Amorphous form of deltamethrin and methods of use thereof

Abstract

The present invention relates to an amorphous form of deltamethrin, which is a pyrethroid compound useful as a pest control agent. The present invention further relates to a process of preparing the novel amorphous form, and to methods of controlling pests using the novel amorphous form.

Description

Attorney Docket No. 243735.000472AMORPHOUS FORM OF DELTAMETHRIN AND METHODS OF USE THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. Provisional Patent Application Serial No. 63 / 714,564, filed October 31, 2024, which is hereby incorporated by reference in its entirety.STATEMENT AS TO FEDERALLY FUNDED RESEARCH

[0002] This invention was made with government support under 2118890 and 2018298 awarded by the National Science Foundation. The government has certain rights in the invention.FIELD OF INVENTION

[0003] The present invention relates to amorphous form of a pyrethroid compound deltamethrin, which is useful as a pest control agent, and methods of preparing and using thereof.BACKGROUND OF THE INVENTION

[0004] Crystals are solid structures held together by attractive forces between atomic or molecular constituents with periodic translation order extending over long distances. For example, diamonds are crystals made of carbon atoms held together in a network by covalent bonds and arranged in a specific pattern. Graphite is a crystal composed of carbon atoms held together in layers through covalent bonds but with the layers stacked on top of each other by weaker intermolecular forces often referred to as van der Waals forces. Graphite and diamond possess distinct properties as a consequence of the ordering of the atoms and the forces that hold them together (Bernstein, J., “Polymorphism in Molecular Crystals,” lUCr Monographs on Crystallography; first publ. in paperback.; Clarendon Press: Oxford (2007)). Diamond is hard. Graphite is soft, making it a great tool for writing. Graphite pencils leave carbon marking a page whereas you would be hard-pressed to write with a diamond (Falcao, E. H. and Wudl, F., “Carbon Allotropes: Beyond Graphite and Diamond,” J. Chem. Technol. Biotechnol. 82(6):524-531 (2007)). Many insecticides form crystals and can exist in the form of crystals when they are contacted by insects. Until recently, however, their mechanism of action and effectiveness were not studied comprehensively; most of the science was “insect centric.” Once inside the organism,Attorney Docket No. 243735.000472 the efficacy of the insecticide is dependent on several factors, the concentration of insecticide present and the physiology of the organism (Ren et al., “Insect Cuticle and Insecticide Development,” Arch. Insect. Biochem. Physiol. 114(4):e22057 (2023)). While the physiology of the insect cannot be dictated, the concentration of insecticide inside the insect after exposure can be controlled.

[0005] Different spatial arrangements of the same insecticide in solids can lead to markedly different lethality as it dictates how easily molecules of the insecticide are picked up (Erriah et al., “Crystallography of Contemporary Contact Insecticides,” Insects 13(3):292 (2022)). Polymorphism, common for molecular crystals, is the existence of two or more solid crystalline phases of the same compound. Relatively weak intermolecular interactions are associated with shallow potential energy hypersurfaces, resulting in great structural variability leading to solid forms with distinct chemical and physical properties. The chemical potential of molecules at the surface of a crystal is different for each polymorph and each symmetry-independent facet of each polymorph. The higher the chemical potential, the lower the barrier to cuticular adsorption. Solids with weaker intermolecular interactions liberate molecules more easily and in turn, each interaction leads to a more rapid uptake of the insecticide and a higher concentration of insecticide inside the organism. This has been demonstrated for many insecticides, such as lindane, dichlorodiphenylethane (DDT), difluorodiphenyltrichloroethane (DFDT), and imidacloprid (Yang et al., “Inverse Correlation Between Lethality and Thermodynamic Stability of Contact Insecticide Polymorphs,” Crystal Growth & Design 19:1839-1844 (2019); Yang et al., “DDT Polymorphism and the Lethality of Crystal Forms,” Angew. Chem. Int. Ed. 56:10165-10169 (2017); Zhu et al., “Manipulating Solid Forms of Contact Insecticides for Infectious Disease Prevention,” J. Am. Chem. Soc. 141:16858-16864 (2019); Yang et al., “A Deltamethrin Crystal Polymorph for More Effective Malaria Control,” PNAS 117:26633-26638 (2020); Zhu et al., “Imidacloprid Crystal Polymorphs for Disease Vector Control and Pollinator Protection,” J. Am. Chem. Soc. 143: 17144- 17152 (2021)).

[0006] Crystals have long-range order and relatively strong intermolecular interactions. Amorphous solids on the other hand do not have long-range order and the molecules are ordered randomly, which can reduce the strength of intermolecular interactions. Thermodynamically, this property may be quantified by the free energy of the solid, a higher free energy typically correlates with weaker intermolecular interactions.Attorney Docket No. 243735.000472

[0007] Deltamethrin, a pyrethroid insecticide, (S)-cyano(3-phenoxyphenyl) methyl (lR,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-l-carboxylate, which is represented by the following Formula I:

[0008] Deltamethrin has been a leading compound providing crop protection and malaria control during the past half-century. Even though deltamethrin is a comparatively complex compound, the fractional crystallization of the most potent 1R, cis, aS, stereoisomer (Formula I), followed by epimerization of the 1R, cis, aR stereoisomer, alleviated the cost of wasted byproducts and the separation of diastereoisomers (Casida, J. E. “Michael Elliott’s Billion-Dollar Crystals and Other Discoveries in Insecticide Chemistry,” Pest. Manag. Sci. 66: 1163-1170 (2010)).

[0009] Despite the success of deltamethrin products, notably in long-lasting insecticidal bed nets, mosquito resistance to the pyrethroid class of insecticides, to which deltamethrin belongs, now threatens gains against malaria made during the past generation (Kleinschmidt et al., “Implications of Insecticide Resistance for Malaria Vector Control With Long-Lasting Insecticidal Nets: a WHO-Coordinated, Prospective, International, Observational Cohort Study,” Lancet Infect Dis. 18(6):640-649 (2018)).

[0010] Accordingly, there is a strong, unmet need for improved pest control agents, e.g., improved pyrethroid pesticides, to help satisfy the ongoing need to counteract the significant problem of pesticide resistance.SUMMARY OF THE INVENTION

[0011] Various non-limiting aspects and embodiments of the invention are described below.

[0012] In one aspect, the present disclosure provides an amorphous form of deltamethrin.

[0013] In another aspect, the present disclosure provides a composition comprising the amorphous form according to the present disclosure.

[0014] In another aspect, the present disclosure provides a process for preparing the amorphous form of deltamethrin. This process comprises providing a crystalline form ofAttorney Docket No. 243735.000472 deltamethrin; heating the crystalline form of deltamethrin to form a molten deltamethrin; and cooling the molten deltamethrin to room temperature to form the amorphous form of deltamethrin.

[0015] In yet another aspect, the present disclosure provides a process for preparing the amorphous form of deltamethrin. This process comprises providing a crystalline form of deltamethrin; dissolving the crystalline form of deltamethrin in a suitable solvent to form a solution of deltamethrin; and forming the amorphous form of deltamethrin by evaporating the solvent from the solution of deltamethrin.

[0016] In another aspect, the present disclosure provides a method of controlling a pest. This method comprises applying to the pest or its locus the amorphous form according to the present disclosure or the composition according to the present disclosure.

[0017] In yet another aspect, the present disclosure provides a method of controlling a pest. This method comprises applying to a surface the amorphous form according to the present disclosure or the composition according to the present disclosure.

[0018] In some embodiments, the pest is an insect.

[0019] In some embodiments, the insect is selected from adelgids, ants, aphids, annual bluegrass weevil (adults), azalea lace bugs, bagworms, bees, bed bugs, billbugs (adults), blue bottle flies, black turfgrass ataenius (adults), boxelder bugs, brown, marmorated stink bug, cankerworms, cardamom thrips, carpenter ants, carpenter bees, carpet beetles, centipedes, cecid flies, chinch bugs, clothes moths, clover mites, cluster flies, cockroaches, crickets, darkling beetles, dermestids, earwigs, elm leaf beetles, elm spanworms, European pine sawflies, fall webworms, firebrats, fleas (indoors & outdoors), flea beetles, flies, flesh flies, fruit flies, fungus gnats (sciarid flies), gnats, grasshoppers, green bottle flies, green-striped mapleworms, ground beetles, gypsy moths (larvae), hide beetles, house flies , hornets, horseflies, imported willow leaf beetles, Indian meal moth, Japanese beetles, June beetles (adults), killer bees, leafhoppers, leaf-feeding caterpillars, leaf skeletonizers, leaf rollers, leather beetles, lice, loopers, maize weevils, mealybugs, midges, millipedes, mimosa webworms, mites, mole crickets, moths, mosquitoes, multicolored Asian lady beetles, orange-striped oakworms, pantry beetles, pantry moths, pillbugs, pine shoot beetles, pine tip moths, pinyon spindlegall midges, plant bugs, pharaoh's ants, phorid flies, red-humped caterpillar, red imported fire ants, red flour beetles, rice weevils, saw-toothed grain beetle, sawfly larvae, scale insects (crawlers), scorpions, silverfish, spiders, sod webworms, sowbugs, springtails,Attorney Docket No. 243735.000472 stable flies, pantry pests, stored product pests, tent caterpillars, ticks (indoors & outdoors), yellowjackets, yellow-necked caterpillar, wasps, and webworms.

