissue). Parasitic pests or those that transmit external diseases include, for example, larvae, ticks, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, hookworms, and helminths. The polymorphs of the invention may be particularly suitable for combating external parasitic pests. The polymorphs of the invention may be suitable for systemic and/or non-systemic control of infestation or parasite infection in animals.

[0188] The polymorphs of the invention may be suitable for combating parasitic invertebrate pests that infest animal subjects including those in wild animals, livestock and agricultural work. Cattle is the term used to refer (singularly or plurally) to a domesticated animal intentionally bred in an agricultural setting to produce products such as food or fiber, or for its labor; examples of livestock include cattle, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, chickens, turkeys, ducks, and geese (e.g., raised for meat, milk, butter, eggs, fur, leather, feathers and/or wool). By combating parasites, fatalities and reduced performance (in terms of meat, milk, wool, skins, eggs, etc.) are reduced, such that the application of the polymorphs of the invention allows for more economical and simple breeding of animals.

[0189] The polymorphs of the invention may be suitable for combating parasitic invertebrate pests that infest companion animals and pets (e.g., dogs, cats, pet birds and aquarium fish), research and experimental animals ( e.g., hamsters, guinea pigs, rats and mice), as well as animals bred for/in zoos, wild habitats and/or circuses.

[0190] In one embodiment of this invention, the animal is preferably a vertebrate, and more preferably a mammal, bird or fish. In a particular embodiment, the animal subject is a mammal (including great apes, such as humans). Other mammalian subjects include primates (e.g., monkeys), bovines (e.g., cattle or dairy cows), porcines (e.g., swine or pigs), sheep (e.g., goats or sheep ), equines (e.g., horses), canines (e.g., dogs), felines (e.g., domestic cats), camels, deer, donkeys, buffaloes, antelopes, rabbits, and rodents (e.g. ., guinea pigs, squirrels, rats, mice, gerbils and hamsters). Birds include Anatidae (swans, ducks and geese), Columbidae (e.g. doves and pigeons), Phasianidae (e.g. partridges, capercaillie and turkeys), Thesienidae (e.g. domestic chickens), Psittacines (e.g., parakeets, macaws, and parrots), game birds, and flightless birds (e.g., ostriches).

[0191] Birds treated or protected by the polymorphs of the invention can be associated with both commercial and non-commercial poultry farming. These include Anatidae, such as swans, geese, and ducks, Columbidae, such as doves and domestic pigeons, Phasianidae, such as partridges, capercaillies, and turkeys, Thesienidae, such as domestic chickens, and Psittacines, such as parakeets, macaws, and farmed parrots. for the pet or collection animal market, among others.

[0192] For purposes of the present invention, the term "fish" is understood to include, without limitation, the group of Teleosti fish, i.e., teleosts. Both the order Salmoniformes (which includes the family Salmonidae) and the order Perciformes (which includes the family Centrarchidae) are contained within the Teleosti grouping. Examples of potential recipient fish include Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae, among others.

[0193] Other animals are also contemplated to benefit from the inventive methods, including marsupials (such as kangaroos), reptiles (such as farmed turtles), and other economically important domestic animals for which the inventive methods are safe and effective in treating or prevention of infection or parasitic infestation.

[0194] Examples of parasitic invertebrate pests controlled by administering a pesticide-effective amount of the polymorphs of the invention to an animal to be protected include ectoparasites (arthropods, mites, etc.) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, acanthocephalans, etc.).

[0195] The disease or group of diseases generically described as helminthiasis is due to the infection of an animal host with parasitic worms known as helminths. The term "helminths" is intended to include nematodes, trematodes, cestodes and acanthocephalans. Helminthiasis is a prevalent and serious economic problem with domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats and poultry.

[0196] Among helminths, the group of worms described as nematodes causes widespread and sometimes serious infection in several species of animals.

[0197] The ematodes that are contemplated to be treated by the polymorphs of the invention include, without limitation, the following genera: Acanthocheilonema, Aelurostrongylus, Ancylostoma, Angiostrongylus, Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema, Diphyllobothrium, Dirofilaria, Dracunculus, Enterobius, Filaroides, Haemonchus, Heterakis, Lagochilascaris, Loa, Mansonella, Muellerius, Necator, Nematodirus, Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca Stephanofil, aria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris, Uncinaria and Wuchereria.

