Multiple emulsion technology is mainly used in the formulation of cosmetics, pharmaceutical and cleaning products in order to provide prolonged active ingredient delivery systems.

EP-A-0,507,693 describes water-in-oil-in-water (W/O/W) cosmetic formulations using a perfluoropolyether as a medium oily layer, esters of sucrose as a hydrophilic emulsifier system, polyglyceryl methacrylate as a water soluble gelling agent and dodecylglycol polyethoxylated or lecithin as lipophilic emulsifier system. EP-A- 0,614,660 describes another W/O/W cosmetic formulations for skin-care effects based on hydrophilic active ingredients, such as biolysat hafnia, UV filter, sodium lactate, and lipophilic active ingredients, such as UV filter, vitamin A palmitat, using aqueous gelling agents such as xanthan gum, carbomers, polyglyceryl methacrylate, and polyethoxylated hydrogenated castor oil as the lipophilic emulsifier system. EP- A-0,715,842 and EP-A-0,717,978 describe rinse-off W/O/W cream formulations for delivery of a topically-active ingredient to skin or hair, where cyclic volatile silicone compounds (e. g. cyclomethicone) are used as the medium oily layer and polyethoxylated and/or polypropoxylated ether of fatty acid (C6 to C22) alcohol are used as the lipophilic emulsifier system and a hydrophilic emulsifier capable of forming liquid crystals was optionally incorporated. US-A-4,931,210 relates to a process for producing cosmetic W/OMI multiple emulsions using a polyglycerol polyricinoleate as emulsifier and heating the water-in-oil (W/O) primary emulsion to 50-80°C. WO-A-99/707463 relates to W/O/W medicinal compositions, using dodecane as a medium oily layer, lecithin or polyethoxylated alkylamides as hydrophilic emulsifier system, polyvinylpyrrolidone, polyethyleneglycol (PEG) or xanthan gum as water soluble thickeners and polyglyceryi polyricinoleate or lecithin as a lipophilic emulsifier system. Liquid controlled release formulations, such as microporous microcapsufes, are provided by using WIONV formulations as the support medium of the technology and subsequently removing an organic solvent from the same medium (US-A-4,857,335).

US-A-4,875,927 describes a process of preparing herbicidal W/O/W multiple emulsion comprising 75 g/i or more of a salt of a herbicidal bipyridylium diquaternary cation as an active ingredient. This multiple emulsion has a lower oral toxicity than conventional aqueous formulations and incorporate a condensate of p-nonylphenol with propylene oxide and ethylene oxide as hydrophilic emulsifier system and a block c-polymer of poly-12-hydroxy stearic acid and polyethoxylated or a reaction product of polyisobutylene succinic anhydride and ethanolamine as lipophilic emulsifier.

EP-A-0,391,124 relates to an oil-in-water-in-oil (01/W/02) cosmetic formulation with skin-care effect, using a ceramide fat as inner oily phase (01), fatty acid esters of polyethoxylated sorbitan or sucrose as hydrophilic emulsifier system, polyol as a water soluble humectant, phospholipides or polydimethylsiloxanes as a lipophilic emulsifier system and polysiloxanes as the outer oily phase (02). EP-A-0,559,013 describes other 01 N11/02 cosmetic formulations using polyglycerol ricinoleate as the hydrophilic emulsifier system and polyoxyalkylene polysiloxanes as the lipophilic emulsifier system.

Conventional pesticide formulations, especially with insecticides, can sometimes exhibit a rather high acute oral toxicity and severe irritation to skin and eyes. Besides this, it is often a problem to co-formulate two or more active ingredients of pesticides, which can not be formulated directly together due to their chemical and/or-physical properties (i. e. risk of decomposition).

Tadros in Colloidal Aspects of Pesticidal and Pharmaceutical Formulations-An Overview, Pesticide Science, 26 (1), p. 72-73 (1989) suggests a two-stage manufacture process for O/W/0 formulations in which a primary oil-in-water emulsion is then emulsified into oil at low shear to avoid inversion of the first emulsion. The constraint of low shear implies that the multiple droplets are fairly large with an average diameter of 30 to 50 microns.

