Patent Description:
The mammalian toxicological properties of pyrethroids (as well as their insecticidal properties) can also be modulated by the formulation type, so that formulations where the pyrethroid is dissolved (e.g. emulsion concentrate, EC) have a higher acute oral toxicity than those where the active ingredient is present as a finely milled colloidal dispersion (e.g. suspension concentrate, SC) (e.g. suspension concentrate, SC) (<NPL>).

The corollary of the previous statements is that the improved safety profile of a pyrethroid SC formulation comes at the cost of a more restricted biological efficacy, when compared to a pyrethroid EC formulation, which shows higher oral acute toxicity, but also broader and higher biological efficacy.

Thus, it would be desirable to combine the high insecticidal efficacy properties of pyrethroid EC formulations, with the lower mammalian toxicological profile of pyrethroid SC formulations.

One such approach would be to mix SC pyrethroid formulations with adjuvants capable of increasing the insecticidal efficacy of the milled pyrethroid. SC formulations of pyrethroids can be made more biologically active through the addition of selected chemical adjuvants, for instance by the addition of polymers (<CIT>), carboxylate esters (<CIT>), oils (<NPL>)) )) In an ideal situation, these adjuvants would be directly co-formulated with the pyrethroid, so that no extra steps must be taken before the formulation is used. That is, it is more desirable to offer the user a ready-to-use (RTU) formulation, also called an in-can adjuvanted formulation, which necessitates no extra addition of adjuvants on the part of the user in order to exploit the full biological potential of the pyrethroid. However, because these adjuvants tend to show a potential for solubilization of the active, a suspension concentrate stored in the presence of polymers, or carboxylate esters, or phosphates is unstable towards crystal growth, as a result of Ostwald ripening (<NPL>.

It is known that the instability of fine milled dispersions towards crystal growth in the presence of adjuvants capable of dissolving the milled active can be addressed by encapsulating the adjuvant. It is known that certain oils, which are known to function as pyrethroid adjuvants, can be encapsulated inside polyurea membranes (<CIT>, <CIT>). It is also known that mixtures of encapsulated oils and suspension concentrates are resistant towards crystal growth, so that it is possible to use such encapsulated oils in in-can adjuvanted suspension concentrates without affecting the long-term stability of the suspension concentrate, or its biological efficacy. This is indeed the case although the polyurea membrane physically separates the dispersed active ingredient from the adjuvant (<CIT>). Therefore, since mixtures of SC formulations with encapsulated adjuvants (so called ZC formulations) behave in their insecticidal properties rather as formulations where the pyrethroid is dissolved, one would expect that the mammalian toxicological properties of such ZC formulations would be similar to those of EC formulations.

We have now surprisingly found that ZC formulations made up of finely milled pyrethroids and encapsulated adjuvants are surprisingly capable of selectively enhancing the insecticidal efficacy of pyrethroid suspension concentrates against insects, without increasing the mammalian toxicity of the formulation. That is, according to the invention, pyrethroid ZC formulations behave like a pyrethroid EC formulation against agricultural relevant pests, while showing significantly improved toxicity against mammals than the corresponding EC formulation.

As used herein, the term "pyrethroid" refers to substances belonging to the IRAC Mode of Action Group 3A (sodium channel modulator).

Examples of "pyrethroid" are Acrinathrin, Allethrin, d-cis-trans Allethrin, d-trans Allethrin, Bifenthrin, Bioallethrin, Bioallethrin S-cyclopentenyl, Bioresmethrin, Cycloprothrin, Cyfluthrin, beta-Cyfluthrin, Cyhalothrin, lambda-Cyhalothrin, gamma-Cyhalothrin, Cypermethrin, alpha-Cypermethrin, beta-Cypermethrin, theta-Cypermethrin, zeta-Cypermethrin, Cyphenothrin [(1R)-trans- isomers], Deltamethrin, Empenthrin [(EZ)- (1R)- isomers], Esfenvalerate, Etofenprox, Fenpropathrin, Fenvalerate, Flucythrinate, Flumethrin, tau-Fluvalinate, Kadathrin, Pyrethrins (pyrethrum), Halfenprox, Phenothrin [(1R)-trans- isomer], Prallethrin, Resmethrin, Silafluofen, Tefluthrin, Tetramethrin, Tetramethrin [(1R)-isomers], Tralomethrin, Transfluthrin, Permethrin. In a preferred embodiment the pyrethroid is Deltamethrin.

As used herein, the term "adjuvant/adjuvant mixture" refers to.

Examples of "trialkyl phosphate" are trimethyl phosphate, triethyl phosphate, tripropyl phosphate, tributyl phosphate, tripentyl phosphate, trihexyl phosphate, triheptyl phosphate, trioctyl phosphate, tris(<NUM>-ethyl hexyl) phosphate, trinonyl phosphate, tridecyl phosphate, wherein tris(<NUM>-ethylhexyl) phosphate is most preferred.