[0198] Of the above nematode genera, the most common that infect the animals referred to above are Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara , Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Some of these, such as Nematodirus, Cooperia and Oesophagostomum mainly attack the intestinal tract, while others, such as Haemonchus and Ostertagia, are more prevalent in the stomach, while others, such as Dictyocaulus, are found in the lungs. Still other parasites may be located in other tissues such as the heart and blood vessels, subcutaneous and lymphatic tissue and the like.

[0199] Trematodes that are contemplated to be treated by the invention and inventive methods include, without limitation, the following genera: Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus and Schistosoma.

[0200] Cestodes that are contemplated to be treated by the invention and inventive methods include, without limitation, the following genera: Diphyllobothrium, Diplydium, Spirometra and Taenia.

[0201] The most common genera of parasites of the human gastrointestinal tract are Ancylostoma, Necator, Ascaris, Strongy hides, Trichinella, Capillaria, Trichuris and Enterobius. Other medically important parasite genera that are found in the blood or other tissues and organs outside the gastrointestinal tract are filarial worms such as Wuchereria, Brugia, Onchocerca and Loa, as well as Dracunculus and extraintestinal stages of the intestinal worms Strongyloides and Trichinella.

[0202] Numerous other genera and species of helminths are known in the art, and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in Textbook of Veterinary Clinical Parasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods and Protozoa (65 Edition of Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby, Williams and Wilkins Co., Baltimore, Md.

[0203] The polymorphs of the invention can be effective against a number of animal ectoparasites (e.g., arthropod ectoparasites of mammals and birds).

[0204] Insect and mite pests include, e.g., biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, bedbugs, parasitic worms, and the like.

[0205] Adult flies include, e.g., the horn fly or Haematobia irritans, the horse fly or Tabanus spp., the stable fly or Stomoxys calcitrans, the pea tripid or Simulium spp., the deer fly or Chrysops spp., the malophagus fly or Melophagus ovinus, and the tsetse fly or Glossina spp. Parasitic fly larvae include, e.g., the sheep nasal maggot (Oestrus ovis and Cuterebra spp.), the blow fly or Phaenicia spp., the devourer fly or Cochliomyia hominivorax, the hypoderma larva or Hypoderma spp., the sheep fleece larvae and horse Gastrophilus. Mosquitoes include, for example, Culex spp., Anopheles spp. and Aedes spp.

[0206] Mites include Mesostigmalphatalpha spp., for example, mesostigmatids such as the chicken mite, Dermalphanyssus galphallinalphae; scabies or scabies mites such as Sarcoptidae spp., for example, Salpharcoptes scalphabiei; scabies mites such as Psoroptidae spp., including Chorioptes bovis and Psoroptes ovis; Trombiculidae, e.g., Trombiculidae spp., e.g. the North American trombiculidae, Trombiculalpha alphalfreddugesi.

[0207] Ticks include, for example, soft-bodied ticks including Argasidae spp., for example Argalphas spp. and Ornithodoros spp.; hard-bodied ticks including Ixodidae spp., for example Rhipicephalphalus sanguineus, Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Ixodes scapularis and other Rhipicephalus spp. (including the ancient genus Boophilus).

[0208] Lice include, e.g., sucking lice, e.g., Menopon spp. and Bovicola spp.; biting lice, e.g., Haematopinus spp., Linognathus spp., and Solenopotes spp.

[0209] Fleas include, for example, Ctenocephalides spp. such as dog flea (Ctenocephalides canis) and cat flea (Ctenocephalides felis); Xenopsylla spp. such as eastern rat flea (Xenopsylla cheopis); and Pulex spp. such as man flea (Pulex irritans).

[0210] Bed bugs include, for example, Cimicidae or for example, the common bed bug (Cimex lectularius); Triatominae spp., including triatomid bugs also known as kissing bugs; for example, Rhodnius prolixus and Triatoma spp.

