GB2621401A

GB2621401A - A crystalline form of spinosad, a process for its preparation and use of the same

Info

Publication number: GB2621401A
Application number: GB2211803.8A
Authority: GB
Inventors: Timothy Bristow James
Original assignee: Rotam Agrochem International Co Ltd
Current assignee: Rotam Agrochem International Co Ltd
Priority date: 2022-08-12
Filing date: 2022-08-12
Publication date: 2024-02-14
Also published as: FR3138778A1; GB202211803D0; CN117586328A; ES2963729A2

Abstract

Crystalline modification I of Spinosad characterised by X-ray powder diffraction, IR spectrometry and differential scanning calorimetry. Also claimed is a method for preparing the crystalline modification of Spinosad, the method comprising the steps of: i) dissolving Spinosad in a solvent system to form a Spinosad solution; ii) precipitating the crystalline modification of Spinosad from the Spinosad solution; and iii) isolating the precipitated crystalline modification of Spinosad. Preferably, the solvent system comprises a carbonate, e.g. ethylene carbonate and/or dimethyl carbonate. The crystallisation may be promoted by adding seed crystals of the desired crystalline modification and/or by cooling the solvent system. Further claimed is a composition comprising the aforementioned crystalline form of spinosad and at least one auxiliary (e.g. surfactant, diluent, inert filler). Such a composition may be a suspension concentrate. The crystalline modification of spinosad may be used for the control of insects and mites.

Description

A CRYSTALLINE FORM OF SP INOSAD, A PROCESS FOR ITS PREPARATION AND USE OF THE SAME The present invention relates to a crystalline form of Spinosad, to its preparation processes and to its use in agrochemical preparations.

Spinosad is a broad spectrum insecticide and miticide. It was developed and first introduced as a commercial product by DOW in 1995. Spinosad is entirely derived through fermentation of the soil bacteria Saccharopolyspora spinosa. Spinosad is active through a novel mode of action, primarily targeting binding sites on nicotinic acetylcholine receptors (nAChRs) of the insect nervous system.

Spinosad is used for the protection of a wide variety of commercial crops, such as maize, soybean, cotton, various fruits, various vegetables, such as potato, rice and turf, in particular for the control of bollworm, tobacco budworm, armyworms and loopers. Spinosad exhibits a low toxicity and an environmental profile similar to that of most biological insecticides. As a result Spinosad is suitable for Integrated Pest (IPM) and Insecticide Resistance Management (IRM) programs.

Spinosad is a combination of two spinosoids having the molecular formulae Cal H65NOici (Spinosyn A) and C42H67NO10 (Spinosyn D), and the chemical names (2R, 3aS, 5aR, 5bS, 9S, 13S, 14R, 16aS, 16bR)-2-(6-deoxy-2,3,4-tri-O-methyl-a- L-mannopyranosyloxy)-13-(4-dimethylamino-2,3,4,6-tetradeoxy-p-D- erythropyranosyloxy)-9-ethy1-2,3,3a,5a,5b, 6,7,9,10,11,12, 13,14,15, 16a,16bhexadecahydro-14-methyl-1H-as-indaceno[3,2-d]oxacyclododecine-7, 15-dione and (25,3aR,5aS,5bS,9S, 13S, 14R,16aS, 16 b5)-2-(6-deoxy-2,3,4-tri-O-m ethyl-a-L- mannopyranosyloxy)-13-(4-dimethy lamino-2, 3,4, 6-tetradeoxy-p-D- erythropyranosyloxy)-9-ethyl-2,3,3a,5a,5b,6,7,9,10,11,12, 13, 14, 15,16a,16b- hexadecahydro-4, 14-dim ethy1-1H-as-indaceno[3,2-d] oxacyclododecine-7,15-dione. Spinosad typically contains Spinosyn A and Spinosyn D present in the proportions from 50 to 95% by weight Spinosyn A and 5 to 50% by weight Spinosyn D. Commercial formulations of Spinosad typically employ Spinosyn A and Spinosyn D in a weight ratio of 85:15.

Spinosad has the chemical structures: wherein Spinosad A: R=H and Spinosad D: R=CH3.

The commercially available Spinosad is typically manufactured by the process described in EP 1 062 345 and is present in an amorphous state. It has been found that Spinosad in an amorphous state exhibits a high tendency to aggregate when formulated, especially during prolonged periods of storage. As a result, commercially available Spinosad is not well suited for being used in an economical formulation. There is a need to provide a technique for improving the formulation of Spinosad, especially to improve its storage stability.

There has now been found a new and stable crystalline form of Spinosad, which exhibits significantly improved properties. In particular, the new crystalline form of Spinosad exhibits an increased stability and reduced tendency to aggregate when formulated, allowing formulations to be stored for prolonged periods of time without degradation and loss of efficacy.

In a first aspect, the present invention provides a crystalline modification of Spinosad, hereinafter termed "crystalline modification I", exhibiting at least three of the following reflexes, in any combination, as 28±0.20 degree in an X-ray powder diffractogram (X-RPD) recorded using Cu-Ka radiation at 25°C: 20 = 7.374 ± 0.20 (1) 28 = 9.565 ± 0.20 (2) 28 = 11.550 ± 0.20 (3) 28 = 11.823 ± 020 (4) = 12.328 ± 0.20 (5) = 15.433 ± 0.20 (6) 20 = 15.822 ± 0.20 (7) = 16.851 ± 0.20 (8) = 17.482 ± 0.20 (9) = 18.533 ± 0.20 (10) 28 = 19.993 ± 0.20 (11) 28 = 21.105 ± 0.20 (12) 28 = 23.078 ± 0.20 (13) = 24.195 ± 0.20 (14) The crystalline modification I of Spinosad exhibits 3 of the aforementioned reflexes, preferably at least 4, more preferably at least 5, more preferably still at least 6, still more preferably at least 7, especially at least 8 of the aforementioned 5 reflexes In a preferred embodiment, the crystalline modification I of Spinosad exhibits at least 3, preferably at least 4, more preferably at least 5, more preferably still at least 6, still more preferably at least 7, especially at least 8 or all of the following reflexes, in any combination, as 29±0.20 degree in an X-ray powder diffractogram recorded using Cu-Ka radiation at 25°C: = 9.565 ± 0.20 (2) = 11.550 ± 0.20 (3) 28 = 11.823 ± 0.20 (4) 28 = 15.433 ± 0.20 (6) 28 = 15.822 ± 0.20 (7) 28 = 16.851 ± 0.20 (8) 28 = 17.482 ± 0.20 (9) 28 = 19.993 ± 0.20 (11) 28 = 21.105 ± 0.20 (12) 20 = 24.195 ± 0.20 (14) In one preferred embodiment, the crystalline modification I of Spinosad exhibits an X-ray powder diffractogram substantially as shown in Figure 1.

