EP1496744A1

EP1496744A1 - Parasite control in animals

Info

Publication number: EP1496744A1
Application number: EP03746283A
Authority: EP
Inventors: Andreas Turberg; Olaf Hansen; Venkata-Rangarao Kanikanti; Reinhold LÖHR; Dirk Mertin; Kirkor Sirinyan
Original assignee: Bayer Healthcare AG
Current assignee: Bayer AG
Priority date: 2002-04-16
Filing date: 2003-04-03
Publication date: 2005-01-19
Also published as: NO20044906L; KR20040105876A; ZA200408310B; CA2482877A1; MXPA04010208A; RU2004133661A; US20050214336A1; CN1662140A; DE10216737A1; AU2003226776A1; PL372855A1; IL164595A0; BR0309335A; JP2005522484A; WO2003086075A1; HRP20041064A2

Abstract

The invention relates to the systemic and non-system control of parasites in animals by means of phenyl ketoenol derivatives.

Description

Control of parasites in animals

The present invention relates to the systemic and non-systemic control of parasites in animals using phenylketoenol derivatives.

Phenylketoenols are known compounds. It is also known that these keto-enols have excellent ^' insecticidal, acaricidal, herbicidal and fungicidal activity (EP-A-0528156, WO 98/05638 and WO 97/01535). *

It has now surprisingly been found that certain phenylketoenol derivatives are particularly suitable for systemic and non-systemic control of parasites such as fleas, lice or flies, on animals and in the environment.

Because of their effectiveness at developmental stages and _. With zeal, these compounds are not necessarily suitable as arthopodicidal agents in the veterinary field. In the case of the selected compounds, biological effects against relevant ectoparasites and hygiene pests were surprisingly found in combination with certain dosage forms. The compounds described are particularly suitable for use against single-host tick species, lice and

Mites on farm animals, to control stable flies e.g. in the feed-through process and for combating flea, mite and tick populations in pet farming. Resistant species are also recorded.

^'The invention relates to the use of Phenylketoenol derivatives of the general formula (I), in which

X represents alkyl, halogen, alkoxy or haloalkyl,

Y represents hydrogen, alkyl, halogen, alkoxy, haloalkyl,

Z represents alkyl, halogen alkoxy,

n represents a number from 0 to 3, or the radicals X and Z together with the phenyl radical to which they are attached, the naphthalene radical of the formula

, form,

in which Y has the meaning given above,

G for hydrogen (a) or for the groups -CO— R ¹ (b) (c) -SO; - R ³ (d)

stands,

A and B can be the same or different and are hydrogen, optionally substituted by halogen substituted alkyl, alkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, optionally cycloalkyl interrupted by heteroatoms or optionally substituted by halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, Aralkyl or hetaryl,

or in what

A and B together with the carbon atom to which they are attached form a saturated or unsaturated, optionally interrupted by heteroatoms and optionally substituted cycle,

D represents oxygen, sulfur or -NH-,

E ^{+ represents} a metal ion equivalent or an ammonium ion,

L and M represent oxygen and / or sulfur,

Rl for optionally halogen-substituted alkyl, alkenyl, alkoxyalkyl, alkylthioalkyl. Polyalkoxyalkyl or cycloalkyl, which can be interrupted by heteroatoms, optionally substituted phenyl, optionally substituted phenylalkyl, substituted hetaryl, substituted phenoxyalkyl or substituted hetaryloxyalkyl and

R ^ represents alkyl, alkenyl, alkoxyalkyl, polyalkoxyalkyl or phenyl or benzyl which is optionally substituted by halogen,

R3, R4 and R ^ independently of one another for optionally halogen-substituted alkyl, alkoxy, alkylamino, dialkylamino. Alkylthio, alkenylthio, alkynylthio, cycloalkylthio and represent optionally substituted phenyl, phenoxy or phenylthio,

R6 and R ^ independently of one another represent hydrogen, optionally alkyl substituted by halogen, alkenyl, alkoxy, alkoxyalkyl, optionally substituted phenyl, optionally substituted benzyl,

or where R ^ and R ^ together represent an alkylene radical which may be interrupted by oxygen,

with the exception of the following connections:.

3 - (2-methoxyphenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3 - (2-chlorophenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3 - (2-methoxyphenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-fluorophenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2,

and the enantiomerically pure forms of compounds of the formula (I),

for the manufacture of medicaments for combating parasites in animals and in their environment., Including the different meanings (a), (b), (c), (d), (e), (f) and (g) of group G of the general formula (I), the following main structures (la) to (Ig):

wherein

A, B, D, E, L, M, X, Y, Z _n , R ¹ , R ² , R ³ , R ⁴ , R ⁵ ₅ R ⁶ and R ^{7 have} the meanings given above.

Compounds of the formula (I) or of the formulas (Ia) to (Ig) and their preparation are described in detail in EP-A-0 528 156, WO 98/05638 and WO 97/01535.

Compounds of the formula (I) are preferably used

in which X for C i -Cg alkyl. Halogen, C \ -Cg alkoxy or C \ -C3 haloalkyl,

Y represents hydrogen, C ^ -Cg-alkyl, halogen, C ^ -Cg-alkoxy, C1-C3 -haloalkyl,

Z represents C 1 -Cg alkyl, halogen, C -Cg alkoxy,

n stands for a number from 0 to 3,

or wherein the radicals X and Z together with the phenyl radical to which they are attached form the naphthalene radical of the formula

in which Y has the meaning given above,

A and B are identical or different and are hydrogen or straight-chain or branched C 1 -C 12 -alkyl which is optionally substituted by halogen, C ₃ -C ₈ -alkenyl, C ₃ -C ₈ -alkynyl, Ci-Cg-polyalkoxy-C2-Cg-alkyl, -C-Cιo-alkylthio-C2-Cg-alkyl, cycloalkyl with 3 to 8

Ring atoms which can be interrupted by oxygen and / or sulfur or optionally aryl, hetaryl substituted by halogen, Ci-Cg-alkyl, C] -Cg-haloalkyl, C ^ -Cg-alkoxy, Ci-Cg-haloalkoxy, nitro or aryl-Ci-Cg-alkyl,

or in what A and B together with the carbon atom to which they are attached, a saturated or unsaturated, optionally interrupted by oxygen and / or sulfur and optionally by halogen, Cj-Cg-alkyl, C5-Cg-alkoxy, Cι -C4 haloalkyl, Ci-Ci-haloalkoxy, -C-C4-alkyl-thio or optionally substituted aryl substituted 3- to 8-membered ^• ring,

G for hydrogen (a) or for the groups

-CO— R ¹ (b) (c) -SO5 - R ^J (d)

stands in which

E ^{+ represents} a metal ion equivalent or an ammonium ion,

L and M represent oxygen and / or sulfur,

R ¹ for C1-C20-alkyl which is optionally substituted by halogen, C ₂ -C20-alkenyl, kyl, -C-C8-polyalkoxy-C2-Cg-alkyl or cycloalkyl with 3 to 8 ring atoms, which can be interrupted by oxygen and / or sulfur atoms,

represents phenyl optionally substituted by halogen, nitro, Cj-Cg-alkyl, C] _-Cg-alkoxy, Ci-Cg-haloalkyl, Ci-Cg-haloalkoxy, optionally substituted by halogen, Ci -CG alkyl, Cj-Cg alkoxy, C _j -CG-haloalkyl, Ci-Cg-halogenoalkoxy phenyl C [is -CG alkyl,

represents hetaryl optionally substituted by halogen and / or Ci-Cg-alkyl,

represents phenoxy-Cl-Cg-alkyl optionally substituted by halogen and Ci-Cg-alkyl,

represents hetaryloxy-C-Cg-alkyl optionally substituted by halogen, amino and Ci-Cg-alkyl,

