NZ195796A

NZ195796A - Pesticidal compositions containing carboxylic acid derivatives

Info

Publication number: NZ195796A
Application number: NZ195796A
Authority: NZ
Inventors: W Bonin; J Martel
Original assignee: Roussel Uclaf
Priority date: 1979-12-10
Filing date: 1980-12-09
Publication date: 1984-08-24
Also published as: AU6520780A; FR2471187B1; AU543379B2; OA06650A; GB2065475B; FR2471187A1; IT8050334A0; AU561371B2; AU3165184A; DE3046527C2; JPS5692818A; GB2065475A; ZA807621B; IT1146066B; DE3046527A1

Description

New Zealand Paient Spedficaiion for Paient Number 1 95796 1 6 AMENDED under Section Patents A« 1953 from of,the ASSISTANT COMMISSIONER OF PATENTS 24 AUG 1984 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION "COMPOSITIONS FOR THE CONTROL OF PARASITES IN WARM-BLOODED ANIMALS" Priority Date(s): . J 4*.''?f(.

Complete Specification Filed: 3: Class: Publication Data: . 24. -:384. - • P.O. Journal, No: . . . ..

/WE ROUSSEL-UCLAF, a French Body Corporate of 35 Boulevard des Invalides, Paris 7eme/ France, hereby declare the invention, for which/we pray that a patent may be granted to nig/us, and the method by which it is to be performed, to be particularly described in and by the following statement:- -I - flowed by page - lAr 195796 This invention relates to new compositions adapted for administration to a portion of the surface of. the body 5 of warm-blooded animals for controlling parasites on the said animals as well as to methods of using such compositions.

The compounds of general formula If a-co2-b (I) wherein A represents a_group of formula: h3c ch3 z 1 ~2 [in which either and Z^ each represents a methyl radical 15 or Z^ represents a hydrogen atom and Z^ represents a radical of formula: R R / 195796 1C (in which R^ represents a hydrogen o7_ halogen atom and Rj and . which may bo the same or different, each represents a halogen atom or a ^ al.kyl radical)]; or a group of formula: (in which-Y^ and which may be at any of the possible positions on the benzene nucleus and which may be the same or different, each represents a hydrogen or halogen atom, a alkyl radical or a alkoxy radical): and B represents a benzyl radical (optionally substituted hv one or more subst i.tuents selected from Cj L alkyl radicals, ^ alkenvl radical?, C^ alkenyloxy radicals, ^ alkadienvl radicals, methylene-5 dioxy radicals, benzyl radicals and halogen atoms); 15 a group of formula: 195796 (in which R^ represents an organic ^ aliphatic radical containing one or more carbon-carbon unsaturations); a group of formula: II n- (in which -R^ represents a group of I formula -C. = N or -C=CII, R^ represents a chlorine atom or a methyl radical and n is 0, 1 or 2); or a group of formula: 100° 195796 -CH 2 0 (in which , R^ , Rg and Rg, which may be the same or different, each represents a hydrogen atom, a chlorine atom or a methyl radical and the symbol S/I indicates 5 an aromatic ring or a dihydro or tetrahydro analogue thereof), are known products; see for example British Patent Specifications Nos. 1,168,796; 1 .££9.615; 1.439,616 and 1,413,491. "be present in one or more isomeric forms as well as mixtures, thereof, show interesting pesticidal properties and especially insecticidal, acaricidal , nematocidal and/or fungicidal properties. Thus, certain compounds of formula I display only one of these properties but others display several or indeed all of these properties.

Hitherto the methods of administration known for the compounds of formula I in their use to control parasites of warm-blooded animals were methods of administration by digestive, parenteral or topical 20 routes and consequently only the corresponding compositions were known.

We have now found that it is possible to obtain excellent results in the control of parasites on warmblooded animals by administering these compounds of The compounds of general formula I, which may general formula I according to a method 1 Q r I X <-> "pour on" method which consists of painting a small surface f and preferably the dorsal spine, of the body of the animal with a solution containing the active product to obtain an effect over the whole body of the animal.

That this method would be suitable and indeed advantageous for the compounds of general formula I could not have been predicted since this method is of course not generally applicable to any active product but can be applied only to chemical compounds capable of passing through the skin barrier and of migrating whilst either keeping their activity, that is to say without being degraded, or of being degraded into metabolites which are themselves active. Nothing in the prior art suggests the use of "the compounds of general formula I in such a'method.