In a second aspect, the present invention provides a crystalline modification I of Spinosad exhibiting an infrared (IR) spectrum with characteristic 5 functional group vibration peaks at wavenumbers (cm-1, ±0.2%) of 2930.01, 2870.55, 2824.68, 1705.98 and 1659.87cm-1.

In one preferred embodiment, the crystalline modification I of Spinosad exhibits an infrared (IR) spectrum substantially as shown in Figure 2.

In one preferred embodiment, the crystalline modification I of Spinosad exhibits an X-ray powder diffractogram according to the first aspect of the present invention and an infrared (IR) spectrum according to the second aspect of the present invention.

In a third aspect, the present invention provides a crystalline modification I of Spinosad exhibiting a Differential Scanning Calorimetry (DSC) profile with an endothermic melting peak with onset at 112.3°C and a peak maximum at 126.1°C, further optionally with a melting enthalpy of 24.56J/g.

In one preferred embodiment, the crystalline modification I of Spinosad exhibits a Differential Scanning Calorimetry (DSC) profile substantially as shown in Figure 3.

In one preferred embodiment, the crystalline modification I of Spinosad exhibits an X-ray powder diffractogram according to the first aspect of the present invention, and/or infrared (IR) spectrum according to the second aspect of the present invention and a Differential Scanning (DSC) profile according to the third aspect of the present invention.

In one preferred embodiment, the crystalline modification I of Spinosad is characterized by a powder X-ray diffraction pattern substantially as shown in Figure 1, and/or an IR spectrum substantially as shown in Figure 2, and/or a Differential Scanning Calorimetry (DSC) thermogram as substantially shown in Figure 3.

It has been found that the crystalline modification I of Spinosad exhibits a significant improvement in its storage stability compared with known forms of Spinosad, which in turn significantly reduces the aggregation problem encountered with current commercially available formulations. In addition, it has been found that the crystalline modification I of Spinosad exhibits a high degree of stability when formulated compared to amorphous Spinosad prepared in accordance with the disclosure of EP 1 062 345. In particular, the crystalline modification exhibits a very low tendency to aggregate when formulated. This in turn allows the preparation of commercial formulations, such as suspension concentrates (SC) having improved properties, including increased stability and improved efficacy. Further, by virtue of having good stability properties, the crystalline modification I of Spinosad provides an advantageously long storage period for formulations.

Methods for preparing amorphous Spinosad are well known in the art.

Amorphous Spinosad is manufactured and available on a commercial scale. A particularly suitable method for preparing amorphous Spinosad is described in EP 1 062 345.

In a fourth aspect, the present invention provides a method for preparing a crystalline modification I of Spinosad, the method comprising the steps of: dissolving Spinosad in a solvent system to form a Spinosad solution; ii) precipitating the crystalline modification I of Spinosad from the Spinosad solution; and iii) isolating the precipitated crystalline modification I of Spinosad.

The present invention also provides a crystalline modification I of Spinosad obtainable by the aforementioned process, more preferably a process substantially as described in either of Examples 2 or 3.

In step i) of the method, a solution of Spinosad in a solvent system is prepared from a Spinosad starting material. Any suitable form of Spinosad may be used as the starting material. In one preferred embodiment, the Spinosad starting material in step i) is amorphous Spinosad.

A solution of Spinosad is formed by dissolving Spinosad in a solvent system. The solvent system may consist of a single solvent or comprise a mixture of two or more solvents.

The solvent system may be formed from any suitable solvent that allows the crystalline modification 1 of Spinosad to precipitate from solution. Suitable solvents may be selected from halogenated hydrocarbons, for example, trifluoro methyl benzene, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene and trichlorobenzene; ethers, for example, ethyl propyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dimethyl glycol, diphenyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, isopropyl ethyl ether, methyl tertbutyl ether, methyltetrahydrofuran, dioxane, dichlorodiethyl ether, polyethers of ethylene oxide and/or propylene oxide; nitrated hydrocarbons, for example nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene and onitrotoluene; aliphatic, cycloaliphatic or aromatic hydrocarbons, for example pentane, octane, such as n-octane, nonane, ethyl benzene, mesitylene, cymene, hydrocarbon fractions having a boiling range of from 70°C to 190°C, ligroin, and benzene; carbonates, for example dimethyl carbonate, diethyl carbonate, dibutyl carbonate and ethylene carbonate; and mixtures thereof.

Preferably, the solvent system comprises one or more carbonates. Preferred carbonates are ethylene carbonate, dimethyl carbonate and mixtures thereof.

The dissolution of Spinosad in step i) may be carried out at any suitable 5 temperature. For example, the dissolution may be conducted at ambient or room temperature, or at an elevated temperature. If an elevated temperature is employed in step i), the temperature is preferably below the boiling point of the solvent system.

Preferably, dissolution of Spinosad in step i) is conducted at a minimum temperature of 20°C, more preferably at least 30°C, still more preferably at least 40°C. Depending upon the solvent system being used, the temperature may be up to 90°C, preferably up to 85°C, more preferably up to 80°C, still more preferably up to 75°C. Suitable temperatures are a temperature of from 20 to 90°C, preferably from 30 to 90°C, more preferably from 30 to 80°C, even more preferably from 40 to 70°C, more preferably still to a temperature of from 40 to 60°C.

