EA044796B1 - POLYMORPHS - Google Patents

Description

The present invention relates to solid forms of an isoxazoline derivative, compositions containing solid forms, and methods of using them as insecticides.

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

Mixtures of this compound with other insecticides are disclosed in WO 2012/163960, and with fungicides in WO 2012/163945.

To date, new solid forms of this compound and its isomers, compositions based on them, as well as methods for their preparation and use have been discovered.

There are four isomers of the compound of formula I: A, B, C and D, as shown below.

The present invention relates to new crystalline forms of the compound of formula IA, designated Form A(a). This crystalline polymorph, which is form A(a), can be characterized using the unit cell parameters of its single crystal, shown in Table. 1. The polymorph was obtained using the method described in example 1.

Table 1

Class Orthorhombic Space group P212121 Cell length indicators (A) a = 5.06, b = 18.92, c = 24.17 Cell Angles (°) a = 90, β = 90, γ = 90 Unit cell volume (A ³ ) 2315 Z 4

In the table, a, b, c=length of unit cell edges; α, β, γ=unit cell angles; and Z=number of molecules per cell.

Thus, in one embodiment of the present invention, the crystalline polymorph, designated form A(a), has the following lattice parameters: a=5.06 A±0.01 A, b=18.92 A±0.01 A, c =24.17 A±0.01 A, α=90°±0.01°, β=90°±0.01°, γ=90°±0.01° and volume=2315 A ³ ±1 A ³ .

The crystalline polymorph, designated form A(a), can also be characterized by powder X-ray diffraction patterns based on 2Θ angles or interplanar distances d. Thus, in another embodiment of the present invention, the crystalline polymorph is characterized by an X-ray powder diffraction pattern containing at least three, at least six, or all 2θ angle values selected from the group consisting of

- 1 044796 out 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 interplanar distance d values are shown in Table. 2 below.

These 2Θ angle values are obtained from the X-ray powder diffraction pattern of the polymorph prepared using the method of Example 1. The values are obtained using an average wavelength of 1.54056 A with a 2θ step size of 0.02°.

In another embodiment, the crystalline polymorph, designated 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/min.

The crystalline polymorph, designated form A(a), can also be characterized using Raman spectra based on the Raman shift (cm ^-1 ). Thus, in another embodiment of the present invention, the crystalline polymorph is characterized by Raman spectra containing 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.

Also described is an additional crystalline form of the compound of formula IA, designated form A(b), which can be characterized by powder x-ray diffraction patterns based on 2θ angles or interplanar distances d. This crystalline polymorph is characterized by an X-ray powder diffraction pattern containing 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 interplanar distance d values are shown in Table. 3 below.

These 2θ angle values are obtained from the X-ray powder diffraction pattern of the polymorph prepared using the method of Example 1. The values are obtained using the average length

- 2 044796 waves 1.54056 A with a 2θ step size of 0.02°.

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/min.

The present invention also provides an additional new crystalline form of the compound of formula IA, designated form A(h), which is a hydrate. This crystalline polymorph, which is form A(h), can be characterized using the unit cell parameters of its single crystal shown in Table. 4. The polymorph was obtained using the method described in example 1.

Table 4

Class Monoclinic Space group P21 Cell length indicators (A) a = 8.03, b = 16.10, c = 20.37 Cell Angles (°) a = 90, β = 97.02, γ = 90 Unit cell volume (A ³ ) 2615 Z 2

In the table, a, b, c = length of the edges of the unit cell; α, β, γ=unit cell angles; and Z=number of molecules per cell.

Thus, in one embodiment of the present invention, the crystalline polymorph, designated form A(h), has the following lattice parameters: a=8.03 A±0.01 A, b=16.10 A±0.01 A, c =20.37 A±0.01 A, α=90° ±0.01°, β=97.02° ±0.01°, γ=90° ±0.01° and volume=2615 A ³ ±1 A ³ .

The crystalline polymorph, designated form A(h), can also be characterized by powder X-ray diffraction patterns based on 2θ angles or interplanar distances d. Thus, in another embodiment of the present invention, the crystalline polymorph is characterized by an X-ray powder diffraction pattern containing at least three, at least six, or all 2θ angle 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 interplanar distance d values are shown in Table. 5 below.

These 2θ angle values are obtained from an X-ray powder diffraction pattern calculated using intensity data for a single crystal of the polymorph obtained using the method of Example 1. The values are obtained using an average wavelength of 1.54056 A with a 2± step size of 0.02°.

Also described is a crystalline form of the compound of formula IA, designated form A(c), to

- 3 044796 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/min. It should be noted that the crystalline forms of the compound of formula ID will have parameters identical to those of the compound of formula IA. Therefore, new crystalline forms of the compound of formula ID that have the physical parameters listed above for the compound of formula IA can also be described.

Also described is the crystalline form of the compound of Formula IB, which can be characterized by powder X-ray diffraction patterns based on 2Θ angles or d interplanar distances. This crystalline polymorph is characterized by an X-ray powder diffraction pattern containing 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 interplanar distance d values are shown in Table. 6 below.

These 2θ angle values are obtained from an X-ray powder diffraction pattern calculated using intensity data for a single crystal of the polymorph obtained using the method of Example 1. The values are obtained using an average wavelength of 1.54056 A with a 2± step size of 0.02°.

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/min.

Also described is the crystalline form of the compound of formula IC, which can be characterized by powder X-ray diffraction patterns based on 2θ angles or d interplanar distances. This crystalline polymorph is characterized by an X-ray powder diffraction pattern containing 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 interplanar distance d values are shown in Table. 7 below. It should be noted that the X-ray powder diffraction profile of the compound of formula IC is identical to that of the compound of formula IB.

- 4 044796

These 2Θ angle values are obtained from an X-ray powder diffraction pattern calculated using intensity data for a single crystal of the polymorph obtained using the method of Example 1. The values are obtained using an average wavelength of 1.54056 A with a 2± step size of 0.02°.

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/min.

The present invention also relates to an additional new crystalline form of the racemate of the compounds of formula IA and formula ID, which can be characterized by a powder x-ray diffraction pattern based on 2Θ angles or interplanar distances d. This crystalline polymorph is characterized by an X-ray powder diffraction pattern containing 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 interplanar distance d values are shown in Table. 8 below.

These 2θ angle values are obtained from the X-ray powder diffraction pattern of the polymorph prepared using the method of Example 1. The values are obtained using an average wavelength of 1.54056 A with a 2± step size of 0.02°.

The crystalline polymorph of the racemate of the compounds of formula IA and ID has 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/min.

- 5 044796

In the context of the present invention, a polymorph is a specific crystalline form of a chemical compound that, in the solid state, can exist in more than one crystalline form. The crystalline form of a compound contains its constituent molecules, forming ordered repeating structures extending in all three spatial dimensions (in contrast, in the amorphous solid form there is no long-range order in the arrangement of the molecules). Different polymorphs of a compound are characterized by different arrangements of atoms and/or molecules in their crystal structure. If the compound is a biologically active compound, such as an insecticide, differences in crystal structures may cause different polymorphs to have different chemical, physical and biological properties. Properties that may vary include crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, dissolution rate, and bioavailability. In this regard, a particular polymorph may have properties that make it preferable in a particular application compared to another polymorph of the same compound: in particular, the physical, chemical and biological properties listed above can have a significant impact on the development of production methods and formulations, indicator the ease with which the compound can be combined in a formulation with other active ingredients and formulation components, and the quality and effectiveness of plant treatments such as insecticides. It should be noted that it is not possible to predict whether a compound in the solid state may be represented by more than one polymorph, nor is it possible to predict the properties of any of these crystalline forms.

In particular, the use of a particular polymorph may enable the use of new formulations compared to existing polymorphic/amorphous forms of the compound. This may be appropriate for a number of reasons. For example, a suspension concentrate (SC) formulation may be preferred over an emulsion concentrate (EC) formulation because the lack 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 the compound is not stable in such SC formulations, polymorphic transformation may occur, leading to undesirable crystal growth. This crystal growth is unfavorable because it leads, for example, to thickening and possible hardening of the composition, which can lead to clogging of equipment for applying the compositions, for example, in spray nozzles in agricultural machinery. The use of a stable polymorphic form will solve these problems.

Analysis of the solid phase for the presence of crystals can be carried out using traditional methods known in the art. For example, the use of powder X-ray diffraction techniques is practical and generally accepted. 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 particularly useful in determining crystal structures.

The polymorphs of the present invention can be used in unmodified form, but it is more preferable to introduce them into agrochemical compositions using traditional methods. Accordingly, in a further aspect, the present invention provides an agrochemical, more preferably insecticidal, composition comprising a polymorph of the present invention as defined above, and at least one agriculturally acceptable carrier or diluent.

In addition, the compositions of the present invention may contain more than one polymorph of the present invention. In particular, the compound of formula IA is more biologically active than the compounds of formulas IB, IC and ID. In this regard, although the compositions of the present invention may contain a mixture of compounds IA, IB, IC and ID in the polymorphic forms disclosed herein or otherwise in any amounts, they may also be enriched with a compound of formula IA or a polymorph of the compound of formula IA. In particular, they may be enriched in a polymorph designated form A(a). Enriched means that the mole fraction of a compound or polymorph of formula IA compared to the total amount of compounds of formula IA, IB, IC and ID is greater than 50%, e.g., at least 55, 60, 65, 70, 75, 80, 85, 90 , 95, 96, 97, 98 or at least 99%.

Agrochemical compositions containing the polymorph or polymorphs of the present invention are active ingredients that are important in the field of pest control for prevention and/or treatment even at low application rates, have a satisfactory biocidal spectrum and are well tolerated by warm-blooded species, fish and plants. The compositions of the present invention may act on all or only certain stages of development of commonly susceptible as well as resistant animal pests such as insects or members of the order Acarina. The insecticidal or acaricidal activity of the compositions can manifest itself directly, i.e., in the form of destruction of pests, which occurs either immediately or after some time, for example during molting, or indirectly, for example, by reducing egg laying

- 6 044796 and/or brood yield, with proper activity corresponding to a kill rate (mortality) of at least 50-60%.

Thus, agrochemical, more preferably insecticidal compositions containing the polymorph or polymorphs of the present invention can be used to control plant pathogenic insects on several plant species. Accordingly, the present invention also provides a method of preventing or controlling insect infection on plants or plant propagation material, comprising treating the plant or plant propagation material with an insecticidal effective amount of a composition according to the present invention.

The term insecticide as used herein means a compound or composition that controls or modifies the growth of insects. The term insecticidal effective amount means the amount of such a compound or composition or combination of such compounds or compositions that can kill, control or infect insects by inhibiting the growth or reproduction of insects, reducing the size of insect populations and/or reducing plant damage caused by insects.

By plant propagation material we mean seeds of all types (fruits, tubers, bulbs, grains, etc.), shoots, cuttings, etc.

Examples of the above-mentioned pest animals are: from the order Acarina, e.g.

Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp,

Acarus siro, Amblyomma spp., Ar gas 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/ from the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp. · from _{the T} series 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 Initida, 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 spp, Maecolaspis spp, Maladera castanea, Megascelis spp, Melighetes aeneus, Mel olontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp., Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp., Somaticus spp., Sphenophorus spp, Sternechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp/ from the order Diptera, e.g.

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, Scale Ila spp., Sciara spp., Stomoxys spp., Tab anus spp., Tannia spp. and Tipula spp.;

- 7 044796 from 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., Edessa spp, Euchistus spp., Eurydema pulchrum, Eurygaster spp. ., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes spp., Murgantia histrionic, Neomegalotomus spp, Nesidiocoris tenuis, Nezara spp., Nysius simulans, Oebalus insularis, Piesma spp., Piezodorus spp., Rhodnius spp., Sahlbergella singularis , Scaptocoris castanea, Scotinophara spp. , Thyanta spp., Triatoma spp., and Vatiga illudens;

from 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., Aonidiella 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, Cryptomyzus spp, Cicadulina spp , Coccus hesperidum, Dalbulus maidis , Dialeurodes spp., Diaphorina citri, Diuraphis noxia, Dysaphis spp, Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp., Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp, Metcalfapruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp., Neotoxoptera sp, Nephotettix spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspi s ruthae, Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis, Perkinsiella spp, Phorodon humuli, Phylloxera spp, Pianococcus spp., Pseudaulacaspis spp., 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;

from 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.;

from the order Isoptera, for example,

Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminated;

- 8 044796 from 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 per spectalis , Cydia spp., Diaphania perspectalis, Diatraea spp., Dipar opsis 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, Leucopter a scitella, Lithocollethis spp., Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyone tia 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, Perileucopter a coffeeUa, 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., Sy lepta derogate, Synanthedon spp. ., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tuta absoluta.px Yponomeuta spp., from the order Mallophaga, e.g. Damalmea spp. and Trichodectes spp.;

from the order Orthoptera, for example,

Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp:, from the order Psocoptera, for example, Liposcelis spp.;

from the order Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis; from 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 from the order Thysanura, for example Lepisma saccharina.