Examples of "vegetable oil alkyl esters" are.

Most preferred the vegetable oil alkyl ester is rape seed oil methyl ester, while the most preferred mixture of trialkylphosphat and vegetable oil alkyl ester is tris(<NUM>-ethylhexyl) phosphate and rape seed oil methyl ester.

As used herein, the term "dispersant" refers to substances known in the state of the art to stabilize solid colloids of active ingredient. In the context of the present invention, "dispersant" refers to surfactants used in the manufacturing of pyrethroid suspension concentrate formulations. Some of the below described dispersantsor chemically similar compounds may also serve as emulsifiers when being used in the context of this invention as emulsifiers for liquid organic compounds for the preparation of capsule suspension formulations. That surfactants of the same chemical class may serve to prepare dispersions or emulsions, depending on the solvent and/or compound to be stabilized, is known in the state of the art (<NPL>). Suitable dispersants in the context of the present invention are selected from the group comprising:.

Preferably, suitable dispersantare selected from the group comprising dispersants c1), c2), c3), c7), c8), c9), c13) and c16).

Further preferably, suitable dispersantare selected from the group comprising dispersants c1), c2), c3), c7), c8), and c13).

Most preferably, suitable dispersantdispersants are selected from the group comprising dispersants c1), c2), c3), c7), and c8).

The above-described dispersantcan be used either individually or in combination, preference being given to combinations of the dispersants selected from the group of dispersants c1), c2), c7), c8), c9), c13) and c16).

The above-described dispersants can be used either individually or in combination, further preference being given to combinations of the dispersants selected from the group of dispersants c1), c2), c3), c7), c8), and c13).

The above-described dispersants can be used either individually or in combination, even further preference being given to combinations of the dispersants selected from the group of dispersants c1), c2), c3), c7), and c8).

The above-described dispersants can be used either individually or in combination, most preference being given to combinations of the dispersants selected from the group of dispersants c1) and c2),.

As used herein, the term "wetting agent" refers to substances known in the state of the art to enhance the wetting of leaf surfaces of plants. These materials are particularly able to dynamically reduce the surface tension of water, so that after <NUM> the surface tension has been reduced to <<NUM> mN/m.

Suitable wetting agents are all substances which are customarily used for this purpose in agrochemical compositions. Preference is given to alkylated siloxanes, particularly to alkoxylated alkylated siloxane derivatives, further preferably to ethoxylated/propoxylated alkylated siloxane derivatives. Examples of the above-mentioned compounds are the Silwet line products of Momentive, and the Break-Thru® line products of Evonik. Particularly preferred are Silwet HS <NUM>, Silwet HS <NUM>, Break-Thru® S200, Break-Thru® S240, Break-Thru® S279, Break-Thru® S301, Break-Thru® SD <NUM>.

As used herein, the term "rheological modifier" refers to substances known in the state of the art to stabilize dispersions of active ingredient by affecting the rheological properties of the dispersion.

Rheology modifier e1) is preferably selected from the group of modified cellulose ethers, more preferably from the group of methyl celluloses and most preferred is hydroxypropyl methylcellulose HPMC, for example Vivapur® K <NUM> from JRS Pharma.

Rheology modifier e2) is preferably selected from the group of hydrophilic synthetic amorphous silica, hydrophobic synthetic amorphous silica, as well as fumed and precipitated silica, for example any product from the Aerosil® or Sipernat product line from Evonik.

Preferred rheology modifiers e2) are Aerosil®<NUM>, or Sipernat <NUM> from Evonik.

Rheology modifier e3) is preferably selected from the group of modified polysaccharides and polysaccharide gums (all other than e1)) (e.g. gellan gum, jelutong gum, xanthan gum, guar gum, gum arabic, gum tragacanth, gum karya, tara gum, locust gum, agar agar, carrageenan, alginic acid, alginates (e.g. sodium, potassium, ammonium, or calcium alginates)), starch and its derivatives.

Preferred rheology modifiers e3) are polysaccharide gums. The rheology modifier is in particular xanthan gum, e.g. Rhodopol® G, Rhodopol® <NUM> from Solvay or Satiaxane® CX911 from Cargill.

Mixtures of any of the aforementioned rheology modifiers e1) - e3) are also suitable, further preferred are mixtures of rheology modifiers e2) and e3), most preferred are rheology modifiers e3).

Excluded as rheological modifiers according to the invention are clays including montmorillonite, bentonite, smectite, sepiolite, attapulgite, laponite, hectorite. Examples are VANATURAL®,Veegum® R, Van Gel® B, Bentone® CT, HC, EW, Pangel® M100, M200, M300, S, M, W, Attagel® <NUM>, Laponite® RD, VEEGUM®, Attaclay®, VAN GEL®.