R ² for C1-C20-alkyl which is optionally substituted by halogen, C1-C20-alkenyl, -C -C-alkoxy ~ C2-Cg-alkyl, Ci-Cg-polyalkoxy-

C2-Cg-alkyl is,

represents phenyl or benzyl optionally substituted by halogen, nitro, Ci-Cg-alkyl, Ci-Cg-alkoxy, Ci-Cg-haloalkyl,

R ³ , R ⁴ and R ^ independently of one another for Ci-Cg-alkyl optionally substituted by halogen, Ci-Cg-alkoxy, Ci-Cg-alkylamino, di- (Cι -Cg -) - alkylamino, Ci-Cg- Alkylthio, C2-C5-alkenylthio, C2-C5-alkynylthio, C3-C7-cycloalkylthio, for optionally by halogen, nitro, cyano, -C-C4-alkoxy, -C-C4-haloalkoxy, Cι ^ C4-alkylthio, Cι-C4 -Halogenal- alkylthio, C1-C4- alkyl, -CC-C4-haloalkyl substituted phenyl, phenoxy or phenylthio,

R6 and R ⁷ independently of one another for hydrogen, optionally substituted by halogen C1-C20-alkyl, C1-C20-alkoxy, C2-Cg-alkenyl, -C-C20-alkoxy-Cι-C20-alkyl, for optionally by halogen, Cι-C20 haloalkyl, -C-C20 ~ alkyl or C1-C20-alkoxy substituted phenyl for benzyl optionally substituted by halogen, C1-C20-alkyl, -C-C20-haloalkyl or -C-C20-alkoxy or together for an optionally interrupted by oxygen C2-Cg -Alkylene ring stand,

with the exception of the following connections:

3- (2-methoxyphenyl) -4-hydoxy- Δ -dihydrofuranon-2, 3- (2-chlorophenyl) -4-hydoxy- Δ -dihydrofuranon-2, 3- (2-methoxyphenyl) -4-hydoxy- Δ - dihydrofuranone 2,

3- (2-fluorophenyl) -4-hydoxy- Δ -dihydrofuranon-2,

as well as the enantiomerically pure forms of compounds of the formula (I).

Compounds of the formula (I) are particularly preferably used

in which

X represents C 1 -Cg-alkyl, halogen, C \ -Cg-alkoxy or C \ -C2-haloalkyl,

Y represents hydrogen, Ci-Cg-alkyl, halogen, Ci-Cg-alkoxy, Cι-C2-haloalkyl,

Z represents C1-C4-alkyl, halogen, C 1 -C 4 -alkoxy,

n stands for a number from 0 to 3,

in which Y has the meaning given above,

A and B are the same or different and represent hydrogen, optionally by

- Halogen-substituted straight-chain or branched CI -CI Q- alkyl, C ₃ -Cg-alkenyl, C ₃ -Cg-alkynyl, C ₁ -C ₈ -alkoxy-C ₂ -Cg-alkyl, Ci -Cg-polyalkoxy- C2-Cg-alkyl, Cι-Cg-alkylthio-C2-Cg-alkyl, cycloalkyl with 3 to 7 ring atoms, which can be interrupted by 1 to 2 oxygen and / or sulfur atoms or optionally by halogen, C1-C4- alkyl,

-C4-Haloalkyl-, -C-C4-alkoxy-, nitro-substituted aryl, hetaryl or aryl-Cι-C4-alkyl,

or in what

A and B together with the carbon atom to which they are attached, a saturated or unsaturated, optionally interrupted by oxygen and / or sulfur and optionally by halogen, -C -C-alkyl, Ci-Cs-alkoxy, Cι-C3-haloalkyl, C 1 -C 4 haloalkoxy, C 3 -C 3 alkyl thio or aryl substituted aryl substituted by halogen, alkyl, alkoxy substituted 3- to 8-membered ring,

G for hydrogen (a) or for the groups

stands in which '

E ^{+ stands} for a metal ion equivalent or an ammonium ion,

L and M each represent oxygen and / or sulfur,

R ¹ for C ₁ -C 6 alkyl optionally substituted by halogen, C ₂ -C! - Alkenyl, -C -C -alkoxy-C2-Cg-alkyl, -Cι -CC-alkylthio-C2-Cg-alkyl, -C-Cg-polyalkoxy-C2-Cg-alkyl or cycloalkyl with 3 to 7 ring atoms, that can be interrupted by 1 to 2 oxygen and / or sulfur atoms,

represents phenyl which is optionally substituted by halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C 1-C3 -haloalkyl, '-C-C3-haloalkoxy,

represents phenyl-C-C4-alkyl optionally substituted by halogen, C1-C4-alkyl, C1-C4-alkoxy, C-C3-haloalkyl, C-C3-haloalkoxy,

represents hetaryl optionally substituted by halogen and / or Ci-Cg-alkyl, stands for optionally substituted by halogen and C1-C4-alkyl-substituted phenoxy -CC-C5-alkyl,

represents hetaryloxy-C5-C5-alkyl optionally substituted by halogen, amino and -CC-alkyl,

^R2 C2-Cg-alkyl is optionally substituted by halogen, C ^ -Cig alkyl, ^C 2- ^C lg-alkenyl, C2-Cι g-alkoxy-C2-Cg-alkyl, Ci-Cg-polyalkoxy,

represents phenyl or benzyl optionally substituted by halogen, nitro, C1-C4-alkyl, C1-C3-alkoxy, C \ -C3-haloalkyl,

R ³ , R ⁴ and R ^ independently of one another for Ci-Cg-alkyl optionally substituted by halogen, Cj-Cg-alkoxy, Ci-Cg-alkylamino, di- (Cι -Cg -) - alkylamino, Ci - Cg-alkylthio, C3-C4-alkenylthio, C2-C4-alkynylthio, C3-Cg-cycloalkylthio, for optionally by fluorine, chlorine, bromine, nitro, cyano, Cι-C3 alkoxy, Cι-C3-haloalkoxy, Cι -C3 -Alkylthio, -C-C3-haloalkylthio, -C-C3-alkyl, C1-C3 -haloalkyl substituted phenyl, phenoxy or phenylthio,

R6 and R ⁷ independently of one another for hydrogen, optionally substituted by halogen-C20 "alkyl, C1-C20-alkoxy, C2-Cg-alkenyl, -CC-C20" alkoxy-Cι-C20- ^a lkylj for optionally by halogen, C 1 -C 5 haloalkyl, C 1 -C 5 alkyl or C 1 -C 5 alkoxy substituted phenyl, which represents benzyl optionally substituted by halogen, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl or C 1 -C 5 alkoxy,

with the exception of the following connections: 3- (2-methoxyphenyl) -4-hydoxy- Δ-dihydrofuranone-2,3, (2-chlorophenyl) -4-hydoxy- Δ-dihydrofuranone-2,3, (2-methoxyphenyl) -4-hydoxy- Δ - dihydrofuranon-2, 3- (2-fluorophenyι) -4-hydoxy- Δ -dihydrofuranon-2,

as well as the enantiomerically pure forms of compounds of the formula (I).

