CA2048543C - Processes and agents for combating fleas - Google Patents

Abstract

The present invention relates to processes and agents for combating fleas on, and in the surroundings of, domestic animals, which is characterised in that the domestic animals are treated with collars which contain active compounds which inhibit insect development.

Description

The present invention relates to processes and agents for combating fleas on, and in the surroundings of, domestic animals, which contain substances which inhibit insect development.
Adult fleas usually live preferably in the coat of their host animals. They feed on the Tatter's blood and lay their eggs in the coat of the particular host animal.
Since the eggs deposited do not adhere to the coat of the host, they fall off rapidly and can therefore be found above all in the surroundings of the host animalva, for example in their beds and bedding.
This means that preferably beds and bedding of the host animals are infested with flea eggs, fram which flea larvae hatch within a few days. Three developmental stages can be distinguished in the larvae, each of which lasts approximately 3 days. The third larval stage spins a cocoon and pupates. Under favourable conditions (20 --30°C, 60 - 80~ relative humidity), the developmewt from the egg to the pupa lasts approximately 10 days. After about ~ more days, development of the fleas is complete, and fleas ~rhich are ready to hatch can be found in the cocoons lying on the floor (carpets, sleeping places etc.). The young flea can remain in its cocoon for months. _ Le A 27 'T49 - 1 -L
Under unfavourable conditions, however, the developmewt from the egg to the adult young flea can last as long as 4 - 5 months. In order to reach sexual maturity, that is to say to lay ferule eggs, fleas require blood as food.
Ideally, this blood is from the particular specific host.
However, particularly after a relatively long fasting period, fleas can also accept the blood of other hosts.
Infestation by fleas of domestic animals such as dogs and cats is not only a nuisance for the 9_nfested animal, but also causes considerable pain (injuries by biting, itching and allergies) and harm (loss of blood) to the infested animals. Fleas can also pass on various species of tapeworm. They therefore also represent a medical problem fox the infested animals and for the animal owners. However, it is also possible for the anima3. owner to be bitten by fleas. In some humans, this causes allergy to flea bites. For this reason, effective control of fleas in dogs and cats has always been desirable and necessary, especially since these domestic animals live 2Q in an increasingly greater number and in increasingly c.~.~Se contact with man.
A large number of insecticidal active compounds has been disclosed to date for combating fleas. Examples of such active compounds are, from the class of the carbamates propoxur, bendiocarb and carbaryl, from the class of the phosphates fenthion and dia~inone, sand from the class of the pyrethroids permethrin, cypermethrin and resmethrin.
:Ge A 27 7~9 - 2 -These active compounds are contact insecticides which act mainly on adult fleas. These active compounds have no effect on eggs or on the pupated stages of the fleas.
The active compounds are used on the host animal, and applied, for example by spraying, douching, washing, as a powder, or by pouring-on or spotting-on. They can also be incorporated into collars. The active compounds are also used in the immediate or further surroundings of the host animals in the form of aerosols, spray formulations ZO and dusts. For this purpose, beds and the home and areas outside the home are treated.
It is also known that insect development inhibitors such as methoprene or cyroma~ine can be added to the agents with which the surroundings of the host anima:~s are treated. This stops the development of adult fleas from eggs and larvae and pupae. However, 'to date it was necessary for the entire surroundings of the host animals, that is to say the entire home of the human, to be treated.
It is also known that reinfestation of dogs and cats by fleas can be prevented by treating dogs and cats orally or parenterally with active compounds which inhibit the growth of fleas (EP-i7S (European Published Specification) 255,803).
It is furthermore known that dogs and cats can be protected against fleas by spraying with an aerosol ~e A 27 7~9 - 3 -~~a formulation containing methoprene. In doing so, it was possible to prevent flea larvae developing from the deposited eggs (International Pest Cowtrol 27, 19~a, pp . l0-.14 ) .
There are also known animal collars which have been impregnated with a solution containing methoprene (EP-OS
(European Published Specification) 124,404).
ell insecticide-based or insect-development-inhibitor-based methods which are known to date for combating fleas in domestic animals involve treatment of the host animal (dog or cat), its bedding or its entire surroundings.
Treatment of the host animals alone is of little promise since for weeks and even months there is the risk o~
reinfestation by freshly hatched fleas from the 1~ surroundings. Treatment of only the bedding Of thE3 host animal is also of little promise since the animals change their beds, and some beds are not even known or (in particular in the case of cats ) are not accessible for treatment.
The greatest success can therefore be achieved when the host animals as well as their entire surroundings are treated. Treatment of the surroundings is labour-intensi.ve and xequires plenty of material. Possibilities should therefore be sought which reduce the amount of labraur and the material emplayed for the treatment.
This is made possible by the present invention.
Le .A. 27_ 749 - 4 -Tt has been found that fleas on, and in the surroundings of, domestic animals can be combated by treating the domestic animals with collars which contain insect-development inhibitors.
New animal collars have been found which contain insect-development inhibitors. a~n exception are collars based on absorptive material which has been impregnated with methoprene.
In this way, the treated animals provide, simultaneously with the distribution of the flea eggs, for a targeted distribution of the active compound to those locations from which a reinfestation with fleas may occur. Hence, the animals themselves provide the targeted distribution of the active compaund. In this way, neither are locations left out which must be treated, nor is active compound wasted in locations in which the host animal does not stay. Moreover, the labour in connection with the application of the active compound is dispensed with.
It was surprising that an effect could be achieved by a0 this way of applying the active compound. In the methods known to date, the eggs or larvae in the surroundings were treated directly or came into contact with the active compound on the an9.mals when the latter were treated.
However, it could not have been expected that efficient control of fleas in the surroundings is possible by the Le A 27 749 - 5 -treatment according to the invention.
The success of the treatment can even be increased by adding, to the collars, an insecticide which is active against fleas (adulticide) for combat:Lng the adult fleas.
Domestic animals which may be mentioned are dogs and cats. The following may be mentioned as fleas: Ctenocep halides spec., Pulx spec., Xenopsylla spec., Ceratophyllus spec., ~chidnophaga spec., Tunga spec..
The following may be mentioned as active compounds which have an insect-development-inhibiting action: juvenile hormones or juvenile-hormone-type substances, substituted diaryl ethers, benzoylureas and triazine derivatives.
These compounds are known. The juvenile hormones and juvenile-hormone-type substances include, in particular, compounds of the following formulaes Le A 27 7~g ° 6 -.~C~HS
v C2H5 CH3 -' ~ ~ i '°°'° ~ -O C H ~
~ CHI CH3 i so--H~C3 w.