Accordingly, in its broadest aspect, the present invention provides a method of controlling parasites on a non-human warm-blooded animal which comprises administering to the said animal by the "pour-on" method (as herein defined) a compound of formula I as hereinbefore defined.

In one embodiment, the present invention provides a method of treating or preventing an infestation by para- \ sites of a non-human warm-blooded animal which comprises applying to a portion of the surface of the body of the said animal an effective amount of a composition comprising at least one compound of formula I as hereinbefore defined in association with a vehicle capable of permitting passage of the compound of formula I through the skin barrier of the animal.

According to a further feature of the present invention 195796 there is provided a composition suitable for use in a method as defined above comprising as active ingredient at least one compound of formula I as hereinbefore defined in association with a vehicle capable of permitting passage of the active ingredient through the skin barrier of the animal.

As described above the compositions according to the invention can be applied to animals by the "pour on" method and thus, due to this unexpected finding, such compositions are of great interest industrially as they enable excellent pesticidal results to be obtained very quickly and in a lasting manner using very small amounts of the compounds of general formula I.

.The compositions according to the invention permit simple, clean and economic application of the -compounds of general formula I, showing a number of advantages over the hitherto known compositions for administration by other methods. Thus, whilst . administration by the digestive route gives good results, it must be discarded if possible for it can cause gastric disorders and must be reserved particularly for the control of parasites located in the stomach.

Administration by the use of baths also gives quite good results. Unfortunately, however, it requires a fairly large amount of active product and, particularly in the case of pyrethrinoids it is necessary to renew the bath often since these compounds, generally speaking, are easily degraded.

Administration by the parenteral route is to be avoided wherever possible, since it is not easy to inject all the animals of a group.

The compositions according to the invention, mqw amended - 7 - 195796 however, may easily and quickly be painted on a portion of the body surface of the animal. They can be appli< to all warm-blooded animals and especially stock animals such as, for example, cattle, sheep or pigs as to domestic animals such as for example dogs ai The compositions according to the invention parasites to be combatted, whether they b( external parasites. They permit especiajdy the control of acarids e.g. ticks, larvae, nymphae, helminths, warble flies, insects sue various kinds of stinging flies.

Among the compositions according to the invention, preferred compositions are th^se which contain/at least one 'compound of formula I yjKerein A represeiyfs a radical of. formula: :h. especially one in whicl represents a hydrogen atom and ayxadical of formu. . 7 - 195796 AS AMENDED hcwever, may easily and quickly be painted (e.g. poured) on a portion of the "body surface of the animal. They can be applied to all warm-blooded animals and especially stock animals such as, for example, cattle, sheep or pigs as well as to domestic animals such as for example dogs and cats.

The oonpositions according to the invention especially enable the control of acarids e.g. ticks, larvae, nymphae and scabies, helminths, warble flies, insects such as lice, bugs and various kinds of stinging flies.

Among the compositions according to the invention, preferred compositions are those which contain at least one"compound of formula I wherein A represents a radical -of- formula: especially one in which represents a hydrogen atom and Z^ a radical of formula: 195796 (in which R^ , R2 and R^ are as defined above and particularly in which R^ represents a hydrogen atom and more particularly, in which R^ and R2 each represent a halogen atom, for example a bromine or chlorine atom).

Particularly preferred as active ingredients of formula I are (S) oL-cyano-3-phenoxybenzyl (1R. cis)-2 ,2-dimethyl-3- (2 ,2-idibromovinyl )cyclopropane - 1-carboxylate and (S) cC-cyano-3-phenoxybenzyl (1R, cis)-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane-1-carboxyla te.

Other compounds of general formula I which may be mentioned include, for example, the following: (RS) (fc-cyano-3-phenoxybenzyl (1R, cis)-2,2-dimethyl-3-^(2 ,2-dichlorovinyl )cyclopropane-1-carboxylate , (RS)"'iXrcyano-3-phenoxybenzyl (1R, cis)-2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane-1-carboxylate, Orcyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutyrate /f" % 195796 "TVvC, amount; of active product of formula I to be applied to the animal will vary depending upon the condition of the animal to be treated, the species, the environment as well as the result sought. In general, however it will be desirable to administer from 0.5 to 10 mg of the compound of formula I per kg of bodyweight of the treated animal. The number of treatments which should be carried out will also vary depending, upon the same parameters as those which have been set out above to determine the amount of product to be administered. As illustrated hereinafter, however, excellent results may be obtained with a single, application.