Compounds of the formula (I) are very particularly preferred

in which

X represents methyl, ethyl, propyl, i-propyl, fluorine, chlorine, bromine, methoxy, ethoxy and trifluoromethyl,

Y for hydrogen, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, tert-butyl,

Fluorine, chlorine, bromine, methoxy, ethoxy and trifluoromethyl,

Z represents methyl, ethyl, i-propyl, butyl, i-butyl, tert-butyl, fluorine, chlorine, bromine, methoxy and ethoxy,

n stands for a number from 0 to 3,

or wherein the radicals X and Z together with the phenyl radical to which they are attached form the radical of the formula

form, in which Y has the meaning given above,

A and B are the same or different and are hydrogen, optionally substituted by halogen, straight-chain or branched C 1 -C 6 -alkyl, C ₃ -C 4 -alkenyl, C ₃ -C 4 -alkynyl, C ₁ -C 6 -alkoxy-C2-C4-alkyl, Cι-C4-poly-alkoxy-C2-C4-alkyl, Cι _l -CG-alkylthio-C2-C4-alkyl, cycloalkyl having 3 to 6 ring atoms, which may be interrupted by 1 to 2 oxygen and / or sulfur atoms or optionally aryl, pyridine, imidazole, pyrazole, triazole, indole, thiazole or aryl C1- substituted by fluorine, chlorine, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, trifluoromethyl, nitro C3 -alkyl,

or in what

A and B together with the carbon atom to which they are attached, a saturated or unsaturated, optionally interrupted by oxygen and / or sulfur and optionally by fluorine, chlorine, C1-C4-alkyl, -C-C4-alkoxy, trifluoromethyl, Cι- C -alkylthio or aryl which is optionally substituted by fluro, chlorine, methyl, methoxy form a substituted 3- to 8-membered ring,

G for hydrogen (a) or for the groups

-CO— R ¹ (b) (c) -SO; - R (d)

stands in which E ^{+ represents} a metal ion equivalent or an ammonium ion,

L and M each represent oxygen and / or sulfur,

R ¹ for optionally substituted by fluorine or chlorine Cj-C 14 alkyl, Ci-C 14 alkyl, C2-C 14 alkenyl, -C -C4 alkoxy-C2-Cg-alkyl,

-C-C4-alkylthio-C2-Cg-alkyl, -C -C-polyalkoxy-C2-C4-alkyl and cycloalkyl with 3 to 6 ring atoms, which can be interrupted by 1 to 2 oxygen and / or sulfur atoms,

represents phenyl optionally substituted by fluorine, chlorine, bromine, methyl, ethyl, propyl, i-propyl, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy, nitro,

represents optionally substituted by fluorine, chlorine, bromine, methyl, ethyl, propyl, i-propyl, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy-substituted C 1 -C 3 -alkyl,

for optionally substituted by fluorine, chlorine, bromine, methyl, ethyl

Pyridyl, pyrimidyl, thiazolyl and pyrazolyl,

represents optionally substituted by fluorine, chlorine, methyl, ethyl-substituted phenoxy -CC-C4-alkyl,

represents optionally substituted by fluorine, chlorine, amino, methyl, ethyl-substituted pyridyloxy -CC-C4-alkyl, pyrimidyloxy -CC-C ₄ -alkyl and thiazolyloxy -CC-C5-alkyl, R ² for optionally substituted by fluorine or chlorine Ci -C 14 alkyl, C2-Ci4-alkenyl, -C-C4-alkoxy-C2-Cg-alkyl, -C -C4-polyalkoxy-

C2-Cg-alkyl is,

or for optionally by fluorine, chlorine, nitro, methyl, ethyl, propyl, i-

Propyl, methoxy, ethoxy, trifluoromethyl-substituted phenyl or benzyl,

R ³ , R ⁴ and R5 independently of one another for C1-C4-alkyl, C1-C4-alkoxy, C 1 -C 4 -alkylamino, di- optionally substituted by fluorine or chlorine

(-C-C4-alkyl) -amino, Cι ^ C4-alkylthio, for optionally by fluorine, chlorine, bromine, nitro, cyano, C1-C2-alkoxy, Cι-C4-fluoroalkoxy, Cι-C2-chloroalkoxy, Cι-C _2- alkylthio, -C-C2-fluoroalkylthio,

-C-C2-chloroalkylthio, C1-C3-alkyl substituted phenyl, phenoxy or phenylthio,

R6 and R ⁷ independently of one another, optionally substituted by fluorine, chlorine, bromine, Ci-CiQ-alkyl, Cj-C 10- alkoxy, -C-Cιo-alkoxy- (Cl-Cιo) alkyl, for optionally by fluorine, chlorine, bromine C 1 -C 20 haloalkyl, C 1 -C 20 alkyl or C 1 -C 4 alkoxy substituted phenyl, for benzyl optionally substituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 -haloalkyl or C 1 -C 4 alkoxy,

with the exception of the following connections:

3- (2-methoxyphenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-chlorophenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-methoxyphenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-fluorophene) -4-hydoxy- Δ ³ -dihydrofuranon-2,

as well as the enantiomerically pure forms of compounds of the formula (I). According to a preferred embodiment of this invention, dihydrofuranone derivatives, ie compounds of the formula (I) in which D represents oxygen, are used. The other substituents can assume the meanings given above.

According to a further preferred embodiment of this invention, pyrrolidinedione derivatives, i.e. Compounds of formula (I) in which D is -NH- is used. The other substituents can assume the meanings given above.

The following specific connections, which can be used with particular preference, are expressly pointed out:

Compounds of the formula (Ia) which are mentioned in Table 1 of EP-A-528 156.

Compounds of formula (Ib), which are mentioned in Table 2 of EP-A-528 156.

Compounds of formula (Ic), which are mentioned in Table 3 of EP-A-528 156.

Compounds of formula (Id), which are mentioned in Table 4 of EP-A-528 156.

Compounds of the formula (Ie), which are mentioned in Table 5 of EP-A-528 156. Compounds of formula (If), which are mentioned in Table 6 of EP-A-528 156.

Compounds of formula (Ig), which are mentioned in Table 7 of EP-A-528 156.

Individual compounds of the formulas (Ia), (Ib), (Ic), (Id), (Le) and (Ig), which are mentioned as preparation examples in EP-A-528 156, may also be mentioned as particularly preferred.

Furthermore, compounds of the type Ilc can be used as particularly preferred. mentioned, which are disclosed in WO98 / 05638, in particular Examples Ilc-1 to llc-21. Compounds of the type Ilc which are disclosed in WO97 / 01535, in particular the examples Ilcl to Ilc-9, may also be mentioned as particularly preferred.

The following two compounds A to D are very particularly preferred for the use according to the invention:

A: 2,2-Dimethyl-, 3- (2,4-dichlorophenyl) -2-oxo-l-oxaspiro [4,5] dec-3-en-4-yl-butanoate:

B: 2-oxo-3 - (2,4,6-trimethylphenyl) -1-oxaspiro [4,4] non-3-en-4-yl-3,3-dimethylbutanoate:

C: 3- (2,5-Dimethylphenyl) -8-methoxy-2-oxo-l-azaspiro [4.5] dec-3-en-4-yl-ethyl carbonate

D: 3 - (4-Chloro-2,5-dimethylphenyl) -8-methoxy-2-oxo-1-azaspiro [4.5] dec-3-en-4-yl-ethyl carbonate

The active substances mentioned are suitable for favorable warm-blood toxicity for the systematic and / or non-systemic control of parasites which occur in animal husbandry and animal breeding in domestic and farm animals as well as zoo, laboratory, experimental and hobby animals. They are effective against all or individual stages of development of the pests and against resistant and normally sensitive types of pests.

Parasites are particularly arthropods. The preparations according to the invention are preferably used to control ectoparasites. The above-mentioned ectoparasites include: tick ticks, leather ticks, mite mites, running mites, flies (stinging and licking), parasitic fly larvae, lice, hair lice, featherlings and fleas.