It has now been found, that the present invention has overcome the above mentioned problems for pesticides and that additionally an increase in the efficacy of the formulated pesticides could be detected. A stable formulation was achieved by using high shearing effects in the final preparation step, which reduced the size of the multiple droplets.

The invention is characterized by an oil-in-water-in-oil multiple emulsion (01/W/02) with a multiple droplet size of less than 25 microns, preferably in the range of 3 to 24 microns, which comprises of an inner oily phase (01), an aqueous intermediate layer (W) and an outer oily phase (02) and which comprises one or more pesticides.

Preferably the inner oily phase or the inner and outer oily phase comprises one or more pesticides.

'Multiple droplet'as used herein means the water droplet (W) containing emulsified droplets of the inner oily internal phase (01).

The inner oily phase (01) generally comprises an organic solvent having an acute oral LD 50 toxicity value for rats higher than 2000 mg/kg body weight, a molecular weight lower than 500, preferably lower than 240, and a cinematic viscosity, measured in all cases at 20°C with a rotation viscometer, lower than 20 mm2/sec, preferably less than 5 mm2/sec, where LD 50 is the dose, which causes 50 % mortality of the tested animals.

The inner oily phase (01) preferably comprises an oil from the group of: a) vegetable and/or animal oils, which may be a mixture of fatty acids, and their esterified forms, such as fatty esters, resulting from the reaction between vegetable and/or animal oils, such as coconut oil, rape oil, sunflower oil, cotton oil, maize oil, linseed oil, palm oil, palm kern oil, soya oil, thistle oil, castor oil, tallow oil, beef tallow and Ci to C5 alcohols, preferably Ci to C3 alcohols, such as methyl, ethyl, n-propyl, isopropyl alcohol ; aliphatic esters, preferably with methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and esters of fatty acids, preferably Ci to Cis fatty acids, such as caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, oleic acid and mixtures thereof and preferably mixtures of caprylic and capric acids methyl esters (e. g. eRadia 7983, Fina Chemicals, Belgium); b) acid esters, including mono-, di-and tri-esters, such as ester derivatives of lactic acid, preferablylauryl lactate and/or 2-ethyl hexyl lactate, adipic acid, preferably as diisopropyl adipate (e. g. eCrodamol DA, Croda Oleochemicals, UK) and diisobutyl adipate; citric acid, preferably tributyl citrate and/or acetyl tributyl citrate, glutaric acid, succinic acid, preferably dibasic esters, more especially mixtures of methyl esters of adipic, glutaric and/or succinic acids; c) terpenes, such as d-limonene.

The organic solvents for the inner oily phase (01) are optinally, depending on chemical and/or physical properties of the pesticides, combined with ketones, such as 2-heptanone, n-octyl pyrrolidone, n-dodecyl pyrrolidone, acetophenone and/or cyclohexanone to ensure that the active ingredients stays in the inner oily phase (01).

The inner oily phase (01) optionally comprises further additives and/or auxiliaries : e. g. a) one or more non ionic hydrophilic emulsifiers, preferably non ionic hydrophilic emulsifiers having a HLB number in the range of 9 to 12, especially 11 to 11.5, more preferred from the group of polyethoxylated derivatives, preferably 5 and/or 6 EO (EO means an ethylene oxide unit) moles, of fatty alcohols, such as oleic alcohol (e. g. eVolpo N5, Croda Oleochemicals, UK, main component oleic alkohol polyethoxylated- (5)-) and/or castor oil and polyethyleneglycol with a molecular weight of about 400 (PEG 400), fatty acid esters, such as oleates, especially PEG 400 monooleate (e. g. eRadiasurf 7403, Fina Chemicals, Belgium ; sCithrol 4 MO, Croda Oleochemicals, UK).

HLB is the abbreviation for hydrophilic-lipophilic-balance, as described by Griffin, J.

Soc. Cosmet. Chem 1,34 (1949) and 5,249 (1954). b) one or more antifreeze agents, preferably of diols, monopropylene glycol, hexylen glycol, urea and/or sugar derivatives thereof. c) one or more pesticide stabilising agents preferably acetic acid, citric acid, 2,6-di- tert.-butyl-4- (dimethylaminomethyl) phenol, 2-tert.-butyl-4-methoxyphenol and 3-tert.- butyl-4-methoxyphenol.