CHO i H3 I H3 ~~
H3C C\
~CH

C H 3 0--w o a 0 HSC~~ ! C2H5 ~'H3 0 v H~.C OCH~
H3C_ 0 CH3 CH3 II
a HOC OCH~
Le A 27 749 ° '1 The substituted diaryl ethers include, in particular, substituted alkoxydiphenyl ethers or -diphenylmethanes of the general formula T
R1 r- c c~ y- c cH y-a;-H~ c, R~
where R1 represents hydrogen, halogen, alkyl, alkoxy, alkylthio, halogenoalkyl, halogenoalkoxy, halogenoalkylthia, dioxyalkylene, dioxyhalogeno-alkylene, CN, I~C2, alkenyl, alkinyl, alkaxyalkyl, 1p alkoxyalkoxy or hydroxyalkoxy, RZ represents the radicals mentioned under R1, R3 represents the radicals mentioned under R1, R4 represents hydrogen, alkyl, halogenoalkyl or halogen, RS represents the radicals mentioned under R4, ~Iet represents optionally subst~.~tuted heteroaryl which is not banded to the remaining radical via the heteroatom, ~ and Y independently of one another represent -0- or -S-, Z represents -0-, -S-, -CHfz-, -CHCH3-, -C(CI33)z-, m and n independently of one another represent 0, 1, 2 or ~, but their total is equal to, or greater than, ~.
Preferred compounds of the formula T are those in which R1 represents hydrogen, fluorine, chlorine, bromine, Cl_4-alkyl, C1_~,-alkoxy, Cl_4-alkylthio, Cl_4-halo-genoalkyl having up to 5 halogen atoms, in particular trichloromethyl, ~trifluoroanethyl, C~_~--halogenoalkoxy having up to 5 halogen atoms, in particular trichloromethoxy, trifluoromethoxy, C~_4-halogenoalkylthio having up to 4 halogen atoms, in particular trifluoromethylthio, CN, X102, CZ_3-alkenyl, C1_~,-alkoxy-C1_2-alkyl, in particular ethoxymethyl, methoxyethyl, C~_z-alkoxy-Cl_g-alkoxy, in particular methoxyethoxy, C1_4-~hydroxyalkoxy, in particular hydroxyethoxy, dioxyethylene, dioxymethylene, difluorodioxymethylene, trifluorodioxyethylene or dichlorooxymethylene, RZ represents the radicals mentioned under R1, R3 represents the radicals mentioned under R', R~ represents hydrogen, Cl_,,-alkyl, C1_4-halogenoalkyl having up to 5 halogen atoms, chlorine, fluorine or bromine, 7Le A ~7 74~

Ft5 represents the radicals mentioned under R, Het represents pyridyl, pyridazinyl, pyrimidinyl, or pyra~inyl, each of which is aptionally sub-stituted by one ar mare identical or different radicals Pram the group comprising C1_~-alkyl, such as methyl, ethyl, t-butyl, halogen, such as fluorine, chlorine, bromine, IdOa, C1_$-alkoa~y, C1_4-alkylthio, Ci_~-alkoxy, Cl_4-alkyl~thio, C1,4-halagenoalkyl having up to 5 halogen atoms, C1_4-halogenaalkoxy having up to ~ halogen stems ar C1_~-halogenaalkylthia having up to a halagen atoms, X and Y independently of one another represent -t7- or -S-r ~ represents -0-, -~-, -CH2-, -CHCH3-, -C ( CI~3 ) a-, m represents 1 ox' 2, and n represents 1 or 2a Particularly preferred campaunds of 'the formula I are these in which represents hydrogen, methyl, trifluaramethyl, me~thax~r, trifluoromethaxy, chlorine ar fluorine, represents hydrogen, R~ represents hydrogen, fluorine, chlorine or methyl, R4 represents hydrogen or methyl, RS represents methyl, ethyl, trifluoromethyl or hydrogen, Het represents pyridyl or pyrids~iny.l, each of which is optionally substituted by fluorine, chlorine, methyl, ~TOz, metl~ao~cyor methylmercapto 0 X represewts O, Y represents 0, represents 0, CHz or 'C ( CH3 ) z', m represents 1 n represents 1 The following comgounds be mentioned lndlVldllt''Allys may R1 ~ J R6 ~ ' Ck3~ - CH' Cr' N
R