[0211] Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks and helminths cause tremendous losses in the livestock and pet farming sectors. Arthropod parasites are also a nuisance to humans and can be vectors of disease-causing organisms in humans and animals.

[0212] Numerous different parasitic invertebrate pests are known in the art, and are also contemplated to be treated by the polymorphs of the invention. These are enumerated in great detail in Medical and Veterinary Entomology, D. S. Kettle, John Wiley and Sons, New York and Toronto; Control of Arthropod Pests of Livestock: A Review of Technology, R. O. Drummand, J. E. George, and S. E. Kunz, CRC Press, Boca Raton, FIa.

[0213] The polymorphs of the invention may also be effective against ectoparasites including: flies such as Haematobia (Lyperosia) irritans horn fly), Simulium spp. (black fly), Glossina spp. (tsetse fly), Hydrotaea irritans (head fly), Musca autumnalis (face fly), Musca domestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horsefly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green blowfly), Calliphora spp. (blow fly), Protophormia spp., Oestrus ovis (sheep nasal larva), Culicoides spp. (sandflies), Hippobosca equine, Gastrophilus intestinalis, Gastrophilus haemorrhoidalis and Gastrophilus nasalis; lice such as Bovicola (Damalinia) bovis, Bovicola equi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger, Lignonathus setosus and Trichodectes canis; flies such as Melophagus ovinus; and mites such as Psoroptes spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites).

[0214] The treatments of the invention are by conventional means such as by enteral administration in the form of, for example, tablets, capsules, drinks, potions, granules, pastes, boli, nutritional procedures, or suppositories; or by parenteral administration, such as, for example, by injection (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implants; or by nasal administration.

[0215] When polymorphs of the invention are applied in combination with an additional biologically active ingredient, they can be administered separately, e.g., as separate compositions. In this case, the biologically active ingredients can be administered simultaneously or sequentially. Alternatively, biologically active ingredients may be components of a composition.

[0216] The polymorphs of the invention can be administered in a controlled release form, for example in slow release formulations administered subcutaneously or orally.

[0217] Typically, a parasiticidal composition according to the present invention comprises a polymorph of the invention, optionally in combination with an additional biologically active ingredient, or N-oxides or salts thereof, with one or more pharmaceutically or veterinarily acceptable carriers comprising excipients and auxiliaries selected with respect to the intended route of administration (e.g., oral or parenteral administration such as injection) and in accordance with common practice. Additionally, a suitable carrier is selected based on compatibility with the one or more active ingredients in the composition, including such considerations as pH stability and moisture content. Therefore, polymorphs of the invention for protecting an animal from an invertebrate parasitic pest comprising a parasiticidally effective amount of a polymorph of the invention, optionally in combination with an additional biologically active ingredient and at least one carrier, are of note.

[0218] For parenteral administration including intravenous, intramuscular and subcutaneous injection, the polymorphs of the invention can be formulated in suspension, solution or emulsion in oily or aqueous vehicles, and can contain adjuncts such as suspending, stabilizing and/or dispersing agents.

[0219] The polymorphs of the invention can also be formulated for bolus injection or continuous infusion. Pharmaceutical compositions for injection include aqueous solutions of water-soluble forms of active ingredients (e.g., a salt of an active compound), preferably in physiologically compatible buffers containing other excipients or auxiliaries as are known in the art of pharmaceutical formulation. Additionally, suspensions of the active compounds can be prepared in a lipophilic vehicle. Suitable lipophilic carriers include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or materials such as liposomes.

[0220] Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or multi-dose containers. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.

[0221] In addition to the formulations described above, the polymorphs of the invention can also be formulated as a depot preparation. Such long-acting formulations may be administered by implantation (e.g. subcutaneously or intramuscularly) or by intramuscular or subcutaneous injection.

[0222] The polymorphs of the invention can be formulated for this route of administration with suitable polymeric or hydrophobic materials (for example, in an emulsion with a pharmacologically acceptable oil), with ion exchange resins, or as a sparsely soluble derivative such as, without limitation, a sparingly soluble salt.