Examples of soil-dwelling pests that can damage crops in the early stages of plant development include the following:

from 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., Dipar opsis castanea, Elasmopalpus spp., Heliothis spp. ., Mamestra brassicae, Phthorimaea operculella, Plutella xylostella, Scirpophaga spp., Sesamia spp., Spodoptera spp. and Tortrix spp.;

from the order Coleoptera, for example,

- 9 044796

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. nZabrus spp., from the order Orthoptera, for example Gryllotalpa spp.; from the order Isoptera, for example, Reticulitermes spp.;

from the order Psocoptera, for example, Liposcelis spp.;

from the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp. \ from the order Homoptera, for example, Eriosoma larigerum;

from the order Hymenoptera, for example,

And its tu g those, Atta spp., Cephus spp., Lasius spp.,

Monomorium pharaonis, Neodiprion spp., Solenopsis spp. and Vespa spp.

from the order Diptera, for example, Tipula spp.; cruciferous flea beetle (Phyllotreta spp.), root maggots (Delia spp.), rapeseed seed worm (Ceutorhynchus spp.) and aphids.

The compositions may also be useful for the control of nematodes. Thus, agrochemical compositions containing the polymorph of the present invention can be used to control plant pathogenic nematodes on several plant species. Accordingly, a method may be contemplated for controlling damage to a plant and its parts by plant parasitic nematodes (endoparasitic, semi-endoparasitic and ectoparasitic nematodes), the method comprising treating the plant or plant propagation material with a nematicidally effective amount of a composition according to the present invention.

The term nematicide as used herein means a compound or composition that controls or modifies the growth of nematodes. The term nematicidally effective amount means the amount of such a compound or composition or combination of such compounds or compositions that can kill, control or infect nematodes by inhibiting the growth or reproduction of nematodes, reducing nematode population numbers and/or reducing plant damage caused by nematodes.

Examples of the above plant-parasitic nematodes are the following:

root-nodule nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii and other Heterodera species; seed root-knot nematodes, Anguina spp.; stem and leaf nematodes, Aphelenchoides spp.; sting nematodes, Eelonolaimus longicaudatus and other Belonolaimus species; conifer nematodes, Bursaphelenchus xylophilus and other Bursaphelenchus species; ring nematodes, Criconema spp., Criconemella spp., Criconemoides spp., Mesocriconema spp.; stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; Spine-nosed nematodes, Dolichodorus spp.;

spiral nematodes, Heliocotylenchus multicinctus and other Helicotylenchus species; tunicate and tunicate nematodes, Hemicycliophora spp. and Hemicriconemoides spp.; Hirshmanniella spp.; lanceolate nematodes, Hoploaimus spp.; root growth nematodes, Nacobbus spp.; needle nematodes, Longidorus elongatus and other Longidorus species; short-bodied nematodes, Pratylenchus spp.; wounding nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; burrowing nematodes, Radopholus similis and other Radopholus species; kidney nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema spp.; nematodes that cause underdevelopment of root crops, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; dwarfing nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus species; citrus nematodes, Tylenchulus spp.; dagger nematodes, Xiphinema spp.; and other plant-parasitic nematodes such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp. and Quinisulcius spp.

In particular, nematodes of the species Meloidogyne spp., Heterodera spp., Rotylenchus spp. can be controlled using the compositions of the present invention. and Pratylenchus spp.

The compositions according to the present invention can be used to control, i.e. contain or destroy, pests of the above type which occur in particular on plants, especially useful plants and ornamental plants in agriculture, horticulture and forestry, or on organs such plants, namely fruits, flowers, leaves, stems, tubers or

- 10 044796 roots, and in some cases even on plant organs that form at a later date, while remaining protected from these pests.

Suitable target crops include, in particular, cereal crops such as wheat, barley, rye, oats, rice, maize or sorghum; beets such as sugar beets or fodder beets; fruit crops, for example pome, stone fruit or berry crops, such as apple, pear, plum, peach, almond, cherry or berry varieties, for example strawberry, raspberry or blackberry varieties; legumes such as varieties of beans, lentils, peas or soybeans; oilseeds such as oilseed rape, mustard, poppy, olive, sunflower, coconut, castor, cocoa or peanut varieties; cucurbits such as pumpkin, cucumber or melon varieties; fibrous plants such as cotton, flax, hemp or jute; citrus fruits such as orange, lemon, grapefruit or tangerine varieties; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or bell peppers; members of the family Lauraceae, such as avocado, Cinnamonium or camphor; as well as tobacco, varieties of nuts, coffee tree, eggplant varieties, sugar cane, tea bush, pepper, cultivated grape varieties, hops, plantain and rubber plants.

The compositions and/or methods of the present invention can also be applied to any ornamental and/or vegetable crops, including flowers, shrubs, broadleaf trees and evergreens.

For example, the present invention can be applied to any of the following types of ornamental plants:

Ageratum spp., Alonsoa spp., Anemone spp.

Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (for example B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp., Brassica spp. (ornamental species), 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 grand'iforum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerber a 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. Zona/e), Viola spp. (tricolor violet), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (rose), Rudbeckia spp., Saintpaulia spp., Salvia spp., Scaevola aemola, Schizanthus w isetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp.

and other plants for flower garden decoration.

For example, the present invention can be applied to any of the following types of vegetable crops:

Allium spp. (A. sativum, A., sulfur, A. oschaninii, A.

Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus

- 11 044796 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. me Io), 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.

Preferred ornamental plant 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, bell pepper, tomato and cucumber.

The polymorphs of the present invention are particularly suitable for the control of Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, corn, rice and soybean crops. The polymorphs according to the present invention are also particularly suitable for the control of Mamestra (preferably in vegetable crops), Cydia pomonella (preferably in apple varieties), Empoasca (preferably in vegetable crops, vineyards), Leptinotarsa (preferably in potato varieties) and Chilo supressalis ( preferably in rice).

Agricultural crops should be understood as those crops that are found in nature, obtained through traditional breeding methods, or obtained through genetic engineering. They include crops that are characterized by so-called introduced product attributes (for example, improved shelf life, higher nutritional value and improved flavor properties).

Crops are also understood to be those crops that have been made tolerant to herbicides like bromoxynil or to classes of herbicides such as ALS, EPSPS, GS, HPPD and PPO inhibitors. An example of a crop that has been engineered to tolerate imidazolinones, such as imazamox, through traditional breeding techniques is Clearfield® rapeseed. Examples of crops that have been genetically engineered to tolerate herbicides include, for example, glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I®, and LibertyLink®.

Crops also include those that are inherently resistant or have been made resistant to damaging insects. These include plants transformed using recombinant DNA technologies, for example, so that they are capable of synthesizing one or more selective toxins, such as those known, for example, from toxin-producing bacteria. Examples of toxins that may be expressed include δ-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonizing nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.

An example of a crop that has been modified to express Bacillus thuringiensis toxin is KnockOut® Bt maize (Syngenta Seeds). An example of a crop that contains multiple genes that encode insect resistance, and thus expresses multiple toxins, is VipCot® (Syngenta Seeds). Agricultural crops or their seed material can also be resistant to several types of pests (so-called transgenic objects with packaged genes, if created through genetic modification). For example, a plant may have the ability to express an insecticidal protein while also being tolerant to herbicides, such as Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).

Additional fields of application for the compositions according to the present invention are the protection of stored goods and storage areas and the protection of raw materials such as wood, fabrics, floor coverings or building materials, as well as applications in the field of sanitation, in particular for the protection of people, domestic animals and productive livestock from pests of the mentioned type.

The present invention also provides a method for controlling pests (such as mosquitoes and

- 12 044796 other disease carriers; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, a method of controlling pests includes applying the compositions of the present invention to a target pest, to a location, or to a surface or substrate by brushing, rolling, spraying, spreading, or dipping. As an example, the method of the present invention involves IRS application (indoor residual spraying of pesticides) to a surface such as a wall, ceiling or floor surface. In another embodiment, the compositions are applied to a substrate such as non-woven or woven material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents. Therefore, a further object of the present invention is a substrate selected from non-woven and woven material containing a composition which contains a compound of formula (I).

A method of controlling such pests involves applying a pesticidal effective amount of the compositions of the present invention to the target pests, to their location, or to a surface or substrate so as to provide an effective level of residual pesticide activity on the surface or substrate. Such application of the pesticide composition of the present invention can be carried out by brushing, rolling, spraying, spreading or dipping. By way of example, the method of the present invention involves IRS application to a surface, such as a wall, ceiling or floor surface, thereby providing an effective level of residual pesticide activity on the surface. In another embodiment, such compositions are used for residual mediated pest control on a substrate such as woven fabric in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.

Substrates, including non-woven fabrics, woven fabrics or mesh to be processed, can be made from natural fibers such as cotton, raffia, jute, linen, sisal, burlap or wool, or from synthetic fibers such as polyamide, polyester, polypropylene, polyacrylonitrile or the like. Polyesters are particularly suitable. Methods for treating fabric are known, for example, from WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, WO 2006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.

Additional areas of application for the compositions of the present invention include tree administration/trunk treatment for all ornamental trees and all varieties of fruit and nut trees.

In the field of tree administration/trunk treatment, the polymorphs according to the present invention are particularly suitable against wood-boring insects from the order Lepidoptera mentioned above and from the order Coleoptera, especially against the wood-boring insects listed in the following tables. A and B.

Table A

Examples of introduced woodborers of economic importance

Family View Host or infected culture Buprestidae Agrilus planipennis Ash Cerambycidae Anoplura glabripennis Hardwood Scolytidae Xylosandrus crassiusculus Hardwood X. mutilatus Hardwood Tomicus piniperda Conifers

- 13 044796

Table of Local Economic Significance

Family View Host or infected culture Buprestidae Agrilus anxius Birch Agrilus politus Willow, maple Agrilus sayi Voskovnitsa, Comptonia Agrilus vittaticolllis Apple, pear, cranberry, serviceberry, hawthorn Chrysobothris femorata Apple tree, apricot, beech, ash maple, cherry, chestnut, currant, elm, hawthorn, hackberry, hickory, buckeye chestnut, linden, maple, rowan, oak, pecan, pear, peach, persimmon, plum, poplar, quince, crimson, serviceberry, plane tree, walnut, willow Texania campestris American linden, beech, maple, oak, sycamore, willow, tulip tree Cerambycidae Goes pulverulentus Beech, elm, Texas red Scolytidae Goes tigrinus Neoclytus acuminatus Neoptychodes trilineatus Oberea ocellata Oberea tripunctata Oncideres cingulata Saperda calcar ata Strophiona nitens Corthylus columbianus Dendroctonus frontalis Dryocoetes betulae oak, willow, California black oak, red swamp oak, black oak, sycamore Oak Ash, hickory, oak, walnut, birch, beech, maple, Virginia hopshorn, dogwood, persimmon, scarlet, holly, hackberry, black locust, honey locust, tulip tree, chestnut, orange mackerel, sassafras, lilac, cercocarpus, pear, cherry , plum, peach, apple tree, elm, American linden, amber wood Fig, alder, mulberry, willow, mesh frame Sumac, apple tree, peach, plum, pear, currant, blackberry Dogwood, viburnum, elm, oxidendrum arborescens, blueberry, rhododendron, azalea, laurel, poplar, willow, mulberry, hickory, pecan, persimmon, elm, oxidendrum arborescens, American linden, honey locust, dogwood, eucalyptus, oak, hackberry, maple, fruit trees Poplar Chestnut, oak, hickory, walnut, beech, maple Maple, oak, tulip tree, beech, ash maple, sycamore, birch, American linden, chestnut, elm Pine Birch, amberwood, wild cherry, beech, pear Monarthrum fasciatum Oak, maple, birch, chestnut, amberwood, nyssa sylvestris, poplar, hickory, mimosa, apple, peach, pine Phloeotribus liminaris Peach, cherry, plum, late bird cherry, elm, mulberry, rowan Pseudopityophthorus pruinosus Oak, American beech, late bird cherry, plum

- 14 044796

narrow-leaved, chestnut, maple, hickory, hornbeam, hop hornbeam Sesiidae Paranthrene simulans Oak, American chestnut Sarmina uroceriformis Persimmon Synanthedon exitiosa Peach, plum, nectarine, cherry, apricot, almond, late bird cherry Synanthedon pictipes Peach, plum, cherry, beech, late bird cherry Synanthedon rubrofascia Tupelo Synanthedon scitula Dogwood, pecan, hickory, oak, chestnut, beech, birch, late bird cherry, elm, rowan, viburnum, willow, apple tree, Japanese medlar, bladderwort, waxwort Vitacea polistiformis Grape

The present invention can also be used to control any insect pests that may be present in lawn grass, including, for example, beetles, caterpillars, fire ants, mealybugs, millipedes, woodlice, mites, mole crickets, scale insects, mealybugs, ixodid mites , pennits, southern earthen bugs and beetle larvae. The present invention can be used to control insect pests at various stages of their life cycle, including the eggs, larvae, nymphs and adults.