The compositions according to the invention contain a vehicle permitting passage of the active ingredient ..through the skin barrier. Particular compositions which may be mentioned are solutions, preferably oily solutions, alcoholic:.solutions , especially ethanolic and isopropanolic solutions, solutions in esters of monocarboxylic acids, especially isopropyl myristate, in esters of dicarboxylic acids or else solutions of esters of aliphatic acids, in general with glycols. All these solutions preferably contain a dispersing agent such as, e.g. dimethylformamide, dimethylsulphoxide or dimethylacetamide or some other dispersing agents known in the pharmaceutical industry to facilitate passage through the skin barrier, insofar as the solubility of the compounds of general formula I permits this, such as, for example, pyrrolidin-2-one, N-alkyl-pyrrolidin-2-ones, methyl ethyl ketone, acetone, polyethyleneglycols and their ethers and esters, propylene glycol and synthetic triglycerides. 19 The oily solutions used preferably contain a vegetable oil such as e.g. olive oil, peanut oil, sesame oil, pine oil, linseed oil or castor oil.

A particularly preferred vehicle for the' compositions according to the invention is an oily solution of dimethylformamide.

The compositions according to the invention may, for example, contain from 1 to 5% by weight of active ingredient, from 0.1 to 50% by weight of dispersing agent and from 98.9 to 45% by weight of solvent.

The compositions according to the invention may if desired, include an emulsifying agent and/or a surface-active agent.

; The use and activity of the compositions according to the invention may be illustrated as follows: EXPERIMENTAL PART In the experimental part set out hereinafter, (S)$(-cyano-3-phenoxybenzyl' (1R, cis )-2 ,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane-l-carboxylate is called product "A11; (S)<jL-cyano-3-phenoxybenzyl (1R, cis )-2 ,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane-1-carboxylate is called product "B", 1 Test 1: Study of the acaricidal activity of Product B on the calf: activity on "Boophilus" Microplus" The activity was investigated in the following test: calves were infested with ticks of the species "Boophilus Microplus". The ticks are in all the stages of development. The dorsal spine of the animals is painted on day Df using a solution containing either 5 mg or 10 mg of Product B per kg weight of animal treated. The live ticks are counted on days D(before treatment), D + 1, D + 2, D + 4 and D + 7 and the presence or absence of larvae and nymphae is observed.

The results obtained are as follows: Days DOSE mg/kg mg/kg D •123 adult ticks larvae (many) nymphae 61 adult ticks larvae (many) nymphae D + 1 2 adult ticks larvae and nymphae 3 adult ticks larvae and nymphae D + 2 0 adult tick larvae and nymphae 0 adult tick larvae and nymphae D + 4 0 adult tick larvae and nymphae 0 adult tick larvae and nymphae D + 7 0 adult tick neither larvae nor nymphae 0 adult tick neither larvae nor nymphae Conclusion: Product B shows excellent activity in the control of ticks of the species "Boophilus Microplus". 195796 I Test 2; Insecticidal activity of Product A: activity on cattle lice Cattle are infested with lice. They are treated by painting their dorsal spine with 40 ml (per animal) of. a solution containing 0.5% of product A. A single treatment is carried out. Very good results are obtained. 1.3 195796 Test 3: Test of tolerance of product A: administered Healthy cows are treated by painting their dorsal spines with 20 mi of a soLullon containing >0 g/.l of product A. A daily local examination is carried out for 10 days. It is observed that product A is perfectly The following non-limiting example serves to illustrate a composition according to the invention.

Example 1: Example of composition A composition was prepared, corresponding.to the following formulation: bv "oour on", in the cow well tolerated Product B Dimethylformamide Olive oil ....... 1700 mg 40 cc 40 cc

Claims

WHAT WE CLAIM IS;

1. A method of controlling parasites on a non-human warmblooded animal which comprises administering to said animal by the "pour on" method (as herein defined) a compound of formula I a-co2-b wherein A represents a group of formula: (I) [in which either Z1 and Z2 each represents a methyl radical or Z^ represents a hydrogen atom and Z2 represents a group of formula: /R3 r (in which R^ represents a hydrogen or halogen atom and R-^ and R2, which may be the same or different, each represents a halogen atom or a C^_g alkyl radical)] or a group of formula: (in which Y^ and Y2, which may be at any of the possible positions on the benzene nucleus and which may be the same or different, each represents a hydrogen or halogen atom, a Cl-8 radical or a alkoxy radical): and - 1 195796 B represents a benzyl radical (optionally substituted by one or more substituents selected from Cj u alkyl radicals, c2_5 alkenyl radicals, ^2.-6' alkenyloxy radicals, ^ alkadienyl radicals, Methylene-5 dioxy radicals, benzyl radicals and halogen atoms); a group of formula: (in which R_ represents an organic C„ r aliphatic radical containing one or more carbon-carbon unsaturations); 10 a group of formula: (in which R^ represents a group of I formula -C = N or--C=CH, represents a chlorine atom 15 or a methyl radical and n is 0, 1 or .2); or a group of formula: pv \ 16 (in which R c, R_, R-, and RQ, which may be the same or t> / o y different, each represents a hydrogen atom, a chlorine atom or a methyl radical and the symbol S/I indicates an aromatic ring or dihydro or tetrahydro analogue thereof).