[0020] These and other aspects of the present invention will become apparent to those skilled in the art after a reading of the following detailed description of the invention, including the appended claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0022] Figure 1 shows a polarized light optical micrograph of droplets of amorphous deltamethrin deposited from acetone.

[0023] Figures 2A-2C show micrograph of amorphous droplets and crystals taken between cross polarizers, later processed for data extraction. Fig. 2A shows a polarized light micrographs of amorphous droplets where crystalline material is viewed as bright spots. Fig. 2B is a thresholder image separating amorphous and crystalline material based on color allowing for quantification of crystalline percentage. Fig. 2C shows reverse calculation of that in Fig. 2B for error checking.

[0024] Figures 3 shows scanning electron microscopy (SEM) images of 2: 1 HDPE:LDPE melt extruded fibers containing 1 wt% deltamethrin with agglomerates / droplets of deltamethrin on PE surface with a nucleated droplet in the center.

[0025] Figure 4A-4B show differential scanning calorimetry (DSC) thermograms of D- Fense Dust, cycled from 25°C to 120°C, then back to 25°C. Fig. 4A depicts the first cycle which shows an endotherm with onset at 98°C, characteristic of deltamethrin melting. No recrystallisation was observed upon cooling. Fig. 4B shows the second cycle, the same program was followed. No endotherm was visible at 98°C.

[0026] Figures 5A-5C show 4D scanning transmission electron microscopy (4D STEM) characterization of amorphous deltamethrin. Fig. 5A is a virtual bright-field image from 4D-STEM set. Fig. 5B is a virtual image from 4D-STEM, inset: area for 2D data in Fig. 5C. Fig. 5C is a sum of 2D data sets in box of Fig. 5B.Attorney Docket No. 243735.000472

[0027] Figure 6 shows Raman spectra of deltamethrin solid forms. From top to bottom: deltamethrin Form I as purchased, Form II grown from the melt, Form I as transformed from Form II. amorphous deltamethrin following deposition from acetone, amorphous deltamethrin as deposited from dichloromethane.

[0028] Figure 7 is a bar graph showing percentage of fruit fly population knocked down due to exposure to the amorphous droplets as compared to exposure to the crystalline form. The dosage mimics that which is commonly found in long-lasting insecticidal nets (LLINs), 55 mg / m2. The amorphous form is represented in dark green and the crystalline form in blue. A comparative lower dose of the amorphous form was also shown to emphasize the greater lethality of the amorphous form as compared to the crystalline form.

[0029] Figures 8A-8B show DSC curve of deltamethrin and 30nm-pore porous carrier, cycled from 25°C to 135°C, then back to 25°C. Fig. 8A shows the first run. Fig. 8B shows the same sample 14 hours later.

[0030] Figure 9 shows percentage of a fruit fly population that's knocked down at a particular time. Each data point on the graph represents a fruit fly, and the points are independent of one another. Commercial D-Fence dust (Dark blue). Heated D-Fense Dust (orange). New formulation (green). Heated new formulation (light blue). Numbers represent respective KD50 values associated with each formulation.

[0031] Figures 10A-10B show ATR-IR measurement of a sample of 9 % w / w deltamethrin (DM) on silica (Fig. 10A) and ATR-IR measurement of a sample of 10 %w / w DM on Florisil (Fig. 10B). In Fig. 10A, red - DM powder; blue - DM on glass drop cast from acetone (aged at ambient for more than a month); yellow - 2days aged 9 %w / w DM on nano silica; and green - 3weeks aged 9 % w / w DM on nano silica). In Fig. 10B, purple - DM powder; red - DM on glass drop cast from acetone (aged at ambient for more than a month); yellow - 2days aged 10 %w / w DM on Florisil; and green - 2weeks aged 10 w% DM on Florisil).DETAILED DESCRIPTION

[0032] Detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the invention that may be embodied in various forms. In addition, each of the examples given in connection with theAttorney Docket No. 243735.000472 various embodiments of the invention is intended to be illustrative, and not restrictive. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the present invention.

[0033] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0034] As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, a reference to “a method” includes one or more methods, and / or steps of the type described herein and / or which will become apparent to those persons skilled in the art upon reading this disclosure.

[0035] Ranges can be expressed herein as from “about” or “approximately” one particular value and / or to “about” or “approximately” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value.

[0036] By “comprising” or “containing” or “including” is meant that at least the named compound, element, particle, or method step is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles, or method steps, even if the other such compounds, material, particles, or method steps have the same function as what is named.

[0037] A “pest”, as used herein, refers to not only insects, but also is a generic term for small animals that may directly or indirectly damage, and thereby affect, humans, produce, machines, equipment, and so on, by colonizing, attacking, irritating, or feeding upon them, or competing for host nutrients. Examples of pests include mosquitos, flies, ants, spiders, centipedes, cockroaches, geckos, mice, pigeons, crows, and any other similar animals.

[0038] As used herein the term “to control a pest” means to expel, kill, destroy, or exterminate pests, prevent, or mitigate proliferation of pests, protect targets from pests, and control (or inhibit) the growth of pests. Controlling pests includes enticing pests in order to exert the pest control effects described above.Attorney Docket No. 243735.000472

[0039] As used herein the term “pesticidal composition” refers to a composition comprising a substance or mixture of substances capable of expelling, killing, destroying, exterminating, preventing, or mitigating any pest.

[0040] As used herein the term “effective” applied to dose or amount refers to that quantity of a pesticide that is sufficient to result in a desired pesticidal action or activity.

[0041] It is also to be understood that the mention of one or more method steps does not preclude the presence of additional method steps or intervening method steps between those steps expressly identified. Similarly, it is also to be understood that the mention of one or more components in a device or system does not preclude the presence of additional components or intervening components between those components expressly identified.

[0042] Contact insecticide activity depends on the solid state of the active ingredient. Amorphous solids are invariably more active than crystalline solids. As shown in the present disclosure, deltamethrin, a commonly used anti-malarial insecticide, can be prepared as a comparatively stable amorphous solid in a variety of ways, and as such may provide greater protection against malaria-transmitting mosquitoes and other vectors of infectious disease. Until 2021, however, its mechanism of action and effectiveness was not comprehensively studied and was limited to its interactions once inside the organism. To use deltamethrin effectively, its solid- state form must be considered as it can have a drastic effect on its lethality. Crystal polymorphism, the occurrence of two or more solid crystalline phases of the same compound, can be consequential to insects. The two crystalline forms of deltamethrin, the commercially available, thermodynamically most stable form, and a metastable form named Form II. Form II is more than six times faster acting than the commercial form Drosophila melanogaster (common fruit fly), which is expected as the lethality of an insecticide is directly related to the free-energy of its solid form. When molecules are more easily liberated from their source, they are more easily picked up by the intended target, creating a higher concentration of insecticide inside the organism. It follows that the amorphous form of deltamethrin, if stable, should be more effective. The present disclosure provides an analysis of amorphous deltamethrin, its biological activity, and physical properties.

[0043] In one aspect, the present disclosure provides an amorphous form of deltamethrin.

[0044] Deltamethrin, (S)-cyano(3-phenoxyphenyl) methyl (lR,3R)-3-(2,2-dibromovinyl)- 2, 2-dimethylcyclopropane- 1 -carboxylate, is a pyrethroid insecticide, which is represented by the following Formula I:Attorney Docket No. 243735.000472

[0045] Two different crystal forms of deltamethrin have been reported. One crystal structure has been reported in the Cambridge Structural Database, which has been designated herein as Form I (CSD refcode: PXBVCP10) (Owen, J. “Absolute Configuration of the Most Potent Isomer of the Pyrethroid Insecticide a-Cyano-3-phenoxybenzyl Cis-3-(2,2-Dibromovinyl)- 2,2-dimethylcyclopropanecarboxylate by Crystal Structure Analysis.” J. Chem. Soc., Perkin Trans. 1(0): 1865-1868 (1975), which is hereby incorporated by reference in its entirety).

[0046] The crystal structure of Form II, the metastable form, was previously described by Yang et al., “A Deltamethrin Crystal Polymorph for More Effective Malaria Control,” PNAS 117:26633-26638 (2020), which is hereby incorporated by reference in its entirety.