[0223] For administration by inhalation, the polymorphs of the invention may be delivered in the form of an aerosol spray using a pressurized package or a nebulizer and a suitable propellant, e.g., without limitation, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide. carbon. In the case of a pressurized aerosol, the dosage unit can be controlled by providing a valve to dispense a metered amount.

[0224] Capsules and cartridges of, for example, gelatin can be formulated for use in an inhaler or insufflator containing a powder mixture of the compound and a suitable powder base such as lactose or starch.

[0225] The polymorphs of the invention may have favorable pharmacokinetic and pharmacodynamic properties providing systemic availability from oral administration and ingestion. Therefore, upon ingestion by the animal to be protected, parasiticidally effective concentrations of a polymorph of the invention in the bloodstream can protect the treated animal from blood-sucking pests such as fleas, ticks and lice. Therefore of note is a composition for protecting an animal from an invertebrate parasitic pest in a form for oral administration (i.e., comprising, in addition to a parasiticidally effective amount of a polymorph of the invention, one or more selected carriers of binders and fillers suitable for oral administration and feed concentrate carriers).

[0226] For oral administration in the form of solutions (the most readily available form for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boli, powders, granules, rumen retention blocks and feed/water/blocks to lick, the polymorphs of the invention may be formulated with binders/fillers known in the art to be suitable for compositions for oral administration, such as sugars and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol), starch ( e.g., corn starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin ), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g. magnesium stearate), disintegrating agents (e.g. cross-linked polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can be added. Pastes and gels also often contain adhesives (e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to help keep the composition in contact with the oral cavity and not be easily ejected. .

[0227] In one embodiment, a composition of the present invention is formulated into a chewable and/or edible product (e.g., a chewable snack or edible tablet). Such a product will ideally have a flavor, texture and/or aroma to the liking of the animal to be protected so as to facilitate oral administration of the compounds of the invention.

[0228] If the parasiticidal compositions are in the form of feed concentrates, the carrier is typically selected from high performance feeds, feed cereals or protein concentrates. Such compositions containing feed concentrates may, in addition to the parasiticidal active ingredients, comprise additives promoting the health or growth of the animal, improving the quality of meat of animals for slaughter or otherwise useful for animal husbandry. These additives may include, for example, vitamins, antibiotics, chemotherapeutics, bacteriostatic agents, fungistatics, coccidiostats and hormones.

[0229] The polymorph of the invention can also be formulated into rectal compositions such as suppositories or retention enemas, using, for example, conventional suppository bases such as cocoa butter or other glycerides.

[0230] Formulations for the method of the present invention may include an antioxidant, such as BHT (butylated hydroxytoluene). The antioxidant is generally present in amounts of 0.1-5 percent (wt/vol). Some of the formulations require a solubilizer, such as oleic acid, to dissolve the active agent, particularly if spinosad is included. Common spreading agents used in these pour-on formulations include isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated C12-C18 fatty alcohols, oleic acid, oleyl ester, ethyl oleate, triglycerides, silicone oils, and methyl ether. dipropylene glycol. Pouring formulations for the method of the present invention are prepared according to known techniques. Where the pour-on formulation is a solution, the parasiticide/insecticide is mixed with the carrier or vehicle, using heating and agitation if required. Auxiliary or additional ingredients may be added to the mixture of active agent and carrier, or may be mixed with the active agent before adding the carrier. Pouring formulations in the form of emulsions or suspensions are similarly prepared using known techniques.

[0231] Other delivery systems for relatively hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well-known examples of delivery vehicles or carriers for hydrophobic drugs. Additionally organic solvents such as dimethyl sulfoxide can be used if necessary.

[0232] The application rate required for effective control of parasitic invertebrate pests (e.g., "pesticide-effective amount") will depend on such factors as the species of parasitic invertebrate pest to be controlled, the life cycle of the pest , the life stage, its size, location, time of year, host culture or animal, feeding behavior, mating behavior, ambient humidity, temperature and the like. One skilled in the art can readily determine the pesticide-effective amount necessary for the desired level of parasitic invertebrate pest control.