The outer oily phase (02) generally comprises a mineral oil having an acute oral LD 50 toxicity value for rats higher than 2000 mg/kg body weight, preferably higher than 5000 mg/kg, a distillation range from 200°C to 350°C, preferably 230°C to 310°C, a cinematic viscosity higher than 5 mm2/s and lower than 50 mm2/sec, preferably from 10 to 30 mm2/sec, and an average molecular weight of 200 to 400, preferably 230 to 320.

Examples of such mineral oils for the outer oily phase (02) include : a) light grade polyisobutenes, such as eNapvis X10 and eNapvis X35 (both from BP Chemicals, main component polyisobuten) ; b) isoparaffins, such as eIsopar V (Exxon, main component isoparaffin); c) C5-, C6-, C7-cycloparaffins, such as Nyflex 800 and eNytex 801 (both from Nynas, main components cycloparaffins).

The outer oily phase (02) optionally comprises further additives and/or auxiliaries such as non ionic lipophilic emulsifiers preferably having a molecular weight higher than 500: e. g. a) a non ionic lipophilic emulsifier having an HLB number of 4.5 to 7, preferably 6 to 6.5, preferably oleic derivatives and/or glycerol derivatives, more preferably a combination of them, such as glycerol dioleate and/or trioleate, glycerol olostearate (polyethoxylated or not), polyglycerol polyoleate, such as triglycerol monooleate (e. g.

#Drewpol 3.1.0, Stepan), tetraglycerol tetraoleate, decaglycerol tetraoleate (e. g.

#Drewpol 10.4.0, Stepan), decaglycerol octaoleate, decaglycerol decaoleate, especially tetraglycerol tetraoleate (e. g. 3Nitconol 14, CK Witco, USA), b) a second non ionic lipophilic emulsifier, preferably a block co-polymer of poly-12- hydroxy stearic acid and/or polyalkylene glycol, such as eAtlox 4912 (Uniquema), and/or random polymeric structure compounds (tridimensional networks) synthesized from polyols, polyethylenglycol, aliphatic carboxylic acids, aliphatic polycarboxylic acids and/or anhydrides, such as eAtlox 4914 (Uniquema).

Light grade polybutenes as described above are preferably manufactured from a wholly aliphatic mixed C4 feedstock consisting essentially of iso-butene with n- butenes.

Light napthenic distillates, such as cycloparaffins, as described above are preferably manufactured from a Venezuelan heavy naphtenic feedstock free from n-paraffins and consisting essentially of bitumen and heavy distillates.

Isoparaffinic structure as described above are pure synthetic products.

Pesticides, as active ingredients, are disclosed in the'The Pesticide Manual', 12th Ed., Editor: C D S Tomlin, British Crop Protection Council, Farnham 2000, especially insecticides, acaricides, nematicides, fungicides, herbicides, plant growth regulators, rodenticides and anthelminthics, preferably insecticides, more preferred insecticides selected from the group of : neonicotinoids, e. g. imidacloprid, acetamiprid, thiamethoxam, thiacloprid, tefuranitozine, clothianidin ; carbamates, e. g. triazamate, aldicarb, thiodicarb, formetanate, carbaryl, pirimicarb; pyrethroids, e. g. acrinathrin, tralomethrin, fenvalerate, lambda-cyhalothrin, tefluthrin, etofenprox, cypermethrin, deltamethrin ; organophosphates, e. g. triazophos, ethoprofos; fiproles, e. g. fipronil, ethiprole ; cyclodienes, e. g. endosulfan ; benzhydrazides, e. g. tebufenozid.

The following terms and/or abbreviations are used to describe the invention: oil-in- water-in-oil multiple emulsion (01/W/02), which is a synonym for the oil-in-water-in- oil formulation (O/W/O) ; the inner oily phase (01), the aqueous phase (Wp), which results in the aqueous intermediate layer (W); the inner oil-in-water emulsion (01/W) and the outer oily phase (02).