As used herein, the term "isocyanate" refers to substances typically employed in the preparation of capsules by the interfacial polymerization method. Suitable isocyanates in the context of the present invention are selected from the groups comprising:.

The isocyanates f1-f4 comprise mono, di, and/or polyisocyanate mixtures, or the product of a reaction of mixtures of isocyanates.

Additionally, modifications like for example allophanates, uretdione, urethane, isocyanurate, biuret, iminooxadiazindion or oxadiazintrione containing structures, are suitable components for the building of the diiosocyanates from groups f1-f4. Multiply functionalized substances like polymeric MDI (pMDI like for instance PAPI-<NUM> from Dow or Desmodur® 44V20 types from Covestro) are suitable components for the building of the diisocyanates in groups f1-f4.

Preferred are modifications with an isocyanate functionality (NCO) of <NUM> to <NUM>.

More preferred are modifications with an isocyanate functionality (NCO) of <NUM> to <NUM>.

Particularly preferred are modifications with an isocyanate functionality (NCO) of <NUM> to <NUM>.

More particularly preferred are modifications with an isocyanate functionality (NCO) of <NUM> to <NUM>.

Most particularly preferred are modifications with an isocyanate functionality (NCO) of <NUM> to <NUM>.

Preferred isocyanate/polyisocyanate functional group content is between <NUM> und <NUM> %w/w, more preferred between <NUM> und <NUM> % w/w, particularly preferred between <NUM> % und <NUM> %w/w and most particularly preferred between <NUM> und <NUM> %w/w.

Mixtures of any of the aforementioned isocyanates f1) - f4) are also suitable.

Most preferred are mixtures of isocyanates from groups f1)-f2).

As used herein, the term "cross linker" refers to substances known in the art to serve as cross linkers during polyurea interfacial polymerization of isocyanates.

Examples of such substances are aliphatic diamines, aliphatic triamines, aryl diamines, aryl triamines. The amines can be primary, or secondary.

Examples are Ethylendiamine (EDA), Diethylentriamine (DETA), Monoisopropylamine, <NUM>-Aminopyridine (<NUM>-AP), n-Propylamine, Ethylen- or Propylenimin-based Polyaziridine, Triethylenetetraamine (TETA), Tetraethylenpentamine, <NUM>,<NUM>,<NUM>'-Triaminodiphenylether, Bis(hexamethylen)-triamine, Trimethylendipiperidine (TMDP), Guanidine carbonate (GUCA), Phenylendiamine, Toluendiamine, Pentamethylenhexamine, <NUM>,<NUM>-Diamino-<NUM>-methyl-<NUM>,<NUM>,<NUM>-triazine, <NUM>,<NUM>-Diaminocyclohexane, <NUM>,<NUM>'-Diaminodiphenylmethane, <NUM>,<NUM>-Diaminonaphthalenisophorondiamine, Diaminopropane, Diaminobutane, Piperazine, Aminoethylenepiperazine (AEP), Poly(propyleneglycol)-bis(<NUM>-aminopropylether) or o,o'-Bis(<NUM>-aminopropyl)polypropylenglycol-polyethylenglycol-polypropylenglycol, Hexamethylendiamine, Bis-(<NUM>-aminopropyl)amine, Bis-(<NUM>-methylaminoethyl)methylamine, <NUM>,<NUM>-Diaminocyclohexanw, <NUM>-Amino-<NUM>-methyl-aminopropane, N-Methyl-bis-(<NUM>-aminopropyl) amine, <NUM>,<NUM>-Diamino-n-butane und <NUM>,<NUM> Diamino-n-hexane.

Preferred are primary aliphatic diamines, and primary aliphatic triamines.

Particularly preferred are ethylene diamine, trimethylene diamine, tetramethylene diamine, pentamethylene diamine, hexamethylene diamine, diethylene triamine, bis(<NUM>-aminoethyl)amine, bis(<NUM>-aminopropyl)amine, bis(<NUM>-aminobutyl)amine, bis(<NUM>-aminopentyl)amine, bis(<NUM>-aminohexyl)amine.

Further particularly preferred are hexamethylene diamine, diethylene triamine, bis(<NUM>-aminohexyl)amine.

Examples of cross linkers are also primary and secondary, as well as aromatic dialcohols and polyalcohols. Examples are ethanediol, propanediol (<NUM>,<NUM>), propanediol (<NUM>,<NUM>), butanediol (<NUM>,<NUM>), pentanediol (<NUM>,<NUM>), hexanediol (<NUM>,<NUM>), glycerin and <NUM>,<NUM>-propanediol.

Examples of cross linkers are also aminoalcohols. Examples are triethanolamine, monoethanolamine, triisopropanolamine, diisopropylamine, N-methylethanolamine, N-methyl-diethanolamine.