H H CHI ~-C1 0 H H CHI H C(CI9~)2 Z \_..-/ I R6 R3 o-CHZ-CH-a--(~~~
N
Ri Ft3 R5 R6 ~

Z(CH2)~-0-Hei, ~R1 ~R--~3 F3~ ~d~ Z H~i H H p N
H H O
N
H H O "°
N--N
Le .Pb 2 7 7 4 9_ ° ~. ~ -°

The substituted diaryl ethers also include the compounds of the formula zz R1 ~ ~ ~ ~ Y-(CH)m-(CH)n~Z-13~t X~ 6 O
R
where ~ represents 0, S, NH, -CH2-, -CHCH3~, -C ( CH3 ) ~-, Y represents ~ or S, represents 0 or S, R1 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, Zp alkoxy or halogenoalkyl, R2 represents identical ar different radicals from the group comprising hydrogen, halogen, alkyl, alkenyl, halagenoalkyl, alkoxy, alkylthio, halogenaalkoxy or halogenoalkylthio, R3 represents hydrogen, alkyl, halogenoalkyl, alkoxyalkyl, alkenoxyalkyl, alkenyl or alkinyl, R" represents the radicals mentioned under R3, R3 and R4 together with the adjacent C atoms can represent saturated or unsaturated 5- to 7-membered carbocyclic rings, m represents 1 or 2, n represents 1 or 2, o represents 1, ~ or 3 and Het represents optionally substituted heteroaryl which is not bonded to the remaining radical ~a.a the heteroatom.
The following may be mewtioned in par~t.~cular~
Zo(-~t-7C~-Het b ~~ 3 X
H2 s H2 ~ Hit ~2H5 -CHI°CH°
Q. 1.3 ~C1~
i ~' 3 5 H °CH~-CH

