GB1605029A - Synergistic acaricidal compositions - Google Patents

Description

(54) SYNERGISTIC ACARICIDAL COMPOSITIONS (71) We, THE WELLCOME FOUNDATION LIMITED, of 183-193 Euston Road, London N.W. 1 a company incorporated in England do hereby declare the invention which was communicated from Wellcome Investments (Australia) Limited of 53, Phillips Street, Concord, 2137, a company in the State of New South Wales, Commonwealth of Australia, for which we pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to novel potentiating compositions and to their use for controlling acarina. The compositions of the invention comprise as one ingredient a thiourea derivative, as defined below, together with a pyrethroid selected from a specified class as the other component.

The pyrethroid ingredient is selected from all of the esters of 2,2-dimethyl-3alkenyl cyclopropane carboxylic acid as defined in formula (II) of British Patent Specification No. 1 413 491. In particular, the pyrethroid ingredient may be selected from the esters of formula (I) below:

wherein R1 and R2 may be the same or different and each is halo such as fluoro, chloro or bromo and wherein R, the alcohol moiety of the ester, is 3-phenoxy benzyl, e-cyano 3-phenoxy benzyl, 5-benzyl-3-furyl methyl, or 2-methyl-3- ( 2-propenyl ) -4-oxo-2-cyclo- penten-l-yl.

Structural formula (I) exemplifies the esters of formula (II) of British Patent Specification No. 1 413 491 and is intended to encompass all the geometric and optical isomers. More particularly the acid moiety of the esters may be selected from the ( + )- cis-isomer, the ( + )-trans-isomer, the ()-cis-isomer, the ()-trans-isomer and the (+)-cis-trans-isomer; the stereochemistry referring to that of the cyclopropane ring.

Moreover, when the group R contains an assymetric carbon centre, the alcohol moiety of the ester may be selected from the ( + ) -isomer, the ( - ) -isomer or the ( i ) -isomer.

Particularly useful esters are those wherein R1 is selected from chloro and bromo.

The preferred pyrethroids of this invention are: 3 - phenoxybenzyl - (i) - cis, trans2,2 - dimethyl - 3 - (2,2 - dichlorovinyl)cyclopropane - 1 - carboxylate (permethrin) and (-) - a - cyano - 3 - phenoxybenzyl - (+) - cis - 2,2 - dimethyl - 3 - (2,2dibromovinyl)cyclopropane - 1 - carboxylate (decamethrin).

It has now been found that the acaricidal activity of these esters is potentiated when used in combination with a thiourea derivative selected from the compounds defined in formula (III) below:

wherein Rs and R' are the same or different and are selected from alkyl of 1 to 4 carbon atoms, and halo; RS is selected from alkyl, alkoxy, both of 1 to 4 carbon atoms and alkenyl of 3 to 4 carbon atoms; and R6 is selected from hydrogen, alkyl of 1 to 5 carbon atoms, alkenyl of 3 to 5 carbon atoms, alkynyl of 3 to 5 carbon atoms and hydroxy- or cyano-substituted alkyl, cycloalkyl-alkyl, tetrahydrofuryl-alkyl or benzyl.

The compounds of formula (III) are already known to be active either against Arachnida (see for example German Offenlegenschrift No. 2 337122) or Insecta and Acarina (see for example British Patent No. 1 138 714) and some of the compounds of formula (III) are active against Arachnida, Insecta and Acarina.

In particular useful potentiation is achieved with combinations containing N'-(4' chloro-2'-methylphenyl ) -N,N-dimethylthiourea (chlormethiuron) in combination with either permethrin or with decamethrin. The potentiating compositions of this invention are effective against strains of acarine ectoparasites and are particularly effective agairst those strains within species such as the cattle-tick Boophilus microplus, which are resistant to conventional organo-phosphorus and carbamate pesticides.

The compositions of this invention may be used as pesticides, especially to control acarine ectoparasites of animals. These pests include mites and ticks. Particular pests include those ticks of the genera Boophilus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermacentor and Anocentor, and mites of veterinary importance for example the sheep scab mite Psoroptes ovens, and other ectoparasites of the suborders Ixodides and Sarcoptiformes.