In the preferred oil-in-water-in-oil multiple emulsion (01/W/02) : the inner oily phase (01) is in the range of 15 to 50 % (w/w), preferably 20 to 37 % (wlw) ; the non ionic hydrophilic emulsifier or a mixture thereof is in the range of 1.5 to 5 % (w/w), preferably 2.0 to 2.5 % (w/w) ; the antifreeze agent is in the range of 1 to 3.5 % (w/w), preferably 1.5 to 2.5 % (w/w) ; the pesticide stabilising agent is in the range of 0.01 to 0.2% (w/w) ; the aqueous intermediate layer is in the range of 10 to 35% (w/w), preferably 15 to 25 % (wlw) ; the outer oily phase (02) is in the range of 30 to 60 % (w/w), preferably 35 to 55 % (w/w) ; the non ionic lipophilic emulsifier or a mixture thereof is in the range of 3 to 7 % (w/w), preferably 3 to 5%.

The concentration of pesticides in the oil-in-water-in-oil multiple emulsion (01/W/02) is preferably 0.01 to 100 g active ingredienVI, e. g. 0.05 to 50 g active ingredient/I.

The oil-in-water-in-oil multiple emulsions (01/W/02), according to the invention, are often"non classified"in terms of acute toxicity. They can contain multiple, formerly incompatible active ingredients, which could not be formulated directly together due to their chemical and/or physical properties (e. g. risk of decomposition). Additionally, these oil-in-water-in-oil multiple emulsions (01/W/02) enhance biological activity with respect to speed and dosage compared with standard formulations.

Besides this, the oil-in-water-in-oil multiple emulsions (01/W/02) are still liquid, which allows e. g. low and/or ultra low volume spray applications, and which are considered by customers as a safe and convenient way to protect widely crops against different types of weeds, diseases and pests, where a mixture of suitable pesticides is needed.

The process for the manufacture of an emulsion (01/W/02) according to the invention usually comprises two steps: The first step is the preparation of an inner oil-in-water emulsion (01/W), comprising a) preparation of an inner oily phase (01) by dissolving one or more pesticides in one or more organic solvents followed by the addition of one or more non ionic hydrophilic emulsifiers, which promotes the formation of an inner oil-in-water emulsion (oit), by using low shearing mixing effects, carried out by a mixer (e. g. paddle agitator). b) preparation of an aqueous phase (Wp), preferably obtained by dissolving an one or more antifreeze agents at room temperature using low shearing mixing effects, preferably carried out by a mixer (e. g. paddle agitator). The mixing operation is maintained until a homogeneous aqueous solution is obtained. c) preparation of an inner oil-in-water emulsion (01/W), containing one or more pesticides, by dispersing, an inner oily phase (01), obtained in a), in an aqueous phase (Wp), obtained in b), at room temperature using high shearing mixing effects, carried out for instance by Ultra-Dispenser stirrer, such as a rotor-stator mixer available from companies like Silverson (UK) and IKA (Germany). The mean diameter of the inner oily phase (01) droplets, dispersed in an aqueous phase (Wp), should be lower than 1.5 microns to ensure later on a good and stable quality of the oil-in-water-in-oil multiple emulsion.

The second step is the preparation of a final oil-in-water-in-oil emulsion (01/W/02) by dispersing an inner oil-in-water emulsion (01/W) from the fist step in an outer oily phase (02) comprising the d) preparation of an outer oily phase (02), e. g. by dissolving one or more pesticides in one or more organic solvents followed by the addition of one or more lipophilic emulsifiers using low shearing mixing effects, carried out preferably by a mixer (e. g. paddle agitator), to promote the later formation of the water-in-oil emulsification, in which the dispersed phase is the inner oil-in-water emulsion (01/W). e) preparation of a final oil-in-water-in-oil emulsion (01/W/02) by dispersing an inner oil-in-water emulsion (01/W), obtained in c), in an outer oily phase (02), obtained in d), at room temperature using high shearing mixing effects, carried out by Ultra- Dispenser stirrer, such as a rotor-stator mixer available from companies like Silverson (UK) and IKA (Germany) for high shearing mixing effects. The choice of the speed for the shearing mixing effects is crucial for the final size of the multiple droplets.

At the end of the manufacturing process the droplet average characteristics of an oil- in-water-in-oil multiple emulsion (01/W/02), containing one or more pesticides, are determined using a microscope.

The terms'low shearing mixing effects'and'high shearing mixing effects'used to explain the manufacture process of a multiple emulsion (01/W/02) according to the invention, correspond to different average sizes of the resulting multiple droplets.

