Aqueous formulations of parasiticides for skin applications

• US 7,384,938 B2
• Filed: 01/17/2003
• Issued: 06/10/2008
• Est. Priority Date: 02/23/1998
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer AG
• Inventors: Heukamp, Ulrich, Sirinyan, Kirkor, Dorn, Hubert
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US10/347,003
• Publication Number:
  US 20030162773A1
• Time in Patent Office: 1,971 Days
• Field of Search: 514/226.8, 514/340, 514/226.08
• US Class Current: 514/226.8
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 25/02 containing liquids as carriers, diluents or solvents
• CPC Class Codes: A01N 31/04 Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
• CPC Class Codes: A01N 43/08 with oxygen as the ring hetero atom
• CPC Class Codes: A01N 43/36 five-membered rings
• CPC Class Codes: A01N 51/00 Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
• CPC Class Codes: A01N 61/00 Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/14 Ectoparasiticides, e.g. scabicides
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to water-containing formulations for the dermal control of parasitic insects on animals, having the following composition

• • a) agonists or antagonists of the nicotinic acetylcholine receptors of insects in a concentration of from 1 to 20% by weight based on the overall weight of the formulation;
  • b) water in a concentration of from 2.5 to 15% by weight;
  • c) solvents from the group alcohols such as benzyl alcohol, tetrahydrofuryl alcohol or optionally substituted pyrrolidones in a concentration of at least 20% by weight based on the overall weight of the formulation;
  • d) solvents from the group of the cyclic carbonates or lactones in a concentration of from 5 to up to 50% by weight based on the overall weight of the formulation;
  • e) if desired, further auxiliaries from the group thickeners, spreading agents, colorants, antioxidants, propellants, preservatives, adhesives, emulsifiers, in a concentration of from 0.025 up to 10% by weight based on the overall weight of the formulation.

Claims

1. A water-containing formulation for the dermal control of parasitic insects on animals by means of agonists or antagonists of the nicotinic acetylcholine receptors of insects, comprising:

a) agonists or antagonists of the nicotinic acetylcholine receptors of insects in a concentration of from 1 to 20% by weight based on the overall weight of the formulation, wherein the agonists or antagonists are selected from one or more compounds of formula (I)

2. The water-containing formulation of claim 1, wherein

R represents hydrogen or optionally substituted radicals selected from the group consisting of acyl, alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl,

wherein

acyl radicals are selected from the group consisting of formyl, alkylcarbonyl, aryl-carbonyl, alkylsulphonyl, arylsulphonyl, (alkyl-)-(aryl-) phosphoryl, each of which is optionally substituted,

alkyl is C_1-10-alkyl, which is optionally substituted,

aryl is selected from the group consisting of phenyl, and naphthyl,

aralkyl is selected from the group consisting of phenylmeth and phenylethyl,

heteroary is selected from the group consisting of theinyl, furyl, thiazolyl, imidazolyl, pyridyl, and benzothizolyl,

heteroarylalkyl is selected from the group consisting of heteroarylmethyl and heteroarylethyl, wherein the heteroaryl radicals contain up to 6 ring atoms and heteroatoms selected from the group consisting of N, O, and S,

heterocyclyl is tetrahydrofuranyl,

and wherein substituents are selected from the group consisting of alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 5 halogen atoms and wherein the halogen atoms may be identical or different and are selected from the group consisting of fluorine, choloring or bromine, hydroxyl, halogen, cyano, nitro, amino, monoalkyl and dialkylamino having 1 to 4 carbon atoms per alkyl group, carboxyl, carbalkoxy having 2 to 4 carbon atoms, sulpho (—

SO₃H);

alkylsulphonyl having 1 to 4 carbon atoms, phenylsulphonyl chioropyridylamin and chlorophridylethylamino;