According to one preferred embodiment, the crystalline modification I of Spinosad is prepared by dissolving Spinosad, preferably amorphous Spinosad, in a solvent system comprising a solvent or a solvent mixture by heating from ambient temperature to a temperature at or below the reflux temperature of the solvent system. In one embodiment, the Spinosad solution is prepared at the reflux temperature of the solvent system.

The dissolution of Spinosad in step i) may be carried out with agitation, preferably with stirring and/or shaking.

In step ii) of the method, Spinosad present in solution in the solvent system is precipitated in the form of the crystalline modification I. Any suitable technique may be used to precipitate Spinosad from solution. Suitable techniques include one or a combination of cooling the solution, removing solvent to concentrate the solution, adding an agent to reduce the solubility of Spinosad in the solvent system, and the addition of seed crystals to the solution.

In one preferred embodiment, the Spinsad solution prepared in step i) is cooled to ambient temperature or a temperature from about 0 to 30°C to crystallize the desired crystalline form from the solvent system. In one preferred embodiment, the solution is cooled to a temperature of from 20 to 25°C.

Cooling the solution to effect precipitation may be performed at any suitable rate. For example, the solution formed in step i) may be cooled at a rate of from 0.5 to 3°C per minute, preferably from 1 to 2.5°C per minute, for example about 2°C per minute.

The crystalline modification I of Spinosad may be crystallized out of the Spinosad solution by concentrating the solution by removing the solvent system to a volume whereby precipitation of Spinosad occurs. Techniques for removing the solvent system from the solution are known in the art and include evaporating the solvent system, for example under the action of an applied reduced pressure or vacuum In one embodiment, crystallization of crystalline modification I of Spinosad is obtained by adding seed crystals to the solution prepared in step i) of the method. The seed crystals are preferably crystals of Spinosad, more preferably crystals of the crystalline modification I of Spinosad.

The seed crystal amount added to the concentrated Spinosad solution is typically in the range of 0.001% to 10% by weight, more particularly in the range of 0.005% to 0.5% by weight, based on the weight of Spinosad used for the preparation of concentrated solution in step (i). The seed crystals may be added to the solution at any suitable temperature and are preferably added to the concentrated solution at a temperature below the boiling point of the solvent system being employed.

In step iii) of the method, the precipitated crystalline modification I of Spinosad is isolated from the solution. Any suitable technique for separating the crystalline material from the solution may be employed. Suitable techniques include one or more of filtration, centrifugation and decantation.

The crystalline modification I of Spinosad isolated from the solution may be used directly. More preferably, the isolated crystalline solid is washed with solvent one or more times. Preferably, the solvent employed in the washing stage is one or more of the components of the solvent system employed for the preparation of the concentrated Spinosad solution in step i), as described hereinbefore. More preferably, the solvent system used to was the isolated crystalline solid has the same composition as the solvent system used in step i) of the method.

The washing operation may be carried out at any suitable temperature that avoids a significant loss of crystalline material being washed, preferably a temperature from 0°C to ambient or room temperature.

In one embodiment, the crystalline modification I of Spinosad isolated in step iii) is dissolved again in a solvent system and recrystallized by repeating steps i) to Hi) of the method.

The washings and/or the solvent remaining after step Hi) may be concentrated to obtain solid Spinosad, which may then be recycled for use in step i) of the method.

The crystalline modification I of Spinosad employed in the present invention and/or obtained by the method of the present invention preferably has a crystalline modification I of Spinosad content of at least 05% by weight, more preferably at least 98% by weight.

As discussed above, Spinosad is active as an insecticide and acaricide. The crystalline modification I of Spinosad exhibits this activity. Accordingly, in a further aspect, the present invention provides an insecticidal/acaricidal composition comprising the crystalline modification I of Spinosad and at least one auxiliary.

Spinosad may be present in the composition in any suitable amount, depending upon the type of formulation and/or the intended end use. Spinosad may be present in the composition from 1% by weight, preferably from 5%, more preferably from 10%, still more preferably from 15%, more preferably still from 20%, especially from 25%, more especially from 30% by weight. Spinosad may be present in the composition in an amount up to 90% by weight, preferably up to 80%, more preferably up to 75%, still more preferably up to 70%, more preferably still up to 65%, especially up to 60%, more especially up to 55% by weight. Spinosad may be present in the composition in an amount of from 5 to 90% by weight, preferably from 10 to 80%, more preferably from 20 to 70%, still more preferably from 25 to 65%, more preferably still from 30 to 60%, especially from 40 to 50% by weight. In one preferred embodiment, Spinosad is present in the composition in an amount of from 45 to 50% by weight, especially from 47 to 49%, more especially about 48% by weight.

The use of Spinosad as an insecticide and acaricide is well known in the art and Spinosad is used on a commercial scale. The crystalline modification I of Spinosad is also active in controlling insects and mites. As a result, the techniques of formulating and applying Spinosad known in the art for amorphous Spinosad, for example as disclosed in the prior art documents discussed hereinbefore, can also be applied in an analogous manner to Spinosad in the form of the crystalline modification I of the present invention.

Accordingly, the present invention furthermore provides processes for preparing compositions for controlling insects and mites using the crystalline modification I of Spinosad.

The crystalline modification I of Spinosad may be employed in any suitable type of formulation. For example, the insecticidal/acaricidal composition may be in the form of suspension concentrates (SC), oil-based suspension concentrates (OD), water-soluble granules (SG), dispersible concentrates (DC), emulsifiable concentrates (EC), emulsion seed dressings, suspension seed dressings, granules (GR), microgranules (MG), suspoemulsions (SE) and water-dispersible granules (WG). The crystalline modification I of Spinosad can be included in these formulations in a known manner using suitable auxiliaries as known in the art.