[0047] Crystalline and amorphous forms are commonly characterized by Raman spectroscopy and / or attenuated total infrared reflectance (ATIR). A Raman and / or ATIR pattern of reflections (peaks) can be a fingerprint of an amorphous form. It is well known that the relative intensities of the peaks can widely vary depending on, inter alia, the sample preparation technique, filters, the sample mounting procedure, and the particular instrument employed. In some instances, new peaks may be observed or existing peaks may disappear, depending on the type of instrument or the settings. As used herein, the term "peak" refers to a relative height / intensity of at least about 4% of the maximum peak height / intensity.

[0048] In some embodiments, the amorphous form of deltamethrin has a Raman spectrum comprising the peaks at 0-150 cm1. For example, the amorphous form of deltamethrin has a Raman spectrum substantially as shown in Figure 6.

[0049] In some embodiments, the amorphous form of deltamethrin has a broad feature at low frequency below 150 cm1in a Raman spectrum.

[0050] In some embodiments, the amorphous form of deltamethrin has an ATIR spectrum comprising the peak at 692 cm'1. For example, the amorphous form of deltamethrin has an ATIR spectrum substantially as shown in Figure 10 A.Attorney Docket No. 243735.000472

[0051] In some embodiments, the amorphous form of deltamethrin has 4D scanning transmission electron microscopy (4D STEM) images indicating that it is substantially free from diffraction spots.

[0052] In some embodiments, the amorphous form of deltamethrin is anhydrous and nonsolvated. By “anhydrous” is meant that the amorphous form of deltamethrin contains essentially no bound water. By “non-solvated” is meant that the amorphous deltamethrin form contains no bound solvent molecules.

[0053] In some embodiments, the amorphous form of the invention is substantially isolated. By “substantially isolated” is meant that a particular amorphous form of deltamethrin is at least partially isolated from impurities. For example, in some embodiments an amorphous form of the invention comprises less than about 50%, less than about 40%, less than about 30%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 2.5%, less than about 1%, or less than about 0.5% of impurities. Impurities generally include anything that is not the substantially isolated amorphous form including, for example, crystalline forms and other substances.

[0054] In some embodiments, an amorphous form of deltamethrin is substantially free of crystalline forms. The phrase “substantially free of crystalline forms” means that an amorphous form of deltamethrin comprises no more than 40%, no more than 30%, no more than 20%, no more than 10%, no more than 5%, no more than 1% by weight of the crystalline forms.

[0055] In another aspect, the present disclosure provides a process for preparing the amorphous form of deltamethrin. This process comprises providing a crystalline form of deltamethrin; heating the crystalline form of deltamethrin to form a molten deltamethrin; and cooling the molten deltamethrin to room temperature to form the amorphous form of deltamethrin.

[0056] In some embodiments, the crystalline form of deltamethrin is crystalline Form I of deltamethrin.

[0057] In some embodiments, the crystalline form of deltamethrin is heated to a temperature above the melting temperature of deltamethrin.

[0058] In some embodiments, the crystalline form of deltamethrin is provided as D-Fense Deltamethrin Dust.

[0059] In another aspect, the present disclosure provides a process for preparing the amorphous form of deltamethrin. This process comprises providing a crystalline form ofAttorney Docket No. 243735.000472 deltamethrin; dissolving the crystalline form of deltamethrin in a suitable solvent to form a solution of deltamethrin; and forming the amorphous form of deltamethrin by evaporating the solvent from the solution of deltamethrin.

[0060] Any suitable solvent or combination of suitable solvents can be used to dissolve the crystalline form of deltamethrin. In some embodiments, the solvent is an organic solvent. Suitable organic solvents that can be used include, without limitation, acetone, tetrahydrofuran, dichloromethane, pentane, hexane, diethyl ether, ethyl acetate, methanol, and chloroform or a combination thereof.

[0061] The solution of deltamethrin can contain from about 0.01 % to about 50 %, about 0.05 % to about 40 %, about 0.05 % to about 30 %, about 0.05 % to about 20 %, about 0.05 % to about 10 %, about 0.05 % to about 5 %. about 0.05 % to about 1 %, about 0.1 % to about 50 %, about 0.1 % to about 40 %, about 0.1 % to about 30 %, about 0.1 % to about 20 %, about 0.1 % to about 10 %, about 0.1 % to about 5 %, about 0.1 % to about 1 %, about 1 % to about 50 %, about 1 % to about 40 %, about 1 % to about 30 %, about 1 % to about 20 %. about 1 % to about 10 %, or about 1 % to about 5 % of deltamethrin by weight.

[0062] According to the present disclosure, the step of forming the amorphous form of deltamethrin can further include providing an inert carrier; depositing the solution of deltamethrin on the inert carrier; and allowing the solvent to evaporate to form the amorphous form of deltamethrin.

[0063] In some embodiments, the solution of deltamethrin is deposited on the inert carrier in the form of droplets or thin film.

[0064] Any suitable inert carrier can be used for deposition. Suitable inert carriers that can be used include, but are not limited to, glass, plastic, florisil (amorphous magnesium silicate), calcium carbonate, diatomaceous earth, kaolin clay, or amorphous silica.

[0065] According to the present disclosure, the step of forming the amorphous form of deltamethrin can further include providing an inert carrier; combining the solution of deltamethrin with the inert carrier to form a suspension; and allowing the solvent to evaporate to form the amorphous form of deltamethrin dispersed in the inert carrier.

[0066] In some embodiments, the inert carrier is a fumed silica.

[0067] Another aspect of the present disclosure relates to the amorphous form of deltamethrin prepared using any of the methods described above.Attorney Docket No. 243735.000472Compositions and Methods of Pest Control

[0068] In one aspect, the present invention provides a composition comprising the amorphous form of deltamethrin.

[0069] Compositions comprising amorphous form of deltamethrin can include a silica- based material. These silica-based materials can be amorphous with pores having a diameters of greater than 50 nm, about 2 nm to about 50 nm, or less than 2 nm.

[0070] In some embodiments, the amorphous silica-based material is porous and has pores having a diameters of less than 10 nm, less than 90 nm, less than 80 nm, less than 70 nm, less than 60 nm, less than 55 nm, less than 50 nm, less than 45 nm, less than 40 nm, less than 35 nm, less than 30 nm, less than 25 nm, less than 20 nm, less than 15 nm, less than 10 nm, less than 5 nm, less than 2 nm, less than 1.5 nm, less than 1 nm, less than 0.5 nm, or less than 0.1 nm.

[0071] Compositions comprising amorphous form of deltamethrin can include an inert carrier. Suitable inert carriers that can be used include, without limitation, chalk, calcium carbonate, glass, florisil (amorphous magnesium silicate), and amorphous silica.

[0072] Amorphous form of deltamethrin may be present in the composition in an amount of about 0.01 % to about 100 %, about 0.01 % to about 90 %, about 0.01 % to about 80 %, about 0.01 % to about 70 %, about 0.01 % to about 60 %, about 0.01 % to about 50 %, about 0.01 % to about 40 %, about 0.01 % to about 30 %, about 0.01 % to about 20 %, about 0.01 % to about 10 %, 0.1 % to about 100 %, about 0.1 % to about 90 %, about 0.1 % to about 80 %, about 0.1 % to about 70 %, about 0.1 % to about 60 %, about 0.1 % to about 50 %, about 0.1 % to about 40 %, about 0.1 % to about 30 %, about 0.1 % to about 20 %, about 0.1 % to about 10 %, 1 % to about 100 %, about 1 % to about 90 %, about 1 % to about 80 %, about 1 % to about 70 %, about 1 % to about 60 %, about 1 % to about 50 %, about 1 % to about 40 %, about 1 % to about 30 %, about 1 % to about 20 %, about 1 % to about 10 %, 10 % to about 100 %, about 10 % to about 90 %. about 10 % to about 80 %, about 10 % to about 70 %, about 10 % to about 60 %, about 10 % to about 50 %, about 10 % to about 40 %, about 10 % to about 30 %, about 10 % to about 20 %. about 0.05 % to about 30 %, about 0.1 % to about 30 %, about 0.5 % to about 30 %, about 1 % to about 30 %, about 5 % to about 30 %, about 0.05 % to about 25 %, about 0.05 % to about 20 %, about 0.1 % to about 20 %, about 0.5 % to about 20 %, about 1 % to about 20 %, about 5 % to about 20 %, about 0.05 % to about 15 %, about 0.05 % to about 10 %, or about 0.05 % to about 5 % by weight.Attorney Docket No. 243735.000472In some embodiments, the amorphous form of deltamethrin may be present in the composition in an amount of about 0.01 %, about 0.05 %, about 0.1 %, about 1 %, about 5 %, about 10 %, about 15 %. about 20 %, about 25 %, or about 30 % by weight.