[0233] In general, for veterinary use, the polymorphs of the invention are administered in a pesticide-effective amount to an animal, particularly a homeothermic animal, to be protected from parasitic invertebrate pests.

[0234] A pesticide-effective amount is the amount of active ingredient necessary to achieve an observable effect of decreasing the occurrence or activity of the target parasitic invertebrate pest. One skilled in the art will appreciate that the pesticide-effective dose may vary for the various compounds and compositions useful in the method of the present invention, the desired pesticide effect and duration, the target species of the parasitic invertebrate pest, the animal to be protected, the mode of application and the like, and the amount necessary to achieve a particular result can be determined through simple experimentation.

[0235] For oral or parenteral administration to animals, a dose of the compositions of the present invention administered at suitable intervals typically ranges from about 0.01 mg/kg to about 100 mg/kg, and preferably from about 0.01 mg /kg to about 30 mg/kg of animal body weight.

[0236] Suitable intervals for administering the compositions of the present invention to animals vary from about once a day to about once a year. Administration intervals ranging from about once a week to about once every 6 months are of note. Of particular note are monthly administration intervals (i.e., administration of the compounds to the animal once each month).

[0237] The present invention will now be described by way of the following non-limiting examples and figures, in which:

[0238] FIG. 1 shows the measured powder X-ray diffraction pattern of the polymorph designated Form A(a).

[0239] FIG. 2 shows the predicted powder X-ray diffraction pattern of the polymorph designated Form A(a).

[0240] FIG. 3 shows a DSC trace of the polymorph designated Form A(a).

[0241] FIG. 4 shows the measured powder X-ray diffraction pattern of the polymorph designated Form A(b).

[0242] FIG. 5 shows a DSC trace of the polymorph designated Form A(b).

[0243] FIG. 6 shows the measured powder X-ray diffraction pattern of the hydrate of the compound of formula IA.

[0244] FIG. 7 shows the predicted powder X-ray diffraction pattern of the hydrate of the compound of formula IA.

[0245] FIG. 8 shows the measured powder X-ray diffraction pattern of the polymorph of the compound of formula IB.

[0246] FIG. 9 shows a DSC trace of the compound of formula IB.

[0247] FIG. 10 shows the predicted powder X-ray diffraction pattern of the polymorph of the compound of formula IB.

[0248] FIG. 11 shows the measured powder X-ray diffraction pattern of the racemate polymorph of the compounds of formulas IA and ID.

[0249] FIG. 12 shows a DSC trace of the racemate polymorph of compounds of formulas IA and ID.

[0250] FIG. 13 shows a Raman spectrum of the polymorph designated Form A(a).

[0251] FIG. 14 shows a DSC trace of the polymorph designated Form A(c).

EXAMPLES 57. Preparation of Polymorphs

[0252] The compound of formula I was prepared by methods described in document WO 2011/067272. This resulting solid precipitate and liquid filtrate were analyzed by HPLC as indicated in WO 2011/067272. The compound of formula IA was present in the filtrate and the compound of formula IC in the solid precipitate. When crystallized from the filtrate, the Form A(c) polymorph was identified by DSC (see FIG. 14).

1a. Preparation of Form A(a)

[0253] A purified sample of the compound of formula IA was slurried in dimethyl carbonate for 2 weeks at 25°C, after which the crystals were isolated and characterized by DSC, powder X-ray diffraction and X-ray diffraction single crystal. A measured powder X-ray diffraction pattern for the polymorph of the compound of formula IA (designated Form A(a)) is shown in FIG 1. The pattern predicted from the single crystal intensity data is shown in FIG 2. A DSC trace of Form A(a) is shown in FIG. 3.

1b. Preparation of Form A(b)

[0254] An additional sample of the compound of formula IA was subjected to slow evaporation at room temperature from a number of solvents. The sample isolated after evaporation from 20% water/methanol was analyzed by DSC and X-ray powder diffraction. A measured X-ray powder diffraction pattern for the polymorph of the compound of formula IA (designated Form A(b)) is shown in FIG. 4. A DSC trace of Form A(b) is shown in FIG. 5.