In a preferred embodiment, the composition of the present invention is in the 10 form of a suspension concentrate (SC).

The aforementioned formulations may prepared in a known manner by mixing the crystalline modification I of Spinosad with formulation components customary in the art, for example, one or more surfactants, liquid diluents, solid diluents, wetting agents, dispersants, thickening agents, anti-foaming agents, anti-freezing agents, preservatives, antioxidants, solid adherents, inert fillers and other formulation ingredients.

Surfactants can be an emulsifier, dispersant or wetting agent of ionic or nonionic type. Examples which may be used include, but are not limited to, salts of polyacrylic acids, salts of lignosulphonic acid, salts of phenylsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols, especially alkylphenols, sulphosuccinic ester salts, taurine derivatives, especially alkyltaurates, or phosphoric esters of polyethoxylated phenols or alcohols.

Liquid diluents include, but are not limited to, water, N,N-dimethylmamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffins, alkylbenzenes, alkyl naphthalenes, glycerine, triacetine, oils of olive, castor, linseed, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, ketones such as 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as hexyl acetate, heptyl acetate and octyl acetate, and alcohols such cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol.

Solid diluents can be water-soluble or water-insoluble. Water-soluble solid diluents include, but are not limited to, salts such as alkali metal phosphates, for example sodium dihydrogen phosphate, alkaline earth phosphates, sulfates of sodium, potassium, magnesium and zinc, sodium and potassium chloride, sodium acetate, sodium carbonate and sodium benzoate, and sugars and sugar derivatives such as sorbitol, lactose, sucrose and mannitol. Examples of water-insoluble solid diluents include, but are not limited to clays, synthetic and diatomaceous silicas, calcium and magnesium silicates, titanium dioxide, aluminum, calcium and zinc oxide.

Wetting agents include, but are not limited to, alkyl sulfosuccinates, laureates, alkyl sulfates, phosphate esters, acetylenic diols, ethoxyfluornated alcohols, ethoxylated silicones, alkyl phenol ethyoxylates, benzene sulfonates, alkyl-substituted benzene sulfonates, alkyl a-olefin sulfonates, naphthalene sulfonates, alkyl-substituted napthalene sulfonates, condensates of naphthalene sulfonates and alkyl-substituted naphthalene sulfonates with formaldehyde, and alcohol ethoxylates. Polyalkylene glycol ether is particularly useful for the compositions of the present invention.

Dispersing agents include, but are not limited to, sodium; calcium and ammonium salts of ligninsulfonates, which may be optionally polyethoxylated; sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenolsulfonic acid; and naphthalene sulfonate-formaldehyde condensates. Of note are compositions comprising up to 10% by weight of dispersant. Ligninsulfonates, such as sodium ligninsulfonates, are particularly useful for the composition of the present invention. Sodium alkyl naphthalene sulfonate-formaldehyde condensate is particularly useful for the compositions of the present invention.

Thickening agents include, but are not limited to, guar gum, pectin, casein, carrageenan, xanthan gum, alginates, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. Synthetic thickeners include derivatives of the former categories, and also polyvinyl alcohols, polyacrylamides, polyvinylpyrrolidones, various polyethers, their copolymers as well as polyacrylic acids and their salts. Xanthan gum is particularly useful for the compositions of the present invention.

Anti-foaming agents include all substances which can normally be used for this purpose in agrochemical compositions. Suitable anti-foam agents are known in the art and are available commercially. Particularly preferred antifoam agents are mixtures of polydimethylsiloxanes and perfluroalkylphosphonic acids, such as the silicone antifoaming agents available from GE or Compton.

Preservatives include all substances which can normally be used for this purpose in agrochemical compositions of this type and again are well known in the art. Suitable examples that may be mentioned include PREVENTOLO (from Bayer AG) and PROXELO (from Bayer AG).

Antioxidants include all substances which can normally be used for this purpose in agrochemical compositions, as is known in the art. Preference is given to butylated hydroxytoluene Solid adherents include organic adhesives, including tackifiers, such as celluloses or substituted celluloses, natural and synthetic polymers in the form of powders, granules, or lattices, and inorganic adhesives such as gypsum, silica or 25 cement.

Inert fillers include but are not limited to, natural ground minerals, such as kaolins, alum inas, talc, chalk, quartz, attapulgite, montmorillonite, and diatomaceous earth, or synthetic ground minerals, such as highly dispersed silicic acid, aluminum oxide, silicates, and calcium phosphates and calcium hydrogen phosphates. Suitable inert fillers for granules include, for example, crushed and fractionated natural minerals, such as calcite, marble, pumice, sepiolite, and dolomite, or synthetic granules of inorganic and organic ground materials, as well as granules of organic materials, such as sawdust, coconut husks, corn cobs, and tobacco stalks.

Suitable antifreezing agents are liquid polyols, for example ethylene glycol, propylene glycol or glycerol. The amount of antifreeze agents is generally from about 1% to about 20% by weight, in particular from about 5 to about 10% by weight, based on the total weight of the composition.

Biocides may also be included in the compositions of the present invention. Suitable biocides are those based on isothiazolones, for example Proxel® from ICI or Acticide® RS from Thor Chem ie or Kathon® MK from Rohm & Haas. The amount of biocides is typically from 0.05% to 0.5% by weight, based on the total weight of composition.

Other formulation ingredients can also be used in the present invention, such as dyes, antifoaming agents, drying agents, and the like. These ingredients and their use are known to one skilled in the art and are commercially available.

As noted above, the crystalline modification I of Spinosad of the present invention is active in the control of insects and mites.

Accordingly, in a further aspect, the present invention provides the use of a crystalline modification I of Spinosad as hereinbefore described or a composition comprising a crystalline modification I of Spinosad as hereinbefore described in the control of insects and mites.

Still further, the present invention provides a method of controlling infestations of insects and/or mites at a locus, the method comprising applying to the locus a crystalline modification I of Spinosad as hereinbefore described or a composition comprising a crystalline modification I of Spinosad as hereinbefore described.