Another example is the use of water as a reagent which releases the cross linker. This occurs upon the reaction of isocyanate with water, by means of which an amine is released.

The amount of cross-linker g) to isocyanate f) is kept in a certain ratio, generally between <NUM> to <NUM> times the weight of cross linker g) to weight of isocyanate f).

Preferred is the ratio between <NUM> to <NUM> times the weight of cross linker g) to weight of isocyanate f).

Most preferred is the ratio between <NUM> to <NUM> times the weight of cross linker g) to weight of isocyanate f).

As used herein, the term "emulsifier" refers to substances known in the state of the art to stabilize emulsions. In the context of the present invention, "emulsifier" refers to surfactants used in the manufacturing of adjuvant capsule suspension formulations. Some of the below described emulsifiers may also serve as dispersants when being used in the context of this invention as dispersants for the preparation of suspension concentrate formulations. That surfactants of the same chemical class may serve to prepare dispersions or emulsions depending on the system/formulation and compounds used in is known in the state of the art (<NPL>). Suitable emulsifiers in the context of the present invention are selected from the groups comprising:.

Preferred are emulsifiers selected from the groups comprising h1), h2), h3), h7).

Particularly preferred are emulsifiers selected from the groups comprising h1), h3), h7). Most preferred are emulsifiers selected from the groups comprising h3), h7).

Most particularly preferred are emulsifiers selected from the group comprising of h3)
Mixtures of the aforementioned emulsifiers h1)-h7) are also suitable.

Most preferred are mixtures of emulsifiers from the groups comprising h3) and h7).

As used herein, the term "pH Buffer"refers to substances known in the state of the art capable of maintaining a defined pH in an aqueous solution. Examples of such buffers are listed in the CRC Handbook of Chemistry and Physics (ISBN: <NUM>-<NUM>-<NUM>-<NUM>).

Preferred are acetic acid, citric acid, formic acid, phosphoric acid, sulfuric acid.

Further preferred are acetic acid, citric acid.

As used herein, the term "antifoam" refers to substances known in the state of the art capable of prevent excess foaming in a formulation during manufacturing and/or application by the customer. Suitable defoaming performance is such that the FAO limits for foam persistence codified in the CIPAC Method <NUM> are maintained by agrochemical formulations at all times of its useful life.

Suitable antifoams are all substances which are customarily used for this purpose in agrochemical compositions.

Preference is given to silicone oils and magnesium stearate.

As used herein, the term "biocide" refers to substances known in the state of the art capable of preventing microbial/fungal growth in water-based formulations.

Suitable preservatives are all substances which are customarily used for this purpose in agrochemical compositions of this type. Examples which may be mentioned are Preventol® (from Lanxess) and Proxel GXL®.

As used herein, the term "antifreeze" refers to substances known in the state of the art capable of preventing freezing of agrochemical formulations. Suitable antifreeze substances which are customarily used for this purpose in agrochemical compositions are propylene glycol, glycerin and urea.

As used herein, the term "antioxidant" refers to substances known in the state of the art capable of preventing oxidation of agrochemical formulations. Suitable antioxidant substances which are customarily used for this purpose in agrochemical compositions are butylhydroxytoluene (BHT), and suitable derivatives thereof.

The In-Can Adjuvanted Pyrethroid ZC formulations are exemplified as shown below:.

An alternative embodiment of the present invention contains a pyrethroid formulated as suspension concentrate in the concentration range of <NUM>-<NUM> % w/w,.

One embodiment of the present invention contains an encapsulated adjuvant/adjuvant mixture in the concentration range of <NUM>-<NUM> %w/w,.

Another embodiment of the present invention contains a dispersant in the concentration range of <NUM>-<NUM> % w/w,.

An alternative embodiment of the present invention contains a dispersant in the concentration range of <NUM>-<NUM> % w/w,.

Another embodiment of the present invention optionally contains a wetting agent in the concentration range of <NUM>-<NUM> %w/w,.

Another embodiment of the present invention must contain a wetting agent in the concentration range of <NUM>-<NUM> %w/w,.

Another embodiment of the present invention contains an isocyanate in the concentration range of <NUM>-<NUM>% w/w,.

An alternative embodiment of the present invention contains an isocyanate in the concentration range of <NUM>-<NUM>% w/w,.

Another embodiment of the present invention contains a cross-linker in the concentration range of <NUM>-<NUM>% w/w,.

An alternative embodiment of the present invention contains a cross-linker in the concentration range of <NUM>-<NUM>% w/w,.

An alternative embodiment of the present invention contains no cross-linker.

Another embodiment of the present invention contains an emulsifier in the concentration range of <NUM>-<NUM>% w/w,.

Another embodiment of the present invention contains a rheology control agent in the concentration range of <NUM>%-<NUM>% w/w, preferably <NUM>-<NUM> % w/w.