Such ectoparasites infest stock, domestic animals and fowl depending upon the location of the host and the particular ectoparasite. Common hosts are cattle, pigs, sheep, goats, horses, camels, chickens, dogs and cats.

The compositions of this invention may be applied in a known manner directly to acarine pests or to their environment or in a diluted form in known fashion, as a dip, a spray, a dust, a paste, cream, gel, foam, shampoo or grease, or a pour-on formulation.

Dips are not applied per se, but the animals are immersed in a dipping bath containing the dip wash. Sprays may be applied by hand or by means of a spray race or arch or automatic treadle or pressure pack. Dusts may be distributed over the animals by means of a powder gun by hand application from suitable containers or incorporated in perforated bags attached to trees or rubbing bars. Pastes, foams, creams, gels, shampoos and greases may be applied manually or distributed over the surface of an inert material against which animals rub and transfer the material to their skins. Pour-on formulations are dispensed as a unit of liquid of small volume on to the backs of animals such that all or most of the liquid is retained on the animals.

The compositions may be presented either as formulations ready for use on the animals cr as formulations requiring further dilution prior to application, but both types of formulations comprise a pyrethroid as defined above in combination with a thiourea derivative as defined above in intimate admixture with one or more carriers or diluents.

The carriers may be gaseous or solid or liquid cr comprise mixtures of such substances and may be selected from one or more of the following:- a solvent, an inert carrier, wetting, stabilising, emulsifying, thickening, dispersing and surface active agents.

Dusts may be prepared by intimate admixture of the chosen compound with a powdered solid mert carrier for example suitable clays, kaolin, talcs, powdered chalk, calcium carbonate, Fuller's Earth, gypsum, diatomaceous earths and vegetable carriers.

Sprays of a composition of this invention may comprise a solution in an organic solvent (e.g. those listed below) or an emulsion or suspension in water (dip wash or spray wash) prepared in the field from an emulsifiable concentrate (otherwise known as a water miscible oil) or a water dispersible powder or wettable dispersible powder which may also be used for dipping purposes. The concentrate preferably comprises a mixture of the active ingredients, with or without an organic solvent and one or more emulsifiers. Solvents may be selected from kerosene, ketones, alkanols, xylene, aromatic naphtha, and other solvents known in the formulating art. The concentration of emulsifiers may be varied within wide limits and are conveniently non-ionic or a mixture of non-ionic and anionic surfactants. The non-ionic surfactants will include polyoxyalkylene ethers of alkyl phenols, or of alcohols. The anionic compounds will be salts of alkylaryl sulphonic acids.

Dip washes may be prepared not only from emulsifiable concentrates, but also from wettable powders comprising a composition of this invention in intimate admixture with an inert carrier and one or more surface active agents, and possibly a stabiliser and/or an antioxidant.

Greases may be prepared from vegetable oils, synthetic esters of fatty acids or wool fat together with an inert base such as soft paraffin. A composition of this invention is preferably distributed uniformly through the mixture in solution or suspension.

Greases may also be made from emulsifiable concentrates by diluting them with an ointment base.

Pastes are also semi-solid preparations in which a composition of this invention may be present as an uniform dispersion in a suitable base such as soft or liquid paraffin or made on a non-greasy basis with glycerin, mucilage or a suitable soap. As greases and pastes are usually applied without further dilution they should contain the appropriate percentage of the composition required for treatment.

Pressure packs to apply the active ingredients as aerosol sprays may be prepared as a simple solution of the active ingredients in the aerosol propellant and a co-solvent such as halogenated alkanes and the solvents referred to above, respectively. Pour-on formulations may be made as a solution, emulsion or suspension of a composition of this invention in a liquid medium which is of a viscosity such as to minimize loss of the formulation by run off from the surface of the animals. The pour-on formulation may be applied by a drenching gun, syringe or ladle or any other method known in the art.