s H~t 0 1,3-012 -CHZ-iH-CHZF

0 1.3-012 CHZ iH
i CHZ-F

S 1.3-012 -CHZ'iH- ~

CHZ-F

v 0 3-F5r -CHZ- i H-CHZ-F

CHZ 1.3-012 -CHZ-iH-CHZF

CHZ H -CHZ-iH-CHZ-F

0 H -CHZ-jH- \ y CHZF

S H -CHZ-iH-CHZF

~~~~~c~~9 X Rz H Hit 0 1.3-cy -cH~-cH- ~ I
'''~.r''~"'c x cH~~

I H 3 ~-~c H 3 - ~~N 0 0 1a3-C1~ -CHZ-CH

/ \ N

1 3_C1 -CH -CH- N_~,.N ~'~

IH3 ~CH3 - w~N 0 CHI 1.3-C12 -CH2-CH H

~

-CH- / \ N

0 H -C IJ~N ~"C
Z

0 1.3-012 -CH2CH~0- CH2-CH~-I~ 1 X~Y(-H-)-0-Hit X Y H Het 0 S -CH2GH~OCH~CH~ ~~~ I

I e~
CHZ-F
S o -cH~-cH- r I
cH~-F
r 0 O °CHy CH-I w CfI2-F
r I w CHI-F

0 p -CH2-CH-w 7Le i~. 2 7 7 4 9 ° ~.7 0~5 ~C Y a H~ ~
CHI
N-CH
AN

~

CHI
~--N~O

O 0 - CH 2 CH , - N----N ~--( I . CH3 CHZF

~ ~CI~~
~~

---N N-CH

I NN ~--J 'C 1-I ~

CHEF

CHI
CH 0 -CH -~~
-CH- ~--N~

2 I , ~---N
N

o O -cH~-cH---~~~---N o i N.---N ~

CHI

0 O _CFI~_CH_ ,~-N O

I N~N

ccz~ cH~

r~

S 0 -CHI-CHw -~~---N
O

I N~N ~

CC1~

~e A 27 749 - lg -The substituted diaryl ethers furthermore include the compounds of the formula (III) R~ R4 R1 s ~ ~ ~. _CHs ,,.CH_ ~ ~5 X 2 ~ Y ° (ITI) F~
where x represents 0, S, D1H, -CHI-, --CHCH3-, -~ ( CH3 ) 2-Y represents straight-chain or branched alkylene which is optionally interrupted by oxygen, R1 represents identical or different radica7.s from the group comprising hydrogen, halogen, alkyl, alkaxy and halogenaalkyl, R2 represents identical ax different radica~.s from the group comprising hydrogen, halogen, alkyl, alkenyl, halagenoalkyl, alkoxy, alkylthio, halogenoalko~cy and halogenoalkylthia, R3 represents hydrogen, alkyl, halagenaalkyl, alkaxyalkyl, alkenaxyalkyl, alkenyl ar alkinyl, R" repxesents the radicals mentioned under R~, R3 and R~ tagethes can represent a direct bond, an~cl Le ~4 27 749 - 19 -v~5 RS repre~ent~ hydrogen, halogen, alkyl, halogeno-alkyl, al3soxy, amino, alkyl, alkylamino, dialkyld amino ox acylamino.
The following array ~e mentioned in particulars _ ~~ ~\
~ z Ct ~"
~--- 5 0 1.3 C1~ -CH2-CHZ-0-CH~-CH- 3-NH2 iH3 S H -CHICH-0-CHZ-CH- 5-N~a o. 1.3-C1~ -CH2-CHZ-0-CH~CH~- 4-NF-l~

p 1.3-C12 -CH2-CH~-0-CH~CHZ- 3-oCH3 S 1.3-Clz -CHI-CHI-C3-CHZCH~- S-OCH3 Q 3-8r -CHI-CH~-0-CH~CP4~- S-OCH3 CH2 1.3-C1~ -CHI-CHZ-0-CH~CH2-0-CH~CH~-CH2 H -CHI-CHI-O-CH2-CH 5-C~"3 0 H -CH2-~H-0-CHZ-iH- 5N~

S H CH~-iHO-CH~-CH2- 5-NON-CH3 0 1.3-C1~ -CHZ-CHZ-0-CH2CH2-3-NH-C-NH f~_\ ~~\
~I

!H3 ~CH3 0 1.3-C12 -CHZ-CH-0-CH2CH2- 5-~N~O

~....~

S 1.3-C1~ -CHI-CH-0-CHZ-rH2-5-N~

Le A 2? ?49 - 21 -X F~'~ a R 5 iH3 ,~CH3 CHI 1.3-C1~ -CHI-CH-0-CH~CH~° 5-N~0 O H -CHI°CHZ-0-CH2CH2° 5°N~O

O 1.3°C1~ --CHZCI-1~0-CHZ°CH~- 3°NH-C-NH ~
ii -CH- H -CH2CH~°O°CNZCH~° 4°OCH3 i i O H 3°NH°C-NH ~

0 H -CH2CHZ°0°CHZCH2CH2° 4°NH°C-NH' F3 i ~l 7~~ A 27 7~9 - 22 -The diaryl ethers furthermore include the compounds of the formula (IV) Het-X
o cp n c;-cH~~ ~-Z (xV~
~s in which Het represents an optionally sulastituted hetero-aromatic radical represents O, S, -CHZ°, °O-CH2-, -''a-~I~Ig~-, -C:HZ-O-O
I I
_C°D _C_ N-O-C1-~4-alkyl , Y represents O, -0-CHZ-, S, Z represents an optianally substituted aromatic or heteroaromatic radical;
m represents integers from 1 to ~&, n represents 0, 1, 2, 3 or 4, o represents 0, 1, 2, 3 or ~, where n and o must not simultaneously represent 0, Le A 27 749 - 23 °

p represents integers from 1 to 4, R2, R3, R~, 'R5, R6 independently of one another represent hydrogen, C1-C6-alkyl, which is optionally sub-stituted by halogen or C1_4-alko~cy; two radicals which axe adjacent to each other can also, together with the C atoms to which they are bonded, form a saturated carbocyclic 5- or 6-ring, and R1 represents identical or different radicals from the group comprising hydrogen, halogen, CN, C1_4-alkyl, 1-5-halogeno-C1_~-alkyl, C1_4-alkoxy, C1_4-alkylthio, 1-5-halogeno-C1_~-al3coacy, 1-5-halogeno--C1_4-alkylthio, phenyl or phenoxy.
The following may be mentioned in particulars x ~'~r-o ( -a d D o-sae ~.
~°N X ~ ~' ~1 a x R 1 B ~I ~t t j~~s o a . a-cy -c~az-c~-Le A z~ ~~~ - z4 -X R1 ~ Hit CF"3 H -CHI-CH I

0 1.3-C1~ -CH2-CH- r I
I h~

CHEF

0 1.3C1~ -CHZ-CH I
I std CHZ-F' S 1.3-C12 _CH2-CH- r I
I

CHZ-~' CHZ 1.3-C12 _CH~-CH- r I
I h~

CH2_F

CH2 H -CH2-CH- r I
I .~-'N

CH2_F

0 H CH~-CH-~t~P

CHEF' S H -CHI-CH- r I
~N

CH~~"
T~e da 2"7 a~9 - 25 -H1 ~ Het 0 1.3-C1~ -CHI-CH-CHEF

iH3 ~CH3 0 1 -CH ! ~ N
3-Cl -CH-. 2 0 Z

H3 /~'~CH3 S 1 -CH ~~~~ --3J 0 . 2 p,~'~"T~ ~.--~

CH2 1.3-C1~ _CH~-CH_ ! ~ N

H

0 H -CH ! ~ IJ~O
-CH-C;H3 ~H3 I

0 1.3-C12 -CHaGH~O-CHI-CH~- v Le A 27 749 - 2~ --~ n ~i 1 xYC-B-)-o-Hat X Y B Het r O S -CH2CH20CH~CH~
°
0 0 CH2-CHZ-0-CH~-CHI
s 0 S -CHI-iH-S 0 -CH2-iH-CHI-F
0 0 -CH2-CH- °
CHc -~' CH~_F

ri Le A 27 749 - ~7 ~-X Y ~~ Het I H --~~---N~N-cH ~
0 O -CHI-CH- N-°'N
CHI
~~---_N'~o O o -CHZ-CH- N-N
cH3 cH~F
/CHI
S O - CH ~ - C i - --~-~N~N--CH
N...aN \C H 3 CHEF
CHI
Ck.p~ O °CH~-CH- '.~N O
I N--mN \"'°"~
CFA CHI
O O -CH2 CH ~~~N~,O
I N°'-N

O O _C~I~_CH- -'-~N O
N-N
CC;I ~ CHI
o - CH z _ c ~ _ --,~~---.NCO
N-°-N
CCl~
La A 27 7~9 - 28 -The benzoylureas inolude compounds of the formula (V):

R~ V
~ ~-NH-coNH( ) '°~R4 RZ