These parasites include:

From the order of the Anoplurida e.g. Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.

From the order of the Mallophagida and the subordinates Amblycerina as well

Ischnocerina e.g. Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Trichodectes spp., Felicola spp.

From the order Diptera and the subordinates Nematocerina and Brachycerina e.g. Aedes spp., Anopheles spp., Culex spp., Simulium spp.,

Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp ., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp.

From the order of the Siphonapterida e.g. Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp ..

From the order of the Heteropterida e.g. Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.

From the order of the Blattarida, for example Blatta orientalis, Periplaneta americana, Blattella germanica, Supella spp. From the subclass of Acaria (Acarida) and the orders of the Meta- and Mesostigmata e.g. Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Stemostoma spp., Varroa spp.

From the order of the Actinedida (Prostigmata) and Acaridida (Astigmata) e.g. Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypppectoles spp ., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp., Laminosioptes spp.

Livestock and breeding animals include mammals such as Cattle, horses, sheep, pigs, goats, camels, water buffalos, donkeys, rabbits, fallow deer, reindeer;

Fur animals such as Mink, chinchilla, raccoon; such as. Chickens, geese, turkeys, ducks.

Laboratory and experimental animals include mice, rats, guinea pigs, golden hamsters, dogs and cats.

The pets include dogs and cats.

The application can be prophylactic as well as therapeutic.

The active substances for systemic control of parasites are preferably used directly or in the form of suitable preparations enterally, parenterally, dermally or nasally, in particular orally, transdermally, by means of pour-on formulations or as an injection. The enteral application of the active ingredients happens, for. B. orally in the form of powder, tablets, capsules, pastes, drinkers, granules, orally administrable solutions, suspensions and emulsions, boluses, medicated feed or drinking water. The dermal application happens for. B. in the form of diving (dipping), spraying (spraying) or pouring (pour-on or spot-on). Parenteral use happens e.g. B. in

Form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.

Injection solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly additives such as solubilizers, acids,

Bases, buffer salts, antioxidants, preservatives can be added. The solutions are sterile filtered and filled.

Examples of solvents which may be mentioned are: physiologically compatible solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, N-methylpyrrolidone and mixtures thereof.

If appropriate, the active compounds can also be dissolved in physiologically tolerable vegetable or synthetic oils which are suitable for injection.

The following may be mentioned as solubilizers: solvents which require the active ingredient to be dissolved in the main solvent or prevent it from precipitating out. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Examples of preservatives which may be mentioned are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.

Examples of suitable preparations for oral administration are: tablets, homogeneous solutions, emulsions, suspensions. Oral solutions are applied directly. Concentrates are used orally after previous dilution to the application concentration. Oral solutions and concentrates are prepared as described above for the injection solutions, whereby sterile work can be dispensed with.

Suitable preparations for transdermal application are known to be active substance-containing solutions which may contain substances which promote resorption. Resorption-promoting substances are, for example, DMSO (dimethyl sulfoxide), DMF (dimethylformamide), triglycerides and long-chain aliphatic fatty acid esters, azones and their derivatives, terpenes and essential oils, amino acid derivatives.

Said preparations contain the active ingredient in concentrations of 0.1 to 65% by weight, preferably from 1.0 to 40% by weight.

For systemic parasite control in animals, it has generally proven advantageous to administer amounts of approximately 0.5 to 100 mg of active ingredient / kg of body weight in order to achieve good effects.

The dermal application happens e.g. in the form of bathing, diving (dipping), spraying (spraying), pouring on (pour-on or spot-on), washing, shampooing,

Watering, pudding or by means of solid preparations.

Suitable preparations are:

Solutions or concentrates for administration after dilution, sprays, spot on,

Pour on solutions for direct application, infusion formulations, gels;

Emulsions and suspensions for dermal use and solid or semi-solid preparations; Formulations in which the active ingredient is processed in an ointment base or in an oil in water or water in oil emulsion base;

Solutions for use on the skin are dripped on, spread on, rubbed in, sprayed on, sprayed on or applied by dipping (dipping), bathing or washing.

The solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.

The following may be mentioned as solvents: water, alkanols, glycols, polyethylene glycols, propylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkyl glycol alkyl ethers such as dipropylene glycol monomethyl ether, butyl glycol ether, diethylene glycol Acetone, methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2-pyrrolidone, 2-dimethyl-4-oxy-methylene-l, 3-dioxolane, 2- (l-No - nyl) -l, 3-dioxolane, transcutol, solketal, propylene carbonate, propylene glycol diacetate, lactic acid.

The active ingredients can optionally also be dissolved in physiologically compatible vegetable or synthetic oils.

The following may be mentioned as solubilizers: solvents, the solution of the active ingredient in

Promote major solvents or prevent them from failing. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol. It may be advantageous to add thickeners when preparing the solutions. Thickeners are: inorganic thickeners such as bentonites, colloidal silica, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and metacrylates.

Gels that are applied or spread on the skin are produced by adding enough thickening agent to solutions that have been prepared as described above to produce a clear mass with an ointment-like consistency. The thickeners specified above are used as thickeners.

Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient being distributed over the surface of the body. Pour-on formulations are also conceivable in which the active ingredient penetrates the skin and has a systemic effect.

Pour-on formulations are prepared by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If necessary, further auxiliaries such as dyes, antioxidants, light stabilizers and adhesives are added. In the case of pour-on formulations which act systemically, substances which promote resorption can advantageously also be added.

Dyes are all dyes approved for use on animals, which can be dissolved or suspended.

Auxiliaries are also spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid,

Butylated hydroxytoluene, butylated hydroxyanisole, tocopherol. Light stabilizers are, for example, substances from the class of benzophenones or novantisolic acid.

Adhesives are e.g. Cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

Resoφtionsfördemde substances are such. B. DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Emulsions can be used orally, dermally or as injections. They are either of the water in oil type or the oil in water type.

They are produced by dissolving the active ingredient either in the hydrophobic or in the hydrophilic phase and homogenizing it with the solvent of the other phase with the aid of suitable emulsifiers and, if appropriate, other auxiliaries such as dyes, substances requiring resorption, preservatives, antioxidants, light stabilizers, viscosity-increasing substances ,

The following may be mentioned as hydrophobic phase (oils): paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid bigylceride, triglyceride mixture with vegetable fatty acids of chain length C ₈ . ₁₂ or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids which may also contain hydroxyl groups, mono- and diglycerides of C ₈ / CIO fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length ₆ -C ₈ , isopropyl myristate, isopropyl palmitate, caprylic / capric alcohol ester of the saturated fatty length ₁₂ -Cιg,

Isopropyl stearate, oleic acid oleyl ester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as dibutyl phthalate, adipic acid diisopropyl ester, the latter related ester mixtures, inter alia fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol.

Fatty acids such as Oleic acid and its mixtures.

The following can be mentioned as the hydrophilic phase:

Water, alcohols such as e.g. Propylene glycol, glycerin, sorbitol and their mixtures.

The following may be mentioned as emulsifiers: nonionic surfactants, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether; mpholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;

anionic surfactants such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoetl anolamine salt; cationic surfactants such as cetyltrimethylammonium chloride.

The following may be mentioned as further auxiliaries: substances which increase viscosity and stabilize the emulsion, such as carboxymethyl cellulose, methyl cellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, Waxes, colloidal silica or mixtures of the listed substances.

Suspensions can be used orally, dermally or as an injection. They are produced by suspending the active ingredient in a carrier liquid, optionally with the addition of further auxiliaries such as wetting agents, dyes, substances which promote absorption, preservatives, antioxidants or light stabilizers. All homogeneous solvents and solvent mixtures may be mentioned as carrier liquids.