Another embodiment of the present invention optionally contains a pH buffer agent in the concentration range of <NUM>-<NUM>% w/w. Preferably the pH buffer agent is mandatory and present in <NUM>-<NUM> % w/w.

Another embodiment of the present invention also contains an antifoam as in the concentration range of <NUM>-<NUM> % w/w.

Another embodiment of the present invention also contains a biocide as in the concentration range of <NUM>-<NUM>% w/w.

Another embodiment of the present invention also contains an antifreeze as in the concentration range of <NUM>-<NUM>% w/w.

Another embodiment of the present invention also contains an antioxidant as in the concentration range of <NUM>-<NUM>% w/w.

The compositions of the present invention contain water as filler to <NUM>% w/w.

An embodiment of the present invention is a process for the preparation of ZC agrochemical formulations. In-can adjuvanted pyrethroid formulations are prepared by mixing in the desired ratios the following formulations:.

The resulting formulation is referred to as a ZC formulation.

The pyrethroid SC formulations may be isolated and stored for further use or prepared in situ shortly before mixing with the corresponding adjuvant CS formulations in order to produce ZC formulations according to the invention (Table <NUM>). In situ preparation of the pyrethroid SC formulation means that the water content of the SC pyrethroid formulation was not filled to <NUM>% as described in Table <NUM>, but rather the water content was reduced to accommodate the concentration of the CS formulation with which the SC formulation is to be mixed to produce a ZC formulation according to the invention.

An embodiment of the present invention is a mixture of SC:CS in the range of a <NUM>:<NUM>% w/w to a <NUM>:<NUM> % w/w ratio.

Assessment of formulation characteristics takes place analogously to DIN <NUM> "Sensory analysis - Simple descriptive test". For this purpose, the samples to be examined are examined visually and, if required, by means of shaking and tilting, for shape, state of matter and colour and further peculiarities (especially, for example, lumps, caking, sediment formation, subsequent thickening, marbling of the sediment etc.).

Particle size is determined either by laser diffraction according to CIPAC MT <NUM> Malvern Mastersizer, medium: propylene glycol) or by using an optical microscope (40x magnification). Stable and convenient formulations are expected to contain small particles in order to ensure both good storage stability in concentrate as well as good suspension stability in aqueous dilution.

Agglomeration is determined either by using an optical microscope (40x magnification). Stable and convenient formulations are expected to contain no agglomerates in order to ensure both good storage stability in concentrate as well as good suspension stability in aqueous dilution.

Suspension stability is evaluated following simplified method according to CIPAC MT <NUM> and is measured in <NUM>% aqueous dilution in CIPAC C or CIPAC D water and determined after <NUM> hour standing time. Stable and convenient formulations are expected to exhibit no or only very little sediment formation at the bottom of the test vessel in order to ensure a homogeneous application of the spray solution.

Storage stability testing is performed for a given number of weeks (w) at different temperatures such as <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or thaw-freeze cycling (= TW; constant temperature change from -<NUM> to +<NUM> and back within one week).

Phase separation directly after storage is reported as sediment fraction and calculated from the quotient H1 [level of the interface layer between sediment phase and supernatant] divided by H0 [total fill height of the sample]: <MAT>.

Alternatively, phase separation directly after storage is reported as separation percentage and calculated from the quotient H0-H1 [total fill height of the sample minus level of the interface layer between sediment phase and supernatant] divided by H0 [total fill height of the sample]: <MAT>.

Stable and convenient formulations are expected to exhibit no or only little phase separation upon storage at elevated temperatures for a prolonged period of time and are easily rehomogenized. Marked phase separation after a short storage time indicates limited storage stability and a significant tendency to formation of sediments that are dispersible only with difficulty, if at all, during storage.

All formulation constituents according to the experiments described in Table <NUM> are combined in a <NUM> Polyethylene screwtop bottle, and <NUM> of glass beads (size <NUM>-<NUM>) are added. The bottle is closed, clamped in an agitator apparatus (Retsch MM301) and treated at <NUM> for <NUM> minutes; in the course of this, the samples heat up. After the time has elapsed, the samples are cooled down to room temperature and the consistency of the formulation is assessed. Appearance is examined by means of a microscope (Zeiss transmitted light microscope, <NUM>-fold magnification), and the particle size is determined by laser dispersion. A very small particle size indicates good grindability, while the presence of agglomerates is a sign of poor dispersion characteristics.

Out of the experiments in Table <NUM> we can select the most suitable dispersants for the preparation of the Pyrethroid SC formulations. Suitable are all combinations where no agglomerates can be seen in the microscopic pictures of the formulations, e.g. examples <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> - <NUM>.

An embodiment of the present invention is also the process directed to the preparation of Suspension Concentrate agrochemical formulations as mentioned below. For the purposes of testing the formulability of pyrethroids as SC formulations with the dispersants identified in Example <NUM>, pyrethroid SC formulations can be prepared by one of the below mentioned methods:.