where R1 represents halogen, Rz represents hydrogen or halogen, R3 represents hydrogen, halogen or C1_4-alkyl, R4 represents halogen, 1-5-halogeno-C1_4-alkyl, Cl_4-alko~cy, 1-5-halogeno-C1_4-alkoxy, Cl_4-alkyl-thin, 1-5-halogens-C1_~,-alkylthio, pheno:Ky or ltd pyridyloxy, each of whioh aan be optionally substituted by halogen, C1_m-alkyl, 1-5-halogeno-Cl_4-alkyl, C1_4-alkoary, 1-5-halogeno-Cl_4--alkoxy, C1_4-alkylthio, or 1-5-halogeno-C1-C4-alkylthio.
The following may be mentioned in particular:
R~
ONHCONH ° ~ ~ R'~

- ~e :~ 27 749 - 29 -F F CFS

F F SCFS

H F OCFS

F F 0 ~~~ C1 F F 0 ~~~ CF3 F F 0 ~~.~ CF3 the ~triazines include compounds of the formula (VT) N, IN (VI) .

wheria he A ~7 74~ m 30 -~~~
R1 represents cyclopropyl or isopropyl;
Rz represents hydrogen, halogen, C1-Clz--alkyl-carbonyl, cyclopropylcarbonyl, Cz-Clz-alkl-carbamoyl, C~-Clz-alkylthiocarbamoyl or Cz-C6-alkenylcarbamoyl; and R3 represents hydrogen, C1-C~z-alkyl, cyclopropyl, Cz-Cs-alkenyl, C1-Ciz-alkylcarbonyl, cyclopropyl-carbonyl, C1-Clz-alkylcarbamoyl, C1-Clz-alkylthio-carbamoyl or Cz-C6-alkenylcarbamoyl, and their acid addition salts which are non-toxic to warm-blooded species.
The following may be mentioned in particularo Cyclopropyi H H

Cyclopropyi H CHI

Cyclopropyl H CZHS

Cyclapropyl H C~H7-n Cyc 1 opropyl H C,~Hc~-n Cyclopropyl H CSHqq-n Cyclopropyl H C6Hq~-n Cyclopropyl H C~HqS-n Cyclopropyl H C~H1?-n ~e A 27 749 - 31 -( con-tinua~ion) Cyclopropyl H C12H25 n Cyclopropyl H CH2-CgH9-t Cyclopropyl H CH2CH(CH3)C2H5 Cyelopropyl H CH2CH-CH2 Cyclopropyl C1 Cyclopropyl C1 C6H13-n Cyclopropyl C1 C8H1~.-n Cyclopropyl C1 C12H25"n Cyclopropyl H Cyclopropyl Cyclopropyl H COCH3 Cyclopropyl H COCH3'HC1 Cyeloprapyl H C0C2H5'HC1 Cyclopropyl H COC2H5 Cyclopropyl H COC3H~-n Cyclopropyl H COC3Hp-i Cyclopropyl H COC4H9-tHCl Cyclopropyl H COCaH9-n Cyclopropyl H
COC~H13-n Cyclopropyl H COC11-H23-n Cyclopropyl COCH3 COC2H5 Cyclopropyl COC3H~-n COC6H13-n Cyclopropyl COCH3 COC3H~-n Cyclopropyl COC2H5 COC3H'-n Cyclopropyl H COCyclopropyl Cyclopropyl COCylclopropyl COCyclopropyl Cycloprapyl COCH3 COCH3 T~opropyl H H

Le A 27 749 ~ 32 (continuation) H1 R2 ~3 Isopropyl H COCHC

Isopropyl H COC~H~-n Cyclopropyl H CONHCH3 Cyclopropyl H C0NHC3H7-i Cyclopropyl CONHCH~ CONHCH~

Cyclopropyl H CSNHCH3 Cyclopropyl H CONHCH~CH=CHI

Cyclopropyl CONHCHZCH=CHZ CONHCHZCH=CHz Cyeloprapyl CSNHCH~ CSNHCH3 The abovementioned substituted diaxyl ethers of the formula I must be particularly emphasised.
Insecticides which may be incorporated into the collars according to the invention in addition to the development inhibitors mentioned axe: phosphates, such as, for example, fenthion, caxbamates such as, fox example, propoxux, pyrethxoids such as, fox example, cyfluthrin ox flumethxin.
1Q Substances which can be used for producing the collars according to the invention axe polyvinyl resins, poly-urethanes, polyacrylates, epoxy resins, cellulose, cellulose derivatives, polyamides and polyesters which axe suff~.ciewtly compatible with th~ abovementioned active compounds. The polymers must have suffic:Lently Le A 27 749 - 33 -high strength and flexibility so as not to crac3c or became brittle when formed into a collar. They must be sufficiently durable so as to be resistant to normal wear and tear. Moreover, the polymers must permit sufficient migration of the active compounds to the surface of the moulding. These properties are met, in particular, by solid polyvinyl resins, that is to say po:Lymers which are formed by polymers of a vinyl double bond.
Examples of typical vinyl resins are polyvinyl halides, such as polyvinyl chloride, polyvinyl chloride/vinyl acetate and polyvinyl fluoride; polyacrylate esters and polymethacrylate esters such as polymethyl acrylate and polymethyl methacrylate; and polyvinylbenzenes such as polystyrene and palyvinyltoluene.
Z5 Suitable plasticisers for the production of the collars according to the invention on the basis of polyvinyl resin are those which are customarily used for plastic-ising solid vinyl resins. The plasticiser to be used depends on the resin and .its compatibility with the 2~J plasticiser. Examples of suitable plasticisers are esters of phosphoric acid, such as tricresyl phosphate, esters of phthalic acid, such as dimethyl phthalate and dioctyl phthalate, and esters of adipic acid, such as diisobutyl adipate. It is also possible to use other esters, s7,ach as 25 the esters of azelaic acid, malefic acid, ric:inoleic acid, myristic acid, palmitic acid, oleic acid, sebacic acid, stearic acid and tr:imellitic acid, and also complex linear polyesters, polymeric plasticisers and epox:i.dised Le A 27 749 - 34 -soybean oils. The amount of plasticiser is approximately to 50~ by weight, preferably about 20 to 45~ by weight, of the entire composition.
The collars can also contain other components such as 5 stabilisers, spreading agents, lubricants, fillers and colourants, without this changing the basic properties of the composition. Suitable stabilisers are antioxidants and agents which protect 'the collars from ultraviolet rays and undesired degradation during processing, such as 10 extrusion moulding. home stabilisers, such as epoxidised soybean oils, also act as secondary plasticisers.