In particular, the present invention can be used to control insect pests that feed on the roots of lawn grass, including beetle larvae (such as Cyclocephala spp. (e.g., masked beetle, C. lurida), Rhizotrogus spp. (e.g., European beetle, R. majalis), Cotinus spp. (e.g. green beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonicd), Phyllophaga spp. (e.g. May/June beetle), Ataenius spp. ( e.g. Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g. Asian garden beetle, M. castanea) and Tomarus spp.), scale insects (Margarodes spp.), mole crickets (dark yellow, southern and short-winged; Scapteriscus spp. ., Gryllotalpa africand) and larvae of centipede mosquitoes (marsh centipede, Tipula spp.).

The present invention can also be used to control insect pests of turf grass that live in thatch, including worms (such as the armyworm Spodoptera frugiperda and the armyworm Pseudaletia unipuncta), fall armyworm caterpillars, weevils (Sphenophorus spp., such as S venatus verstitus and S. parvulus) and moths (such as Crambus spp. and tropical moths, Hepetogramma phaeopteralis).

The present invention can also be used to control insect pests of turfgrass that live above ground and feed on turfgrass leaves, including turfgrass bugs (such as southern turfgrass bugs, Blissus insularis), Bermuda grass mite (Eriophyes cynodoniensis), and Guiana worm. (Antonina graminis), two-striped pennies (Propsapia bicincta), leafhoppers, fall armyworm caterpillars (family Noctuidae) and cereal aphids.

The present invention can also be used to control other lawn grass pests, such as imported red fire ants (Solenopsis invicta), which create anthills on the surface of the lawn.

In the field of sanitation, the compositions in accordance with the present invention are active against ectoparasites such as hard mites, soft mites, scabies, red beetles, flies (stinging and licking), parasitic fly larvae, lice, head lice, lice and fleas in birds.

Examples of such parasites are the following.

From the order Anoplurida Haematopinus spp., Linognathus spp., Pedicuius spp. and Phtirus spp., Solenopotes spp.

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

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..

- 15 044796

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

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

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

From the subclass Acaria (Acarida) and the orders Meta- and Mesostigmata, for example,

Argas spp., Omithodoras 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..

From the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example,

Acarapis spp., Cheyletiella spp., Omithocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp.,

Trombicula spp., Listrophoras spp., Acaras 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..

The compositions according to the present invention are also suitable for protection against insect infestation in the case of materials such as wood, fabrics, plastics, adhesives, adhesives, paints, paper and cardboard, leather, floor coverings and building materials.

The compositions in accordance with the present 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 branneus, 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, as well as hymenoptera insects 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 bristletails such as Lepisma saccharina.

The rate at which the agrochemical compositions of the present invention are used will depend on the particular type of insect being controlled, the degree of control required, and the timing and method of application, and can be readily determined by one skilled in the art. In general, the compositions of the present invention can be applied at application rates ranging from 0.005 kilograms/hectare (kg/ha) to approximately 5.0 kg/ha based on the total amount of active ingredient (where active ingredient means the polymorph or polymorphs of the present invention) in composition. Preferred application rates are from about 0.1 kg/ha to about 1.5 kg/ha, with application rates from about 0.3 kg/ha to 0.8 kg/ha being particularly preferred.

In practice, agrochemical compositions containing the polymorph or polymorphs of the present invention are used in the form of a formulation containing various auxiliaries and carriers known or used in the industry.

These compositions may be in various physical forms, for example, dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent tablets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil emulsions. pourable formulations, aqueous dispersions, oil 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 forms known, for example, from Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can either be applied directly or diluted before use. Dilute solutions can be produced, for example, using water, liquid fertilizers, micronutrients, biological organisms, oil or solvents.

The compositions can be prepared, for example, by mixing the polymorph or polymorphs (active ingredient) with formulation auxiliaries to formulate the compositions in the form of fine solids, granules, solutions, dispersions or emulsions. The active ingredient may also be formulated with other excipients such as fine solids, mineral oils, vegetable or animal oils, modified vegetable or animal oils, organic solvents, water, surfactants, or combinations thereof.

The active ingredient may also be contained in very small microcapsules. Microcapsules contain the active ingredient in a porous carrier. This allows the active ingredient to be released into the environment in controlled quantities (eg slow release). Microcapsules typically have a diameter ranging from 0.1 to 500 microns. They contain the active ingredient in an amount of from about 25 to 95% by weight of the capsule. The active ingredient may be in the form of a monolithic solid, in the form of fine particles in a solid or liquid dispersion, or in the form of a suitable solution. Encapsulating membranes may contain, 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 known to one skilled in the art. Alternatively, very fine microcapsules may be formed in which the active ingredient is contained in the form of fine particles in a solid matrix of the base substance, but the microcapsules are not themselves encapsulated.

Formulation aids that are suitable for preparing the compositions according to the present invention are known per se. The following 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 acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, K,K-dimethylformamide, dimethyl sulfoxide, 1,4- Dioxan, dipropylene glycol, simple methyl ether of dipopylene glycol, dibenzoate of dipropylene glycol, diproxyol, alkylpyrrolidone, ethylacetate, 2-elhexanol, ethylenekarbonate, 1.1.1-thigh-roller, 2-heptanon, alfapinen, d-limonen, ethyllactate, ethylene mudp Tille ether of ethylene glycol , ethylene glycol methyl ether, gamma-butyrolactone, glycerin, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, mxylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, methyl ether propylene glycol, P-Ksilol, Toluol, triathylphosphate, triathilen glycol, xylolololsulfonic acid, paraffin, mineral oil, trichloretilene, perchlorethylene, ethylacetate, amylacetate, butylacterate, simple methyllyclico ether, simple methylene ester, methanol, ethinol, ethinol, isop zero and high molecular weight alcohols, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerin, K-methyl-2-pyrrolidone, etc.

Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheat flour, soya flour, pumice, wood flour, ground shells walnuts, lignin and similar substances.

A large number of surfactants can be used successfully in both solid and liquid formulations, especially in those formulations that can be diluted with a vehicle before use. Surfactants may be anionic, cationic, nonionic, or polymeric, and may be used as emulsifiers, wetting agents or suspending agents, or for other purposes. Typical surfactants include, for example, alkyl sulfate salts such as diethanolammonium lauryl sulfate; alkylaryl sulfonate salts such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products such as nonylphenol ethyloxylate; alcohol/alkylene oxide addition products such as tridecyl alcohol ethoxylate; soaps such as sodium stearate; alkyl naphthalene sulfonate salts such as sodium dibutyl naphthalene sulfonate; dialkyl esters of sulfosuccinate salts such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters such as sorbitolate; quaternary amines such as lauryl trimethylammonium chloride, polyethylene glycol fatty acid esters such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide and salts of mono- and dialkyl phosphate esters; as well as additional substances described, for example, in

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McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).

Additional adjuvants that may be used in pesticide formulations include crystallization inhibitors, viscosity modifiers, suspending agents, colorants, antioxidants, foaming agents, light absorbers, mixing aids, antifoams, complexing agents, pH neutralizing or modifying agents, and buffers. corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, glidants, lubricants, dispersants, thickeners, antifreeze, microbiocides, and liquid and solid fertilizers.

The compositions of the present invention may include an additive comprising a vegetable or animal oil, mineral oil, alkyl esters of such oils, or mixtures of such oils and oil derivatives. The amount of oil additive in the compositions in accordance with the present invention is usually from 0.01 to 10%, based on the amount of mixture to be used. For example, an oil additive can be added to the sprayer reservoir at the required concentration after preparing the spray mixture. Preferred oil additives include mineral or vegetable oils, such as canola oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of vegetable oils, such as methyl derivatives, or an animal oil, such as fish oil or beef oil. salo. Preferred oil additives include alkyl esters of C ₈ -C ₂₂ fatty acids, especially methyl derivatives of C ₁₂ C ₁₈ fatty acids, for example, methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from Compendium of Herbicide Adjuvants, ^10th Edition, Southern Illinois University, 2010.

The compositions of the present invention generally contain from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of the polymorphs of the present invention and from 1 to 99.9% by weight of a formulation aid, which preferably includes from 0 to 25% by weight of surfactant. Since commercial products may preferably be formulated as concentrates, the end user will typically use diluted formulations.

Application rates vary widely and depend on soil properties, method of application, crop plant, pest being controlled, prevailing climatic conditions and other factors determined by application method, time of application and target crop. As a general guide, the polymorphs of the present invention can be applied at a rate of from 1 to 2000 l/ha, in particular from 10 to 1000 l/ha.

Preferred compositions may be characterized by the following compositions (wt.%).

Emulsifiable concentrates:

active ingredient: 1-95%, preferably 60-90%;

surfactant 1-30%, preferably 5-20%;

substance:

liquid carrier: 1-80%, preferably 1-35%.

Dust preparations:

active ingredient: 0.1-10%, preferably 0.1-5%; solid carrier: 99.9-90%, preferably 99.9-99%.

Suspension concentrates:

active ingredient: 5-75%, preferably 10-50%; water: 94-24%, preferably 88-30%; surfactant 1-40%, preferably 2-30%.

substance:

Wettable powders:

active ingredient: 0.5-90%, preferably 1-80%; surfactant 0.5-20%, preferably 1-15%;

substance: solid carrier: 5-95%, preferably 15-90%. Granules: active ingredient: 0.1-30%, preferably 0.1-15%; solid carrier: 99.5-70%, preferably 97-85%.

- 18 044796

The following examples further illustrate the present invention, but do not limit it.

Wettable powders A) b) With) active ingredient 25% 50% 75% sodium lignosulfonate 5 % 5 % - sodium lauryl sulfate 3% - 5% sodium diisobutylnaphthalene sulfonate - 6% 10% polyethylene glycol phenolic ether - 2% - (7-8 mol ethylene oxide) highly dispersed silicic acid 5 % 10% 10% kaolin 62% 27% -

The combination is thoroughly mixed with the excipients and the mixture is thoroughly ground in a suitable mill to obtain wettable powders which can be diluted with water to obtain suspensions of the required concentration.___________________________

Powders for dry seed treatment A) b) With) active ingredient 25% 50% 75% light mineral oil 5 % 5% 5% highly dispersed silicic acid 5 % 5% - kaolin 65% 40% - talc - 20

The combination is thoroughly mixed with the excipients and the mixture is thoroughly ground in a suitable mill to obtain powders that can be used directly for seed treatment.__________________________________________________________

Emulsifiable concentrate active ingredient 10% polyethylene glycol octylphenol ether 3% (4-5 mol ethylene oxide) calcium dodecylbenzenesulfonate 3% castor oil polyglycol ether (3 5 mol ethylene oxide) 4% cyclohexanone thirty% xylene mixture 50%

From this concentrate, by diluting with water, one can obtain emulsions of any required degree of dilution, which can be used to protect plants.

Dust preparations A) b) With) active ingredient 5 % 6% 4% talc 95% - - kaolin - 94% - mineral filler - - 96%

Ready-to-use powdered preparations are prepared by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry seed treatment.

- 19044796

The combination is mixed and crushed with auxiliary agents and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

Extruded granules active ingredient 15 % sodium lignosulfonate 2% carboxymethylcellulose 1 % kaolin 82%

Coated Granules active ingredient 8% polyethylene glycol (molecular weight 200) 3% Kaolin 89%

The finely ground combination in a mixing device is evenly applied to the kaolin moistened with polyethylene glycol. In this way, dust-free, coated granules are obtained.

Suspension concentrate

active ingredient 40% propylene glycol 10% polyethylene glycol nonylphenol ether (15 mol ethylene oxide) 6% sodium lignosulfonate 10% carboxymethylcellulose 1 % silicone oil (in the form of a 75% emulsion in water) 1 % water 32%

The finely ground combination is thoroughly mixed with auxiliary agents to obtain a suspension concentrate, from which suspensions of any desired degree of dilution can be obtained by diluting with water. Using such diluted solutions, living plants, as well as plant propagation material, can be treated and protected from contamination by microorganisms by spraying, watering or dipping.

Flowable seed treatment concentrate

active ingredient 40% propylene glycol 5% copolymer of butanol and PO/EO 2% tristyrenephenol with 10-20 moles of EO 2% 1,2-Benzisothiazolin-3-one (as a 20% solution in water) 0.5% calcium salt of monoazopigment 5 % silicone oil (in the form of a 75% emulsion in water) 0.2% water 45.3%

The finely ground combination is thoroughly mixed with auxiliary agents to obtain a suspension concentrate, from which suspensions of any desired degree of dilution can be obtained by diluting with water. Using such diluted solutions, living plants, as well as plant propagation material, can be treated and protected from contamination by microorganisms by spraying, watering or dipping.

Slow release capsule suspension.