[0073] Amorphous form of deltamethrin may contain some amount of the crystalline forms. In some embodiments the amorphous form of deltamethrin comprises no more than 40%, no more than 35%, no more than 30%. no more than 25%, no more than 20%, no more than 15%, no more than 10%, no more than 5%, or no more than 1% by weight of the crystalline forms.

[0074] Amorphous form of deltamethrin, and compositions comprising amorphous form of deltamethrin, may be used as agents to control pests, i.e. as pesticides and / or pest repellents.

[0075] Another aspect of the present disclosure relates to a method of controlling a pest. This method comprises applying to the pest or its locus the amorphous form of deltamethrin according to the present disclosure or the composition according to the present disclosure.

[0076] Yet another aspect of the present disclosure relates to a method of controlling a pest. This method comprises applying to a surface the amorphous form of deltamethrin according to the present disclosure or the composition according to the present disclosure.

[0077] Amorphous form of deltamethrin can be applied to any suitable surface. Suitable surfaces include, without limitation, glass, plastic, florisil (amorphous magnesium silicate), calcium carbonate, diatomaceous earth, kaolin clay, amorphous silica, zeolite, rice husk, zinc- layered hydroxide, silicon dioxide nanoparticles, methoxy-modified kaolinite, poly(hydroxybutyrate), poly(hydroxybutyrate-valerate), water hyacinth, ultrafine fibre cellulose, carboxymethyl chitosan, polyvinyl / alginate-montmorillonite composite, chitosan, bentonite alginate, lignin, chitosan copolymer with poly(lactide) and l,2-dipalmitoylsn-glycero-3- phosphoethanolamine, straw ash-based biochar and biosilica, layered zinc hydroxide nitrate, starch-silver nanoparticles, azidobenzaldehyde -carboxymethyl chitosan, silica nanocapsules, chitosan-polylactide graft copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), organobentonite, alginate nanoparticles, polylactic acid, sepiolite, mesoporous silica nanoparticles, nanobentonite, chitosan / tripolyphosphate, alginate / chitosan nanoparticles, N- (octadecanol-l-glycidyl ether)-O-sulphate chitosan, poly(e-caprolactone), and neem leaf powder- alginate.

[0078] In some embodiments, the surface to which the amorphous form of deltamethrin is applied is capable of being in contact with the pest.Attorney Docket No. 243735.000472

[0079] In some embodiments, the surface is suitable for forming amorphous deltamethrin by evaporation of deltamethrin solutions and droplets.

[0080] In some embodiments, the surface is suitable for forming amorphous deltamethrin by cooling of deltamethrin melts.

[0081] Some embodiments of using amorphous form of deltamethrin and compositions comprising amorphous form of deltamethrin cover a range of applications involving humans, nonhuman animals (including domesticated companion animals, livestock, and wildlife), and plants, including recreational, veterinary, agricultural, silvicultural, horticultural, and environmental applications. Other embodiments encompass disease control applications, such as controlling the spread of disease among animals and / or plants by controlling the vector for that disease. Exemplary vector-borne diseases of humans and non-human animals include, but are not limited to: Lyme disease; Dengue Fever; Yellow Fever; tick-borne babesiosis; tuleremia; powassan-like virus infection; tick-borne encephalitis; relapsing fever; malaria; encephalitis, such as the disease caused by the West Nile Virus, Eastern equine encephalitis, St. Louis encephalitis, Venezuelan equine encephalitis, Western equine encephalitis and Lacrosse encephalitis; Colorado Tick Fever; ehrlichiosis; Rocky Mountain Spotted Fever; and the Plague. Exemplary, non-limiting vector- borne diseases of plants are Dutch Elm disease, elm yellows phytoplasmas, and apply powdery mildew. Some disclosed pest control compositions may offer certain advantages, such as long term effect due to extended residual action, or high levels of safety and efficacy for veterinary, agricultural, and nuisance pest applications.

[0082] In any particular embodiment, a composition is administered in an effective amount. That amount may depend on a variety of factors, including (but not limited to) the area to be treated, the pest to be treated, its metabolism, its behavior (e.g., feeding habits, breeding, daily or seasonal activity cycles, development, nesting habits, etc.), and behavior of the host the pest infests.

[0083] In some embodiments, amorphous form of deltamethrin and / or a composition comprising amorphous form deltamethrin is applied once, while alternative embodiments employ plural applications of the same composition or different compounds or compositions. In particular embodiments, a composition is administered on an hourly, daily, weekly, monthly, quarterly, or annual basis. In any particular embodiment, the frequency of application may be regular or irregular, and the time elapsed between successive applications may be the same or different. ForAttorney Docket No. 243735.000472 example, and without limitation, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied every eight to twelve hours; four times per day at irregular intervals; every evening: four times per week; every other day; every other week; every other month; twice a month; every three months; every six months; every nine months; or annually. Alternatively, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied at least every week, at least every 2 weeks, at least every 3 weeks, at least every 4 weeks, at least every 2 months, at least every 3 months, at least every 4 months, at least every 5 months, at least every 6 months, at least every 7 months, at least every 8 months, at least every 9 months, at least every 10 months, at least every 11 months, or at least every 12 months. Like the amount of the compound or composition used in an embodiment, the frequency and number of applications of that compound or composition may depend on a variety of factors, including (but not limited to) the area to be treated, the pest to be treated, its metabolism, and its behavior (e.g., feeding habits, breeding, daily or seasonal activity cycles, development, nesting habits, etc.), and behavior of the host the pest infests.

[0084] Included are embodiments where amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin is applied to a particular human, nonhuman animal, plant, inanimate object, or environmental locus. Amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied directly to the pest, thus causing the pest to directly contact the composition, or may be applied to some locus or host that is expected to come into contact with the pest.

[0085] If applied to a locus, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied to the locus generally, such as by an aerosol or fumigant, or applied to a human, non-human animal, plant, or inanimate object within that locus. The size of a particular locus may vary considerably according to the method of application. For example, in area-wide applications, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin is dispersed over a locus of an environment, rather than intentionally directed at a particular pest, human, plant, or inanimate object. The locus of an area-wide application may be several hundred to thousands of acres, if amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin is used for agricultural spraying or to control the spread of a vector-borne disease; in structural applications, such as controlling pests within a home or restaurant, the locus may beAttorney Docket No. 243735.000472 several hundred several thousand square feet. However, in personal, veterinary, or horticultural applications, such as using topical pest repellent spray or ointment, or using a flea shampoo to bathe a pet. the locus may be limited to the area in the immediate vicinity of the animal, plant, or human host.

[0086] The size of the locus also may vary according to such factors as the intended application, presence of humans or non-human animals, level of human or non-human activity within the locus, type of formulation embodying amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin, and environmental factors, such as wind speed, humidity, temperature, and anticipated rainfall.

[0087] Methods of application include dusting, spraying, atomizing, immersing, coating, dressing, scattering, and pouring. A particular method of application may be selected in accordance with the intended objectives of and circumstances related to a particular use.

[0088] The frequency of application also may depend on the residual action of amorphous form of deltamethrin. “Residual action” refers to the length of time a compound or composition may exist in a particular environment and remain effective.

[0089] Amorphous form of deltamethrin and / or the compositions comprising amorphous form of deltamethrin described herein may be employed in formulations intended for use in public or private homes, residences, businesses, restaurants, hospitals, or other similar places of human activity. In such embodiments, the formulations may be used to kill or repel pests, such as mosquitoes, ants, spiders, or roaches, and may be applied directly to the pests or a locus the pest is expected to contact. For example, flea bomb or other fumigant containing amorphous form of deltamethrin as an active ingredient could be used within a home (such as applied within a particular room of a home to control fleas). As another example, a commercial spray containing amorphous form of deltamethrin as an active ingredient could be applied to the floors and other interior spaces of a restaurant to control cockroaches. In any such embodiment, the formulation may kill or repel a pest by directly contacting the pest, may be induced into the atmosphere of the locus, or may be applied to a human, non-human animal, plant, or inanimate object (e.g., the surface of a floor) expected to come into contact with the pest.

[0090] Certain embodiments employ formulations for use on humans, non-human animals, or plants for their protection. For example, certain formulations may be insecticides and / orAttorney Docket No. 243735.000472 acaricides sprayed onto the leaves of indoor plants for controlling aphids. Other formulations may include lotions or oils that repel pests.

[0091] Certain embodiments encompass protection of homes, buildings, or other structures from nuisance insects, such as termites, cockroaches, and / or ants. In such methods, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied to a locus within or outside the structure protected, such as spraying onto floors or inside cupboards, or soaking the ground outside the structure. Additionally, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be embedded within materials used to construct the structure, such as siding, wall studs, or beams.