Examples of lubricants which can be used are stearates, stearic acid and low-molecular-weight polyethylenes.
These components can be used in a concentration of up to approximately 5~ by weight of the entire composition.
In the production of the collars according to the invention on a vinyl basis, the various components are mixed in the dry state using known mixing methods, and the mixture is moulded using known extruding or injection-moulding methods.
The choice of the processing method for the productian of the collars according to the invention depends technically in principle on the rheological properties of the collar material and the shape of the desired collar.
The processing methods can be adjusted to suit the processing technology or the nature of the shaping process. In the case of process technology, the methods Le A 27 749 - 35 -can be divided on the basis of the rheological states which the material assumes. Accordingly, pouring, pressing, inject on moulding and coating are suitable for viscous collar materials, and injection moulding, extruding, calendering, rolling and, if appropriate, edging in the case of elastoviscous polymers. Divided according to the nature of shaping, the mouldings according to the invention can be produced by casting, dipping, compression moulding, injection moulding, extruding, calendering, embossing, bending, thermoforming etc..
These processing methods are known and need no further explanation. What has been illustrated above by way of example for polyvinyl resins is also true in principle in the case of other polymers.
Other support materials fox the collars according to the invention are polyurethanes. These are prepared in a manner known per se by reacting polyisocyanates with high-molecular compounds which have at least two groups which are reactive towards isocyanates and, if appropriate, with low-molecular chain extenders and/or monofunctional chain terminators.
They are prepared by methods known in principle (for example compare European Offenlegungsschrift (Eux°opean Published Specification) 50,72, German 0ffenlegungs-schrift (German Published Specification) 2,715,595 and the references cited therein).
Le A 27 7~9 - 35 -~h~ concentrations of the active compounds in the support polymers are 0.05-20 ~ by weight. preferred concentrations are 0,1~5 ~ by weight. A concentration of active compound of around approximately 1 per cent by weight is particularly preferred.

In the examples below the following active compounds are used:
Pyriproxyfen: 2-[ 1-methyl-2-(4-phenoxyphenoxy)-ethoxyJ-pyridine Triflumuron = 1-(2-chloro't~nzoyl)-3-(4-trifluoromethoxyphenyl)-urea PrOpoxur = 2-isopropoxyphenyl-IV-methyl carbarnate Cyfluthrin: Cyano-(4-fiuoro-3-phenoxyphenyl)-methyl-3-(2,:~-dichlorovinyl)-2,2-dimethyl- cyclopropane carboxylate ~ A 27 719 - ~7 example A
The test is carried owt using PVC collars which contain 1~ by weight of the compound pyriproxyfen of the formula ~o~ c~az-cry-o l~\ /~..\ ! /-..\
xo Tiled pens of approx. 170 x 270 cm are covered with carpet ( 3 . 4 mZ) , the area of the reed bowls and litter tray remaining uncovered, and 2 cats wearing the collars to be tested are placed in the pens. After i week, the g5 carpets are removed from the pens and in each case 20 test discs of 80 mm diameter are cut out. T;he discs should be distributed on the carpet as uniformly as possible.
2p The carpet discs are scattered with a spatula-tipful of blood meal (specifications blood meal (powder) for feed purposes; manufactured by sniff ) , and infested with eggs or Ll larvae of the flea species to be tested. They are kept in an incubation cabinet at 2~°C/~0~ relative 25 humidity. The development of the flea larvae is checked every three days. The dishes in which larva development takes place are sealed tightly after about i4 days using Parafilm o~ Tesafilm so as to prevent the adult fleas 2a from escaping. The test is concluded one week after the fleas in the untreated controls have hatched. The dishes in which the development of adult f leas took place are k~pt for 2~ hours in a freezer at -15 - 1~°C and are then evaluated. even though larvae hatch from the eggs, no 25 adult fleas develop, even after 1~ weeks.
Le A 27 749 Production exarn~les Examples of polyurethane collars:
The collars are produced continuously by the casting process with the aid of a belt conveyor system.
The polyether, the active compound ar active compound combination, the colouring paste, the xeolite paste, the spreading agent and 1,4-butanediol are mixed together in a healable vessel and i ~ heated to 50°C. The catalyst (dibutyl tin dilaurate) is then added.
'The resulting mixture is component A, which is mixed with component B in a weight ratio of 1:1 using a mixing apparatus. The mixing head is attached to an oscillating traversing device. The reaction mixture flows continuously from the mixing head on to a supporting material (e.g. coating t 5 on a plastic belt). The reaction mixture begins to react 30 sets after issuing from the mixing head and hardens after about 60 sets.