The crystalline modification I of Spinosad may be used alone or in combination with one or more other active compounds, such as one or more insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, 10 fungicides, growth-regulating substances, herbicides, safeners, fertilizers, semiochemicals, or agents for improving plant properties. The crystalline modification I of Spinosad may be combined with one or more other active compounds in a single composition, as hereinbefore described. Alternatively, the crystalline modification I of Spinosad may be employed in combination with one or more other active compounds using two or more compositions.

The crystalline modification I of Spinosad may be employed in combination with one or more inhibitors which act to reduce degradation of the active compounds after their application in the environment of the plant, on the surface of plant parts or in plant tissues.

Spinosad, which is an active ingredient of the insecticidal composition of the present invention, is effective against a range of insects The crystalline modification I of Spinosad may be used to control this range of insects, such as Lepidoptera including Southern army worm, codling moth, cutworms, clothes moths. Indian meal moth, leaf rollers, corn eel-worm, cotton bollworm (also called Tomato fruit worm), European corn borer, imported cabbageworm, cabbage looper, pink bollworm, American bolioworm, tomato hornworrn, bagworms, Eastern tent caterpillar, sod webworm, diamondback moth, tomato pinworm, grape berry moth, cotton leafworm, beet armyworm, and fall armyworm; members of the order Hornoptera, including cotton aphid leafhoppers, plant hoppers, pear psylla, scale insects, ^Aihiteflies, and spittle bugs; and members of the insect order Diptera including house flies, stable flies, blow flies and mosquitoes; mites; and ants The compounds and formulations described herein can also be used to treat members of the order Thysanoptera, including melon thrips and Western flower thrips; members of the order Coleopte,ra, including Colorado potato beetles; members of the order Orthoptera; and Leaf miners of the orders Lepicloptere (moths and butterflies), Hymenoptera (leaf mining sawflies), Coieoptera (beetles), and Diptera (true flies). Other pests against which the crystalline modification I of Spinosad may be used include ants, green peach aphids, adult house flies, western tent caterpillar larvae, and two-spotted spider mites.

The benefits of the present invention are especially realized when the crystalline modification I of Spinosad or its insecticidal composition are applied to kill insects or mites in a range of crops of useful plants, in particular maize, soybean, cotton, fruit, vegetable, potato, rice and turf for control of bollworm, tobacco budworm, armyworms and loopers.

The crystalline modification I of Spinosad may be used to treat all plants and plant parts. In the present context, plants are to be understood as meaning all plants and plant populations such as desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants may be plants which can be obtained by conventional breeding and optimization methods, by biotechnological and genetic engineering methods, or by combinations of these methods, including the transgenic plants and the plant cultivars which can or cannot be protected by plant breeders' rights. Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. Harvested materials, and vegetative and generative propagation materials, for example, cutting, tubers, meristem tissue, rhizomes, offsets, seeds, single and multiple plant cells and any other plant tissues, are also included.

Treatment of the plants and plant parts with the crystalline modification I of Spinosad or compositions or formulations of the same may be carried out directly on the plants themselves or by allowing the compositions or formulations to act on their surroundings, habitat or storage space. The plants may be treated by the customary treatment methods. Examples of these customary treatment methods include dipping, spraying, vaporizing, fogging, broadcasting, painting on in the case of propagation material, and applying one or more coats particularly in the case of seeds.

In this specification, references to properties are, unless stated otherwise, to properties measured under ambient conditions, that is at atmospheric pressure and at a temperature of about 20°C.

Where upper and lower limits are quoted for a property then a range of values defined by a combination of any of the upper limits with any of the lower limits may also be implied.

As used herein, the term "about" or "around" when used in connection with a numerical amount or range, means somewhat more or somewhat less than the stated numerical amount or range, and for example to a deviation of ± 10% of the stated numerical amount or endpoint of the range.

"Surrounding," as used herein, refers to the place on which the plants are growing, the place on which the plant propagation materials of the plants are sown or the place on which the plant propagation materials of the plants will be sown.

"Precipitation" as used herein, refers to the sedimentation of a solid material (a precipitate), including the sedimentation of a crystalline material, from a liquid solution in which the solid material is present in amounts greater than its solubility in the amount of liquid solution.

All percentages are given in weight % unless otherwise indicated.

Embodiments of the present invention are described in more detail hereinafter, having reference to the accompanying figures, in which: Figure 1 is an X-ray powder diffractogram of a crystalline modification I of Spinosad; Figure 2 is a an infrared (IR) spectrograph of a crystalline modification I of Spinosad; Figure 3 is a Differential Scanning Calorimetry (DSC) thermogram of a crystalline modification I of Spinosad; and Figure 4 is an X-ray powder diffr -togram of amorphous Spinosad.

Embodiments of the present invention will now be described, for illustrative purposes only, by way of the following examples.

All X-ray diffractograms were determined using a powder diffractometer in reflection geometry at 25° C, using the acquisition parameters summarized in Table 1 below:

Table 1

X'Pert Pro MPD from PANalytical B.V.

Theta compensating slit and graphite monochromator Copper (K-alpha) radiation, 40 kV, 40 mA Step size: 0.03 degree 2-theta Count time: 1.0 second Maximum peak intensity: 1705 counts per second Scan range: 3-60 degrees 2-theta IR spectra were measured with the resolution of 4 cm-1 and with the number of scans of 16 for the crystallized samples. The crystalline modification I of Spinosad can be identified by its characteristic functional group vibration peaks at wavenumbers (cm-1, ±0.2%) of 2930.01, 2870.55, 2824.68, 1705.98 and 1659.87cm-1as shown in Figure 2.