A composition of the present invention preferably contains (5-95) O/o of a defined pyrethroid for example one selected from formula (I) and between (5-95) O/o of a thiorea derivative selected from formula (III) as defined hereinabove. The concentration of a composition applied to the pests or to their environment may be in the range of (0.0001-20)0/c weight/volume of the active ingredients.

It will be appreciated from the foregoing that the invention includes: (a) A novel composition comprising a pyrethroid as defined above, and especially an ester exemplified by structural formula (I) in combination with a thiourea derivative exemplified by structural formula (III); (b) A pesticidal formulation comprising a composition as defined in paragraph (a) together with a carrier therefor;, (c) A method of producing such a formulation; and (d) A method of controlling pests of the Order Acarina comprising the application to the pest or its environment, a composition or formulation as defined in paragraph (a) or (b).

The following Examples are provided by way of an illustration of the present invention and should not be construed as in any way constituting a limitation thereof.

EXAMPLE 1.

Engorged female ticks of the Biarra strain of Boophilus microplus are immersed, in groups of 20 ticks per concentration, in a range of dilutions of chlormethiuron in combination with 3 -phenoxybenzyl ()-cis, trans-2,2-dimethyl-3 - ( 2,2-dichlorovinyl) cyclopropane-1-carboxylate (hereinafter referred to as permethrin) at different ratios of chlormethiuron to permethrin.

The composite wash is prepared immediately prior to the test by dilution (with water) of the two constituents. The constituents may be in the form of miscible oil or wettable powder formulations. The desired range of concentrations for the test is obtained by further dilution of this master solution or wash.

The ticks are removed from the wash after 10 minutes, dried, and stuck dorsal side down on double-sided adhesive tape. They remain in this position for 14 days when the numbers laying viable eggs are determined. From this data a regression line is plotted (concentration against % inhibition of egg-production) and the IR90 and 1R99 values determined (Table 1).

IR90 -- concentration at which 90)/c inhibition of egg-production occurs.

IR99 -- concentration at which 99'i inhibition of egg-production occurs.

The values so obtained for the composite wash are compared with similar values obtained for the constituents of the composite wash when used alone. By reference to the equation of the harmonic mean, the factor of potentiation (FOP) is determined (Table 2).

The equation for the harmonic mean is: Proportion of A + Proportion of B X = Proportion of A + Proportion of B IR90 A IR90 B X Y = IR90 mixture of A and B Y x Proportion of A Factor of Potentiation (FOP) = Proportion ofA + B The FOP figures for the IR99 values were calculated in the same way.

EXAMPLE 2.

The activity of mixtures of (- )-a-cyano-3-phenoxybenzyl ( + )-cis-2,2-dimethyl 3-(2,2Zibromovinyl) cyclopropane-l-carboxylate (decamethrin) and chlormethiuron in the form of either a miscible oil or wettable powder formulation were determined in accordance to the method described in Example 1 and the IR90 and IR99 values were determined similarly. (Table 3).

The values so obtained were then used for the evaluation of the factors of potee.

tiation figures for the IR90 and IR99 values respectively. (Table 4).

TABLE 1.

IR 90/99 Values for Chlormethiuron and Permethrin alone and for a 1:1 mixture of Chlormethiuron and Permethrin Compound IR90(%) IR99(%) Chlormethiuron 0.070 0.13 Permethrin 0.066 0.13 Chlormethiuron/Permethrin (1:1) 0.019 0.024 TABLE 2.

Factors of Potentiation for the 1:1 mixture of Chlormethiuron and Permethrin Compound FOP (IR90) FOP (IR99) Chlormethiuron/Permethrin (1:1) 1.8 2.7 F.O.P. -- Factor of Potentiation TABLE 3.

IR 90/99 Values of Chlormethiuron and Decamethrin alone and for a 1:1 mixture of Chlormethiuron and Decamethrin Compound IR90(%) IR99() Chlormethiuron 0.070 0.13 Decamethrin 0.0019 0.0039 Chlormethiuron/Decamethrin (1:1) 0.00072 0.0017 TABLE 4.