The web of material then passes through a cooling zone. The product has solidified to such an extent that it can be passed to the cutting device via a system of slowly rotating '~1-belts.
2~
Example 1 component A:
Trihydroxypalyether (m.w. 4,800) 41.18 parts by weight 1,4-butanediol (crosslinking agent)5.00 "

Pigment (iron oxide) 0.50 "

Zealite paste (1:1 in castor oil)0.50 "

Tsiflumuron 10.00 3t7 1(lexyl laurate (spreading 1800 "
agent) I?ibutyl tin dilaurate 0.02 "

Component B:
35 'Tripropylene-glycol-madiHed 4,4'-diisacyanatodiphenylmethane, isacyanate content: 23°lo by weight 24.80 parts by weight Le A ~7 '7~9 - 39 °

Example 2 a Component A:

Trihydroxypolyether (m.w. 4,800) 39.063 parts by weight 1,4-butanediol 5.000 "

Pigment (iron oxide) 0.500 "

2eolite past ( 1:1 in castor oil) 0.500 ' Propoxur 8.00 "

Pyriproxyfen 1.00 Isopropyl myristate (spreading 22.00 "

agent) Dibutyl tin dilaurate 0.037 "

Component B:
'I'ripropylene-glycol-modified 4,4'-diisocyanatodiphenylmethane, isocyanate content: 23% by weight 23.90 parts by weight Example 3 Component A:
Trihydroxypolyether (m.w. 4,800) 51.48 parts by vsreight 1,4-butanediol 5.00 '"

Pyriproxyfen 1.50 "

Cyfluthrin 7.50 ' Pigment (iron oxide) 0.50 "

Zeolite paste (1:1 castor oil) 0.50 "

Ester of a branched fatty acid with saturated fatty alcohois/Cta-Cts (spreading agent) 8.00 "

Dibutyl tin dilaurate 0.02 ' ~e A 27 749 - 40 -°

Component B:
Tripropylene-glycol-modified 4,4'-diisocyanatodiphenylmethane, isocyanate content: 23% by weight 25.50 parts by weight Examples of PVC collars The active compound, the colourant and the PVC homopolymer are initially fed into a high-speed mixer and mixed thoroughly. The speed of the mixer is increased and the teml~rature raised to ~60°C.
i ~ Then diisobutyl adipate, dioctyl phthalate and the wetting agent are added and the mixture is mixed further until the temperature has again reached 60°C.
The mixture is slowly stirred further until it is dry and powdery in appearance.
Then stearic acid is added.
The mixture is then cooled rapidly with stirring.
This mixture is processed in an injection-moulding machine to foam collars of the appropriate shape.
Example ~~
Pyriproxyfen 0.70 parts by weight l3usobutyl adipate 23.25 Dioctyl phthalate 10.03 Epoxidised soybean oil (wetting agent) 2.54 ~tearic acid 0'gg Iron oxide pigment 0.14 ' PVC homopalymer 62.44 r.o n ~~ 7dA - 41 -Example 5 1'yriproxyfen 0.20 parts by weight Propoxur 10.0V vv Diisobutyl adipate 17.25 "

Dioctyl phthalate 6.03 "

Epoxidised soybean oil 2.54 "

Stearic acid 0.88 PVC homopolymer 62.96 "

I5 Example 6 Pyriproxyfen 0.50 parts by weight Cyftuthrin 10.00 "

Stearic acid 0.88 Iron oxide pigment 0.10 "

PVC homopolymer 60.52 "

Tributyl citrate 18.00 Triacetin 10.00 ~e A 27 749 - 42 -

Claims (23)

1. A collar for domestic animals comprising a surface that, in use, is exposed to the atmosphere and bears one or more insect-development-inhibiting compounds selected from the group consisting of juvenile hormones and juvenile-hormone-type substances, substituted diaryl ethers, benzoyl ureas and triazine derivatives.

2. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group of juvenile hormones and juvenile-hormone-type substances of the following formulae:

3. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group of substituted diaryl ethers of general formula (I):
where R1 represents hydrogen, halogen, alkyl, alkoxy, alkythio, halogenoalkyl, halogenoalkoxy, halogenoalkylthio, dioxyalkylene, dioxyhalogenoalkylene, CN, NO2, alkenyl, alkinyl, alkoxyalkyl, alkoxyalkoxy or hydroxyalkoxy, R2 represents the radicals mentioned under R1, R3 represents the radicals mentioned under R1, R4 represents hydrogen, alkyl, halogenoalkyl or halogen, R5 represents the radicals mentioned under R4, Het represents optionally substituted heteroaryl which is not bonded to the remaining radical via the heteroatom, X and Y independently of one another represent -O- or -S-, Z represents -O-, -S-, -CH2-, -CHCH3-, -C(CH3)2-, m and n independently of one another represent 0, 1, 2 or 3, but their total is equal to, or greater than, 2.

4. The collar of claim 3 wherein with respect to the substituted diaryl ethers of general formula (I):