That means 30 to 50 microns when using'low shearing', less than 25 microns (in the range of 3 to 24 microns) when involving'high shearing'. The assessment of the mean diameter of the resulting multiple droplets is carried out by examination of an oil-in-water-in-oil multiple emulsion (01/W/02) sample under the microscope.

The invention also relates to: a) a method of controlling weeds, diseases and pests, preferably for controlling harmful arthropods, especially insects, which comprises applying an effective amount of oil-in-water-in-oil emulsion (01/W/02), containing one or more pesticides, preferably insecticides, especially a pyrethroid, for treating and/or protecting crops, for instance in the form of a low volume and/or ultra low volume and/or oily dilution. b) the use of oil-in-water-in-oil emulsion (01/W/02), containing one or more pesticides, preferably insecticides, especially a pyrethroid, as a formulation in crop protection, which could be applied for treatment and/or protection of crops, for instance by diluting the oil-in-water-in-oil emulsion (01/W/02) with an oily thinner, e. g. #Norpar 15 (Exxon, main component paraffin), prior to application.

The present invention is illustrated by the following examples, without limiting the invention thereto.

The cited substances are defined as follows : arcadia 7983 (mixture of methyl ester of caprylic and capric acid; manufacturer (Mfc) Total Fina); eCrodamol DA, diisopropyl adipate; Mfc Croda); eVolpo N5 (oleic alkohol polyethoxylated- (5)- Mfc Croda); sRadiasurf 7403 (PEG 400 monooleat ; Mfc Total Fina); eCithrol 4 MO (PEG 400 monooleat ; Mfc Croda); eNapvis X10 and sNapvis X35 (polyisobuten ; Mfc BP Chemicals); # Isopar V (isoparaffin; Mfc Exxon); #Nyflex 800 and #Nytex 801 (cycloparaffins ; Mfc Nynas); eDrewpol 3.1.0 (triglycerol monooleat ; Mfc Stepan); eDrewpol 10.4.0 (decaglycerol tetraoleat ; Mfc Stepan); eWitconol 14 (tetraglycerol tetraoleat ; MfcWitco) ; °Atlox 4912 and #Atlox 4914 (Mfc Uniquema); #Norpar 15 (paraffin; Mfc Exxon). Preparation examples Example 1: Components of Multiple Emulsion Ingredients Concentration (01/W/02) % (w/w) Active Ingredient deltamethrin 0.625 Solvent (Inner Oily Phase, 01) #Radia 7983 36.575 Non Ionic Hydrophilic Emulsifier #Radiasurf 7403 2.230 Aqueous Intermediate Layer (W) Water 20.000 Non ionic Lipophilic Emulsifier #Atlox 4914 1.000 Non ionic Lipophilic Emulsifier #Witconol 14 3.000 Solvent (Outer Oily Phase, 02) #Nyflex 800 36.570 Example 2: Components of Multiple Emulsion Ingredients Concentration (O1/W/O2) % (w/w) Active Ingredient acrinathrin 0.125 Solvent (Inner Oily Phase, 01) #Radia 7983 19.875 Non ionic Hydrophilic Emulsifier #Radiasurf 7403 2.230 Aqueous Intermediate Layer (W) Water 20.000 Non ionic Lipophilic Emulsifier eAtlox 4914 1.000 Non ionic Lipophilic Emulsifier #Witconol 14 3.000 Solvent (Outer Oily Phase, 02) #Nyflex 800 53.770 Example 3: Components of Multiple Emulsion Ingredients Concentration (01/W/02) % (w/w) Active Ingredient endosulfan 0.625 Solvent (Inner Oily Phase, 01) °Radia 7983 36.575 Non Ionic Hydrophilic Emulsifier ORadiasurf 7403 2.230 Aqueous Intermediate Layer (W) Water 20.000 Non ionic Lipophilic Emulsifier eAtlox4912 0.750 Non ionic Lipophilic Emulsifier eWitconol 14 3.250 Solvent (Outer Oily Phase, 02) #Nyflex 800 36.570 Example 4: Components of Multiple Emulsion Ingredients Concentration (01/W/02) % (w/w) Active Ingredient deltamethrin 0.625 Solvent (Inner Oily Phase, 01) #Radia 7983 36.575 Non ionic Hydrophilic Emulsifier #Radiasurf 7403 2.230 Aqueous Intermediate Layer (W) Water 20.000 Non ionic Lipophilic Emulsifier #Atlox 4914 1.000 Non Ionic Lipophilic Emulsifier eWitconol 14 3.000 Solvent (Outer Oily Phase, 02) #Napvis X35 36.570 Example 5: Components of Multiple Emulsion Ingredients Concentration (01/W/02) % (w/w) Active Ingredient fipronil 0.625 Solvent (Inner Oily Phase, 01) XRadia 7983 36.575 Non Ionic Hydrophilic Emulsifier eRadiasurf 7403 2.230 Aqueous Intermediate Layer (W) Water 18.000 Antifreeze Agent monopropylene-2. 000 glycol Non Ionic Lipophilic Emulsifier eAtlox 4914 1.000 Non Ionic Lipophilic Emulsifier eWitconol 14 3. 000 Solvent (Outer Oily Phase, 02) WNyflex 800 36.570 Biological examples Example 1: Efficacy of deltamethrin formulations on Heliothis virescens The efficacy of deltamethrin in different formulations was tested by spraying cotton plants (200 1/ha) infested with Heliothis virescens (tomato budworm). For each formulation type and deltamethrin dosage two independent trials, with 20 larvae each, were conducted. Assessment of mortality, as an indicator of activity, was carried out 24 hours after application. Average values (% dead larvae) are shown below.