All IR spectra were obtained using the acquisition parameters summarized in Table 2 below:

Table 2

FT-IR NicoletTM iS 5 spectrometer Diamond ATR unit Thermo Scientific TM iD5 AIR Wavelength range 550 -4000 cm-1 Resolution 4 cm-1 Number of scans 16 All DSC thermograms were obtained using the acquisition parameters summarized in Table 3 below:

Table 3

Differential Scanning DSC 214 Polyma from NETZSCH-Geratebau GmbH Calorimeter Range 60°C/1.0(K/min)/160°C Sample car./TC DSC 214 Corona sensor /E Segments 1/1 Crucible Pan Al, closed Atmosphere N2, 50.0 ml/min / N2, 70.0 ml/min Corr/m. range 000/5000 pV

EXAMPLES

Example 1: Preparation of amorphous Spinosad in accordance with the disclosure of EP 1 062 345, Example 1 Vegetative cultures of S. spinosa strain NRRL18538 were each grown in 50 ml of CSM medium (trypticase soy broth 30 g/I, yeast extract 3 g/I, magnesium sulfate 2 g/I, glucose 5 g/I, maltose 4 g/1) in 250 ml Erlenmeyer flasks, shaken at 300 rpm at 30°C for 48h. Fermentation cultures contained a 1 ml inoculum of this vegetative culture in 7 ml of INF202, a proprietary medium similar to that described in Strobel & Nakatsukasa (1993).

The cultures were grown in 30 ml plastic bottles arranged in 10x10 modules, shaken at 300 rpm in a 30°C room for 3, 5 or 7 days. Broths were extracted with 4 volumes of acetonitrile, then analyzed for Spinosad A + D by isocratic high pressure liquid chromatography (HPLC) through a C-18 reversed-phase column (Strobel and Nakatsukasa, 1993). The amount of spinosyns present was determined from absorbance at 250 nm. For each time point, Spinosad A + D were determined from 10 fermentation bottles.

Two representative samples from each set of replicates were also analyzed by a slightly modified HP LC system for pseudoaglycone (PSA), the spinosyn precursor which lacks forosamine. In this system the mobile phase is 35:35:30 acetonitrile/methano1/0.5% (w/v) aqueous ammonium acetate (R. Wjayaratne, unpublished).

The resulting Spinosad product was examined using X-ray powder diffraction. As shown in Figure 4, the X-ray powder diffraction pattern of the resulting Spinosad product has no significant signals, which indicates the Spinosad product prepared in accordance with the disclosure of EP 1 062 345 is amorphous.

Example 2: Preparation of the crystalline modification I of Spinosad Crystallization from ethylene carbonate g of the amorphous Spinosad product prepared in Example 1 was taken in a 3-neck round bottom flask along with 50 ml of ethylene carbonate and the resulting slurry was heated to 85°C while stirring, until the Spinosad had dissolved completely. The resulting solution was slowly cooled to a temperature of from 20 to 25°C at a rate of 2°C/min. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20°C for 2h. Thereafter, the resulting slurry was filtered to isolate the solid material, which was washed with 3 ml of ethylene carbonate at 20°C. The filtered crystals were dried under vacuum at 40°C.

The crystalline product obtained had a purity of >98% and the yield was found to be not less than 98%.

The resulting crystals were analyzed by IR spectrometry, X-ray powder diffraction and DSC and found out to be a crystalline modification I of Spinosad. 15 The X-ray powder diffractogram, IR spectogram and DSC thermogram are as shown in Figure 1, 2 and 3 respectively.

The IR spectrum of the crystalline modification I of exhibited the functional group characteristic vibrations at wavenumbers (cm-1, ±0.2%) of 2930.01, 2870.55, 2824.68, 1705.98 and 1659.87cm-1 as shown in Figure 2.

The DSC thermogram of the crystalline modification I exhibited an endothermic melting peak with onset at 112.1°C, a peak maximum at 126.1°C, and a melting enthalpy of 24.56 J/g as shown in Figure 3.

The X-ray powder diffractogram of crystals exhibited the reflexes as shown in Figure 1 and the values of the key reflexes are summarized in Table 4 below.

Table 4

Crystalline Modification I 2 0 (°) d (A) 7.374 ± 0.20 11.98 ± 0.05 9.565 ± 0.20 9.24 ± 0.05 11.550 ± 0.20 7.66 ± 0.05 11.823 ± 0.20 7.48 ± 0.05 12.328 ± 0.20 7.17 ± 0.05 15.433 ± 0.20 5.74 ± 0.05 15.822 ± 0.20 5.60 ± 0.05 16.851 ± 0.20 5.26 ± 0.05 17.482 ± 0.20 5.07 ± 0.05 18.533 ± 0.20 4.78 ± 0.05 19.993 ± 0.20 4.43 ± 0.05 21.105 ± 0.20 4.21 ± 0.05 23.078 ± 0.20 3.85 ± 0.05 24.195 ± 0.20 3.68 ± 0.05 Example 3: Preparation of the crystalline modification I of Spinosad Crystallization from dimethyl carbonate g of the amorphous Spinosad produce prepared in Example 1 was taken in a 3-neck round bottom flask along with 30 ml of dimethyl carbonate and the resulting slurry was heated to 75°C while stirring until the Spinosad had dissolved completely. The solution was slowly cooled to a temperature of from 20 to 25°C at a rate of 2°C/min. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20°C for 2h. The resulting slurry was filtered and the isolated solid washed with 3 ml of dimethyl carbonate. The filtered crystals to were dried under vacuum at 45°C.

The crystalline products obtained had a purity of >98% and the yield was found to be not less than 98%.

The crystals were characterized as being the crystalline modification I of Spinosad using IR spectrometry, X-ray powder diffraction and DSC as described

in Example 2.

Comparative Example 1: Precipitate Spinosad using an aliphatic alcohol Precipitate from methanol g of the amorphous Spinosad product prepared in Example 1 was taken in a 3-neck round bottom flask along with 30 ml of methanol and the resulting slurry was heated to 60°C while stirring until the Spinosad had dissolved completely. The solution was slowly cooled to a temperature of from 20 to 25°C at a rate of 2°C/mm. Upon cooling, a precipitate was formed and the resulting heterogeneous mixture was stirred at 20°C for 2h. The resulting slurry was filtered and the isolated solid washed with 3 ml of methanol. The filtered precipitate was dried under vacuum at 45°C.