Factors of Potentiation for the 1:1 mixture of Chlormethiuron and Decamethrin Compound FOP (IR90) FOP (IR99) Chlormethiuron/Decamethrin (1:1) 2.8 2.2 F.O.P. -- Factor of Potentiation Example 3.

PERMETHRIN/CHLORMETHIURON WETTABLE POWDER Permethrin 15.0% Chlormethriuron 15.0% Celite (Registered Trade Mark) 64.5% Sodium Salt of Condensed Naphthalene 5.0% Sulphonic Acid Sodium Salt of Alkyl Naphthalene 0.5% Sulphonic Acid 0.5% 100.0% Example 4.

DECAMETHRIN/CHLORMETHIURON WETTABLE POWDER Decamethrin 20.0% Chlormethiuron 20.0% Celite 54.0% Sodium Salt of Condensed Naphthalene 5.0% Sulphonic Acid Sodium Salt of Alkyl Naphthalene 1.0% Sulphonic Acid 1.0/o 100.0% Example 5.

PERMETHRIN/CHLORMETHIURON AQUEOUS SUSPENSION Permethrin 10.0% Chlormethiuron 10.0% Fine Silica 10.0% Sodium Salt of Condensed Naphthalene Sulphonic Acid 4.0% Xanthan Gum 0.3% Para Chlorometacresol 0.1% Water 65.6% 100.0% Example 6.

DECAMETHRIN/CHLORMETHIURON AQUEOUS SUSPENSION Decamethrin 15.0 /O Chlormethiuron 15.0% Fine Silica 5.0% Sodium Salt of Condensed Naphthalene Sulphonic Acid 5.0% Xanthan Gum 0.3% Para Chlorometacresol 0.1% Water 59.6% 100.0% WHAT WE CLAIM IS:1. An acaricidal combination comprising a pyrethroid of formula

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (20)

1. **WARNING** start of CLMS field may overlap end of DESC **.

   Example 3.

   PERMETHRIN/CHLORMETHIURON WETTABLE POWDER Permethrin 15.0% Chlormethriuron 15.0% Celite (Registered Trade Mark) 64.5% Sodium Salt of Condensed Naphthalene 5.0% Sulphonic Acid Sodium Salt of Alkyl Naphthalene 0.5% Sulphonic Acid 0.5% 100.0% Example 4.

   DECAMETHRIN/CHLORMETHIURON WETTABLE POWDER Decamethrin 20.0% Chlormethiuron 20.0% Celite 54.0% Sodium Salt of Condensed Naphthalene 5.0% Sulphonic Acid Sodium Salt of Alkyl Naphthalene 1.0% Sulphonic Acid 1.0/o 100.0% Example 5.

   PERMETHRIN/CHLORMETHIURON AQUEOUS SUSPENSION Permethrin 10.0% Chlormethiuron 10.0% Fine Silica 10.0% Sodium Salt of Condensed Naphthalene Sulphonic Acid 4.0% Xanthan Gum 0.3% Para Chlorometacresol 0.1% Water 65.6% 100.0% Example 6.

   DECAMETHRIN/CHLORMETHIURON AQUEOUS SUSPENSION Decamethrin 15.0 /O Chlormethiuron 15.0% Fine Silica 5.0% Sodium Salt of Condensed Naphthalene Sulphonic Acid 5.0% Xanthan Gum 0.3% Para Chlorometacresol 0.1% Water 59.6% 100.0% WHAT WE CLAIM IS:1. An acaricidal combination comprising a pyrethroid of formula

   wherein Rl and R2 may be the same or different and each is halo such as fluoro, chloro or bromo and R is 3-phenoxybenzyl, a-cyano 3-phenoxybenzyl, 5-benzyl-3-furylmethyl or 2-methyl-2-( 2-propenyl) -4-oxo-2-cyclopenten- 1 -yl together with a thiourea of formula