Results Formulation type Active ingredient and Assessment time Mortality application dosage after application (% dead (hours) larvae) EC 25 g/l deltamethrin (10 g/ha) 24 100 (Standard formulation) in deltamethrin (3 g/ha) 24 70 Water1) deltamethrin (1 g/ha) 24 43 SC 50 g/l deltamethrin (10 g/ha) 24 100 (Standard formulation) in deltamethrin (3 g/ha) 24 85 Water 1) deltamethrin (1 g/ha) 24 68 O/W/O 1.25 g/l deltamethrin (10 g/ha) 24 100 (Oil-in-water-in-oil deltamethrin (3 g/ha) 24 100 formulation) in Paraffin 2) deltamethrin (1 g/ha) 24 65 O/W/O 1. 25 g/l No active ingredient 24 15 (Blank formulation) Untreated control No active ingredient 24 20 Paraffin (#Norpar 15) 2) Untreated control No active ingredient 24 0 Water 1) An increase of activity is seen with the use of the oil-in-water-in-oil O/W/O 1.25 g/l formulation compared to the use of standard EC 25 g/l and SC 50 g/l formulations.

Example 2: Efficacy of deltamethrin formulations on Spodoptera littorals Example 1 was repeated, replacing Heliothis virescens with Spodoptera littorals (Egyptian cotton leafworm). Assessment of mortality was carried out 24 hours or 48 hours after application. Results are shown below.

Results Formulation type Active ingredient and Assessment time Mortality application dosage after application (% dead (hours) larvae) EC 25 g/l deltamethrin (10 g/ha) 48 100 (Standard formulation) in deltamethrin (3 g/ha) 48 75 Water1) deltamethrin (1 g/ha) 48 30 SC 50 g/l deltamethrin (10 g/ha) 48 100 (Standard formulation) in deltamethrin (3 g/ha) 48 80 Water1) deltamethrin (1 g/ha) 48 28 O/W/O 1. 25 g/l deltamethrin (10 g/ha) 24 100 (Oil-in-water-in-oil deltamethrin (3 g/ha) 24 100 formulation) in Paraffin 2) deltamethrin (1 g/ha) 24 60 O/W/O 1. 25 g/l No active ingredient 24 20 (Blank formulation) Untreated control No active ingredient 24 20 Paraffin (#Norpar 15) 2) Untreated control No active ingredient 48 0 Water 1) Again, an increase in activity is seen with the use of the oil-in-water-in-oil O/W/O 1.25 g/i formulation compared to the use of the standard EC 25 g/t and SC 50 g/I formulation. Additionally the speed of activity is enhanced by the use of the oil-in- water-in-oil 0/W/O 1.25 gel formulation, which achieved higher control after 24 hours compared with the standard EC 25 g/i and SC 50 g/t formulations after 48 hours.