1c. Preparation of Form A(h)

[0255] An additional sample of the compound of formula IA was subjected to slow evaporation from a water/ethanol mixture. Analysis of the crystals showed that water was incorporated into the structure - with two molecules of water and two molecules of the compound of formula IA in the asymmetric unit. This hydrate (designated Form A(h)) was subjected to analysis by DSC and TGA, as well as powder X-ray diffraction and single crystal X-ray diffraction. A measured powder X-ray diffraction pattern for the hydrate is shown in FIG 6. The pattern predicted from the single crystal intensity data is shown in FIG 7.

1d. Preparation of Form B(a) and Form C(a)

[0256] Samples of compounds of formula IB and IC were prepared by dissolving the samples in acetone, filtering the acetone through a 0.2 μm syringe filter into a clean vial, and leaving the vial in a smoke cabinet to allow the acetone evaporates. The resulting solid samples were analyzed by powder X-ray diffraction and DSC. The powder X-ray diffraction patterns for IB and IC were identical. The pattern for the compound of formula IB is shown in FIG. 8. The DSC for this compound is shown in FIG. 9.

[0257] Crystals suitable for single crystal X-ray diffraction analysis were grown in an isopropanol/water mixture (80/20). The pattern predicted from the single crystal intensity data is shown in FIG. 10.

1 and. Preparation of a racemic mixture of compounds of formula IA and ID

[0258] Equal amounts of compounds of formula IA and ID were dissolved in acetone and then left at room temperature until the solvent had evaporated. The resulting crystalline solid was characterized by X-ray powder diffraction and DSC. A measured X-ray powder diffraction pattern for the racemate polymorph of compounds of formula IA and ID is shown in FIG. 11. A DSC trace of this polymorph is shown in FIG. 12.

58. Analysis of polymorphs

[0259] After preparation, the samples were subjected to analysis by powder X-ray diffraction and/or single crystal X-ray diffraction and/or differential scanning calorimetry (DSC) and/or thermogravimetric analysis (TGA), as detailed above. The methods used for these analysis techniques are detailed below:

[0260] Powder X-ray diffraction analysis of the solid material was carried out using the Bruker D8 powder diffractometer at room temperature and at relative humidities above 40%. The samples were mounted on Perspex sample holders and the samples were flattened. The sample holder was rotated and X-rays were collected from 4° to 34° 2-theta, with a scan time of 25 to 30 minutes depending on pattern intensity.

[0261] Single crystal intensity data was collected on an Oxford Xcalibar PX Ultra diffractometer using Cu Kα radiation (À=1.5418 Â) with a graphite monochromator. The crystal was mounted in 100K Paratone N oil for data collection. Data were resolved using the CRYSTALS software package.

[0262] DSC was carried out using a Mettler Toledo DSC1. A sample load of about 5 mg was used and this was heated from 25 °C to 160 °C at a rate of 10 °C/minute. The lid of the DSC crucible was perforated to allow any gas formed during sample heating to escape.

[0263] Raman spectroscopy was performed using a Thermo Scientific DXR Raman microscope: a 780 nM Raman laser was focused on the sample on a quartz slide.

59. Stability of polymorphs

[0264] A sample of the polymorph designated as Form A(c) was stirred in 5 mL of dimethyl carbonate for two days. Crystals were isolated, air dried and characterized by DSC and pXRD. The DSC curve showed a sharp single melting endotherm with a melting peak at 141 °C and the pXRD pattern matched that of Form A(a), indicating that all of Form A(c) converted to Form (A)a .

[0265] Although the invention has been described with reference to preferred embodiments and examples thereof, the scope of the present invention is not limited only to these described embodiments. As will be apparent to persons skilled in the art, modifications and adaptations of the above-described invention may be made without departing from the spirit and scope of the invention, which is defined and circumscribed by the appended claims. All publications cited herein are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were specifically and individually indicated as being incorporated by reference.