The solid products obtained had a purity of >95% and the yield was found to be not less than 94%.

The solid product was identified as being amorphous using X-ray powder diffraction.

Comparative Example 2: Precipitate Spinosad using a ketone Precipitate from acetone 5 g of the amorphous Spinosad product prepared in Example 1 was taken in a 3-neck round bottom flask along with 30 ml of acetone and the resulting slurry was heated to 50°C while stirring until the Spinosad had dissolved completely. The solution was slowly cooled to a temperature of from 20 to 25°C at a rate of 2°C/mm. Upon cooling, a precipitate was formed and the resulting heterogeneous mixture was stirred at 20°C for 2h. The resulting slurry was filtered and the isolated solid was washed with 3 ml of acetone. The filtered precipitate was dried under vacuum at 45°C.

The solid product obtained had a purity of >94% and the yield was found to be not less than 94%.

FORMULATION EXAMPLES Comparative Example 3 Preparation of suspension concentrate (SC) of amorphous Spinosad All the components listed in Table 5 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate

Table 5

Component Amount Function (%wt) Amorphous Spinosad, 98% (prepared in Example 1) 48 Active ingredient Propylene glycol 5 Anti-freezing agent Modified polydimethylsiloxane formulation (SAG 1529) 0.5 Antifoaming agent Sodium 3 Dispersing agent Alkylnaphthalenesulfonate, formaldehyde condensate (MORVVET D-425® POWDER) Polyalkylene glycol ether (ATLASTm G-5000) 2 Wetting agent Xanthan gum(AG-RHO POL 23/W) 0.2 Thickening agent 1,2-Benzisothiazol-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Balance to Diluent 100%

Example 4

Preparation of Suspension Concentrate (SC) of Spinosad crystalline modification I All the components list in Table 6 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.

Table 5

Component Amount Function (yam) Spinosad, crystalline modification I, 98% (prepared in Example 2) 48 Active ingredient Propylene glycol 5 Anti-freezing agent Modified polydimethylsiloxane formulation (SAG 1529) 0.5 Antifoaming agent Sodium 3 Dispersing agent Alkylnaphthalenesulfonate, formaldehyde condensate (MORVVET D-425® POWDER) Polyalkylene glycol ether (ATLASTm G-5000) 2 Wetting agent Xanthan gum(AG-RHO POL 23/W) 0.2 Thickening agent 1,2-Benzisothiazol-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Balance to Diluent 100%

Example 5

Table 6

Component Amount Function (%wt) Spinosad, crystalline modification I, 98% (prepared in Example 3) 48 Active ingredient Propylene glycol 5 Anti-freezing agent Modified polydimethylsiloxane formulation (SAG 1529) 0.5 Antifoaming agent Sodium 3 Dispersing agent Alkylnaphthalenesulfonate, formaldehyde condensate (MORVVET D-425® POWDER) Polyalkylene glycol ether (ATLASTm G-5000) 2 Wetting agent Xanthan gum(AG-RHO POL 23/W) 0.2 Thickening agent 1,2-Benzisothiazol-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Balance to Diluent 100% Comparative Example 4 Preparation of Suspension Concentrate (SC) of Spinosad All the components list in Table 7 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen 5 AG) to obtain a suspension concentrate.

Table 7

Component Amount Function (%wt) Spinosad, 95% (prepared in Comparative Example 2) 48 Active ingredient Propylene glycol 5 Anti-freezing agent Modified polydimethylsiloxane formulation (SAG 1529) 0.5 Antifoaming agent Sodium 3 Dispersing agent Alkylnaphthalenesulfonate, formaldehyde condensate (MORVVET D-425® POWDER) Polyalkylene glycol ether (ATLASTm G-5000) 2 Wetting agent Xanthan gum(AG-RHO POL 23/W) 0.2 Thickening agent 1,2-Benzisothiazol-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Balance to Diluent 100% Comparative Example 5 Preparation of Suspension Concentrate (SC) of Spinosad All the components list in Table 8 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.

Table 8

Component Amount Function (%wt) Spinosad, 94% (prepared in Comparative Example 3) 48 Active ingredient Propylene glycol 5 Anti-freezing agent Modified polydimethylsiloxane formulation (SAG 1529) 0.5 Antifoaming agent Sodium 3 Dispersing agent Alkylnaphthalenesulfonate, formaldehyde condensate (MORVVET D-425® POWDER) Polyalkylene glycol ether (ATLASTm G-5000) 2 Wetting agent Xanthan gum(AG-RHO POL 23/W) 0.2 Thickening agent 1,2-Benzisothiazol-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Balance to Diluent 100% Comparison of Storage Stability The storage stability of the compositions was tested using procedures 5 according to CIPAC MT 46.3. The procedure followed was as follows: Samples of the compositions prepared in Examples 4 and 5 and Comparative Examples 3 to 5 were stored at 54°C for 1 month, 3 months and 6 months. The concentration of Spinosad in the composition was determined at the end of each storage period by high pressure liquid chromatography (HPLC). The io aggregation of solid Spinosad particles was measured by observation.

The original concentration of Spinosad in each formulation was 48% by weight. The results are summarized in Table 9 below.

Table 9

Sample 1 month 3 month 6 month Concentration of Aggregation Concentration of Aggregation Concentration of Aggregation Spinosad (%wt) Spinosad (%wt) Spinosad (%wt) Comparative 35 ++ 30 +++ 19 +++++

Example 3

Example 4 48 - 48 - 48 - Example 5 48 - 48 - 48 -Comparative 37 ++ 32 +++ 20 +++++

Example 4

Comparative 39 ++ 30 +++ 23 +++++

Example 5

Notes "+" means small amount of aggregation; "+++++" means a lot of aggregation; "2 means no aggregation As can be seen from the results shown in Table 9 above, the suspension concentrate (SC) formulations of Examples 4 and 5 prepared using the crystalline modification I of Spinosad exhibited an excellent stability, with no loss of the Spinosad active ingredient and no detectable agglomeration of the Spinosad particles in the suspension. In contrast, the SC formulations of the Comparative Examples exhibited a significantly lower stability, with a significant loss of Spinosad active ingredient and significant agglomeration of the Spinosad particles in the suspension.