Mix 28 parts of the active ingredient with 2 parts of an aromatic solvent and 7 parts of a mixture of toluene diisocyanate/polymethylene polyphenyl isocyanate (8:1). This mixture is emulsified into a mixture

-20044796 from 1.2 parts of polyvinyl alcohol, 0.05 parts of defoamer and 51.6 parts of water to obtain particles of the required size. To this emulsion is added a mixture of 2.8 parts of 1,6-diaminohexane in 5.3 parts of water. The mixture is shaken until the polymerization reaction is complete. The resulting capsule suspension is stabilized by adding 0.25 parts thickener and 3 parts dispersant. The capsule suspension contains 28% of the active ingredient. The average diameter of capsules is 8-15 microns. The resulting composition is applied as an aqueous suspension to the seeds in a device suitable for this purpose.

Each of the above formulations may be formulated as a package containing the polymorph or polymorphs of the present invention together with other formulation ingredients (diluents, emulsifiers, surfactants, etc.). The compositions can also be prepared using a tank mixing method, whereby the ingredients are prepared separately and combined at the plant growing site.

These compounds can be applied to areas where control is required using traditional methods. Powdered and liquid formulations, for example, can be applied using motorized sprayers, broom and hand sprayers, and combination spray/dusters. The formulations can also be applied from aircraft as a dust formulation, a spray formulation or through rope wick application options. Both solid and liquid formulations can be applied to the soil at the location of the plant to be treated, allowing the active ingredient to penetrate the plant through the roots.

The polymorphs of the present invention and compositions based thereon are also suitable for protecting plant propagation material, for example, planting materials such as fruits, tubers or grains, or seedlings, from pests of the type mentioned above. Propagation material can be treated with polymorph before planting, for example seeds can be treated before sowing. Alternatively, the polymorph can be applied to the seed kernels (coating) either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. The compositions can also be used when planting propagation material relative to the site of application, for example, applied to a seed furrow during row sowing. These methods for treating plant propagation material and the plant propagation material thus treated are further objects of the present invention. Typical application rates will depend on the plant and the pest/fungi being controlled and are typically 1 to 200 g per 100 kg seed, preferably 5 to 150 g per 100 kg seed, e.g. 10 to 100 g per 100 kg seeds

The term seed includes seeds and vegetative parts of plants of all kinds, including, without limitation, true seeds, seed pieces, root shoots, cereal grains, bulbs, fruits, tubers, grains, rhizomes, cuttings, cut shoots, etc., and in in a preferred embodiment means true seeds.

The seeds may be coated, treated with, or contain the polymorph of the present invention. The term coated or treated and/or containing generally means that the majority of the surface of the seed contains the active ingredient at the time of application, although more or less of the ingredient may penetrate into the seed depending on the method of application. If said seed product is planted (replanted), it can absorb the active ingredient. It is possible to obtain plant propagation material with a compound of formula (I) adhered to it. In addition, a plant propagation material containing the composition treated with a compound of formula (I) may be considered.

Seed treatment includes all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting. The use of the compound of formula (I) in seed treatment can be carried out using any known methods, such as spraying on the seeds or dusting the seeds, before sowing or during sowing/planting of the seeds.

Accordingly, the agrochemical compositions and compositions of the present invention are used before the development of the disease. The rates and frequency of application of the formulations are those conventional in the art and will depend on the risk of infection by the insect pathogen.

The activity of compositions containing the compounds and polymorphs of the present invention can be significantly expanded and adapted to prevailing conditions by including other active substances. The active substances may be of a chemical or biological type, and in the case of a biological type, they may be further modified from naturally occurring biological species. Active substances include substances that generally control, repel or attract pests that damage or harm beneficial plants, as well as substances that improve the growth of beneficial plants, such as plant growth regulators, and substances that improve the effectiveness of the active substance, such as synergists. Examples are insecticides, acaricides, nematicides, molluscicides, algaecides, virusicides, rodenticides, bactericides, fungicides, chemosterilants, anthelmintics. Examples of the biologically active substance include baculovirus, plant extract and bacteria.

Accordingly, the use of the composition in accordance with the present invention together with one or more pesticides, plant nutrients or plant fertilizers may be considered. The combination may also cover specific plant traits that are incorporated into the plant using any means, such as traditional breeding or genetic modification.

Mixtures of the polymorphs of the present invention with other active substances may also have additional unexpected benefits, which may also be described more broadly as synergistic activity. For example, this is better tolerance by plants, a reduced degree of phytotoxicity, the ability to control insects at different stages of their development, or better performance regarding their production, for example, grinding or mixing, storage or application.

Individual active substances may occur in more than one group or in more than one class, and in more than one place in a group or class: information on 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 the British Crop Production Council's Pesticide Manual (see http://bcpcdata.com/pesticide-manual.html).

The following are preferred mixtures, where the polymorph or polymorphs of the present invention are designated as I.

Compositions containing an auxiliary agent include I+ compounds selected from the group of substances consisting of petroleum oils.

Compositions containing the acaricide include I+1,1-bis(4-chlorophenyl)-2-ethoxyethanol, I+2,4dichlorophenylbenzenesulfonate, I+2-fluoro-N-methyl-N-1-naphtylacetamide, I+4-chlorophenylphenylsulfone , I+abamectin, I+acequinocyl, I+acetoprol, I+acrinatrine, I+aldicarb, I+aldoxycarb, I+alphacypermethrin, I+amidithion, I+amidoflumet, I+amidothioate, I+amiton, I+amiton hydrooxalate, I+amitraz, I+aramit, I+arsenic oxide, I+AVI 382, I+AZ 60541, I+azinphos-ethyl, I+azinphos-methyl, I+azobenzene, I+azocyclotine, I+azotoate, I+benomyl , I+benoxaphos, I+benzoximate, I+benzyl benzoate, I+biphenazate, I+bifenthrin, I+binapacryl, I+brofenvalerate, I+bromocyclen, I+bromophos, I+bromophosethyl, I+bromopropylate, I+buprofezin, I +butocarboxim, I+butoxycarboxim, I+butylpyridaben, I+calcium polysulfide, I+camphechlor, I+carbanolate, I+carbaryl, I+carbofuran, I+carbophenothione, I+CGA 50'439, I+quinomethionate, I+chlorobenzide , I+chlordimeform, I+chlordimeform hydrochloride, I+chlorfenapyr, I+chlorphenethol, I+chlorphensone, I+chlorphensulfide, I+chlorphenvinphos, I+chlorobenzilate, I+chloromebuform, I+chloromethiuron, I+chloropropylate, I+chlorpyrifos, I+chlorpyrifos-methyl, I+chlorothiophos, I+cinerin I, I+cinerin II, I+cinerins, I+clofentesine, I+closantel, I+coumaphos, I+crotamiton, I+crotoxyphos, I+kufraneb, I+ cyanoate, I+cyflumetofen, I+cyhalothrin, I+cyhexatin, I+cypermethrin, I+DCPM, I+DDT, I+demefion, I+demefion-O, I+demefion-S, I+demeton, I+demetonmethyl, I+demeton-O, I+demeton-O-methyl, I+demeton-S, I+demeton-S-methyl, I+demeton-S-methylsulfone, I+diaphenthiuron, I+dialiphos, I+diazinon, I+ dichlorofluanid, I+dichlorvos, I+dicliphos, I+dicofol, I+dicrotophos, I+dienochlor, I+dimefox, I+dimethoate, I+dynactin, I+dinex, I+dinex-diclexin, I+dinobuton, I+ dinocap, I+dinocap-4, I+dinocap-6, I+dinoctone, I+dinopentone, I+dinosulfone, I+dinoterbone, I+dioxathione, I+diphenylsulfone, I+disulfiram, I+disulfotone, I+DNOC, I+dofenapine, I+doramectin, I+endosulfan, I+endothion, I+EPN, I+eprinomectin, I+ethion, I+ethoatemethyl, I+ethoxazole, I+etrimphos, I+phenazaflor, I+phenazaquin, I+ fenbutatin oxide, I+phenothiocarb, I+fenpropathrin, I+fenpyrad, I+phenpyroximate, I+phenzone, I+fentrifanil, I+fenvalerate, I+fipronil, I+fluacripyrim, I+fluazuron, I+flubenzymine, I+flucycloxuron , I+flucitrinate, I+fluenethyl, I+flufenoxuron, I+flumethrin, I+fluorbenzide, I+fluvalinate, I+FMC 1137, I+formethanate, I+formethane hydrochloride, I+formothione, I+formparanate, I+gamma -HCN, I+gliodine, I+galfenprox, I+heptenophos, I+hexadecylcyclopropanecarboxylate, I+hexythiazox, I+iodomethane, I+isocarbophos, I+isopropyl-O-(methoxyaminothiophosphoryl)salicylate, I+ivermectin, I+jasmoline I , I+jasmoline II, I+iodophenphos, I+lindane, I+lufenuron, I+malathion, I+malonoben, I+mecarbam, I+mephospholane, I+mesulfene, I+metacrifos, I+metamidophos, I+methidathion, 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 +naled, I+NC-184.1 + NC-512.1 + nifluridide, I+nikkomycins, I+nitrilecarb, I+complex of nitrilecarb and zinc chloride 1:1, I+NNI-0101, I+NM-0250, I+omethoate, I+oxamyl, I+oxydeprophos, I+oxydisulfotone, I+pp'-DDT, I+parathion, I+permethrin, I+petroleum oils, I+phencaptone, I+phentoate, I+phorate, I+ fozalone, I+phospholane, I+phosmet, I+phosphamidon, I+phoxim, I+pirimiphos-methyl, I+polychloroterpenes, I+polynactins, I+proclonol, I+profenofos, I+promacil, I+propargite, I+ propetamphos, I+propoxur, I+protidation, I+protoate, I+pyrethrin I, I+pyrethrin II, I+pyrethrins, I+pyridabene, I+pyridafenthione, I+pyrimidifene, I+pyrimitate, I+quinalphos, I+ quintiophos, I+R-1492, I+RA-17, I+rotenone, I+shradan, I+sebuphos, I+selamectin, I+SI0009, I+sophamide, I+spirodiclofen, I+spiromesifen, I+SSI- 121.1 + sulfiram, I+sulfluramide,

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I+sulfotep, I+sulfur, I+SZI-121, I+tau-fluvalinate, I+tebufenpyrad, I+TERP, I+terbam,

I+tetrachlorvinphos, I+tetradiphon, I+tetranactin, I+tetrasul, I+tiaphenox, I+thiocarboxim,

I+thiophanox, I+thiometone, I+thioquinox, I+thuringhiensin, I+triamiphos, I+triarathene, I+triazophos,

I+triazuron, I+trichlorfon, I+trifenophos, I+trinactin, I+vamidothione, I+vaniliprole and I+YI-5302.

Compositions containing 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.

Compositions containing avicid include I+chloralose, I+endrin, I+fenthion, I+pyridin-4-amine and I+strychnine.

Compositions containing 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 Jirmus, 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.

Compositions containing a soil sterilant include I+iodomethane and methyl bromide.

Compositions containing a chemosterilant include I+afolate, I+bisazir, I+busulfan, I+diflubenzuron, I+dimatif, I+chemel, I+chempa, I+metepa, I+methiotepa, I+methylafolate, I+morzide, I+penfluron, I+tepu, I+thiochempu, I+thiotepu, I+tretamine and I+uredepu.

Compositions containing insect pheromone include I+(E)-dec-5-en-1-yl acetate with (E)-dec-5-en1-ol, I+(E)-tridec-4-en-1-yl acetate, I+ (E)-6-methylhept-2-en-4-ol, I+(E,Z)-tetradeca-4,10-dien-1-yl acetate, 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-yne-1-yl acetate, I+(Z)-icos- 13-en-10-one, I+(Z)-tetradec-7-en-1-al, I+(Z)-tetradec-9-en1-ol, I+(Z)-tetradec-9-en-1-yl acetate , I+(7E,9Z)-dodeca-7,9-dien-1-ylacetate, I+(9Z,11E)-tetradeca-9,11diene-1-yl acetate, I+(9Z, 12E)-tetradeca-9,12- dien-1-yl acetate, I+14-methyloctadec-1-ene, I+4-methylnonan-5ol with 4-methylnonan-5-one, I+alpha-multistriatin, I+brevicomin, I+codlelur, I+codemon, I+quelur, I+disparlur, I+dodec-8-en-1-yl acetate, I+dodec-9-en-1-yl acetate, I+dodecu-8, I+10-dien-1-yl acetate, I+ dominicalur, I+ethyl-4-methyloctanoate, I+eugenol, I+frontalin, I+gossyplur, I+grandlur, I+grandlur I, I+grandlur II, I+grandlur III, I+grandlur IV, I+hexalur, I+ipsdienol, I+ipsenol, I+japonilur, I+lineatin, I+litlur, I+luplur, I+medlur, I+megatomic acid, I+methyleugenol, I+muscalur, I+octadeca-2,13-diene -1-yl acetate, I+octadeca-3,13-diene-1-yl acetate, I+orfralur, I+oryctalur, I+ostramon, I+siglur, I+sordidin, I+sulcatol, I+tetradec-11-ene -1-yl acetate, I+trimedlur, I+trimedlur A, I+trimedlur B1, I+trimedlur B ₂ , I+trimedlur C and I+trunk cola.