Claims (15)

1. Crystalline polymorph of the compound of formula IA characterized by the fact that it has a powder X-ray diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 6.0 ± 0.2, 8.8 ± 0.2, 9.4 ± 0.2, 10.1 ± 0.2, 11.9 ± 0.2, 14.5 ± 0.2, 15.9 ± 0.2, 20.2 ± 0.2, 20.7 ± 0 .2, 21.2 ± 0.2, 21.7 ± 0.2, 22.1 ± 0.2 and 22.7 ± 0.2. 2. Crystalline polymorph, according to claim 1, characterized by the fact that it has the following lattice parameters: a = 5.06 Â ± 0.01 Â, b = 18.92 Â ± 0.01 Â, c = 24.17 Â ± 0.01 Â, α = 90° ± 0.01°, β = 90° ± 0.01°, y = 90° ± 0.01° and volume = 2315 Â3± 1 Â3. 3. Crystalline polymorph, according to claim 1 or 2, characterized by the fact that it has a melting point of 141 °C ± 2 °C. 4. Crystalline polymorph of the compound of formula IA, characterized by the fact that it is a hydrate and has a powder X-ray diffraction pattern comprising at least three values of angle 2θ selected from the group consisting of 4.4 ± 0.2, 7.0 ± 0.2, 8.7 ± 0.2, 10.3 ± 0.2, 11.0 ± 0.2, 12.4 ± 0.2, 12.7 ± 0.2, 13, 3 ± 0.2, 14.1 ± 0.2, 15.9 ± 0.2, 17.1 ± 0.2, 18.6 ± 0.2, 19.0 ± 0.2 and 19.6 ± 0.2. 5. Crystalline polymorph, according to claim 4, characterized by the fact that it has the following lattice parameters: a = 8.03 Â ± 0.01 Â, b = 16.10 Â ± 0.01 Â, c = 20.37 Â ± 0.01 Â, α = 90° ± 0.01°, β = 97.02° ± 0.01°, y = 90° ± 0.01° and volume = 2615 Â3± 1 Â3. 6. Crystalline polymorph of the compound of formula IB or IC characterized by the fact that it has a powder X-ray diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 4.1 ± 0.2, 8.3 ± 0.2, 10.2 ± 0.2, 12.4 ± 0.2, 15.5 ± 0.2, 16.5 ± 0.2, 18.2 ± 0.2, 18.4 ± 0.2, 18.7 ± 0 .2, 19.0 ± 0.2, 20.5 ± 0.2, 21.0 ± 0.2 and 21.4 ± 0.2. 7. Crystalline polymorph, according to claim 6, characterized by the fact that it has a melting point of 206 °C ± 2 °C. 8. Crystalline polymorph of the racemate of compounds of formula IA and ID characterized by the fact that it has a powder X-ray diffraction pattern comprising at least three 2θ angle values selected from the group consisting of 4.0 ± 0.2, 8.1 ± 0.2, 9.7 ± 0.2, 11.1 ± 0.2, 12.7 ± 0.2, 15.3 ± 0.2, 15.9 ± 0.2, 16.2 ± 0.2, 16.7 ± 0 .2, 18.4 ± 0.2, 19.5 ± 0.2, 19.8 ± 0.2, 20.3 ± 0.2, 21.8 ± 0.2 and 23.9 ± 0.2 . 9. Crystalline polymorph, according to claim 8, characterized by the fact that it has a melting point of 173 °C ± 2 °C. 10. Agricultural composition, characterized by the fact that it comprises a polymorph defined in any one of claims 1 to 9, and at least one agriculturally acceptable carrier or diluent. 11. Composition, according to claim 10, characterized by the fact that it comprises more than one polymorph of the polymorphs defined in any one of claims 1 to 9. 12. Composition, according to claim 10, characterized by the fact that it is enriched for a polymorph of the compound of formula IA. 13. Composition, according to claim 12, characterized by the fact that it is enriched for the polymorph defined in any one of claims 1 to 3. 14. Composition according to any one of claims 10 to 13, characterized in that it comprises at least one additional insecticide or nematicide. 15. Method of preventing or controlling insect infection in plants or plant propagation material, characterized in that it comprises treating the plant or plant propagation material with an insecticidally effective amount of an agricultural composition defined in any of claims 10 to 14.