Claims

CLAIMS1. A crystalline modification I of Spinosad, exhibiting at least 3 of the following reflexes, in any combination, as 28±0.20 degree in X-ray powder diffractogram (X-RPD) recorded using Cu-Ka radiation at 25°C: 28 = 7.374 ± 0.20 (1) = 9.565 ± 0.20 (2) = 11.550 ± 0.20 (3) = 11.823 ± 0.20 (4) = 12.328 ± 0.20 (5) Lo 20 = 15.433 ± 0.20 (6) = 15.822 ± 0.20 (7) = 16.851 ± 0.20 (8) 28 = 17.482 ± 0.20 (9) 28 = 18.533 ± 0.20 (10) 28 = 19.993 ± 0.20 (11) 28 = 21.105 ± 0.20 (12) = 23.078 ± 0.20 (13) 28 = 24.195 ± 0.20 (14) 2. The crystalline modification I of Spinosad according to claim 1, exhibiting at least 3 of the following reflexes, as 28±0.20 degree in an X-ray powder diffractogram recorded using Cu-Ka radiation at 25°C: = 9.565 ± 0.20 (2) 28 = 11.550 ± 0.20 (3) = 11.823 ± 010 (4) = 15.433 ± 0.20 (6) = 15.822 ± 0.20 (7) = 16.851 ± 0.20 (8) 20 = 17.482 ± 0.20 (9) = 19.993 ± 0.20 (11) = 21.105 ± 0.20 (12) 28 = 24.195 ± 0.20 (14) 3. A crystalline modification I of Spinosad exhibiting an infrared (IR) spectrum with characteristic functional group vibration peaks at wavenumbers (cm-1, ±0.2%) of 2930.01, 2870.55, 2824.68, 1705.98 and 1659.87cm-1.4. A crystalline modification I of Spinosad exhibiting a Differential Scanning Calorimetry (DSC) profile having an endothermic melting peak with onset at 112.3°C and a peak maximum at 126.1°C.5. The crystalline modification I of Spinosad according to either of claims 1 or 2, further exhibiting an infrared (IR) spectrum according to claim 3 and/or a Differential Scanning Calorimetry (DSC) profile according to claim 4.6 The crystalline modification I of Spinosad according to any one of claims 1 to 5, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 1, and/or characterized by an IR spectrum substantially as shown in Figure 2, and/or characterized by a Differential Scanning Calorimetry (DSC) thermogram substantially as shown in Figure 3.7. A method for preparing a crystalline modification I of Spinosad, the method comprising the steps of: i) dissolving Spinosad in a solvent system to form a Spinosad solution; ii) precipitating the crystalline modification I of Spinosad from the Spinosad solution; and iii) isolating the precipitated crystalline modification I of Spinosad.8. The method according to claim 7, where the Spinosad employed in step i) is amorphous Spinosad.9. The method according to either of claims 7 or 8, wherein the solvent system comprises a carbonate.10. The method according to claim 9, wherein the carbonate is ethylene carbonate, dimethyl carbonate or a mixture thereof.11. The method according to any of claims 7 to 9, wherein precipitating in step ii) is effected by one or more of concentrating the solution by removal of solvent system from the solution, cooling the solution, addition of a solubility reducing agent, or adding seed crystals to the solution.12. The method according to claim 11, wherein seed crystals are added to the solution, the seed crystals comprising the crystalline modification I of Spinosad.13. The method according to any of claims 7 to 12, wherein step ii) is effected by cooling to a temperature from 0 to 20°C.14. A crystalline modification I of Spinosad according to any one of claims 1 to 6, obtainable by the process of any one of claims 9 to 13.15. A crystalline modification I of Spinosad obtained according to any one of claims 7 to 13 and having a crystalline modification I of Spinosad content of at least 98% by weight.16. A composition comprising the crystalline modification I of Spinosad according to any one of claims 1 to 6 and 14 and at least one auxiliary.17. The composition according to claim 16, wherein the auxiliary is selected from one or more of: surfactants, liquid diluents, solid diluents, wetting agents, dispersants, thickening agents, anti-foaming agents, anti-freezing agents, preservatives, antioxidants, solid adherents, and inert fillers.18. The composition according to either of claims 16 or 17, which is in the form of a suspension concentrate (SC), an oil-based suspension concentrate (OD), water-soluble granules (SG), a dispersible concentrate (DC), an emulsifiable concentrate (EC), an emulsion seed dressing, a suspension seed dressing, granules (GR), microgranules (MG), a suspoemulsion (SE) or water-dispersible granules (WG).19. The composition according to claim 18, wherein the composition is a suspension concentrate (SC).20. The composition according to any one of claims 16 to 19, which comprises the crystalline modification I of Spinosad in an amount of less than 75 % by weight.21. The composition according to claim 20, which comprises the crystalline modification I of Spinosad in an amount of from 45 to 50% by weight.22. Use of the crystalline modification I of Spinosad according to any of claims 1 to 6 or 14 or a composition according to any of claims 16 to 21 for the control of insects and mites.23. A method of controlling insects and mites, comprising applying the crystalline modification I of Spinosad according to any of claims 1 to 6 or 14 or a composition according to any of claims 16 to 21 to plants, plant parts or their locus.24. The method according to claim 23, wherein the plants are selected from maize, soybean, cotton, fruit, vegetable, potato, rice or turf.25. The method according to either of claims 23 or 24, wherein the crystalline modification I of Spinosad is applied for the control of bollworm, tobacco budworm, armyworms and loopers.