Compositions containing 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+dimethylcarbate, I +dimethylphthalate, I+ethylhexanediol, I+hexamide, I+methoquin-butyl, I+methylneodecanamide, I+oxamate and I+picaridin.

Insecticide containing compositions include I+1-dichloro-1-nitroethane, 1+1,1-dichloro-2,2-6is(4ethylphenyl)ethane, I+, I+1,2-dichloropropane, I+1,2- dichloropropane with 1,3-dichloropropene, 1+1-6rom-2chloroethane, I+2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate, I+2,2-dichlorovinyl-2-ethylsulfinylethyl methylphosphate, I +2-(1,3-dithiolan-2-yl)phenyldimethylcarbamate, I+2-(2-butoxyethoxy)ethylthiocyanate, I+2(4,5-dimethyl-1,3-dioxolan-2-yl)phenylmethylcarbamate, I +2-(4-chloro-3,5-xylyloxy)ethanol, I+2-chlorovinyl diethyl phosphate, I+2-imidazolidone, I+2-isovalerylindane-1,3-dione, I+2-methyl(prop-2ynyl) aminophenylmethylcarbamate, I+2-thiocyanatoethyl laurate, I+3-bromo-1-chloroprop-1-ene, I+3-methyl-1phenylpyrazol-5-yldimethylcarbamate, I+4-methyl(prop-2-ynyl)amino-3, 5-xylylmethylcarbamate, I+5,5dimethyl-3-oxocyclohex-1-enyldimethylcarbamate, I+abamectin, I+acephate, I+acetamiprid, I+acetion, I+acetoprole, I+acrinathrine, I+acrylonitrile, I+alanicarb, I+aldicarb, I+aldoxycarb, I+aldrin, I+allethrin, I+allosamidine, I+allixycarb, I+alpha-cypermethrin, I+alpha-ecdysone, I+aluminum phosphide, I+amidithione, I+amidothioate, I +aminocarb, I+amiton, I+amiton hydrooxalate, I+amitraz, I+anabasine, I+atidation, I+AVI 382, I+AZ 60541, I+azadirachtin, I+azamethiphos, I+azinphos-ethyl, I+ azinphos-methyl, I+azotoate, I+bacillus thuringiensis delta-endotoxins, I+barium hexafluorosilicate, I+barium polysulfide, I+bartrin, I+Bayer 22/190, I+Bayer 22408, I+bendiocarb, I+benfuracarb, I+bensultap, I+beta-cyfluthrin, I+beta-cypermethrin, I+bifenthrin, I+bioallethrin, I+isomer of bioallet-23 044796 puH-S-cyclopentenyl, I+bioethanomethrin, I+biopermethrin, I+bioresmethrin, I +bis(2chloroethyl)ether, I+bistrifluron, I+borax, I+brofenvalerate, I+bromfenvinphos, I+bromocyclen, I+6poM-DDT, I+bromophos, I+bromophos-ethyl, I+bufencarb, I+ buprofezin, I+butacarb, I+butathiophos, I+butocarboxim, I+butonate, I+butoxycarboxim, 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+cartap, I+cartap hydrochloride, I+cevadine, I+chlorobicyclene, I+chlordane, I +chlordecone, I+chlordimeform, I+chlordimeform hydrochloride, I+chlorethoxyphos, I+chlorfenapyr, I+chlorfenvinphos, I+chlorfluazuron, I+chlormephos, I+chloroform, I+chloropicrin, I+chlorfoxime, I+chlorprazophos, I+ chlorpyrifos, I+chlorpyrifos-methyl, I+chlorothiophos, I+chromafenozide, I+cinerin I, I+cinerin II, I+cinerins, I+cis-resmethrin, I+cismethrin, I+clocitrin, I+cloetocarb, I+ closantel, I+clotianidin, I+copper acetoarsenite, I+copper arsenate, I+copper oleate, I+coumaphos, I+cumitoate, I+crotamiton, I+crotoxyphos, I+crufomate, I+cryolite, I+CS 708, I+cyanophenphos, I+cyanophos, I+cyanoate, I+cycletrin, 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+demeton, I+demeton- methyl, I+demeton-O, I+demeton-O-methyl, I+demeton-S, I+demeton-S-methyl, I+demeton-S-methylsulfone, I+diaphenthiuron, I+dialiphos, I+diamidafos, I+diazinon, I+dicaptone, I+dichlorofenthione, I+dichlorvos, I+diclyphos, I+dicresyl, I+dicrotophos, I+dicyclanil, I+dieldrin, I+diethyl-5-methylpyrazol-3-ylphosphate, I+ diflubenzuron, I+dilor, I+dimefluthrin, I+dimefox, I+dimethane, I+dimethoate, I+dimetrin, I+dimethylvinphos, I+dimethylane, I+dinex, I+dinex-diclexin, I+dinoprop, I+ dinosam, I+dinoseb, I+dinotefuran, I+diophenolan, I+dioxabenzophos, I+dioxacarb, I+dioxathion, I+disulfoton, I+dithicrophos, 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+epophenonan, I+eprinomectin, I+esfenvalerate, I+ethaphos, I+ethiophencarb, I+ethione, I+ethiprole, I+ethoate-methyl, I+etoprophos, I+ethyl formate, I+ethyl-DDD, I+ethylene dibromide, I+ethylene dichloride, I+ ethylene oxide, I+etofenprox, I+etrimphos, I+EXD, I+famfur, I+fenamiphos, I+phenazaflor, I+fenchlorvos, I+fenetacarb, I+fenfluthrin, I+fenitrothion, I+fenobucarb, I+fenoxacrim , I+fenoxycarb, I+phenpyritrin, I+fenpropathrin, I+fenpyrad, I+fensulfothione, I+fenthion, I+fenthion-ethyl, I+fenvalerate, I+fipronil, I+flonamid, I+flubendiamide, I+flucofuron , I+flucycloxuron, I+flucitrinate, I+fluenethyl, I+flufenerim, I+flufenoxuron, I+flufenprox, I+flumethrin, I+fluvalinate, I+FMC 1137, I+phonofos, I+formethanate, I+formethanate hydrochloride I +guazatine acetates, I+GY-81, I+galfenprox, I+halofenoside, I+HCN, I+HEOD, I+heptachlor, I+heptenophos, I+heterophos, I+hexaflumuron, I+HHDN, I+hydramethylnon, I+hydrogen cyanide, I+hydroprene, I+hiquincarb, I+imidacloprid, I+imiprotrin, I+indoxacarb, I+iodomethane, I+IPSP, I+isazophos, I+isobenzan, I+isocarbophos, I+isodrine, I +isofenphos, I+isolane, I+isoprocarb, I+isopropyl-O(methoxyaminothiophosphoryl) salicylate, I+isoprothiolane, I+isothioate, I+isoxathione, I+ivermectin, I+jasmoline I, I+jasmoline II, I+iodophenphos , I+juvenile hormone I, I+juvenile hormone II, I+juvenile hormone III, I+kelevan, I+kinoprene, I+lambda-cyhalothrin, I+lead arsenate, I+lepimectin, I+leptophos, I+lindane, I+lyrimphos, I+lufenuron, I+lithidathione, I+mcumenylmethylcarbamate, I+magnesium phosphide, I+malathion, I+malonoben, I+mazidox, I+mecarbam, I+mecarfone, I+menasone, I+mephospholane, I +mercuric chloride, I+mesulfenphos, I+metaflumizone, I+metham, I+metham-potassium, I+metham-sodium, I+metacryphos, I+metamidophos, I+methanesulfonyl fluoride, I+methidathione, I+methiocarb, I+ metocrotophos, I+methomyl, I+methoprene, I+methoquin-butyl, I+methotrin, I+methoxychlor, I+methoxyfenozide, I+methyl bromide, I+methyl isothiocyanate, I+methyl chloroform, I+methylene chloride, I+metofluthrin, I+ metolcarb, I+methoxadiazone, I+mevinphos, I+mexacarbate, I+milbemectin, I+milbemycin oxime, I+mipafox, I+mirex, I+monocrotophos, I+morphothione, I+moxidectin, I+naphthalophos, I+naled , I+naphthalene, I+NC-170, I+NC-184, I+nicotine, I+nicotine sulfate, I+nifluridide, I+nitenpyram, I+nithiazine, I+nitrilecarb, I+nitrilecarb and zinc chloride complex 1 :1, I+NNI-0101, I+NNI-0250, I+nornicotine, I+novaluron, I+noviflumuron, I+O-5-dichloro-4-iodophenylO-ethylethylphosphonothioate, I+O,O-diethyl-O -4-methyl-2-oxo-2H-chromen-7-ylphosphothioate, 1+O,O-diethyl-O6-methyl-2-propylpyrimidin-4-ylphosphothioate, I+O,O,O',O'-tetrapropyldithiopyrophosphate , I+oleic acid, I+omethoate, I+oxamyl, I+oxydemetone-methyl, I+oxydeprophos, I+oxydisulfotone, I+pp'-DDT, I+para-dichlorobenzene, I+parathion, I+parathion-methyl , I+penfluron, I+pentachlorophenol, I+pentachlorophenyl laurate, I+permethrin, I+petroleum oils, I+PH 60-38, I+phencapton, I+phenothrin, I+phentoate, I+phorate + TX, I+phosalone , I+phospholane, I+phosmet, I+phosnichlor, I+phosphamidone, I+phosphine, I+phoxim, I+phoxim-methyl, I+pirimetaphos, I+pirimicarb, I+pirimiphos-ethyl, I+pirimiphos-methyl , I+polychlorodicyclopentadiene isomers, I+polychloroterpenes, I+potassium arsenite, I+potassium thiocyanate, I+prallethrin, I+precocene I, I+precocene II, I+precocene III, I+primidophos, I+profenophos, I+profluthrin I +pyresmethrin, I+pyrethrin I,

- 24 044796

I+pyrethrin II, I+pyrethrins, I+pyridaben, I+pyridalyl, I+pyridafenthione, I+pyrimidifene, I+pyrimitate, I+pyriproxyfen, I+quassium, I+quinalphos, I+quinalphos-methyl, I+quinothione , I+quintiophos, I+R-1492, I+rafoxanide, I+resmethrin, I+rotenone, I+RU 15525, I+RU 25475, I+ryanium, I+ryanodine, I+sabadilla, I+shradan, 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 hexafluorosilicate, I+sodium pentachlorophenoxide, I+sodium selenate, I+sodium thiocyanate, I+sophamide, I+spinosad, I+spiromesifen, I+spirotetramate, I+sulcofuron, I+sulcofuron-sodium , I+sulfluramide, I+sulfotep, I+sulfur fluoride, I+sulprophos, I+tar oils, I+tau-fluvalinate, I+tazimcarb, I+TDE, I+tebufenozide, I+tebufenpyrad, I+tebupyrimphos, I +teflubenzuron, I+tefluthrin, I+temephos, I+TERP, I+terallethrin, I+terbam, I+terbufos, I+tetrachloroethane, I+tetrachlorvinphos, I+tetramethrin, I+theta-cypermethrin, I+thiacloprid, I +thiafenox, I+thiamethoxam, I+ticrofos, I+thiocarboxim, I+thiocyclam, I+thiocyclam hydrooxalate, I+thiodicarb, I+thiofanox, I+thiometon, I+thionazine, I+thiosultap, I+thiosultap-sodium, I+thuringhiensin, I+tolfenpyrad, I+tralomethrin, I+transfluthrin, I+transpermethrin, I+triamiphos, I+triazamate, I+triazophos, I+triazuron, I+trichlorfon, I+trichlorometaphos-3,1 + trichloronate, I+trifenophos, I+triflumuron, I+trimetacarb, I+tryprene, I+vamidothione, I+vaniliprole, I+veratridine, I+veratrine, I+XMC, I+xylylcarb, I+YI-5302, I+zetacypermethrin, I+zetamethrin, I+zinc phosphide, I+zolaprophos and ZXI 8901, I+cyantraniliprole, I+chlorantraniliprole, I+cyenopyrafen, I+cyflumetofen, I+pyrifluquinazone, I+spinetoram, I+spirotetramate, I+sulfoxaflor, I+ flufiprole, I+meperfluthrin, I+tetramethylfluthrin, I+triflumesopyrim.

Molluscicide-containing compositions include I+bis(tributyltin) oxide, I+bromoacetamide, I+calcium arsenate, I+cloetocarb, I+copper acetoarsenite, I+copper sulfate, I+fentin, I+ferric phosphate, I+metaldehyde, I+methiocarb, I+niclosamide, I+niclosamide-olamine, I+pentachlorophenol, I+sodium pentachlorophenoxide, I+tazimcarb, I+thiodicarb, I+tributyltin oxide, I+triphenmorph, I+trimetacarb, I+triphenyltin acetate and hydroxide triphenyltin, I+pyriprole.