[0092] Certain nontoxic compositions comprising amorphous form of deltamethrin may be used to control pests parasitic to a particular subject. The subject may be a human or non-human animal, including domesticated animals and livestock, such as dogs, cats, birds, reptiles, cattle, swine, sheep, fowl, and goats. In such embodiments, the composition may be provided to the human or non-human animal as a topical formulation (such as a cream, lotion, ointment, dip, shampoo, spotting liquid or spray), provided in the form of a wearable product (such as a collar, ear tag, or piece of clothing), or be embedded or incorporated into items commonly used by the animal (such as, household items, like bed nets, bedding, and / or furniture).

[0093] In certain embodiments, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin is applied in an area-wide manner, such as in protection of agricultural crops. In addition to agricultural applications, area-wide applications may include silvicultural, horticultural, or other forms of environmental pest management and control. In such embodiments, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied to plant foliage, such as spraying or dusting, or applied to the soil, such as drenching a particular locus with a liquid formulation or applying the active ingredient in solid form to a locus. In some instances, plants within or adjacent to the locus of application may absorb amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin through their roots. In other instances, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin will remain in the environment, such as when a composition is applied to a stagnant body of water to control mosquito larvae.Attorney Docket No. 243735.000472

[0094] Certain embodiments use amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin described herein for pest control in food production and storage. For example, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be used as an agricultural pesticide to control pests and protect grain, vegetable, herb, spice, or fruit crops. Amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin also may be used to control pests affecting other plants useful or important in agricultural or horticultural production, such as those plants or crops producing cotton, flax, tobacco, hemp, rubber, nuts, nursery stock, and ornamental plant parts.

[0095] Disclosed pest control compositions comprising amorphous form of deltamethrin may be used to protect plant products not only during growth and production, but also during storage or transport of such products. For example, some embodiments use compositions comprising amorphous form of deltamethrin to protect grain stored in silos, bales of cotton or tobacco stored in warehouses, or bushels of fruit being transported from an orchard.

[0096] Amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin also may be used to protect plant propagation material, such as seeds, fruit, tubers, or plant cuttings. The propagation material may be treated with the formulation before planting, such as soaking, coating, or dressing seeds prior to sowing. Compositions also may be applied to the soil where the propagation material will be planted, such as in-furrow application to protect seeds.

[0097] In such applications, amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be applied to provide a certain concentration of an active ingredient of the composition (i.e., amorphous form of deltamethrin) in the environment at a particular locus. That certain concentration may be measured, established, or determined according to the needs of the user. For example, when applying a composition to crops, the rate of application may depend on the nature of soil, the type of application (e.g., spraying crop foliage, burial in soil), the crop plant to be protected, the pest to be controlled, the prevailing climatic conditions, growing season, proximity to residential areas or protected environments, and other factors. As another example, when applying a pest control composition to stored or transported agricultural products, the rate of application may depend on the localized environment (e.g., storage within a warehouse, storage under a covered shelter, transport within a trailer), expectedAttorney Docket No. 243735.000472 duration of storage, product to be protected, the pest to be controlled, economic considerations, and other factors. In certain embodiments, the rates of concentration are in the range from about 0.01 to about 1000 ppm (parts -per-million), such as from about 0.1 to about 500 ppm of each active ingredient. In area-wide applications, rates of application per hectare may be from about 0.5 g / ha to 2000 g / ha, such as particularly from about 10 to 1000 g / ha, or from about 20 to 600 g / ha. As one non-limiting example, pesticides for the control of mosquito vectors of malaria may be used in area-wide applications at a rate of application of about 70 g / ha to about 1.15 kg / ha.

[0098] Use of pesticides is regulated in the United States by state and federal agencies, including the Environmental Protection Agency (EP A) and Food and Drug Administration (FDA). Relevant regulatory programs include the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FD&C Act). Certain articles of manufacture in accordance with these governmental and regulatory considerations may be made using disclosed pest control compositions comprising amorphous form of deltamethrin.