2. A method of treating or preventing an infestation by parasites of a non-human warm-blooded animal which comprises applying to a portion of the surface of the body of the said animal an effective amount of a composition comprising at least one compound of formula I as defined in claim 1 in association with a vehicle capable of permitting passage of the compound of formula I through the skin barrier of the animal.

3. A method of treating or preventing an infestation by parasites of a non-human warm-blooded animal which comprises applying to a portion of, the surface of the body of the said animal an effective amount of a composition comprising at least one compound of formula I as defined in claim 1 in association with a vehicle selected from oils, alcohols, esters of monocarboxylic acids, esters of dicarboxylic acids and esters of aliphatic acids.

4. A method as claimed in claim 2 or claim 3 wherein the vehicle comprises an oil.

5. A method as claimed in claim 4 wherein the said oil is a vegetable oil.

6. A method as claimed in claim 2 or claim 3 wherein the vehicle comprises ethanol or isopropanol.

7. A method as claimed in claim 2 or claim 3 wherein the vehicle comprises isopropyl myristate.

8. A method as claimed in claim 2 or claim 3 wherein the vehicle comprises a glycol ester of a monocarboxylic, dicarboxylic or aliphatic acid.

9. A method as claimed in any one of claims 2 to: B wherein the vehicle contains a dispersing agent. A y t f /, 17

10. A method as claimed in claim 9 wherein the dispersing agent comprises dimethylformamide, dimethylsulphoxide or dimethylacetamide.

11. A method as claimed in claim 9 wherein the dispersing agent comprises pyrrolidin-2-one, an N-alkyl pyrrolidin-2-one, methyl ethyl ketone, acetone, a polyethylene glycol or ether or ester thereof, propylene glycol or a synthetic trigylceride.

12. A method as claimed in any one of the preceding claims wherein the compound of formula I is a compound in which A represents a group of formula in which Z^ and Z2 are as defined in Claim 1.

13. A method as claimed in claim 12 wherein, in the compound of formula I, Z-^ represents a hydrogen atom and Z2 represents a radical of formula: (in which R-^, R2 and R^ are as defined in claim 1) .

14. A method as claimed in claim 13 wherein, in the compound of formula I, R^ represents a hydrogen atom.

15. A method as claimed in claim 14 wherein, in the compound of formula I, R-^ and R2 each represents a halogen atom.

16. A method as claimed in claim 15 wherein, in the compound of formula I, R^ and R2 each represents a bromine atom or a chlorine atom. Z 1 SOW AMENDED - 18 - 195796

17. A method as claimed in claim 16 wherein the compound of formula I is (S) a-cyano-3-phenoxybenzyl (lR,cj/fe) 2,2-dimethyl-3- (2 ,2-dibromovinyl) cyclopropane-l-carb/Dxylate.

18. A method as claimed in claim 16 wherein toe compound of formula I is (S)a-cyano-3-phenoxybenzyl (1R,cis)2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane-^:-carboxylate.

19. A method as claimed in claim 16 wherein the compoundy of formula I is (RS)a-cyano-3-phenoxyben^yl (lR,cis)2,: dimethyl-3-(2,2-dichlorovinyl)-cycloprypane-l-carboxylj£te.

20. A method as claimed in claim 16i&herein the compound of formula I is (RS) a-cyano-3-phenoxybenzyl (lR,c^)-2,2-dimethyl-3- (2 ,2-dibromovinyl) cycldpropane-l-carbo^ylate,

21. A method as claimed in anyyone of claims l,Ao 11 wherein the compound of formu3Ji I is a-cyano-^fphenoxybenzyl 2-(4-chlorophenyl)-3-methylbytyrate.