For the purposes of testing the formulability of pyrethroid as EC formulations all the ingredients specified in Table <NUM> were mixed together in a suitable container (e.g. glass beaker, steel reactor), and stirred with a magnetic stirrer or an overhead stirrer at room temperature until a homogeneous solution is obtained.

An embodiment of the present invention is a process for the preparation of Capsule Suspension agrochemical concentrates. For the purposes of testing the formulability of adjuvants as CS formulations, the CS formulations were prepared by following the steps mentioned below:.

In step (I) adjuvant/adjuvant mixtures b) and isocyanate f) , and, if appropriate an antioxidant m) are mixed together under stirring. Step (I) of the process according to the invention takes place generally at temperature between <NUM> and <NUM>, preferably between <NUM> and <NUM>, particularly preferably between <NUM> and <NUM>, most particularly preferably between <NUM> and <NUM>.

In step (II) an emulgator or a mixture of emulgators h), and, if appropriate, a pH buffer i), an antifoam j), biocides k), an antifreeze <NUM>) are dissolved in water under stirring. Step (II) of the process according to the invention takes place generally at temperature between <NUM> and <NUM>, preferably between <NUM> and <NUM>, particularly preferably between <NUM> and <NUM>, most particularly preferably between <NUM> and <NUM>.

In step (III) the organic phase A) is given to the aqueous phase B) so that an emulsion of A) in B) is obtained. For the preparation of the emulsion one may use the typical emulsifier apparatus utilized for this purpose, for instance a rotor-stator mixer, or a jetstream. Step (III) of the process according to the invention takes place generally at temperature between <NUM> and <NUM>, preferably between <NUM> and <NUM>, particularly preferably between <NUM> and <NUM>, most particularly preferably between <NUM> and <NUM>. The preparation of the emulsion can be made batchwise or continuously.

In step (IV), the emulsion prepared in step (III) is optionally treated with a cross linker g).

In step (V) the mixture obtained in step (III), or optionally in step (IV), is stirred for some time to ensure a full reaction, and efficient formation of the capsules. Generally, step (V) take between <NUM> to <NUM> hours, preferably between <NUM> to <NUM> hours. Step (V) of the process according to the invention takes place generally at temperature between <NUM> and <NUM>, preferably between <NUM> and <NUM>, most preferably between <NUM> and <NUM>.

In step (VI), after the capsule formation reactions are finished, the capsule suspension obtained in step (V) is cooled to room temperature, and subsequently treated with a rheological agent e). If not already done in step (II), a pH buffer i), an antifoam j), biocides k), and an antifreeze L) are added to the obtained capsule suspension.

The according to the present invention process is run under atmospheric pressure.

Based on the quantity of capsule wall forming isocyanate f) and cross linker g), and the obtained particle size of the capsules, it is theoretically possible to calculate the thickness of the capsule wall. This calculated wall thickness of the capsules of the according to the invention obtained capsule suspension lies between <NUM> and <NUM>, preferred between <NUM> and <NUM>, and most preferred between <NUM> and <NUM>.

The adjuvant/adjuvant mixture CS formulation examples are used to prepare ZC formulations according to the invention by mixing the adjuvant/adjuvant mixture CS formulation with a suitable amount of a pyrethroid SC formulation. The adjuvant/adjuvant mixture CS formulation examples prepared according to the invention are listed in Table <NUM>.

The adjuvant CS formulations are stable over time, and show no particle size degradation, capsule instability (Table <NUM>).

Alternatively, the adjuvant/adjuvant mixture (b) can also be formulated as emulsions in water (EW).

Adjuvant, emulsifier, water and optionally polyvinyl pyrrolidone are stirred together until a homogeneous white solution has been obtained. This is then homogenized further with a stator-rotor emulsifier (e.g. Ultra-Turrax®) at <NUM>,<NUM>-<NUM>,<NUM> rpm until a white homogeneous emulsion is obtained. The particle size of the resulting emulsion lies between d50 <NUM>-<NUM>, d90 <NUM>-<NUM> (emulsifier = Pluronic PE <NUM>) or between d50 <NUM>-<NUM>, d90 <NUM>-<NUM> (emulsifier = Aerosil R816). The remaining components are added to the emulsion (biocide, antifoam, antifreeze). Examples of Adjuvant EW Formulations are listed in Table <NUM>.

The technical properties of the EW formulations are shown in Table <NUM>.