The surfactants specified above may be mentioned as wetting agents (dispersants).

Further additives mentioned are those mentioned above.

Semi-solid preparations can be administered orally or dermally. They differ from the suspensions and emulsions described above only in their higher viscosity.

To prepare solid preparations, the active ingredient is mixed with suitable carriers, if appropriate with the addition of auxiliaries, and brought into the desired shape.

All physiologically compatible solid inert substances may be mentioned as carriers. All of these serve inorganic and organic substances. Inorganic substances are e.g. Table salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide, phosphates.

Excipients are preservatives, antioxidants, dyes, which have already been listed above.

Other suitable auxiliaries are lubricants and lubricants such as Magnesium stearate, stearic acid, talc, bentonite.

Ready-to-use preparations contain the active ingredient in concentrations of 1 pp - 80 percent by weight, preferably from 0.01 - 65 percent by weight. Preferred amounts of active ingredient are 1 to 50 percent by weight, particularly preferably 5 to 40 percent by weight. Preparations which are diluted before use contain the active ingredient in concentrations of 0.5-90 percent by weight, preferably from 1 to 50 percent by weight.

In general, it has proven to be advantageous to administer amounts of about 0.5 to about 100 mg, preferably 1 to 50 mg, of active ingredient per kg of body weight per day in order to achieve effective results.

Solid preparations include powders, premixes and concentrates, granules, pellets, tablets, boluses, capsules, aerosols and inhalants and molded articles.

According to a preferred embodiment, the parasite control according to the invention is carried out non-systemically by means of dermal application.

Another preferred embodiment is the non-systemic application via shaped bodies. Shaped bodies include Collars, pendants for collars

(Medallions), ear tags, ribbons for attachment to limbs or body parts, adhesive strips and foils, peel-off foils.

In general, it has proven to be advantageous to release solid formulations according to the invention which release amounts of active ingredient from 10 to about 300 mg, preferably 20 to 200 mg, particularly preferably 25 to 160 mg, per kg of body weight of the animal to be treated over the course of at least three weeks, to apply to achieve good effectiveness.

Thermoplastic and flexible thermosetting plastics as well as elastomers and thermoplastic elastomers come into question for the production of the molded bodies. Polyvinyl resins, polyurethanes, polyacrylates, epoxy resins, cellulose, cellulose derivatives, polyamides and polyesters which are sufficiently compatible with the abovementioned active ingredient may be mentioned as such. The polymers must have sufficient strength and flexibility so that they do not crack or become brittle during molding. They have to be of sufficient durability to be resistant to normal wear and tear his. In addition, the polymers must allow sufficient migration of the active ingredient to the surface of the molded body.

The polyvinyl resins include polyvinyl halides such as polyvinyl chloride, polyvinyl chloride-vinyl acetate and polyvinyl fluoride; Polyacrylate and polymethacrylate esters, such as

Polymethyl acrylate and polymethyl methacrylate; and polyvinylbenzenes such as polystyrene and polyvinyltoluene. Special mention should be made of polyvinyl chloride.

The plasticizers which are usually used to plasticize solid vinyl resins are suitable for the production of the molded bodies based on polyvinyl resin. The plasticizer to be used depends on the resin and its compatibility with the plasticizer. Suitable plasticizers are, for example, esters of phosphoric acid, such as esters of phthalic acid, such as dimethyl phthalate and diocytyl phthalate, and esters of adipic acid, such as diisobutyl adipate. Other esters such as the esters of azelaic acid, maleic acid, ricinoleic acid, myristic acid, palmitic acid, oleic acid, sebacic acid, stearic acid and trimellitic acid, as well as complex linear polyesters, polymeric plasticizers and epoxidized soybean oils can also be used. The amount of plasticizer is about 10 to 50%, preferably about 20 to 45% by weight of the total composition.

The moldings may contain further constituents, such as stabilizers, lubricants, fillers and coloring materials, without changing the basic properties of the composition. Suitable stabilizing agents are antioxidants and agents which protect the tapes from ultraviolet radiation and unwanted degradation during processing, such as extrusion. Some stabilizers, such as epoxidized soybean oils, also serve as secondary plasticizers. For example, stearates, stearic acid and low molecular weight polyethylenes can be used as lubricants. These ingredients can be used in a concentration up to about 5% by weight of the total composition. In the production of the vinyl-based molded bodies, the various constituents are mixed by known processes and compression-molded by known extrusion or injection molding processes.

From a technical point of view, the choice of the processing method for the production of the shaped body depends fundamentally on the rheological properties of the strip material and the shape of the desired strip. The processing methods can be set according to the processing technology or the type of shaping. In process technology, the processes can be subdivided according to the rheological conditions they run through. Then come for viscous tape materials

Casting, pressing, injection molding and application and, for elastoviscose polymers, injection molding, extrusion (extruding), calendering, rolling and possibly edges. Divided according to the type of shaping, the moldings according to the invention can be produced by casting, dipping, pressing, injection molding, extruding, calendering, embossing, bending, deep drawing etc.

These processing methods are known and require no further explanation. In principle, the explanations given above for polyvinyl resins apply to other polymers.

The polyurethanes used as the carrier material are prepared in a manner known per se by reacting polyisocyanates with higher molecular weight compounds having at least two groups which are reactive toward isocyanates, and optionally with low molecular weight chain extenders and / or monofunctional chain terminators.

In this context, the following should be noted:

Polyisocyanates containing isocyanurate groups, as described, for example, in US Pat. No. 3,001,973, in DE Patents 1,022,789, 1,222,067 and 1,027,394 and in DE-OSes 1,929,034 and 2,004,048; Polyisocyanates containing urethane groups, as described, for example, in DE-PS 752261 or in US Pat. No. 3,394,164; Polyisocyanates containing acylated urea groups according to DE-PS 1 230 778; Polyisocyanates having biuret groups, as described, for example, in DE-PS 1 101 394, in US Pat. Nos. 3 124 605 and 3 201 372, and in GB-PS 889 050; polyisocyanates prepared by telomerization reactions, as described, for example, in US Pat. No. 3,654,106; Polyisocyanates containing ester groups, as mentioned, for example, in British Pat. Nos. 965,474 and 1,072,956, in US Pat. No. 3,567,763 and in German Pat. No. 1,231,688; Reaction products of the abovementioned isocyanates with acetals according to DE-PS 1 072 385 and polyisocyanates containing polymeric fatty acid residues according to US Pat. No. 3,455,883.

It is also possible to use the distillation residues obtained in the industrial production of isocyanates and having isocyanate groups, optionally dissolved in one or more of the aforementioned polyisocyanates. It is also possible to use any mixtures of the aforementioned polyisocyanates.

Preferred polyisocyanates are generally the tolylene diisocyanates and the diphenylmethane diisocyanates.

Polyhydroxyl compounds already contained in urethane or urea groups as well as optionally modified natural polyols such as castor oil, carbohydrates or starch, polyester amides and polyamides count e.g. the predominantly linear condensates obtained from polyvalent saturated and unsaturated carboxylic acids or their anhydrides and polyvalent saturated and unsaturated amino alcohols, diamines, polyamines and their mixtures can be used for this purpose. Addition products of alkylene oxides with phenol-formaldehyde resins or with urea-formaldehyde resins can also be used according to the invention.