[0099] In such embodiments, a pest control composition comprising amorphous form of deltamethrin is embodied in an acceptable carrier and stored within a container capable of storing the composition for its shelf life. The container may be made of any suitable material such as plastic or other polymer, glass, metal, or the like. Printed instructions and / or a printed label indicating that the composition may be used to control pests are associated with this container. The instructions and / or label may provide information regarding the use of the composition for pesticidal purposes in accordance with the treatment method set forth herein and may be associated with the container by being adhered to the container, or accompanying the container in a package. The label may indicate the composition is approved for use as a pesticide, and the instructions may specify the pests intended to be controlled by the composition, the method and rate of application, dilution protocols, use precautions, and the like. Additionally, the container may include a feature or device for applying the composition to the pest population or locus to be treated. For example, if the article of manufacture includes a liquid composition, the feature or device may be a handoperated, motorized, or pressurized pressure-driven sprayer. In certain embodiments, the article of manufacture includes, packaged together, a vessel — such as a tube, barrel, bottle, bottle, or can — containing the composition and instructions for use of the composition for controlling a pest. In other embodiments, the article of manufacture is a device that includes the compound as part of the device, such as a surface coated with the compound, for example a bait trap or flea collar. InAttorney Docket No. 243735.000472 alternative embodiments, the article of manufacture includes packaging material containing the composition. Additionally, the packaging material may include a label indicating that the composition may be used for controlling a pest and, in particular embodiments, a pesticide for killing a pest. Examples of articles of manufacture include, but are not limited to, spray bottles of a ready-to-use formulation for household use; bottles, cans, or barrels containing concentrated formulations that may be diluted for area- wide applications; containers of concentrated formulations for use in industrial settings; flea collars or ear tags for domesticated companion animals and livestock; bottles or kits for shampooing, dipping, or cleaning domesticated companion animals or livestock; a bottle containing a formulation for human use as a shampoo or body wash; plastic tubules containing a topical oil for applying to a domesticated animal; and rodent bait boxes or host targeted bait boxes containing a pesticidal composition for killing ectoparisites infesting the host animal.[000100] Amorphous form of deltamethrin and / or a composition comprising amorphous form of deltamethrin may be effective to control a pest. Exemplary pests include, without limitation, the following pests described according to taxonomic designation and / or vernacular name.[000101] Order Acarina, including Acarus siro, Aceria sheldoni, Aculus schlechtendali, Amblyomma species, Argas species, Boophilus species, Brevipalpus species, Bryobia praetiosa, Calipitrimerus species, Chorioptes species, Dermanyssus gallinae, Eotetranychus carpini, Eriophyes species, Elycilomma species, Ixodes species, Olygonychus pratensis, Omithodoros species, Panonychus species, Phyllo coptrum oleivora, Polyphagotarsonemus lotus, Psoroptes species. Rhlpicephalus species, Rhizoglyphus species, Sarcoptes species. Tarsonemus species, Tetranychus species, Dermacentor species, Aponomma species, and Haemaphysalis species.[000102] Order Homoptera, including Aleurothrixus floccosus, Aleyrodes brassicae, Aonidiella species, Aphididae species, Aphis species, Aspidiotus species, Bemisia tabaci, Ceroplaster species, Chrysomphalus aonidium, Chrysomphalus dictyospermi, Coccus hesperidum, Empoasca species, Eriosoma lanigerum, Erylhroneura spp, Gascardia species, Laodelphax species, Lecanium corni, Lepidosaphes species, Macrosiphus species, Myzus species, Nephotettix species, Nilaparvata species, Paratoria species, Pemphigus species, Pianococcus species. Pseudaulacaspis species, Pseudococcus species, Psylia species, Pulvinaria aethiopica, Quadraspidiotus species, Rhopalosiphum species, Saissetia species, Scaphoideus species,Attorney Docket No. 243735.000472Schizaphis species, Sitobion species, Trialeurodes vaporariorum, Trioza erytreae, Unaspis citri; and Homalodisca coagulate.[000103] Order Hymenoptera, including Family Formicidae, Family Apidae, and Family Bombidae, such as Acromyrmex species, Atta species, Cephas species, Diprion species, Diprionidae species, Gilpinia polytoma, Hoplocampa species, Lasius species, Monomorium pharaonis, Neodiprion species. Solenopsis species, and Vespa species.[000104] Order Diptera, including Family Culicidae, Family Simulidae, Family Psychodidae, Family Ceratopogonidae, Family Sarcophagidae, Family Streblidae, and Family Nycteriblidae, such as Aedes species, Antherigona soccata, Bibio hortulanus, Calliphora erythrocephala, Ceratitis species, Chrysomyia species, Culex species, Culex p. pipiens, Cuterebra species. Dacus species, Drosophila species, Fannia species, Gastrophilus species, Glossina species, Hypoderma species, Hyppobosca species, Liriomyza species, Lucilia species, Melanagromyza species, Musca species, Oestrus species, Orseolia species, Oscinella frit, Pegomyia hyoscyami, Phorbia species, Rhagoletis pomonella, Sciara species. Stomoxys species, Tabanus species, Tannia species, and Tipula species.[000105] Order Siphonaptera, including Ceratophyllus species, Xenopsylla cheopis and other Xenopsylla species, Ctenocephalides species, Oropsylla species, Pulex species, Opisocrostis species, Echidnopaga species, and Diamanus species.[000106] Order Thysanura, including Lepisma saccharina.[000107] Order Lepidoptera; including Acleris species, Adoxophyes species, Aegeria species, Agrotis species, Alabama argulaceae, Amylois species, Anticarsia gemmatalis, Archips species, Argyrotaenia species, Autographa species, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo species, Choristoneura species, Clysia ambigueua, Cnaphalocrocis species, Cnephasia species, Cochylis species, Coleophora species, Crocidolomia binotaus, Cryptophlebia leucotreta, Cydia species, Diatraea species, Diparopsis castanea, Earias species, Ephestia species, Eucosma species, Eupoecilia ambiguena, Euproctis species, Euxoa species, Grapholita species, Hedya nubiferana, Heliolhis species, Hellula andalis, Hyphanlria cunea, Keiferia lycopersicella, Leucoptera scitella, Lithocllethis species, Lobesia botrana, Lymantria species, Lyonetia species, Malacosoma species, Mamestra brassicae, Manduca sexta, Operophtera species. Ostrinia nubilalis, Pammene species, Pandemis species, Panolis flammea, Pectinophora gossypieua, Phthorimaea operculeua, Pieris rapae, Pieris species, Plutella xylostella, PraysAttorney Docket No. 243735.000472 species, Scirpophaga species, Sesamia species, Sparganothis species, Spodoptera species, Synanthedon species, Thaumetopoea species, Tortrix species, Trichoplusia ni, and Yponomeuta species.[000108] Order Coleoptera, including Agriotes species, Anthonomus species, Atomaria linearis, Chaetocnema tibialis, Cosmopolites species, Curculio species, Dermestes species, Diabrotica species, Epilachna species. Eremnus species. Leptinotarsa decemlineata, Lissorhoptrus species, Melolontha species, Ory-.ae hihis species, Otiorhynchus species, Phlyctinus species, Popillia species, Psylliodes species, Rhiwpertha species, Scarabeidae, Sitophilus species, Sitotroga species, Tenebrio species, Tribolium species, and Trogoderma species.[000109] Order Orthoptera, including Blatta species, Blattella species, Gryllotalpa species, Eeucophaea maderae, Locusta species, Periplaneta species, and Schistocerca species.[000110] Order Isoptera, including Reticulitermes species.[000111] Order Psocoptera. including Liposcelis species.[000112] Order Anoplura, including Haematopinus species, Phthirus pubis and other Phthirus species, Linognathus species, Pediculus species, Pemphigus species, and Phylloxera species.[000113] Order Mallophaga, including Damalinea species and Trichodectes species.[000114] Order Thysanoptera, including Franklmiella species, Hercinothrips species, Taeniothrips species, Thrips palmi, Thrips tabaci and Scirtothrips aurantia.[000115] Order Heteroptera, including Cimex species, Distantiella theobroma, Dysdercus species. Euchistus species. Eurygaster species, Leptocorisa species. Nezara species, Piesma species, Rhodnius species, Sahlbergella singularis, Scotinophara species and Triatoma species.[000116] Order Scopriones, including Centruriodes species, Euscorpius species, Parabuthus species, and Vaejovis species.[000117] Order Araneae, including Latrodectus species, Loxosceles species, andBrachypelma species.[000118] Order Hemiptera, including Cimicidae species, Enicocephalidae species,Pentatomidae species, Gerridae species, Saldidae species, Belostomatidae species, and Nepidae species.[000119] Class Diplipoda (millipedes).Attorney Docket No. 243735.000472[000120] Class Chilopoda (centipedes).[000121] In particular embodiments, the pest is a member of the taxonomic order or subclass Acarina, including soft and hard ticks; Diptera, including Tabanidae, anophelines. and culecines; or Siphonoptera. In other particular embodiments, the pest belongs to a particular species, such as Ixodes scapularis (deer tick), Aedes aegypti (mosquito), Xenopsylla cheopis (rat flea), Homalodisca coagulata (glassy-winged sharpshooter), or Culex pipiens (mosquito).[000122] Other exemplary arthropod pests and / or parasites include fleas; mosquitoes; bees, yellow jackets, and wasps; cockroaches, including the American and German cockroach; termites; houseflies and silverleaf whiteflies; lacey-winged sharpshooters or glassy-winged sharpshooters; leaf hoppers, such as the grape or potato leafhoppers; cabbage looper (Lepidoptera); ants, such as the pharaoh ant, argentine ant, carpenter ant, and fire ant; stink or lygus bugs: leafminers; western flower thrips; aphids, such as melon aphids and black bean aphids; arachnids, such as spiders, ticks, and plant mites, including two-spotted spider mites, McDaniel mites, Pacific mites, and European mites.[000123] In one embodiment, the pest is an insect selected from adelgids, ants, aphids, annual bluegrass weevil (adults), azalea lace bugs, bagworms, bees, bed bugs, billbugs (adults), blue bottle flies, black turfgrass ataenius (adults), boxelder bugs, brown, marmorated stink bug, cankerworms, cardamom thrips, carpenter ants, carpenter bees, carpet beetles, centipedes, cecid flies, chinch bugs, clothes moths, clover mites, cluster flies, cockroaches, crickets, darkling beetles, dermestids, earwigs, elm leaf beetles, elm spanworms, European pine sawflies, fall webworms, firebrats, fleas (indoors & outdoors), flea beetles, flies, flesh flies, fruit flies, fungus gnats (sciarid flies), gnats, grasshoppers, green bottle flies, greenstriped mapleworms, ground beetles, gypsy moths (larvae), hide beetles, house flies , hornets, horseflies, imported willow leaf beetles, Indian meal moth, Japanese beetles, June beetles (adults), killer bees, leafhoppers, leaf-feeding caterpillars, leaf skeletonizers, leaf rollers, leather beetles, lice, loopers, maize weevils, mealybugs, midges, millipedes, mimosa webworms, mites, mole crickets, moths, mosquitoes, multicolored Asian lady beetles, orange-striped oakworms, pantry beetles, pantry moths, pillbugs, pine shoot beetles, pine tip moths, pinyon spindlegall midges, plant bugs, pharaoh's ants, phorid flies, redhumped caterpillar, red imported fire ants, red flour beetles, rice weevils, saw-toothed grain beetle, sawfly larvae, scale insects (crawlers), scorpions, silverfish, spiders, sod webworms, sowbugs, springtails,Attorney Docket No. 243735.000472 stable flies, pantry pests, stored product pests, tent caterpillars, ticks (indoors & outdoors), yellowjackets, yellownecked caterpillar, wasps, and webworms.EXAMPLES[000124] The following examples illustrate specific aspects of the instant description. The examples should not be construed as limiting, as the examples merely provide specific understanding and practice of the embodiments and their various aspects.Example 1. Materials and Methods[000125] Low-density poly(ethylene) (LDPE, melt index 25 g / 10 min (190 °C / 2.16 kg), p = 0.925 g / cm3) and high-density poly(ethylene) (HDPE, melt index 12 g / 10 min (190 °C / 2.16 kg), p = 0.952 g / cm3) were purchased from Sigma-Aldrich. Polymer batches were grounded in a Spex CertiPrep 6800 Freezer / Mill operated under liquid N2 and subsequently mixed in a weight ratio of 1:2. A solution of deltamethrin in several milliliters of dichloromethane was added dropwise to the ground polymer to achieve a predetermined ratio Iwt % relative to PE. Deltamethrin polymorphs had melting points in the range of 68-98 °C. The deltamethrin-PE mixtures were placed in a 5 mL glass syringe mounted on a New Era Pump Systems syringe pump and heated using a thermokinetic heater control unit and heating pads set to 170 °C. The melt was extruded through a hole of 1 mm in diameter at a rate of 1 mL / min and pulled to approximately 500 pm in diameter while spooled on a motorized rotor.