Compositions containing nematicide include I+AKD-3088, I+1,2-dibromo-3-chloropropane, I+1,2dichloropropane, I+1,2-dichloropropane with 1,3-dichloropropene, I+1,3- dichloropropene, I+3,4dichlorotetrahydrothiophen-1,1-dioxide, I+3-(4-chlorophenyl)-5-methylrhodanine, I+5-methyl-6-thioxo-1,3,5thiadiazinan-3-ylacetic acid, I +6-isopentenylaminopurine, I+abamectin, I+acetoprole, I+alanicarb, I+aldicarb, I+aldoxycarb, I+AZ 60541, I+benclotiaz, I+benomyl, I+butylpyridaben, I+cadusafos, I+carbofuran, I+carbon disulfide, I+carbosulfan, I+chloropicrin, I+chlorpyrifos, I+cloetocarb, I+cytokinins, I+dazomet, I+DBCP, I+DCIP, I+diamidafos, I+dichlorofenthion, I+diclyphos, 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+fostiethane, I+furfural , I+GY-81, I+heterophos, I+iodomethane, I+isamidophos, I+isazophos, I+ivermectin, I+kinetin, I+mecarfon, I+metham, I+metham-potassium, I+metham-sodium , I+methyl bromide, I+methyl isothiocyanate, I+milbemycin oxime, I+moxidectin, I+composition based on Myrothecium verrucaria, I+NC-184, I+oxamyl, I+phorate, I+phosphamidone, I+phosphocarb, I+ sebuphos, I+selamectin, I+spinosad, I+terbam, I+terbufos, I+tetrachlorothiophene, I+thiafenox, I+thionazine, I+triazophos, I+triazuron, I+xylenols, I+YI-5302 and zeatin, I+fluensulfone.

Compositions containing the synergist include I+2-(2-butoxyethoxy)ethylpiperonilate, I+5-(1,3benzodioxol-5-yl)-3-hexylcyclohex-2-enone, I+farnesol with nerolidol, 1+MB-599 , I+MGK 264, I+piperonyl butoxide, I+piprotal, I+propyl isomer, I+S421, I+sesamex, I+sesasmoline and I+sulfoxide.

Compositions containing an animal repellent include I+anthraquinone, I+chloralose, I+copper naphthenate, I+copper oxychloride, I+diazinon, I+dicyclopentadiene, I+guazatine, I+guazatine acetates, I+methiocarb, I+ pyridine-4-amine, I+thiram, I+trimetacarb, I+zinc naphthenate and I+cyram.

Additional compositions include I+broflutrinate, I+cycloxapride, I+difluvidazine, I+phlometoquin, I+fluhexaphone, I+guadipyr, I+Plutella xylostella granulosa virus, I+Cydia pomonella granulosa virus, I+harpin, I+imiciaphos, I +nuclear polyhedrosis virus Heliothis virescens, I+nuclear polyhedrosis virus Heliothis punctigera, I+nuclear polyhedrosis virus Helicoverpa armigera, I+nuclear polyhedrosis virus Helicoverpa zea, I+nuclear polyhedrosis virus Spodoptera frugiperda, I+nuclear polyhedrosis virus Plutella xylostella, I+Pasteuria nishizawae, I+p-cymene, I+piflubumide, I+pyrafluprole, I+pyrethrum, I+QRD 420, I+QRD 452, I+QRD 460, I+terpenoid mixtures, I+terpenoids, I+tetraniliprole and I+ Aterpinen.

The composition also includes mixtures of the polymorph or polymorphs of the present invention and the active substance indicated by the code, such as I+code AE 1887196 (BSC-BX60309), I+code NNI0745 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: [929545-74-4]), I+code SN-1172, I+code HNPC-A9835, I+code HNPC- A9955, I+code HNPCA3061, 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,

- 25 044796

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.

Although compositions containing the polymorph or polymorphs of the present invention and another insecticide, etc. are explicitly disclosed above, one skilled in the art will appreciate that the present invention extends to a three-component mixture as well as a variety of combinations containing the above two-component mixtures.

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

The polymorphs of the present invention are also useful in the veterinary field, for example, they can be used against parasitic invertebrate pests, more preferably against parasitic invertebrate pests, in or on an animal. Examples of pests include nematodes, flukes, cestodes, flies, ticks, ticks, lice, fleas, bedbugs and maggots. The animal may be a non-human animal, such as an agricultural animal such as a cow, pig, sheep, goat, horse or donkey, or a domestic animal such as a dog or cat.

Therefore, the polymorph of the present invention may be considered for use in a therapeutic treatment method.

A method of controlling parasitic invertebrate pests in or on an animal comprises administering a pesticidal effective amount of a polymorph of the present invention. Administration may be, for example, oral administration, parenteral administration, or external administration, for example, application to the surface of the animal's body. The polymorph of the present invention can be used to control parasitic invertebrate pests in or on an animal. The use of a polymorph of the present invention in the manufacture of a medicinal product for the control of parasitic invertebrate pests in or on an animal may also be contemplated.

A method of controlling parasitic invertebrate pests includes introducing a pesticidal effective amount of a polymorph of the present invention into the environment in which the animal lives.

A method of protecting an animal from a parasitic invertebrate pest involves administering to the animal a pesticidal effective amount of a polymorph of the present invention. The polymorph of the present invention may be considered for use in protecting an animal from a parasitic invertebrate pest. In a further aspect, the present invention relates to the use of a polymorph of the present invention in the manufacture of a medicament for protecting an animal from a parasitic invertebrate pest.

A method of treating an animal suffering from a parasitic invertebrate pest comprises administering to the animal a pesticidal effective amount of a polymorph of the present invention. The polymorph of the present invention may be considered for use in the treatment of an animal suffering from a parasitic invertebrate pest. The use of the polymorph of the present invention in the manufacture of a medicinal product intended to treat an animal suffering from a parasitic invertebrate pest may also be contemplated.

Finally, a pharmaceutical composition may be contemplated comprising the polymorph of the present invention and a pharmaceutically acceptable excipient.

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

For example, a combination product may be contemplated containing a pesticidal effective amount of component A and a pesticidal effective amount of component B, wherein component A is a polymorph of the present invention and component B is a compound described below.

The polymorph of the present invention can be used in combination with anthelmintics. Such anthelmintics 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, described in EP357460, EP-444964 and EP-594291. Additional anthelmintics include semisynthetic and biosynthetic derivatives of avermectin/milbemycin, such as those described in US-5015630, WO9415944 and WO-9522552. Additional anthelmintics include benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxybendazole, parbendazole, and other members of the class. Additional anthelmintics include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxanthel or

- 26 044796 morantel. Additional anthelmintics include flucides such as triclabendazole and clorsulon, and cestodocides such as praziquantel and epsiprantel.

The polymorphs of the present invention can be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintics, as well as antiparasitic oxazolines, such as those disclosed in US-5478855, US-4639771 and DE-19520936.

The polymorphs of the present invention can be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitics described in WO-9615121, as well as with anthelmintic active cyclic depsipeptides such as those described in WO9611945, WO-9319053, WO-9325543, EP-626375, EP-382173, WO-9419334, EP-382173 and EP-503538.

The polymorphs of the present invention can be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphorus compounds; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide, etc.; neonicotinoids such as imidacloprid, etc.

The polymorphs of the present invention can be used in combination with terpene alkaloids, for example those described in international patent application publications Nos. WO 95/19363 or WO 04/72086, in particular the compounds disclosed in these documents.

Other examples of such biologically active compounds with which the polymorphs of the present invention may be used include, but are not limited to, the following.

Organophosphorus compounds: acephate, azametifos, azinphos-ethyl, azinphos-methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demetonS-methyl, demeton-S-methylsulfone, dialifos, diazinon, dichlorvos, dicrotophos , dimethoate, disulfoton, ethion, ethoprophos, etrimphos, famfour, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazophos, fonophos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, metacryphos, methamidophos, methidathion, methyl parathion, mevinfos , monocrotophos, naled, omethoate, oxydemetonmethyl, paraoxon, parathion, parathion-methyl, phentoate, fosalone, phospholane, phosphocarb, phosmet, phosphamidon, phorate, phoxim, pirimiphos, pirimiphos-methyl, profenofos, propafos, proetamphos, prothiophos, pyraclofos, pyridapention , quinalphos, sulprofos, temefos, terbufos, tebupirimphos, tetrachlorvinphos, timeton, tiazofos, trichlorfon, vamidothion.

Carbamates: alanicarb, aldicarb, 2-sec-butylphenylmethylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloetocarb, etiophencarb, fenoxycarb, fentiocarb, furatiocarb, HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-ku menylbutyryl( methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiophanox, triazamate, UC-51717.

Pyrethroids: acrinatrine, allethrin, alphamethrin, 5-benzyl-3-furylmethyl (E)-(1R)-cis-2,2dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, cyfluthrin, alpha-cypermethrin, beta-cypermethrin, bioallethrin, bioallethrin ((S)-cyclopentyl isomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythitrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, etofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucitri nat , flumethrin, fluvalinate (D-isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, tau-fluvalinate, tefluthrin, tralomethrin, zeta-cypermethrin.

Arthropod growth regulators: a) inhibitors of chitin synthesis: benzoylurea compounds: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diophenolan, hexythiazox, etoxazole, chlorophentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.

Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-118, azadirachtin, Bacillus thuringiensis, bensultap, biphenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidin , cyromazine, diaclodene, diafenthiuron, DBI-3204, dynactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, etofenprox, phenazaquin, flumite, MTI-800, fenpiroximate, fluacripyrim, flubenzimine, flubrocitrinate, flufenzine, flufenprox, flupro xifen, halofenprox, hydramethylnon , IKI-220, kanemite, NC-196, neem guard, nidinorterfuran, nitenpyram, SD-35651, WL-108477, pyridaril, propargite, protrifenbut, pymetrozine, pyridaben, pyrimidifene, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosin, trinactin, verbutin, vertalek, YI-5301.

Fungicides: acibenzolar, aldimorph, ampropylphos, andoprim, azaconazole, azoxystrobin, benalaxyl, benomyl, bialaphos, blasticidin-S, Bordeaux mixture, bromuconazole, bupirimate, carpropamide, captafol, captan, carbendazim, chlorphenazole, chloroneb, chloropicrin, chlorothalonil, chlosols nat, oxychloride copper, copper salts, cyflufenamide, cymoxanil, cyproconazole, cyprodinil, ciprofuram, RH-7281, diclocimet, diclobutrazol, diclomezin, dicloran, difenoconazole, RP-407213, dimethomorph, domoxystro- 27 044796 bin, diniconazole, diniconazole-M, up din, edifenphos , epoxiconazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramide, fenpiclonil, fenpropidine, fenpropimorph, fentine acetate, fluazinam, fludioxonil, flumetover, flumorph/flumorlin, fentine hydroxide, fluoxastrobin, fluquinconazole, flusilazole, flutolanil, fl utriafol, folpet, fosetyl-aluminum , furalaxyl, furamethapyr, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, kresoxim-methyl, mancozeb, maneb, mefenoxam, mepronil, metalaxyl, metconazole, metominostrobin/phenominostrobin, metrafenone, myclobutanil, neo-asosin, nico bifen, orysastrobin, oxadixil , penconazole, pencycuron, probenazole, prochloraz, propamocarb, propioconazole, proquinazide, prothioconazole, pyrifenox, pyraclostrobin, pyrimethanil, pyroquilone, quinoxifene, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazole, tifluzamide, thiophanate-methyl, thiram, tiadine silt, triadimefon, triadimenol , tricyclazole, trifloxystrobin, triticonazole, validamycin, vinclosin.

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

Bactericides: chlortetracycline, oxytetracycline, streptomycin.

Other biological agents: enrofloxacin, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinom, florfenicol, buserelin, cefovecin, tulathromycin, ceftiofur, carprofen, metaflumizone, Prazi quarantel, triclabendazole.

When used in combination with other active ingredients, the polymorphs of the present invention are preferably used in combination with imidacloprid, enrofloxacin, praziquantel, pyrantel embonate, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, fipronil, ivermectin, omeprazole, tiamulin, benaze Prilom, milbemycin, cyromazine, thiamethoxam, pyriprole, deltamethrin, cefquin, florfenicol, buserelin, cefovecin, tulathromycin, ceftiofur, selamectin, carprofen, metaflumizone, moxidectin, methoprene (including S-methoprene), clorsulon, pyrantel, amitraz om, triclabendazole, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxybendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsipran body, fipronil, lufenuron, ecdysone or tebufenozide; more preferably with enrofloxacin, praziquantel, pyrantel embonate, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulatra icin, ceftiofur, selamectin, carprofen, moxidectin, clorsulone, pyrantel, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxybendazole, parbendazole, tetramizole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole om, epsiprantel, lufenuron or ecdysone; even more preferably with enrofloxacin, praziquantel, pyrantel embonate, febantel, penetamate, moloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulate romycin, ceftiofur, selamectin, carprofen, moxidectin , clorsulon or pyrantel.