   wherein Rs and R4 are the same or different and are selected from alkyl of one to four carbon atoms and halo, Rj is selected from alkyl, alkoxy, both of one to four carbon atoms, and alkenyl of three to four carbon atoms; and Rs is selected from hydrogen, alkyl of one to five carbon atoms, alkenyl of three to five carbon atoms, alkynyl of three to five carbon atoms and hydroxy- or cyanosubstituted alkyl, cycloalkylalkyl, tetra-hydrofurylalkyl or benzyl.
2. 2. A combination according to claim 1 wherein R' and R2 are the same and are chloro or bromo.
3. 3. A combination according to claim 1 or 2 wherein the pyrethroid is 3 - phen oxybenzyl - (+) - cis, trans - 2,2 - dimethyl - 3 - (2.2 - dichlorovinylbcvcloprepane- carboxylate or (-) - ly - cyano - 3 - phenoxybenzyl - ( + ) - cis - 2,2 - dimethyl3 - (2,2 - dibromovinyl ) cyclopropane - 1 - carboxylate.
4. 4. A combination according to any of claims 1 to 3 wherein the thiourea is N' (4' - chloro - 2' - methylphenyl) - N,N - dimethylthiourea.
5. 5. A combination comprising N' - (4' - chloro - 2' - methylphenyl) - N,Ndimethylthiourea together with 3 - phenoxybenzyl - (+) ) - cis, trans - 2,2 - dimethyl3 - (2,2 - dichlorovinyl)cyclopropane - 1 - carboxylate or (-) - a - cyano - 3 phenoxybenzyl - ( + ) - cis - 2,2 - dimethyl - 3 - (2,2 - dibromovinyl)cyclopropane 1 - carboxylate.
6. 6. A combination according to any of claims 1 to 5 comprising from (5-95) % weight by weight of the said pyrethroid together with from (5-95) 4 weight by weight of the said thiourea.
7. 7. A process of preparing a combination as defined in any of claims 1 to 6 comprising the admixture of the said pyrethroid with the said thiourea.
8. 8. An acaricidal formulation comprising a combination as defined in any of claims 1 to 7 in admixture with a carrier or diluent therefor.
9. 9. A formulation according to claim 8 in the form of a miscible-oil, wettable dispersible powder, dusting powder, aqueous suspension, pressure-pack or diluent free formulation.
10. 10. A formulation according to claim 8 or 9 comprising from 0.0001 Y to 20% weight per volume of the active ingredients.
11. 11. A process of preparing a formulation as defined in any of claims 8 to 10 comprising the admixture of a combination as defined in any of claims 1 to 6 with a carrier or diluent therefor.
12. 12. A method of controlling ectoparasites of the Order Acarina of mammals and birds comprising the application of a ccmbination as defined in any of claims 1 to 6 to the ectoparasite or to its environment.
13. 13. A method according to claim 12 wherein the said thiourea is ' - (4'chloro - 2' - methylphenyl) - N,N - dimethylthiourea and the said pyrethroid is 3phenoxybenzyl - (+) - cis,trazzs - 2,2 - dimethyl - 3 - (2,2 - dichlorovinyl)cyclopropane - 1 - carboxylate or ( - ) - sL - cyano - 3 - phenoxybenzyl - (I) - cis - 2,2dimethyl - 3 - (2,2 - dibromovinyl)cyclopropane - 1 - carboxylate.
14. 14. A method according to claim 12 or 13 wherein the ectoparasite is of the genus Boophilus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermacentor or Anocentor.
15. 15. A method according to any of claims 12 to 14 wherein a formulation comprising the said pyrethroid together with the said thiourea in admixture with a carrier or diluent is applied.
16. 16. A method according to claim 15 wherein the formulation is in the form of a dusting-powder, pressure-pack or aqueous suspension.
17. 17. A method according to claim 15 wherein an aqueous emulsion prepared from a miscible-oil, wettable dispersible powder or diluent free formulation is applied.
18. 18. A method according to any of claims 15 to 17 wherein the formulation comprises from 0.0001% to 20% weight per volume of the active ingredients.
19. 19. An acaricidal formulation substantially as hereinbefore described with particular reference to Examples 3, 4, 5 and 6.
20. 20. A method of controlling ectoparasites of the Order Acarina substantially as hereinbefore described with particular reference to Examples 1 and 2.