Representatives of these connections are e.g. in High Polymers, Vol. XVI, "Polyurethane,

Chemistry and Technology ", written by Saunders-Frisch, Interscience Publishers, New York, London, volume 1, 1962, pages 32-42 and pages 44-54 and volume II, 1964, Pages 5 -6 and 198 - 199, as well as in the Plastics Manual, Volume VII, Vieweg-Höchtlen, Carl-Hanser-Verlag, Munich, 1966, eg on pages 45 - 71.

Of course, mixtures of the abovementioned compounds with at least two hydrogen atoms which are reactive toward isocyanates with one

Molecular weight of 400-10,000, e.g. Mixtures of polyethers can be used.

When selecting the higher molecular weight polyol component used for the production of the polyurethane, it should be noted that the finished polyurethane should not be swellable in water. The use of an excess of polyhydroxyl compounds with ethylene oxide units (polyethylene glycol polyether or polyester with diethylene or triethylene glycol as the diol component) should therefore be avoided.

Thermoplastic materials are particularly emphasized for the production of the molded bodies

Elastomers. These are materials that contain elastomeric phases in thermoplastically processable polymers either physically mixed in or chemically bound. A distinction is made between polymer blends in which the elastomeric phases are part of the polymeric structure. Due to the structure of the thermoplastic elastomers, hard and soft areas are side by side. The hard areas form a crystalline network structure or a continuous phase whose spaces are filled with elastomeric segments. Because of this structure, these materials have rubber-like properties.

There are 5 main groups of thermoplastic elastomers:

1. Copolyester

2. Polyether Block Amides (PEBA)

3. Thermoplastic Polyurethanes (TPU) 4. Thermoplastic Polyolefins (TPO)

5. Styrene block copolymers Suitable copolyesters (segmented polyester elastomers) are composed, for example, of a large number of recurring, short-chain ester units and long-chain ester units which are combined by ester linkages, the short-chain ester units making up about 15-65% by weight of the copolyester and having the formula (II) ,

in which

R represents a divalent radical of a dicarboxylic acid which has a molecular weight of less than about 350,

D represents a divalent radical of an organic diol that has a molecular weight of less than about 250.

The long-chain ester units make up about 35-85% by weight of the copolyester and have the formula (HI)

in which

G represents a divalent residue of a long chain glycol which has an average molecular weight of about 350 to 6000. Methods for the synthesis of such copolyesters are known from DOS 2 239 271, DOS 2 213 128, DOS 2449 343 and US Pat. No. 3,023,192

Suitable copolyesters are, for example, under the trade names ^< Ηytrel from Du Pont,

^® Pelpren from Toyobo ^® , Arnitel from Akzo, ^® Ectel from Eastman Kodak and ^® Riteflex from Hoechst.

Suitable polyether block amides are, for example, those which consist of polymer chains which are composed of repeating units corresponding to the formula (TV).

- C-A-C-O-B- II I I (TV)

O O

in which

A is the polyamide chain derived from a polyamide with 2 carboxyl end groups by loss of the latter and

B is the polyoxyalkylene glycol chain derived from a polyoxyalkylene glycol with terminal OH groups by loss of the latter, and

n is the number of units forming the polymer chain.

The end groups here are preferably OH groups or residues of compounds which terminate the polymerization.

The dicarboxylic acid polyamides with the terminal carboxyl groups are obtained in a known manner, for example by polycondensation of one or more lactams or / and one or more amino acids, furthermore by polycondensation of a dicarboxylic acid. bonic acid with a diamine, in each case in the presence of an excess of an organic dicarboxylic acid, preferably with terminal carboxyl groups. These carboxylic acids become part of the polyamide chain during the polycondensation and attach themselves in particular to the end of the chain, whereby an oc-ω-dicarboxylic acid polyamide is obtained. Fe dicarboxylic acid acts as a chain terminator, which is why it is also used in excess.

The polyamide can be obtained starting from lactams and / or amino acids with a hydrocarbon chain consisting of 4-14 C atoms, e.g. of caprolactam, oenantholactam, dodecalactam, undekanolactam, decanolactam, 11-amino-undecanoic or 12-aminododecanoic acid.

Examples of polyamides, such as those formed by polycondensation of a dicarboxylic acid with a diamine, are the condensation products of hexamethylene diamine with adipic, azelaic, sebacic and 1,12-dodecanedioic acid, and the condensation products of nonamethylene diamine and adipic acid.

In the case of the dicarboxylic acids used for the synthesis of the polyamide, that is to say on the one hand for fixing a carboxyl group at each end of the polyamide chain and on the other hand as chain terminators, those having 4-20 C atoms are suitable, in particular alkanedioic acids such as amber, adipic , Cork, azelaic, sebacic, undecanedioic or dodecanedioic acid, furthermore cycloaliphatic or aromatic dicarboxylic acid, such as terephthalic or isphthalic or cyclohexane-1,4-dicarboxylic acid.

The polyoxyalkylene glycols containing terminal OH groups are unbranched or branched and have an alkylene radical with at least 2 carbon atoms. In particular, these are polyoxyethylene, polyoxypropylene and polyoxytetramethylene glycol, as well as copolymers thereof. The average molecular weight of these OH group-terminated polyoxyalkylene glycols can be in a wide range, advantageously between 100 and 6000, in particular between 200 and 3000.

The proportion by weight of the polyoxyalkylene glycol, based on the total weight of the polyoxyalkylene glycol and dicarboxylic acid polyamide used to produce the PEBA polymer, is 5-85%, preferably 10-50%.

Processes for the synthesis of such PEBA polymers are known from FR-PS 7 418 913 (No. of the publication 2 273 021), DOS 2 802 989, DOS 2 837 687, DOS 2 523 991,

EP-S 0 095 893, DOS 2 712 987 and DOS 2 716 004 are known.

Those PEBA polymers which, in contrast to those previously described, have a statistical structure are particularly suitable. Suitable and preferably suitable PEBA polymers are, for example, under the trade names ^® PEBAX from Atochem, ^® Vestamid

Hüls AG, ^® Grilamid from EMS-Chemie and ^® Kellaflex from DSM available.

The application can be prophylactic as well as therapeutic.

In the case of collars, the concentration of the active ingredients is preferably 1 to

50%; in the case of medallions, pendants and ear tags preferably 2.5 to 35%, in the case of foils, adhesive strips preferably 0.1 to 15%.

The new formulations can additionally contain other active ingredients, such as insecticides, attractants, sterilants, bactericides, acaricides, nematicides, fungicides, etc. Insecticides include, for example, phosphoric acid esters, carbamates, carboxylic acid esters, chlorinated hydrocarbons, phenyl HA nstoffe, substances produced by microorganisms, etc.

The active substances mentioned can be in the liquid, solid preparations as well

Shaped bodies are present in a mixture with synergists or other active ingredients. To The active ingredients include insecticides such as phosphorus-containing compounds, ie phosphoric or phosphonic acid esters, natural or synthetic pyrethroids, carbamates, amidines, juvenile hormones and juvenoid synthetic active ingredients.

The phosphoric or phosphoric acid esters include:

0-ethyl-0- (8-clήnolyl) phenyl-tophosphate (Quintiofos),

0.0-diethyl-0- (3-clüoro-4-methyl-7-coumarinyl) -tlιiophosphate (Coumaphos),

0,0-diethyl-0-phenylglyoxylonitiil-oxime-thiophosphate (phoxime),

0.0-diethyl-0-cyanochlorobenzaldoxime thiophosphate (Chlθφhoxim),

0,0-diethyl-0- (4-bromo-2,5-dichlorophenyl) phosphorothionate (bromophos-ethyl),

0,0,0 ', 0'-tetraethyl-S, S'-methylene-di (phosphorodithionate) (ethion),

2,3-p-Dioxanedithiol-S, S-bis (0,0-diethylphosphorodithionat,

2-chloro-1 - (2,4-dichloφhenyl) vinyl diethyl phosphate (chlorfenvinphos),

0,0-Dimemyl-0- (3-yl-4-memylt ophenyl) thionophosphoric acid ester (fenthion).