Of particular note is a combination in which the additional active ingredient has a site of action different from that of the polymorph of the present invention. In certain cases, combination with at least one other active ingredient for control of a parasitic invertebrate pest having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, the combination product of the present invention may contain a pesticidal effective amount of a polymorph of the present invention and a pesticidal effective amount of at least one additional active ingredient for controlling a parasitic invertebrate pest having a similar spectrum of control but a different site of action.

One skilled in the art will appreciate that since salts of chemical compounds are in equilibrium with their corresponding non-salt forms under environmental and physiological conditions, the salts have the same biological utility as the non-salt forms.

Thus, a variety of salts of the polymorphs of the present invention (and active ingredients used in combination with the active ingredients of the present invention) may be useful for the control of 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 acid. The polymorphs of the present invention also include N-oxides. Accordingly, the present invention provides combinations of the polymorphs of the present invention, including

- 28 044796 including their N-oxides and salts, and additional active ingredient, including its N-oxides and salts.

Compositions for veterinary use may also contain formulation auxiliaries and additives known to those skilled in the art as formulation auxiliaries (some of which may also be considered to function as solid diluents, liquid diluents or surfactants). These excipients and formulation additives can be used to control pH (buffers), foaming during processing (antifoams like polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), development of microorganisms in containers (antimicrobials), freezing products (antifreeze), color (dye/pigment dispersions), flushability (film formers or adhesives), evaporation (evaporation retardants) and other formulation properties. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation excipients and additives include those listed in McCutcheon's, Volume 2: Functional Materials, an annual international and North American publication published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and in the publication of the application according to PCT WO 03/024222.

The polymorphs of the present invention can be used without other excipients, but will most often involve the use of a formulation containing one or more active ingredients with suitable carriers, diluents and surfactants, and possibly in combination with nutrients depending on the intended end result. use. One method of application involves spraying an aqueous dispersion or solution based on refined oil in the form of combination products. Compositions with nebulized oils, nebulized oil concentrates, adhesive spreaders, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance the effectiveness of the compound. Such sprays can be applied from a spray container, such as a can, bottle, or other container, either by using a pump or by releasing it from a pressurized container, such as a pressurized aerosol spray can. Such spray compositions can take various forms, for example, sprays, mists, foams, vapors or mist. Therefore, depending on the particular case, such spray compositions may additionally contain propellant gases, foaming agents, and the like. Of note is a spray composition containing a pesticidal effective amount of a compound of the present invention and a carrier. In one embodiment, such a spray composition contains a pesticidal effective amount of a compound of the present invention and a propellant. Representative propellant gases include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Of note is a spray composition (and a method of using such spray composition dispensed from a spray container) used to control at least one parasitic invertebrate pest selected from the group consisting of mosquitoes, midges, true flies, horse flies, gadflies, wasps, true wasps, hornets, ixodid ticks, spiders, ants, midges, etc., including separately or in combinations.

Animal parasite control includes control of external parasites, which are parasites on the surface of the host animal's body (e.g., shoulders, armpits, abdomen, inner thighs), and internal parasites, which are parasites inside the host animal's body (e.g., stomach, intestines). , lung, veins, under the skin, in lymphatic tissue). External parasites or disease-transmitting pests include, for example, thrombiculid mites, ixodid mites, lice, mosquitoes, flies, ticks and fleas. Internal parasites include heartworms, hookworms, and helminths. The polymorphs of the present invention may be particularly suitable for controlling external parasitic pests. The polymorphs of the present invention may be suitable for systemic and/or non-systemic control of infestation or infection by parasites in animals.

The polymorphs of the present invention may be suitable for controlling parasitic invertebrate pests that infect animal subjects, including those in the wild, livestock and farm working animals. Livestock is a term used to designate (singular or plural) a domesticated animal intentionally raised in agriculture for a product, such as food or fiber, or to perform work; examples of livestock include cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, chickens, turkeys, ducks and geese (for example, raised for meat, milk, butter, eggs, down, leather, feathers and /or wool). By controlling parasites, mortality rates and loss of productivity (in relation to meat, milk, wool, skin, eggs, etc.) are reduced, so that the use of polymorphs according to the present invention allows for more economical and simple breeding

- 29 044796 animals.

The polymorphs of the present invention may be suitable for the control of parasitic invertebrate pests that infect domestic animals (eg, dogs, cats, pet birds and aquarium fish), laboratory and experimental animals (eg, hamsters, guinea pigs, rats) and mice), as well as animals bred for or directly in zoos, wildlife habitats and/or circuses.

In an embodiment of the present invention, the animal is preferably a vertebrate animal, and more preferably a mammal, bird or fish. In a specific embodiment, the animal subject is a mammal (including great apes such as humans). Other mammalian subjects include primates (eg, monkeys), ruminants (eg, cattle or dairy cows), porciniformes (eg, wild boars or pigs), ovine (eg, goats or sheep), equidae (eg, horses), canids (eg dogs), felids (eg domestic cats), camels, deer, donkeys, buffalo, antelope, rabbits and rodents (eg guinea pigs, squirrels, rats, mice, gerbils and hamsters). Birds include Anatidae (swans, ducks and geese), Columbidae (such as doves and pigeons), Phasianidae (such as partridges, grouse and turkeys), Thesienidae (such as domestic chickens), Parrots (such as parakeets, macaws and parakeets) , game birds and ratites (for example, ostriches).

Birds treated or protected with the polymorphs of the present invention may be associated with either commercial or non-commercial poultry production. These include Anatidae such as swans, geese and ducks, Columbidae such as doves and domestic pigeons, Phasianidae such as partridges, grouse and turkeys, Thesienidae such as domestic chickens, and Psittacines such as parakeets, macaws and parakeets. bred for sale as pets or collectibles, among other things.

For the purposes of the present invention, the term fish should be understood to include, without limitation, fish that belong to the group Teleostei, i.e., bony fish. The Teleostei group includes both fish of the order Salmoniformes (which includes the family Salmonidae) and fish of the order Perciformes (which includes the family Centrarchidae). Examples of potential recipient fishes include Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae, among others.

Other animals are expected to benefit from the methods of the present invention, including marsupials (such as kangaroos), reptiles (such as farmed turtles), and other economically important domestic animals for which the methods of the present invention are safe and effective in treating or preventing parasitic infections or infestations.

Examples of pests that are parasitic invertebrates controlled by administering a pesticidal effective amount of the polymorphs of the present invention to the animal to be protected include ectoparasites (arthropods, mites, etc.) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, acanthocephalans, etc. .d.).

The disease or group of diseases generally described as helminthiasis is caused by infection of an animal host by parasitic worms known as helminths. The term helminths is intended to include nematodes, trematodes, cestodes and acanthocephalans. Helminthiasis is a common and serious economic problem affecting domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats and birds.

Among the helminths, a group of worms described as nematodes cause common and sometimes serious infections in a variety of animal species.

Nematodes contemplated for treatment with the polymorphs of the present invention include, but are not limited to, 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, O xyuris, Parafilaria, Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca, Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris, Uncinaria and Wuchereria.

Of the above, the most common genera of nematodes infecting the animals mentioned above are

- 30 044796

Haemonchus, Trichostrongylus,

IOstertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia,

Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia,

Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris.

Some of them, such as Nematodirus, Cooperia and Oesophagostomum, primarily affect the intestinal tract, while others, such as Haemonchus and Ostertagia, are more predominant in the stomach, and others, such as Dictyocaulus, are found in the lungs. In addition, other parasites may be found in other tissues, such as the heart and blood vessels, under the skin, in lymphatic tissue, etc.

Trematodes contemplated for treatment by the present invention and the methods of the present invention include, but are not limited to, the following genera: Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus and Schistosoma.

Cestodes contemplated for treatment by the present invention and the methods of the present invention include, but are not limited to, the following genera: Diphyllobothrium, Diplydium, Spirometra and Taenia.

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

Many other genera and species of helminths are known in the art and are also contemplated for treatment by the polymorphs of the present invention. They are listed in detail in the Textbook of Veterinary Clinical Parasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods and Protozoa, ( ^6th Edition of Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby, Williams and Wilkins Co., Baltimore, Md.

The polymorphs of the present invention may be effective against a variety of animal ectoparasites (eg, arthropod ectoparasites in mammals and birds).

Insect and mite pests include, for example, biting insects such as flies and mosquitoes, ticks, ticks, lice, fleas, bedbugs, parasitic larvae, and the like.

Adult flies include, for example, the cow fly or Haematobia irritems, the horse fly or Tabanus spp., the autumn fly or Stomoxys calcitrans, the midge or Simulium spp., the stag fly or Chrysops spp., the bloodsucker or Melophagus ovinus, and the tsetse fly or Glossina spp. Parasitic fly larvae include, for example, the larvae of the nasopharyngeal botfly (Oestrus ovis and Cuterebra spp.), the blue blowfly or Phaenicia spp., the larvae of the blowfly or Cochliomyia hominivorax, the bodfly or Hypoderma spp., the sheep's wool worm, and Gastrophilus of horses. Mosquitoes include, for example, Culex spp., Anopheles spp. and Aedes spp.

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

Ixodid ticks include, for example, soft-bodied Ixodid ticks, including Argasidae spp., for example, Argalphas spp. and Ornithodoros spp.; hard-bodied ixodid ticks, including Ixodidae spp., for example, Rhipicephalphalus sanguineus, Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Ixodes scapularis, and other Rhipicephalus spp. (including representatives of the former genus Boophilus).

Lice include, for example, sucking lice, eg Menopon spp. and Bovicola spp.; lice beetles, for example, Haematopinus spp., Linognathus spp. and Solenopotes spp.

Fleas include, for example, Ctenocephalides spp., such as the dog flea (Ctenocephalides canis) and the cat flea (Ctenocephalides felis); Xenopsylla spp., such as the southern rat flea (Xenopsylla cheopis); and Pulex spp., such as the human flea (Pulex irritans).

Bedbugs include, for example, Cimicidae or, for example, the common bedbug (Cimex lectularius); Triatominae spp., including triatomine bugs, also known as kissing bugs; for example, Rhodnius prolixus and Triatoma spp.

Typically, flies, fleas, lice, mosquitoes, midges, ticks, ticks and helminths cause huge losses in the livestock and pet industries. Arthropod parasites are also a nuisance to humans and can transmit disease-causing organisms to humans and animals.

There are many other parasitic invertebrate pests known in the art that are also contemplated to be treated with the polymorphs of the present invention. They are listed in 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.

The polymorphs of the present invention may also be effective against ectoparasites, including flies such as Haematobia (Lyperosia) irritans, Simulium spp. (midge), Glossina spp. (tsetse fly), Hydrotaea irritans (sweet fly), Musca autumnalis (common field fly), Musca domestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horsefly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green carrion), Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasopharyngeal botfly), Culicoides spp. (biting midges), 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; runts 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).

Treatments according to the present invention are carried out by traditional methods, for example, by enteral administration in the form of, for example, tablets, capsules, drinks, oral infusions, granules, pastes, boluses, by feeding procedures or suppository administration; or by parenteral administration, such as, for example, by injection (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implantation; or by nasal administration.

If the polymorphs of the present invention are used in combination with an additional biologically active ingredient, they can be administered separately, for example, in the form of separate compositions. In such a case, the biologically active ingredients can be administered simultaneously or sequentially. Alternatively, the biologically active ingredients may be components of a single composition.

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

Typically, the parasiticidal composition in accordance with the present invention contains the polymorph of the present invention, optionally in combination with an additional biologically active ingredient or its N-oxides or salts, with one or more pharmaceutically acceptable or veterinary acceptable carriers, which include excipients and excipients , selected based on the intended route of administration (eg, oral or parenteral administration such as injection) and in accordance with standard practice. In addition, a suitable carrier is selected based on compatibility with one or more active ingredients in the composition, including factors such as pH stability and moisture content. Therefore, the polymorph of the present invention should be noted for protecting an animal from a parasitic invertebrate pest, which provides a parasiticidal effective amount of the polymorph of the present invention, optionally in combination with an additional biologically active ingredient and at least one carrier.

For parenteral administration, including intravenous, intramuscular and subcutaneous injection, the polymorphs of the present invention may be formulated as a suspension, solution or emulsion in oily or aqueous carrier media and may contain additional substances such as suspending, stabilizing and/or dispersing agents .

The polymorphs of the present invention can also be formulated for bolus injection or continuous infusion. Pharmaceutical compositions for injection include aqueous solutions of water-soluble forms of the active ingredients (eg, a salt of the active compound), preferably in physiologically compatible buffers containing other excipients or excipients that are known in the pharmaceutical formulation art. In addition, suspensions of the active compounds can be prepared in a lipophilic carrier medium. Suitable lipophilic carrier media include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or materials such as liposomes.

Water-based injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. Injectable compositions may be present in unit dosage form, for example, in ampoules or multiple dosage containers. Alternatively, the active ingredient may be provided in powder form for reconstitution with a suitable carrier medium, such as sterile, pyrogen-free water, prior to use.