For the purposes of testing the formulability of pyrethroids as in-can adjuvanted ZC formulations, pyrethroid SC formulations are stirred together with the adjuvant CS formulations at room temperature, until a homogeneous mixture is obtained. The pyrethroid SC formulations may be isolated and stored for further use or prepared in situ before mixing with the corresponding adjuvant CS formulations in order to produce ZC formulations according to the invention (Table <NUM>). In situ preparation of the pyrethroid SC formulation means that the water content of the SC pyrethroid formulation was not filled to <NUM>% as described in Table <NUM>, but rather the water content was reduced to accommodate the concentration of the CS formulation with which the SC formulation is to be mixed to produce a ZC formulation according to the invention.

Alternatively, it is also possible to mix a pyrethroid SC formulations with an adjuvant/adjuvant mixture CS formulation, and to mix the resulting preliminary ZC formulation with any additional formulation components, or water filler to a final composition of <NUM>%, or to the necessary volume.

Examples of ZC Formulations according to the invention are described in Table <NUM>.

For the purposes of testing the formulability of pyrethroids as in-can adjuvanted SE formulations, pyrethroid SC formulations (Table <NUM>) are stirred together with the adjuvant/adjuvant mixtures EW formulations (Table <NUM>) at room temperature, until a homogeneous mixture is obtained. If necessary, water is added to <NUM>%. SE pyrethroid formulations serve as comparative examples against ZC pyrethroid formulations because the adjuvants added to the pyrethroid SC formulation are not encapsulated and can contribute to crystal growth processes during storage.

The pyrethroid SC formulations may be isolated and stored for further use or prepared in situ shortly before mixing with the corresponding adjuvant EW formulations in order to produce SE formulations (Table <NUM>). In situ preparation of the pyrethroid SC formulation means that the water content of the SC pyrethroid formulation was not filled to <NUM>% as described in Table <NUM>, but rather the water content was reduced to accommodate the concentration of the EW formulation with which the SC formulation is to be mixed to produce an SE formulation.

Comparative examples of SE Formulations are described in Table <NUM>.

The ZC formulations according to the invention are in general stable during storage, and only slightly lose some of their technical properties (Tables <NUM>-<NUM>). On the other hand, the comparative SE formulations are not stable during storage being susceptible to crystal growth or to phase separation of the formulations.

The formulations according to the invention do not show particle size growth, or if any, very limited. This is in contrast to the comparative SE formulations, which always show particle size growth due to the fact that in the SE formulations, the adjuvants are not encapsulated and as such they are directly available to contact the pyrethroid active ingredient. Upon contact with the pyrethroid, the adjuvants can dissolve the pyrethroid and start an Oswald ripening process which leads to the eventual particle size growth of the pyrethroid and a destabilization of the SE formulation, leading to potential settling down of the grown particles. This process is particularly visible for comparative examples <NUM>-<NUM> and <NUM>-<NUM>, and less so for comparative example <NUM>-<NUM>.

In contrast, most of the examples according to the invention are free of crystal growth, and those examples showing some growth, do this to a very small degree. The improved stabilization of the ZC formulations with respect to crystal growth can be attributed to the fact that the adjuvant in the ZC formulations is covered by the capsule's polymeric membrane. This prevents a direct physical contact between the adjuvant and the pyrethroid. This is not possible for the SE formulations, because the adjuvant is emulsified, covered by surfactants, and these emulsifiers do not pose a sufficiently strong barrier to the establishment of physical contacts between the adjuvant and the pyrethroid.

Both comparative and according to the invention formulation examples show good to acceptable stability towards separation during storage and maintain a satisfactory homogeneity over time, as can be seen from the low to acceptable separation percentage. Only after <NUM> weeks at <NUM> do the comparative examples show unacceptable separation.

Also, no significant changes in pyrethroid concentration can be detected during storage for either the comparative or the according to the invention formulation examples.

Pepper plants (Capsicum annuum) or cabbage plants (Brassica oleracea) which are heavily infested by the green peach aphid (Myzus persicae) are treated by being sprayed with the formulation of the desired concentration.

After <NUM> days mortality in % is determined. <NUM> % means all the aphids have been killed; <NUM> % means none of the aphids have been killed.

Cotton plants (Gossypium hirsutum) which are heavily infested by the cotton aphid (Aphis gossypii) are treated by being sprayed with the formulation diluted in water to the desired concentration of active ingredient.

Potato leaves (Solanum tuberosum) are treated by being sprayed with the formulation of the desired concentration and are artificially infested with colorado potato beetles (Leptinotarsa decemlineata).

After <NUM> and <NUM> days mortality in % is determined. <NUM> % means all the beetles have been killed and <NUM> % means none of the beetles have been killed.

Tables <NUM>-<NUM> show that the ZC formulations according to the invention are substantially more active than the comparative SC Formulations, in spite of the fact that both formulations are made of colloidal solid particles of the pyrethroid.

Cabbage leaves (Brassica oleracea) are treated by being sprayed with the formulation diluted in water to the desired concentration and are infested with larvae of the diamondback moth (Plutella xylostella).