The carbamates include:

2-isopropoxyphenylmethyl carbamate (propoxur),

1-naphthyl-N-methyl carbamate (carbaryl).

The synthetic pyrethroids include compounds of the formula I. in which

R ¹ and R ^{2 represent} halogen, optionally halogen-substituted alkyl, optionally halogen-substituted phenyl,

R ^{3 represents} hydrogen or CN,

R ^{4 represents} hydrogen or halogen,

R ^{5 represents} hydrogen or halogen,

Synthetic pyrethroids of the formula I in which are preferred

R ^{1 represents} halogen, in particular fluorine, chlorine, bromine,

R ^{2 represents} halogen, in particular fluorine, chlorine, bromine, trihalomethyl, phenyl, chloro-phenyl,

R ^{3 represents} hydrogen or CN,

R ^{4 represents} hydrogen or fluorine,

R ^{5 represents} hydrogen.

Synthetic pyrethroids of the formula I in which are particularly preferred R ^{1 represents} chlorine,

R ^{2 represents} chlorine, trifluoromethyl, p-chloro-phenyl,

R ^J stands for CN,

R> 4 represents hydrogen or fluorine,

R »5 stands for hydrogen.

Compounds of the formula I may be mentioned in particular

R ^{1 represents} chlorine,

R ^{2 represents} chlorine or p-chlorophenyl,

R ^{3 represents} CN,

R ^{4 represents} fluorine in the 4-position,

R, 5 represents hydrogen.

The following may be mentioned in detail:

3- [2- (4-CMθφhenyl) -2-c orvinyl] -2,2-dimethyl-cyclo-propanecarboxylic acid [(oc-cyano-

4-fluoro-3-phenoxy) benzyl] ester (flumethrin),

2,2-dimethyl-3- (2,2-dichlorovinyl) -cyclopropanecarboxylic acid-oc-cyano (4-fluoro-3-phenoxy) -benzyl ester (cyfluthrin) and its enantiomers and stereomers, oc-cyano-3-phenoxybenzyl (+) - cis, trans-3- (2,2-dibromovinyl) -2,2-dimethylcyclopropane carboxylate (deltamethrin),

2,2-dimemyl-3- (2,2-dicMorvinyl) -cyclopropanecarboxylic acid-oc-cyano-3-phenoxybenzyl ester (cypermethrin),

3-phenoxybenzyl (+) - cis, trans-3 - (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate (permethrin),

oc- (p-Cl-phenyl) isovaleric acid-cc-cyano-3-phenoxy-benzyl ester (Fenvalerate),

2-Cyano-3-phenoxybenzyl-2- (2-cMor- χ:, oc, oc-ttifluor-p-toluidino) -3-methylbutyrate (fluvalinate).

The amidines include:

3-methyl-2- [2,4-dimethyl-phenylimino] thiazoline,

2- (4-CMOR-2-memylphenylimino) -3-methylthiazolidine,

2- (4-CUOR-2-memylphenylimino) -3- (isobutyl-l-enyl) -thiazolidine

1,5-bis (2,4-dime1nylphenyl) -3-methyl-l, 3,5-triazapenta-l, 4-diene (Amitraz).

Juvenile hormones or juvenile hormone-like substances include substituted ones

Diaryl ether, benzoyl urea and triazine derivatives. Juvenile hormones and juvenile hormone-like substances include in particular compounds of the following formulas:

The substituted diaryl ethers include, in particular, substituted alkoxydiphenyl ethers or diphenylmethanes of the general formula I

in which

R ^{1 represents} hydrogen, halogen, alkyl, alkoxy, alkylthio, haloalkyl, haloalkoxy, haloalkylthio, dioxyalkylene, dioxyhalogenalkylene, CN, NO ₂ , alkenyl, alkynyl, alkoxyalkyl, alkoxyalkoxy, hydroxyalkoxy,

R ^{2 represents} the radicals specified for R ¹ ,

R ^{3 represents} the radicals specified for R ¹ ,

R ^{4 represents} hydrogen, alkyl, haloalkyl or halogen,

R ^{5 represents} the radicals indicated for R ⁴ ,

Het stands for optionally substituted heteroaryl which is not bound to the rest of the group via the heteroatom,

X, Y independently of one another represent -O-, -S-

Z represents -O-, -S-, -CH ₂ -, -CHCH ₃ -, -C (CH ₃ ) ₂ -,

m and n independently of one another represent 0, 1, 2, 3 but their sum is equal to or greater than 2. Compounds of the formula I are particularly preferred

in which

R ^{1 is} hydrogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, chlorine, fluorine

R represents hydrogen,

R> 3 represents hydrogen, fluorine, chlorine, methyl,

R ^{4 represents} hydrogen or methyl,

R ^{5 represents} methyl, ethyl, trifluoromethyl or hydrogen,

Het is pyridyl or pyridazinyl which are optionally substituted by fluorine, chlorine, methyl, NO ₂ , methoxy, methylmercapto,

X stands for O,

Y stands for O,

Z represents O, CH ₂ or - (CH ₃ ) ₂ -,

m represents 1,

n stands for 1.

The following connections are specifically mentioned:

Benzoylureas include compounds of the formula (V):

in which

R represents halogen, R ^{2 represents} hydrogen or halogen,

R ^{3 represents} hydrogen, halogen or CM-alkyl,

R ^{4 represents} halogen, 1-5-halogen-C _M -alkyl, CM-alkoxy, 1-5-halogen-C _M -alkoxy, C _M -alkylthio, 1-5-halogen-C _M -alkylthio, phenoxy or pyridyloxy which may optionally be substituted by halogen, C _M - alkyl, 1-5 halogen Cι. _4- alkyl, C ^ - alkoxy, 1-5-halo-C _M alkoxy, C _M -alkylthio, 1-5-halo-C ι-C ₄ alkylthio.

In particular, the following should be mentioned:

Co-active substance and synergist concentrations can be varied widely in each case from 0.1 to 25% by weight, preferably from 1 to 10% by weight. With regard to the action against parasitic protozoa, the following are also interesting: mixtures or combinations of the compounds of the formula (I) with a polyether antibiotic or a synthetically produced coccidiosis.

The following may be mentioned as synthetic coccidiosis or as polyether antibiotics for use in the mixtures according to the invention:

Amprolium, partly in combination with folic acid antagonists

Robenidine toltrazuril

monensin

salinomycin

maduramicin

Lasalocid Narasin

Semduramicin.

Monensin, salinomycin and maduramicin are preferred from this list. The mixture with maduramicin should be particularly emphasized.

Ready-to-use preparations contain the active ingredients in concentrations of 10 ppm to 20 percent by weight, preferably 0.1 to 10 percent by weight.

Preparations which are diluted before use contain the active ingredient in concentrations of 0.5 to 90 percent by weight, preferably 1 to 50 percent by weight.

In general, it has proven to be advantageous to administer amounts of about 0.5 to about 50 mg, preferably 1 to 20 mg, of active ingredient per kg of body weight per day in order to achieve effective results. In a mixture with other coccidiosis agents or polyether antibiotics, the active compounds according to the invention are present in a ratio of 1 to 0.1-10 to 1 to 1-10. The ratio 1 to 5 is preferred.

The active ingredients can also be administered together with the animal's feed or drinking water.