In addition to the formulations described previously, the polymorphs of the present invention can also be formulated as a depot preparation. Such long-acting formulations can be administered by implantation (eg, subcutaneously or intramuscularly) or by intramuscular or subcutaneous injection.

- 32 044796

The polymorphs of the present invention can be formulated for this route of administration with suitable polymeric or hydrophobic materials (eg, in an emulsion with a pharmacologically acceptable oil), with ion exchange resins, or as a sparingly soluble derivative, such as, but not limited to, a sparingly soluble salt.

For administration by inhalation, the polymorphs of the present invention can be delivered in the form of a nebulized aerosol using a pressure pack or nebulizer and a suitable propellant, such as, but not limited to, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, or carbon dioxide. In the case of a pressurized aerosol, the dosage unit can be controlled by providing a valve to deliver a metered amount.

Capsules and cartridges, eg gelatin, for use in an inhaler or insufflator may be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch.

The polymorphs of the present invention may have satisfactory pharmacokinetic and pharmacodynamic properties to provide systemic availability upon oral administration and ingestion. Therefore, once ingested by the animal to be protected, parasiticidal effective concentrations of the polymorph of the present invention in the bloodstream can protect the treated animal from blood-sucking pests such as fleas, ticks and lice. Accordingly, of note is a composition for protecting an animal against a parasitic invertebrate pest in an oral form (i.e. containing, in addition to a parasiticidal effective amount of the polymorph of the present invention, one or more carriers selected from binders and excipients, suitable for oral administration, and carriers of feed concentrates).

For oral administration in the form of solutions (the most readily available form for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen retainers, and feed/water/lick briquettes, the polymorphs of the present invention can 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. maize starch, wheat starch, rice starch, potato starch), cellulose and its derivatives (eg, methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (eg, zein, gelatin) and synthetic polymers (eg, polyvinyl alcohol, polyvinylpyrrolidone). If necessary, lubricants (eg magnesium stearate), disintegration agents (eg cross-linked polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments may be added. Pastes and gels often also contain adhesives (eg, gum arabic, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminosilicate) to help keep the composition in contact with the oral cavity and not be easily discarded.

The composition of the present invention may be formulated as a chewable and/or edible product (eg, a chewable treatment or an edible tablet). Such a product should ideally have a taste, texture and/or aroma preferred by the animal being protected, thereby facilitating oral administration of the compounds of the present invention.

If the parasiticidal compositions are presented in the form of feed concentrates, the carrier is typically selected from high performance feed, feed grains or protein concentrates. Such feed concentrate compositions may, in addition to the parasiticidal active ingredients, contain additives to promote health or growth of the animal, improve the quality of meat from animals for slaughter, or otherwise useful in animal husbandry. These additives may include, for example, vitamins, antibiotics, chemotherapeutic agents, bacteriostatic agents, fungistatic agents, coccidiostatic agents, and hormones.

The polymorph of the present invention can be formulated into compositions for rectal use, such as suppositories or retention enemas, using, for example, traditional suppository bases such as cocoa butter or other glycerides.

Compositions for the method of the present invention may include an antioxidant such as BHT (butylated hydroxytoluene). The antioxidant is typically present in amounts of 0.1-5 percent (w/v). Some of the formulations require a solubilizer such as oleic acid to dissolve the active agent, especially if spinosad is included. Common distribution enhancers used in such spreadable 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 dipropylene glycol methyl ester. . Spreadable compositions for the method of the present invention are prepared according to known techniques. If the spreading composition is a solution, the parasiticide/insecticide is mixed with the carrier or carrier medium, using heat and stirring as necessary. Excipients or additional ingredients can be added to the mixture of the active agent and the carrier, or they can be mixed with the active agent before adding the carrier. Spreadable compositions in the form of emulsions or suspensions are prepared similarly using known techniques.

For relatively hydrophobic pharmaceutical compounds, other delivery systems can be used. Liposomes and emulsions are well-known examples of carrier vehicles or carriers for the delivery of hydrophobic drugs. In addition, organic solvents such as dimethyl sulfoxide can be used if necessary.

The application rate required to effectively control parasitic invertebrate pests (e.g., pesticide effective amount) will depend on factors such as the type of parasitic invertebrate pest being controlled, the pest's life cycle, life stage, size, location , season, host crop or host animal, feeding behavior, mating behavior, environmental humidity, temperature and the like. One skilled in the art can readily determine the pesticide effective amount needed to achieve the desired level of control of parasitic invertebrate pests.

Typically, for veterinary use, the polymorphs of the present invention are administered in a pesticidal effective amount to an animal, especially a homeothermic animal, that is being protected from parasitic invertebrate pests.

A pesticidally effective amount is the amount of active ingredient required to achieve a noticeable effect in reducing the occurrence or activity of the target parasitic invertebrate pest. One skilled in the art will appreciate that the pesticidal effective dose may vary for the various compounds and compositions useful in the method of the present invention, the desired pesticidal effect and its duration, the type of parasitic invertebrate pest targeted, the animal to be protected, the method of application, and of the like, and the quantity required to achieve a particular result can be determined by a simple experiment.

For oral or parenteral administration to animals, the dose of the compositions of the present invention, administered at suitable intervals, will generally range from about 0.01 mg/kg to about 100 mg/kg, and preferably from about 0.01 mg/kg to about 30 mg/kg animal body weight.

Suitable intervals at which the compositions of the present invention are administered to animals range from about one day to about one year. It should be noted that the intervals at which administration is carried out range from approximately weekly to approximately once every 6 months. Of particular note are the monthly dosing intervals (ie, administering the compounds to the animal once a month).

The present invention will now be described with the help of the following non-limiting examples and figures, in which the following are illustrated.

In fig. 1 shows an X-ray powder diffraction pattern based on the measured values for the polymorph designated Form A(a).

In fig. Figure 2 shows an X-ray powder diffraction pattern based on calculated values for the polymorph designated Form A(a).

In fig. Figure 3 shows the DSC curve for the polymorph designated form A(a).

In fig. Figure 4 shows an X-ray powder diffraction pattern based on the measured values for the polymorph designated form A(b).

In fig. Figure 5 shows the DSC curve for the polymorph designated as form A(b).

In fig. 6 shows an X-ray powder diffraction pattern based on the measured values for a hydrate of the compound of formula IA.

In fig. 7 shows an X-ray powder diffraction pattern based on calculated values for a hydrate of the compound of Formula IA.

In fig. 8 shows an X-ray powder diffraction pattern based on the measured values for a polymorph of the compound of Formula IB.

In fig. 9 shows a DSC curve for a polymorph of the compound of formula IB.

In fig. 10 shows an X-ray powder diffraction pattern based on calculated values for a polymorph of the compound of formula IB.

In fig. 11 shows an X-ray powder diffraction pattern based on the measured values for the racemate polymorph of compounds of formulas IA and ID.

In fig. 12 shows a DSC curve for the racemate polymorph of compounds of formulas IA and ID.

In fig. 13 shows the Raman spectra for the polymorph designated Form A(a).

In fig. 14 shows a DSC curve for the polymorph designated Form A(c).

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Examples

1. Obtaining polymorphs.

The compound of formula I was prepared using the methods described in WO 2011/067272. This resulting solid and liquid filtrate were analyzed by HPLC as specified in WO 2011/067272. The compound of formula IA was present in the filtrate and the compound of formula IC in the solid precipitate. After crystallization from the filtrate, the polymorph representing form A(c) was identified by DSC (see FIG. 14).

1a. Obtaining form A(a).

A purified sample of the compound of formula IA was suspended in dimethyl carbonate for 2 weeks at 25°C, after which the crystals were isolated and characterized by DSC, powder X-ray diffraction and single crystal X-ray diffraction. An X-ray powder diffraction pattern based on the measured values for a polymorph of the compound of formula IA (designated Form A(a)) is shown in FIG. 1. An X-ray pattern obtained from measured intensity data for a single crystal is shown in FIG. 2. DSC curve of shape A(a) is shown in Fig. 3.

1b. Obtaining form A(b).

An additional sample of compound of Formula IA was subjected to slow evaporation at room temperature from a range of solvents. The sample isolated after evaporation from a 20% water/methanol mixture was analyzed by DSC and powder X-ray diffraction. An X-ray powder diffraction pattern based on the measured values for a polymorph of the compound of formula IA (designated Form A(b)) is shown in FIG. 4. The DSC curve for form A(b) is shown in Fig. 5.

1s. Obtaining the form A(h).

An additional sample of compound of formula IA was subjected to slow evaporation from a water/ethanol mixture. Analysis of the crystals showed that water was included in the structure - two molecules of water and two molecules of the compound of formula IA in an asymmetric unit. This hydrate (designated form A(h)) was analyzed by DSC and TGA, as well as powder X-ray diffraction and single crystal X-ray diffraction. An X-ray powder diffraction pattern based on the measured values for the hydrate is shown in FIG. 6.

The X-ray pattern obtained on the basis of the calculated values based on the intensity data for the single crystal is presented in Fig. 7.

1d. Obtaining form B(a) and form C(a).

Samples of compounds of formulas 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 fume hood to allow the acetone to evaporate. The resulting solid samples were analyzed by powder X-ray diffraction and DSC. Powder X-ray diffraction patterns for IB and IC were identical. The x-ray diffraction pattern for the compound of formula IB is shown in FIG. 8. DSC data for this connection is presented in FIG. 9.

Crystals suitable for analysis by single crystal X-ray diffraction were grown in an isopropanol/water mixture (80/20). The X-ray pattern obtained on the basis of the calculated values based on the intensity data for the single crystal is presented in Fig. 10.

1e. Preparation of a racemic mixture of compounds of formulas IA and ID.

Equal amounts of compounds of formulas IA and ID were dissolved in acetone and then left at room temperature until the solvent evaporated. The resulting crystalline solid was characterized by powder X-ray diffraction and DSC. An X-ray powder diffraction pattern based on the measured values for the racemate polymorph of the compounds of formulas IA and ID is shown in FIG. 11. The DSC curve for this polymorph is shown in FIG. 12.

2. Analysis of polymorphs.

Once samples were obtained, they were analyzed by X-ray powder diffraction and/or single crystal X-ray diffraction and/or differential scanning calorimetry (DSC) and/or thermal gravimetric analysis (TGA) as detailed above. The methods used for such analysis methods are described in detail below.

Powder X-ray diffraction analysis of solid material was carried out using a Bruker D8 powder diffractometer at room temperature and relative humidity above 40%. The specimens were secured in Perspex specimen clamps and the specimens were straightened. The sample clamp was rotated and the X-rays were captured from 4° to 34° 2-theta, with scanning times ranging from 25 to 30 min depending on the intensity of the pattern.

Intensity data for the single crystal were collected on an Oxford Xcalibar PX Ultra diffractometer using CuKa radiation (λ=1.5418 A) and a graphite monochromator. The crystal was placed in Paratone N oil at 100K for data collection. Data were interpreted using the CRYSTALS software package.

DSC was performed using Mettler Toledo DSC1. Approximately 5 mg of sample was loaded and

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Claims (5)

heated it from 25°C to 160°C at a rate of 10°C/min. The lid of the DSC crucible had holes in it to allow any gas generated during heating of the sample to escape. Raman spectroscopy was performed using a Thermo Scientific DXR Raman microscope: Raman laser, 780 nM, aimed at a sample on a quartz slide. 1. Crystalline polymorph of the compound of formula IA, IA which is characterized by a powder X-ray diffraction pattern containing at least three values of the 2θ angle 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. The crystalline polymorph according to claim 1, which is characterized by a powder X-ray diffraction pattern containing at least six values of the 2θ angle 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. 3. Crystalline polymorph according to claim 1 or claim 2, which is characterized by the following lattice parameters: a=5.06 A±0.01 A, b=18.92 A±0.01 A, c=24.17 A± 0.01 Α, α=90°±0.01°, β=90°±0.01°, γ=90°±0.01° and volume=2315 A ³ ±1 A ³ . 3. Stability of polymorphs. A sample of the polymorph, designated form A(c), was stirred in 5 ml of dimethyl carbonate for two days. The crystals were isolated, air-dried, and characterized by DSC and pXRD. The DSC curve showed a clear single melting endotherm with a melting peak at 141°C, and the pXRD pattern was consistent with that of form A(a), indicating that the entire volume of form A(c) was converted to form (A)a. Although the present invention has been described with reference to preferred embodiments and examples thereof, the scope of the present invention is not limited only to such described embodiments. It will be apparent to those skilled in the art that modifications and adaptations can be made to the invention described above without departing from the spirit and scope of the present invention as defined and limited by the appended claims. All publications cited herein are incorporated herein by reference in their entirety for all purposes to the same extent as if each individual publication had been specifically and separately identified as being so incorporated by reference. CLAIM 4. Crystalline polymorph according to any one of claims 1-3, which is characterized by a melting point of 141°C ± 2°C. 5. Crystal polymorph of the compound of formula IA ΙΑ which is a hydrate and which is characterized by a powder X-ray diffraction pattern containing at least three values of the 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. -