After <NUM> days, mortality in % is determined. <NUM> % means all the caterpillars have been killed and <NUM> % means none of the caterpillars have been killed.

As stated earlier, the pyrethroid biological activity is substantially dominated by the form in which the pyrethroid is formulated. Formulations containing dissolved pyrethroid are more biological active than those in which the active is presents in a colloidal solid form. As such, Deltamethrin EC formulation examples (emulsion concentrate, pyrethroid dissolved) show in Tables <NUM>-<NUM> always a higher biological efficacy (higher %mortality) than the comparative Deltamethrin SC (suspension concentrate, pyrethroid suspended as a solid in water) formulation example.

Surprisingly, the ZC formulation examples according to the invention are substantially more active than the comparative SC Formulations, even though both formulations are made of colloidal solid particles of the pyrethroid. The improved performance of the ZC formulations can be attributed to the presence in the formulation of the encapsulated adjuvant. The encapsulated adjuvant is released out of the capsules upon spraying of the formulation spray broth on the target plant/pest. The released adjuvant can then dissolve the solid particles of pyrethroid, thus turning the solid low active pyrethroid into a dissolved highly active pyrethroid. Crucially, this dissolving process occurs only when the formulation is applied on a biological system, and not during storage of the formulation. Otherwise, a substantial amount of crystal growth would be visible during storage of the formulation, and this is not the case (Table <NUM>).

The biological efficacy of the formulations according to the invention was evaluated under field testing conditions. In some cases, the formulations according to the invention showed a higher efficacy than the comparative example DLT EC <NUM> (Formulation Example <NUM>-<NUM>, Table <NUM>).

In some cases, the formulations according to the invention showed a higher efficacy than the comparative example DLT EC <NUM> (Formulation Example <NUM>-<NUM>, Table <NUM>). This is surprising given that the comparative example contains highly biologically active dissolved pyrethroid, and the examples according to the invention contain low active suspended pyrethroid. The encapsulated adjuvant in the ZC according to the invention formulation examples is able to dissolve the pyrethroid after it has been applied on the target pest/plant.

The detailed toxicity evaluation of formulation Deltamethrin ZC <NUM> (formulation example <NUM>-<NUM>) is presented in this document. As can be seen in Table <NUM>, the toxicological properties of the according to the invention ZC pyrethroid formulation are milder than those of the comparative EC/SC formulations. This is shown by the lower acute oral toxicity compared to the comparative EC <NUM> formulation (FL Example <NUM>-<NUM>), and the absence of eye/skin irritation compared to the EC/SC pyrethroid comparative formulations in the screening assays.

The screening battery was conducted with Deltamethrin ZC <NUM> (formulation example <NUM>-<NUM>).

As can be seen in Table <NUM>, the toxicological properties of the according to the invention ZC pyrethroid formulation are milder than those of the comparative EC/SC formulations. This is shown by the lower acute oral toxicity compared to the comparative EC <NUM> formulation (comparative formulation Example <NUM>-<NUM>), and the absence of eye/skin irritation compared to the EC/SC pyrethroid comparative formulations in the screening assays.

Importantly, the improved toxicological profile of the according to the invention ZC formulation example <NUM>-<NUM> does not come at the expense of lower technical stability, as can be seen by the absence of crystal growth during storage (Table <NUM>).

Also, the milder toxicological profile does not correlate with lower biological efficacy (Tables <NUM>-<NUM>): in the contrary, in Table <NUM>, the formulation examples according to the invention are more often more biologically active than EC formulation comparative examples, which have a higher acute toxicity than the according to the invention ZC formulation examples.

In summary, we have now surprisingly found that ZC formulations made up of milled colloidal pyrethroids and encapsulated adjuvant/adjuvant mixtures are surprisingly capable of selectively enhancing the insecticidal efficacy of pyrethroid suspension concentrates against insects, without increasing the mammalian toxicity of the formulation. That is, according to the invention, pyrethroid ZC formulations behave like a pyrethroid EC formulation against agricultural relevant pests (results in Tables <NUM>-<NUM>) but show a significant improvement in mammalian toxicology than the comparable pyrethroid EC formulations (results in Table <NUM>).

Claim 1:
Capsule suspension concentrate comprising
A) a particulate disperse Phase comprising
a) a capsule obtained by reaction of an isocyanate optionally reacted with a crosslinker,
b) the capsule comprising an adjuvant or adjuvant mixture, wherein the adjuvant or adjuvant mixture is selected from the group consisting of "trialkyl phosphate" according to Figure <NUM>, where R1, R2 and R3 can be equal or different. R1, R2, R3 can be any C1-C10 alkyl fragment
<CHM>
or from a mixture of trialkyl phosphates according to Figure <NUM> mixed with vegetable oil alkyl esters.
B) an aqueous Phase comprising a finely dispersed pyrethroid.