Aqueous formulations of parasiticides for skin applications

• US 20030162773A1
• Filed: 01/17/2003
• Published: 08/28/2003
• Est. Priority Date: 02/23/1998
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Vital GmbH (Bayer AG)
• Inventors: Sirinyan, Kirkor, Dorn, Hubert, Heukamp, Ulrich
• Granted Patent: US 7,384,938 B2
• Time in Patent Office: Days
• US Class Current: 514/217.12
• 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. Water-containing formulations for the dermal control of parasitic insects on animals by means of agonists or antagonists of the nicotinic acetylcholine receptors of insects, of 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 based on the overall weight of the formulation;

c) solvents from the group alcohols 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 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.

2. Water-containing formulations according to claim 1, in which the active compound used is one or more compounds of the general formula (I)

3. Formulations according to claim 2, in which the active compound used is one or more compounds of the formula (I), in which the radicals are as defined below:

R represents hydrogen and also represents optionally substituted radicals from the series acyl, alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl.

As acyl radicals there may be mentioned formyl, alkylcarbonyl, aryl-carbonyl, alkylsulphonyl, arylsulphonyl, (alkyl-)-(aryl-)-phosphoryl, each of which may in turn be substitute.

As alkyl there may be mentioned C_1-10-alkyl, which may in turn be substituted.

As aryl there may be mentioned/phenyl, naphthyl.

As aralkyl there may be mentioned phenylmethyl, phenylethyl.

As heteroaryl there may be mentioned thienyl, furyl, thiazolyl, imidazolyl, pyridyl, benzothiazolyl.

As heteroarylalkyl there may be mentioned heteroarylmethyl, heteroarylethyl, the heteroaryl radicals containing up to 6 ring atoms and N, O, S, as heteroatoms.

As heterocyclyl there may be mentioned tetrahydrofuranyl.

As heterocylcylalkyl there may be mentioned heterocyclylmethyl.

As substituents there may be listed;

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, the halogen atoms being identical or different and being fluorine, chlorine 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, chloropyridylamino and chloropyridylmethylamino.

A represents hydrogen and also represents optionally substituted radicals from the series acyl, alkyl, aryl, which are as defined under R. A furthermore represents a bifunctional group. There may be mentioned optionally substituted alkylene having 1-4, in particular 1-2 carbon atoms, substituents which may be mentioned being the substituents listed earlier above, and it being possible for the alkylene groups to be interrupted by heteroatoms from the series N, O, S.

A and Z may, together with the atoms to which they are attached, form a saturated or unsaturated heterocyclic ring. The heterocyclic ring can contain a further 1 or 2 identical or different heteroatoms and/or hetero groups. Heteroatoms are preferably oxygen, sulphur or nitrogen, and hetero groups are preferably N-alkyl, where the alkyl in the N-alkyl group contains 1 to 4 carbon atoms.

Heterocyclic rings which may be mentioned are pyrrolidine, piperidine, piperazine, hexamethyleneimine, hexahydro-1,3,5-triazine, morpholine, 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 (R being identical or different) where R and the substituents are each as defined above.

Z can form, apart from the abovementioned ring, together with the atom to which it is attached and with the radical

 

instead of X, a saturated or unsaturated heterocyclic ring. The heterocyclic ring can contain a further 1 or 2 identical or different heteroatoms and/or hetero groups. The heteroatoms are oxygen, sulphur or nitrogen, and the hetero groups N-alkyl, in which case the alkyl or N-alkyl group contains 1 to 4 carbon atoms.

As heterocyclic rings there may be mentioned pyrrolidine, piperidine, piperazine, hexamethyleneimine, morpholine and N-methylpiperazine.

4. Formulations according to claim 2, which contain, as active compound, one or more of the compounds of the formula (I), in which the radicals are as defined below

R represents optionally substituted radicals from the series heteroarylmethyl or heteroarylethyl, heteroaryl which may be mentioned being:

thienyl, furyl, thiazolyl, imidazolyl, pyridyl, benzothiazolyl.

As substituents there may be listed;

methyl, ethyl, methoxy, ethoxy, methylthio, ethylthio, trifluoromethyl;

hydroxyl;

fluorine, chlorine and bromine;

cyano;

nitro;

amino;

A represents hydrogen and also represents a bifunctional optionally substituted alkylene group having 2 carbon atoms which is linked to the radical Z, substituents which may be mentioned being the substituents listed earlier above, and it being possible for the alkylene group to be interrupted by 1 heteroatom from the series N, O, S,

A and Z may, together with the atoms to which they are attached, form a saturated or unsaturated 5- or 6-membered heterocyclic ring. The heterocyclic ring can contain a further 1 or 2 identical or different heteroatoms and/or hetero groups. 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′

, —

NR′

R′

(the radicals R′

are identical or different), where R′ and

the substituents are each as defined below;

R′

represents hydrogen and also represents optionally substituted radicals from the series acyl, alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl.

As acyl radicals there may be mentioned formyl, alkylcarbonyl, arylcarbonyl, alkylsulphonyl, arylsulphonyl, (alkyl-)-(aryl-)-phosphoryl.

As alkyl there may be mentioned C_1--alkyl.

As aryl there may be mentioned phenyl.

As aralkyl there may be mentioned phenylmethyl, phenylethyl.

As heteroarylalkyl there may be mentioned heteroarylmethyl, heteroarylethyl, where thienyl, furyl, thiazolyl, imidazolyl, pyridyl, and benzothiazolyl may be mentioned as heteroaryl.

As substituents of the radicals R′

there may be listed;

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

fluorine, chlorine and bromine;

cyano, nitro;

amino;

monoalkyl- and dialkylamino preferably 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.

5. Formulations according to claim 1, which contain, as active compounds, one or more compounds of the general formula (II), (III) and (IV)

6. Formulations according to claim 1, which contain, as active compound, one or more of the following compounds:

7. Process for preparing the compositions according to claim 1, characterized in that (the active compound(s) is/are mixed with water and the stated solvent(s) to give a homogeneous solution and, if appropriate, the other auxiliaries are added.