Feed and food contain 0.01 to 250 ppm, preferably 0.5 to 100 ppm of the active ingredient in combination with a suitable edible material.

Such feed and food can be used for medicinal purposes as well as for prophylactic purposes.

Such feed or food is produced by mixing a concentrate or a premix which is 0.5 to 30%, preferably 1 to

Contains 20% by weight of an active ingredient in a mixture with an edible organic or inorganic carrier with conventional feed. Edible carriers are e.g. Corn meal or corn and soybean meal or mineral salts, which preferably contain a small amount of an edible dust control oil, e.g. Contain corn oil or soybean oil. The premix obtained in this way can then be added to the complete animal feed before it is fed to the animals.

An example of use in coccidiosis is:

For the healing and prophylaxis of coccidiosis in poultry, especially in

Chickens, ducks, geese and turkeys, 0.1 to 100 ppm, preferably 0.5 to 100 ppm, of an active ingredient are mixed with a suitable edible material, for example a nutritious feed. If desired, these amounts can be increased, especially if the active ingredient is well tolerated by the recipient. Accordingly, the administration can take place via the drinking water. For the treatment of individual animals, for example in the case of the treatment of coccidiosis in mammals or toxoplasmosis, amounts of active compound of 0.5 to 100 mg / kg body weight are preferably administered daily in order to achieve the desired results. Nevertheless, it may be necessary at times to deviate from the amounts mentioned, in particular depending on the body weight of the test animal or the type of administration method, but also because of the animal species and its individual response to the active ingredient or the type of formulation and the time or distance, to which it is administered. In some cases it may be sufficient to make do with less than the minimum quantity mentioned above, while in other cases the above upper limit must be exceeded. When administering larger quantities, it may be advisable to divide them into several individual administrations during the day.

The activity of the compounds according to the invention can e.g. in cage experiments with the following experimental arrangement, in which the animals are treated with the respective individual components and with the mixtures of the individual components.

An active ingredient-containing feed is prepared in such a way that the required amount of active ingredient with a nutritionally balanced animal feed, e.g. is thoroughly mixed with the chick feed specified under.

If a concentrate or a premix is to be prepared, which is ultimately to be diluted in the feed to the values stated in the experiment, generally about 1 to 30%, preferably about 10 to 20% by weight of active ingredient with an edible organic or inorganic carriers, for example corn and soy flour or mineral salts, which contain a small amount of an edible defatting oil, for example corn oil or soybean oil, are mixed. The premix thus obtained can then be added to the whole poultry feed prior to administration. The following composition is an example of the use of the substances according to the invention in poultry feed.

52.00% feed grain meal, namely: 40% corn, 12% wheat

17.00% soybean meal extr.

5.00% corn gluten feed

5.00% wheat feed flour

3.00% fish meal

3.00% mineral mixture

3.00% alfalfa grass green flour

2.50% vitamin premix

2.00% wheat germ, crushed

2.00% soybean oil

2.00% meat bone meal

1.50% whey powder

1.00% molasses

1.00% brewer's yeast, bound to beer spent grains

100.00%

Such feed contains 18% crude protein, 5% crude fiber, 1% Ca, 0.7% P and 1200 i.E. per kg. Vitamin A, 1200 i.E. Vitamin D3, 10 mg vitamin E, 20 mg zinc bacitracin.

The active ingredient is added to this feed in amounts of e.g. 1 to 20 ppm (w / w) mixed. Suitable dosages of the active ingredient are e.g. 1 ppm; 2.5 ppm; 5 ppm

(each indicated as parts by weight "(w / w)").

In the following examples, compounds A and B are used as active ingredients. Examples

example 1

Test with resistant single-host cattle ticks / SP-resistant Parkhurst strain

Injection procedure

Test animals: Adult suckled females of Boophilus micoφlus (strain

Parkhurst - SP resistant) Solvent: dimethyl sulfoxide

20 mg of active ingredient are dissolved in one ml of dimethyl sulfoxide, lower concentrations are prepared by dilution in the same solvent.

The test is carried out in 5-fold determination. 1 μl of the solutions is added to the

The abdomen is injected, the animals are transferred to trays and stored in an air-conditioned room. The effects are checked after 7 days on the laying of fertile eggs. Eggs whose fertility is not externally visible are kept in glass tubes until larvae hatch after about 24 days in a climate cabinet. An effect of 100% means that no tick has laid fertile eggs.

In this test, e.g. the following compounds of the preparation examples have a good effect:

Compound A showed 100% activity at 100 μg (inhibition of the deposit of fertile eggs)

Compound B showed 100% activity at 20 μg (inhibition of the deposit of fertile eggs) Example 2

Test for Musca domestica larval development on cattle manure after oral treatment of cattle with active ingredient-containing formulation (feed-through test)

In a capsule formulation, 3 g of active ingredient are fed to 300 kg cattle for three consecutive days. The first larval stages of Musca domestica are set up on dungpobes of the treated cattle and the development to adult flies is compared to the development on manure samples from an untreated control. Such substances are assessed as effective that the

Prevent adult development reliably over a period of four weeks.

Compound A showed 50% efficacy until day 3 after treatment, then a long-lasting 100% efficacy.

Claims

Patentansprfiche

1. Use of phenylketoenol derivatives of the general formula (I),

in which

X represents alkyl, halogen, alkoxy or haloalkyl,

Y represents hydrogen, alkyl, halogen, alkoxy, haloalkyl,

Z represents alkyl, halogen alkoxy,

n stands for a number from 0 to 3, or the radicals X and Z together with the phenyl radical to which they are attached, the naphthalene radical of the formula

form,

in which Y has the meaning given above,

G for hydrogen (a) or for the groups

stands,

A and B may be the same or different and are hydrogen, optionally substituted by halogen substituted alkyl, alkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, optionally cycloalkyl interrupted by heteroatoms or optionally substituted by halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro or aryl, aralkyl or Stand hetaryl,

or in what

D represents oxygen, sulfur or -NH-,

E ^{+ represents} a metal ion equivalent or an ammonium ion,

L and M represent oxygen and / or sulfur, R1 represents alkyl, alkenyl, alkoxyalkyl, alkylthioalkyl, polyalkoxyalkyl or cycloalkyl which may be substituted by halogen, which may be interrupted by heteroatoms, optionally substituted phenyl, optionally substituted phenylalkyl, substituted hetaryl, substituted phenoxyalkyl or substituted hetaryloxyalkyl and

R ^{2 represents} alkyl, alkenyl, alkoxyalkyl, polyalkoxyalkyl, optionally substituted by halogen, or optionally substituted phenyl or benzyl,

R ³ , R ⁴ and R5 independently of one another represent alkyl, alkoxy, alkylamino, dialkylamino, alkylthio, alkenylthio, alkynylthio, cycloalkylthio optionally substituted by halogen and optionally substituted phenyl, phenoxy or phenylthio,

R "and R 'independently of one another represent hydrogen, optionally substituted by halogen, alkyl, alkenyl, alkoxy, alkoxyalkyl, optionally substituted phenyl, optionally substituted benzyl,

or where R6 and R together represent an alkylene radical which may be interrupted by oxygen,

with the exception of the following connections:

3- (2-methoxyphenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-chloro-phenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-methoxyphenyl) -4-hydoxy- Δ ³ -dihydrofuranon-2, 3- (2-fluorophene) -4-hydoxy- Δ ³ -dihydrofuranon-2, and the enantiomerically pure forms of compounds of the formula (I),

for the manufacture of medicines for combating parasites in and around animals.

2. For the control of parasites in animals and in their environment, in which a suitable amount of active ingredient of the formula (I) according to Claim 1 is applied to the animals.