A represents hydrogen or optionally substituted radicals selected from the group consisting of acyl, alkyl, aryl, which are defined above

or

A represents the bifunctional group optionally substituted alkylene having 1-4 carbon atoms, wherein the substituents are as defined above, and the alkylene groups may be interrupted by heteroatoms selected from the group consisting of N, O, and S,

or

A and Z may, together with the atoms to which they are attached, form a saturated or unsaturated heterocyclic ring wherein said heterocyclic ring is selected from the group consisting of pyrrolidine, piperidine, piperazine, hexamethyleneimine, hexahydro-1,3,5-triazine, morpholine, and oxadiazine, each of which may optionally be substituted by methyl,

E represents an electron-withdrawing radical;

X represents —

CH═

or —

N═

;

Z represents optionally substituted radicals alkyl, —

OR, —

SR, —

NRR (wherein R may be identical or different);

and wherein R and the substituents are each as defined above,

or

Z can form together with the atom to which it is attached and with the radical

3. The water-containing formulation of claim 1, wherein

R represents optionally substituted radicals selected from the group consisting of heteroarylmethyl and heteroarylethyl, wherein the heteroaryl may be selected from the group consisting thienyl, furyl, thiazolyl, imidazolyl, pyridyl, and benzothiazolyl and the radical may be optionally substituted with methyl, ethyl, methoxy, ethoxy, methylthio, ethylthio, trifluoromethyl;

hydroxyl;

fluorine, chlorine, bromine, cyano, nitro, or amino;

A represents hydrogen or a bifunctional optionally substituted alkylene group having 2 carbon atoms which is linked to the radical Z, wherein the substituents are as described above, the alkylene group be interrupted by 1 heteroatom selected from the group consiting of N, O, and S,

or

A and Z may, together with the atoms to which they are attached, form a saturated or unsaturated 5- or 6-membered heterocyclic ring wherein the heterocyclic ring may contain a further 1 or 2 identical or different heteroatoms and/or hetero groups, and wherein the heteroatoms are oxygen, sulphur or nitrogen, and hetero groups are N-alkyl, where the alkyl in the N-alkyl group contains 1 or 2 carbon atoms;

E represents NO₂, CN;

X represents —

CH═

or —

N═

;

Z represents optionally substituted radicals alkyl, —

OR′

, —

SR′

, or —

NR′

R′

(wherein the radicals R′

are identical or different wherein)

R′

represents hydrogen or optionally substituted radicals selected from the group consisting of acyl, alkyl, aryl, aralkyl, heteroaryl, and heteroarylalkyl,

wherein

acyl radicals are selected from the group consisting of formyl, alkylcarbonyl, arylcarbonyl, alkylsulphonyl, arylsulphonyl, and (alkyl-)-(aryl-)-phosphoryl,

alkyl is C_1-4-alkyl,

aryl is phenyl,

aralkyl is phenylmethyl, or phenylethyl,

heteroarylalkyl is heteroarylmethyl, or heteroarylethyl, and wherein the heteroaryl is selected from the group consisting of thienyl, furyl, thiazolyl, imidazolyl, pyridyl, and benzothiazolyl,

and wherein substituents of the radicals R′

are selected from the group consisting of

methyl, ethyl, methoxy, ethoxy, methylthio, ethylthio, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5 halogen atoms and wherein the halogen atoms are identical or different and are fluorine, chlorine or bromine, hydroxyl;

fluorine, chlorine, bromine, cyano, nitro;

amino;

monoalkyl- and dialkylamino having 1 or 2 carbon atoms per alkyl group, carboxyl;

carbalkoxy having 2 or 3 carbon atoms, sulpho (—

SO₃H);

alkylsulphonyl having 1 or 2 carbon atoms, phenylsulphonyl, chloropyridylamino and chloropyridylmethylamino.

4. The water-containing formulations of claim 1, wherein the agonists or antagonists are selected from one or more compounds of formula (II), (III) and (IV)

5. The water-containing formulation of claim 1, wherein one or more of the compounds is selected from

6. A process for preparing a water-containing formulation of claim 1, comprising mixing the compound(s) with water and solvent(s) to give a homogeneous solution and, optionally adding auxiliaries.