22. A method as claimed in/any one of the^>receding claims wherein the compound of formula I is applied to the dorsal spine (or to a part thereof) of the

23. A method as claimed in any one ofi^the preceding claims wherein the animal isr selected from yeattle, sheep, pigs, dogs and cats.

24. A method as jelaimed in any o^e of the preceding claims wherein from 0./to 10 mg of a Compound of formula I are applied per kg^of body weight^c>f the animal. 25. A methoil as claimed in ^any one of the preceding claims wherein ths?f said parasites/are acarids. 26. A machod as claimed /in claim 1 substantially as herein describe 27. ycomposition suitable for use in a method as claimed in afw one of the pjjeceding claims comprising as active ingredient at leas^ one compound of formula I as defined claim 1 in association with a vehicle capable of passage of the active ingredient through the skin barrier 0f the animal. 18 " AS AMENDED 195796 17. A method as claimed in claim 16 wherein the compound of formula I is (S) a-cyano-3-phenoxybenzyl (1R,cis)2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane-l-carboxylate. 18. A method as claimed in claim 16 wherein the compound of formula I is (S)a-cyano-3-phenoxybenzyl (1R,cis)2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane-l-carboxylate. 19. A method as claimed in claim 16 wherein the compound of formula I is (RS)a-cyano-3-phenoxybenzyl (1R,cis)2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane-l-carboxylate. 20. A method as claimed in claim 16 wherein the compound of formula I is (RS) a-cyano-3-phenoxybenzyl (1R,cis)-2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane-l-carboxylate. 21. A method as claimed in any one of claims 1 to 11 wherein the compound of formula I is a-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutyrate. 22. A method as claimed in any one of the preceding claims wherein the compound of formula I is applied to the dorsal spine (or to a part thereof) of the animal. 23. A method as claimed in any one of the preceding claims wherein the animal is selected from cattle, sheep, pigs, dogs and cats. 24J. A method as claimed in any one of the preceding claims wherein from 0.5 to 10 mg of a compound of formula I are applied per kg of body weight of the animal.

25. A method as claimed in any one of the preceding claims wherein the said parasites are acarids.

26. A method as claimed in claim 1 substantially as herein described. NOW AMENDED Q R 7 / 1 - 19 - 28. A composition suitable for use in a method as/claimed in any of claims 1 to 26 comprising as active ingredient at least one compound of formula I as defined JLxi claim 1 in association with a vehicle selected from pfils, alcohols, esters of monocarboxylic acids, esters of acids and esters of aliphatic acids. iricarboxylic 29. A composition as claimed in claim/27 or claim 28 wherein the vehicle is as defined iiyany one of claixp^s 4 to 11. 30. A composition as claimed in/any one of claims 27 to 29 wherein the compound of formula I is as define^- in any one of claims 12 to 21. 31. A composition as claimed in any one o£ claims 27 to 30 containing from 1 to 5iy6y weight of actfve ingredient, from 0.1 to 50% by weight of dispersing agejjft and from 98.9 to 45% by weight of solvent. 32. A composition as claimed in a/fy one of claims 27 to 31 further containing an emulsifyii^f agent and/or a surface active agent. 33. A composition suitable ^for use in the control of parasites^on a non-human wfirm-blooded animal by the "pour-on" method (as herein defined) substantially as herein described in Example qtormeys sj CAREY 29 FEB 1984 J 'X£c.„»y AS AMENDED 195796 - 19 -

27. A composition suitable for use in a method as claimed in any of claims 1 to 26 comprising as active ingredient at least one compound of formula I as defined in claim 1 in association with a vehicle selected from oils, alcohols, esters of monocarboxylic acids, esters of dicarboxylic acids and esters of aliphatic acids.

28. A composition as claimed in claim 27 wherein the vehicle is as defined in any one of claims 4 to 11.

29. a composition as claimed in claim 27 or 28 wherein the compound of formula I is as defined in any one of claims 12 to 21.

30. a composition as claimed in any one of claims 27 to 29 containing from 1 to 5% by weight of active ingredient, from 0.1 to 50% by weight of dispersing agent and from 9 8.9 to 45% by weight of solvent.

31. A composition as claimed in any one of claims 27 to 30 further containing an emulsifying agent and/or a surface active agent.

32. a composition suitable for use in the control of parasites on a non-human warm-blooded animal by the "pour-on" method (as herein defined) substantially as herein described in Example 1. 9ATED THIS DAY OF A^cj^st |f A. J. PAH* A SON PER AGENTS FOR THE APPLICANTS