[000126] Samples for scanning electron microscopy (SEM) were coated with 5-10 nm gold films, and crystal morphologies were recorded with a MERLIN field-emission scanning electron microscope (Carl Zeiss) using a standard Everhart-Thornley-type detector at an acceleration voltage of 5-10 kV.[000127] Cabosil-M5 (48 mg) (fumed silica 20-30 nm in diameter, about 50 g per 1 L) was weighed into 2 mL polypropylene (PP) Eppendorf test tube (ca. 1 mL by volume). 1 mL solution of deltamethrin (DM) in filtered acetone (0.2 pm PTFE syringe filter) that contained 4.8 mg of DM (ca. 9 %w) was added to the powder and mixed to form an organogel. The tube was left to dry at RT for 2 days protected by an aluminum foil. The obtained powder was gently crushed with a disposable PP spatula for measurements for ATR / Raman / XRD.Attomey Docket No. 243735.000472Example 2. Results and Discussion[000128] Deltamethrin (DM), a mainstay in the fight against vector-borne diseases, has shown great promise as an amorphous synthetic pyrethroid. DM can be obtained in its amorphous form as follows. When solutions of deltamethrin in organic solvent were deposited onto surfaces, such as glass, they formed films. The solvent in these films rapidly evaporated leaving behind hard amorphous droplets that were devoid of organic solvent, and the droplets remained amorphous for weeks. Crystallization of these droplets occurred through nucleation from mechanical stress followed by dendritic growth, which consumed the stable amorphous droplets. This may be easily visualized in polarized light micrographs (Figure 1) where a group of droplets are shown, and nucleation was initiated in the northeast comer. This clearly illustrated how the dendritic growth spreads, ultimately consuming the nearby droplets as crystals spread towards the opposite comer. In the absence of invading crystal nuclei, the droplets can remain stable for at least one month.[000129] Figure 1 shows droplets of amorphous deltamethrin, photographed between crossed polarizers, deposited from acetone after the acetone has completely evaporated. Crystalline material, on the other hand, will typically exhibit a property known as linear birefringence and will be bright between crossed polarizers. Exploiting this distinction, a method for tracking the amount of crystalline material and the rate of its formation have been established. Digital images are made up of individual pixels, these can then be separated based on brightness (Figures 2A-C). This separation of light and dark pixels over time accounts for the stability of the amorphous phase.[000130] Amorphous droplets of deltamethrin were also observed on the surface of poly(ethylene) long-lasting insecticidal nets (LLINs) where solid solutions of insecticide and plastic were extruded into fibers and woven into nets. This is another manifestation of the resistance of deltamethrin to crystallization, albeit by a process that does not involve rapid solvent drying. Phase separation of polymer and insecticide resulted in the migration of the insecticide to the surface. On the surface, the insecticide was first present in the molecular form. As more insecticide reached the surface, the molecules aggregated to form amorphous droplets. Amorphous droplets were solid agglomerations of molecules but differ from crystals by a lack of long-range order. In this case, these droplets typically adopted semi- spherical shapes (Figure 3) to minimize their free energy.[000131] Differential scanning calorimetry has been used also to characterize deltamethrin in commercial products. Figures 4A-4B show data collected from Control Solutions Inc.’s D-Attorney Docket No. 243735.000472Fense dust. Upon heating to 98°C, deltamethrin melting was indicated by the presence of an endotherm. Upon cooling below its melting point, deltamethrin became amorphous, as evidenced by the absence of an exotherm in the cooling cycle. A second cycle confirmed deltamethrin’ s amorphous nature by the disappearance of the endotherm. The stability in this formulation was hypothesized to stem from the separation of amorphous particles, stopping either dendritic growth or consumption by other sites where nucleation has occurred.[000132] The identity of the amorphous form has also been differentiated from the crystalline form by 4D-STEM (Figures 5A-5C). Analysis of amorphous nanoparticles clearly showed that these droplets were amorphous. Figure 5C shows that there are no diffraction spots, only isotropic diffuse halos. As previously mentioned, crystals have long-range order, which produces defined and regular planes that result in diffraction spots that would be observed in Figure 5C if the material was not amorphous. The distinct physical nature of the amorphous form also was confirmed by low-frequency Raman and infrared spectroscopy.[000133] The amorphous form may be differentiated from the various crystalline forms by Raman spectroscopy. The difference between the Raman spectra of Form I, the commercial form of deltamethrin, and Form II, the metastable form, as previously described by Yang et al., “A Deltamethrin Crystal Polymorph for More Effective Malaria Control,” PNAS 117:26633-26638 (2020), which is hereby incorporated by reference in its entirety, is shown in Figure 6. Unlike data X-ray diffraction, however, where the absence of signal was indicative of amorphous material, here, the amorphous form was well identified by its characteristically broad scattering (at 0-150 cm1), common for organic amorphous materials. Furthermore, the amorphous form has a unique set of peaks, distinct from those characteristic of the crystalline forms.[000134] ATR-IR measurements of a sample containing 9 %'NI'W DM on silica were recorded (Figure 10A). The samples were prepared in a 2 mL Eppendorf PP test tubes. The samples were left open to air at room temperature for 2days. ATR of the first sample was measured after 2days. ATR was measured again after 19 days and no significant change was observed (mainly at 692 cm ). The samples were compared to DM powder and DM on glass drop casted from acetone. Strong indication of a stable amorphous phase on silica was observed.[000135] ATR-IR measurements of a sample containing 10 %w / w DM on Florisil were recorded (Figure 10B). The samples were prepared in a 2 mL Eppendorf PP test tubes. The samples were left open to air at room temperature. ATR of the samples was measured after 9 hoursAttorney Docket No. 243735.000472 and after 2weeks. No significant change was observed. The samples were compared to DM powder and DM on glass drop casted from acetone. Peaks at the regions of 750 and 690 cm'1were shifted to the left relative to the crystalline DM. The position of the DM on Florisil peaks indicated that the compound was mainly crystalline with some undefined features.[000136] A comparative study of the lethality of the neat amorphous form as compared to the crystalline form makes a compelling argument for its use. The percentage of a fruit fly population knocked down after exposure to either the crystalline or the amorphous form is shown in Figure 7. The flies were exposed to the same dosage that is commonly found on bed nets. The amorphous form was effective after merely 5 minutes when nearly 80% of the population was knocked down. In contrast, the first signs of efficacy from the crystalline form were not seen until 15 minutes, when relatively meagre 10% was knocked down, whereas within the same time interval, all the flies exposed to the amorphous form have been knocked down. The crystalline form required four times longer than the amorphous form to knock down the entire population (60 minutes). A comparative ‘half’ dose of the amorphous form was also included to emphasize the speed and lethality of the amorphous form; even half the dose of the amorphous form was substantially more lethal than the full dose of the crystalline form.[000137] Insecticides are seldom used in their pure form, typically they are formulated with several ingredients, this can be advantageous, enhancing properties such as stability, longevity, and ease of use. The commercial product, D-Fense dust, examined in Figures 4A-4B, is an example of the inclusion of a carrier that has made the product easier to use, as the product is more easily dispersed than if it was pure insecticide. Hence, a potential formulation strategy for amorphous deltamethrin is essential for its eventual commercial success. Over 50 experiments were performed in which insecticides and different types of silica-based porous materials were combined and melted. In one example, deltamethrin was mixed with a porous material and heated to 135°C before being cooled down to 25°C. Upon melting, the deltamethrin entered these pores and later solidified. Figure 8A displays the data obtained from the first experiment, where an endotherm was observed at 98 °C indicating the occurrence of melting. However, no exotherm was detected during cooling, like what was observed in Figures 4A-4B. After being left at room temperature for 14 hours, the same DSC experiment was carried out. In the case of Figure 8B, no endotherm was detected during heating, which suggests that the sample remained amorphous and did not crystallize.Attorney Docket No. 243735.000472[000138] Heating a formulation to 100°C, as in the case of D-Fense Dust may be undesirable in some settings. However, dispersible materials can be made by slurries. By combining deltamethrin with Cabosil, a fumed silica material, a stable formulation containing amorphous deltamethrin can be created. Figure 9 displays the percentage of a fruit fly population knocked down when exposed to different insecticide formulations over time. The Cabosil formulation achieved a 50% knockdown of the population after 355 minutes. The heated D-Fense dust was slower, knocking down 50% after 378 minutes. Clearly, amorphous deltamethrin has utility and can be formulated.[000139] The amorphous form of deltamethrin has been generated. The characterization of the mechanism of reversion to the crystalline form is ongoing. State-of-the-art material chemistry analytical methods were employed to probe the physical arrangement of deltamethrin in the amorphous form to differentiate it for its crystalline forms. The markedly higher efficacy of the amorphous form over the crystalline form has been demonstrated. Without wishing to be bound by theory, it is postulated that, due to the relatively weak intermolecular interactions in the amorphous form and its higher free energy relative to crystalline forms, molecules are liberated faster than in the crystalline form, allowing more near immediate effect on target organisms. Ultimately, the amorphous form was comprehensively characterized, formulated, and its superiority over current commercial forms has been shown.* *[000140] As various changes can be made in the above-described subject matter without departing from the scope and spirit of the present invention, it is intended that all subject matter contained in the above description, or defined in the appended claims, be interpreted as descriptive and illustrative of the present invention. Many modifications and variations of the present invention are possible considering the above teachings. Accordingly, the present description is intended to embrace all such alternatives, modifications, and variances which fall within the scope of the appended claims.[000141] All patents, applications, publications, test methods, literature, and other materials cited herein are hereby incorporated by reference in their entirety as if physically present in this specification.

Claims

Attorney Docket No. 243735.000472WHAT TS CLAIMED IS:

1. An amorphous form of deltamethrin.

2. The amorphous form of claim 1 having a Raman spectrum substantially as shown in Figure 6.

3. The amorphous form of claim 1 having an ATIR spectrum substantially as shown in Figure 10 A.

4. The amorphous form of claim 1 whose 4D scanning transmission electron microscopy (4D STEM) images indicate that it is substantially free from diffraction spots.

5. The amorphous form of claim 1 having a broad feature at low frequency below 150 cm1in a Raman spectrum.

6. The amorphous form of any one of claims 1-5 which is substantially free of crystalline forms.

7. The amorphous form of any one of claims 1-6 which comprises no more than 40% crystalline forms.

8. The amorphous form of any one of claims 1-7 which comprises no more than 30% crystalline forms.

9. The amorphous form of any one of claims 1-8 which comprises no more than 20% crystalline forms.

10. The amorphous form of any one of claims 1-9 which comprises no more than 10% crystalline forms.Attorney Docket No. 243735.00047211. The amorphous form of any one of claims 1-10 which comprises no more than 5% crystalline forms.

12. A composition comprising the amorphous form of any one of claims 1-11.

13. The composition of claim 12 further comprising a silica-based material.

14. The composition of claim 13. wherein the silica-based material is amorphous.

15. The composition of claim 13, wherein the silica-based material is porous.

16. The composition of claim 15, wherein the silica-based material has pores having a diameters of less than 2 nm.

17. The composition of claim 15, wherein the silica-based material has pores having a diameters of from about 2 nm to about 50 nm.

18. The composition of claim 15, wherein the silica-based material has pores having a diameters of greater than 50 nm.

19. The composition of any one of claims 13-18, wherein the amorphous form of deltamethrin is dispersed in the silica-based material.

20. The composition of claim 12 further comprising an inert carrier.

21. The composition of claim 20, wherein the inert carrier is selected from chalk, calcium carbonate, glass, florisil (amorphous magnesium silicate), or silica.

22. The composition of any one of claims 12-21, wherein the amorphous form is present in the composition in an amount of about 0.01 % to about 30 % by weight.Attorney Docket No. 243735.00047223. The composition of claim 22, wherein the amorphous form is present in the composition in an amount of about 0.05 % to about 20 % by weight.

24. The composition of claim 22, wherein the amorphous form is present in the composition in an amount of about 0.5 % by weight.

25. A process for preparing the amorphous form of any of claims 1-11, comprising: providing a crystalline form of deltamethrin; dissolving the crystalline form of deltamethrin in a suitable solvent to form a solution of deltamethrin; and forming the amorphous form of deltamethrin by evaporating the solvent from the solution of deltamethrin.

26. The process of claim 25, wherein the solvent is an organic solvent.

27. The process of claim 26, wherein the organic solvent is selected from the group consisting of acetone, tetrahydrofuran, dichloromethane, pentane, hexane, diethyl ether, ethyl acetate, methanol, and chloroform or a combination thereof.

28. The process of any one of claims 25-27, wherein the solution of deltamethrin contains from about 0.05 % to about 20 % of deltamethrin by weight.

29. The process of claim 25, wherein the step of forming the amorphous form of deltamethrin further comprises: providing an inert carrier; depositing the solution of deltamethrin on the inert carrier; and allowing the solvent to evaporate to form the amorphous form of deltamethrin.

30. The process of claim 29, wherein the solution of deltamethrin is deposited on the inert carrier in the form of droplets or thin film.Attorney Docket No. 243735.00047231. The process of claim 29, wherein the inert carrier is glass, plastic, florisil (amorphous magnesium silicate), calcium carbonate, diatomaceous earth, kaolin clay, or silica.

32. The process of claim 29, wherein the step of forming the amorphous form of deltamethrin further comprises: providing an inert carrier; combining the solution of deltamethrin with the inert carrier to form a suspension; and allowing the solvent to evaporate to form the amorphous form of deltamethrin dispersed in the inert carrier.

33. The process of claim 32, wherein the inert carrier is a fumed silica.

34. An amorphous form of deltamethrin prepared according to the process of any one of claims 25-33.

35. A method of controlling a pest comprising: applying to the pest or its locus the amorphous form of any of claims 1-11 or the composition of claims 12-24.

36. A method of controlling a pest comprising: applying to a surface the amorphous form of any of claims 1-11 or the composition of claims 12-24.

37. The method of claim 36, wherein the surface is capable of being in contact with the pest.

38. The method of claims 36 or 37, wherein the surface is suitable for forming amorphous deltamethrin by evaporation of deltamethrin solutions and droplets.

39. The method of claims 36 or 37, wherein the surface is suitable for forming amorphous deltamethrin by cooling of deltamethrin melts.Attorney Docket No. 243735.00047240. The method of any one of claims 36-39, wherein the surface is glass, plastic, florisil (amorphous magnesium silicate), calcium carbonate, diatomaceous earth, kaolin clay, or silica.

41. The method of any one of claims 36-39, wherein the surface is selected from the group consisting of zeolite, rice husk, zinc-layered hydroxide, silicon dioxide nanoparticles, methoxymodified kaolinite, poly(hydroxybutyrate), poly(hydroxybutyrate-valerate), water hyacinth, ultrafine fibre cellulose, carboxymethyl chitosan, polyvinyl / alginate-montmorillonite composite, chitosan, bentonite alginate, lignin, chitosan copolymer with poly (lactide) and 1,2-dipalmitoylsn- glycero-3-phosphoethanolamine, straw ash-based biochar and biosilica, layered zinc hydroxide nitrate, starch-silver nanoparticles, azidobenzaldehyde-carboxymethyl chitosan, silica nanocapsules, chitosan-polylactide graft copolymer, poly(3-hydroxybutyrate-co-3- hydroxy valerate), organobentonite, alginate nanoparticles, polylactic acid, sepiolite, mesoporous silica nanoparticles, nanobentonite, chitosan / tripolyphosphate, alginate / chitosan nanoparticles, N-(octadecanol-l-glycidyl ether)-O-sulphate chitosan, poly(c-caprolactone), and neem leaf powder-alginate.

42. The method of any one of claims 35-41, wherein the pest is an insect.

43. The method of claim 42, wherein the insect is selected from adelgids, ants, aphids, annual bluegrass weevil (adults), azalea lace bugs, bagworms, bees, bed bugs, billbugs (adults), blue bottle flies, black turfgrass ataenius (adults), boxelder bugs, brown, marmorated stink bug, cankerworms, cardamom thrips, carpenter ants, carpenter bees, carpet beetles, centipedes, cecid flies, chinch bugs, clothes moths, clover mites, cluster flies, cockroaches, crickets, darkling beetles, dermestids, earwigs, elm leaf beetles, elm spanworms, European pine sawflies, fall webworms, firebrats, fleas (indoors & outdoors), flea beetles, flies, flesh flies, fruit flies, fungus gnats (sciarid flies), gnats, grasshoppers, green bottle flies, greenstriped mapleworms, ground beetles, gypsy moths (larvae), hide beetles, house flies , hornets, horseflies, imported willow leaf beetles, Indian meal moth, Japanese beetles, June beetles (adults), killer bees, leafhoppers, leaffeeding caterpillars, leaf skeletonizers, leaf rollers, leather beetles, lice, loopers, maize weevils, mealybugs, midges, millipedes, mimosa webworms, mites, mole crickets, moths, mosquitoes, multicolored Asian lady beetles, orange- striped oakworms, pantry beetles, pantry moths,Attorney Docket No. 243735.000472 pillbugs, pine shoot beetles, pine tip moths, pinyon spindlegall midges, plant bugs, pharaoh's ants, phorid flies, redhumped caterpillar, red imported fire ants, red flour beetles, rice weevils, saw-toothed grain beetle, sawfly larvae, scale insects (crawlers), scorpions, silverfish, spiders, sod webworms, sowbugs, springtails, stable flies, pantry pests, stored product pests, tent caterpillars, ticks (indoors & outdoors), yellowjackets, yellownecked caterpillar, wasps, and webworms.

44. The method of any one of claims 35-43, wherein said applying is performed at least every 3 weeks.

45. The method of any one of claims 35-43, wherein said applying is performed at least every 3 months.

46. The method of any one of claims 35-43. wherein said applying is performed at least every 6 months.

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