R1 represents hydrogen, fluorine, chlorine, bromine, C1-4-alkyl, C1-4-alkoxy, C1-4-alkylthio, C1-4-halogenoalkyl having up to 5 halogen atoms, in particular trichloromethyl, trifluoromethyl, C1-4-halogenoalkoxy having up to 5 halogen atoms, in particular trichloromethoxy, trifluoromethoxy, C1-4-halogenoalkylthio having up to 4 halogen atoms, in particular trifluoromethylthio CN, NO2, C2-3-alkenyl, C1-4-alkoxy-C1-2-alkyl, in particular ethoxymethyl, methoxyethyl, C1-2-alkoxy-C1-4-alkoxy, in particular methoxyethoxy, C1-4-hydroxyalkoxy, in particular hydroxyethoxy, dioxyethylene, dioxymethylene, difluorodioxymethylene, trifluorodioxyethylene or dichlorooxymethylene, R2 represents the radicals mentioned under R1, R3 represents the radicals mentioned under R1, R4 represents hydrogen, C1-4-alkyl, C1-4-halogenoalkyl having up to 5 halogen atoms, chlorine, fluorine or bromine, R5 represents the radicals mentioned under R4, Het represents pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, each of which is optionally substituted by one or more identical or different radicals from the group comprising C1-4-alkyl, such as methyl, ethyl, t-butyl, halogen, such as fluorine, chlorine, bromine, NO2, C1-4-alkoxy, C1-4-alkylthio, C1-4-alkoxy, C1-4-alkylthio, C1-4-halogenoalkyl having up to 5 halogen atoms, C1-4-halogenoalkoxy having up to 5 halogen atoms or C1-4-halogenoalkylthio having up to 5 halogen atoms, X and Y independently of one another represent -O- or -S-, Z represents -O-, -S-, -CH2-, -CHCH3-, -C(CH3)2-, m represents 1 or 2, and n represents 1 or 2.

5. A collar according to claim 3 wherein, with respect to the substituted diaryl ethers of general formula (I):
R1 represents hydrogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, chlorine or flourine, R2 represents hydrogen, R3 represents hydrogen, fluorine, chlorine or methyl, R4 represents hydrogen or methyl, R5 represents methyl, ethyl, trifluoromethyl or hydrogen, Het represents pyridyl or pyridazinyl, each of which is optionally substituted by fluorine, chlorine, methyl, NO2, methoxy or methylmercapto, X represents O, Y represents O, Z represents O, CH2 or -C(CH3)2-, m represents 1, n represents 1.

6. A collar according to claim 5 wherein the insect-development-inhibiting compound is of the formula:~~

7. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group of substituted diaryl ethers of general formula (II):
where X represents O, S, NH, -CH2-, -CHCH3-, -C(CH3)2-, Y represents O or S, Z represents O or S, R1 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, alkoxy or halogenoalkyl, 47~

R2 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, alkenyl, halogenoalkyl, alkoxy, alkylthio, halogenoalkoxy or halogenoalkylthio, R3 represents hydrogen, alkyl, halogenoalkyl, alkoxyalkyl, alkenoxyalkyl, alkenyl or alkinyl, R4 represents the radicals mentioned under R3, R3 and R4 together with the adjacent C atoms can represent saturated or unsaturated 5- to 7-membered carbocyclic rings, m represents 1 or 2, n represents 1 or 2, o represents 1, 2 or 3 and Het represents optionally substituted heteroaryl which is not bonded to the remaining radical via the heteroatom.

8. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group of substituted diaryl ethers of general formula (III):
where X represents O, S, NH, -CH2-, -CHCH3-, -C(CH3)2-, Y represents straight-chain or branched alkylene which is optionally interrupted by oxygen, R1 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, alkoxy and halogenoalkyl, R2 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, alkenyl, halogenoalkyl, alkoxy, alkylthio, halogenoalkoxy and halogenoalkylthio, R3 represents hydrogen, alkyl, halogenoalkyl, alkoxyalkyl, alkenoxyalkyl, alkenyl or alkinyl, R4 represents the radicals mentioned under R3, R3 and R4 together can represent a direct bond, and R5 represents hydrogen, halogen, alkyl, halogenoalkyl, alkoxy, amino, alkyl, alkylamino, dialkylamino or acylamino, mixed with a polymer selected from the group consisting of polyvinyl halides, polyacrylate or polymethacrylate esters, polyvinyl benzenes and polyurethanes, to form a mixture which is molded to form the exposed surface layer of the collar.

9. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group of substituted diaryl ethers of general formula (IV):
in which Het represents an optionally substituted heteroaromatic radical, X represents O, S, -CH2-, -O-CH2-, -S-CH2-, -CH2-O- Y represents O, -O-CH2-, S
Z represents an optionally substituted aromatic or heteroaromatic radical;
m represents integers from 1 to 4, n represents 0, 1, 2, 3 or 4, o represents 0, 1, 2, 3 or 4, where n and o must not simultaneously represent 0, p represents integers from 1 to 4, R2, R3, R4, R5, R6 independently of one another represent hydrogen, C1-6-C-alkyl, which is optionally substituted by halogen or C1-4-alkoxy; two radicals which are adjacent to each other can also, together with the C atoms to which they are bonded, form a saturated carbocyclic 5- or 6-ring, and R1 represents identical or different radicals from the group comprising hydrogen, halogen, CN, C1-4-alkyl, 1-5-halogeno-C1-4-alkyl, C1-4-alkoxy, C1-4-alkylthio, 1-5-halogeno-C1-4-alkoxy, 1-5-halogeno-C1-4-alkylthio, phenyl or phenoxy.

10. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group of benzoyl ureas of general formula (V):

where R1 represents halogen, R1 represents hydrogen or halogen, R3 represents hydrogen, halogen or C1-4-alkyl, R4 represents halogen, 1-5-halogeno-C1-4-alkyl, C1-4-alkoxy, 1-5-halogeno-C1-4-alkoxy, C1-4-alkylthio, 1-5-halogeno-C1-4-alkylthio, phenoxy or pyridyloxy, each of which can be optionally substituted by halogen, C1-4-alkyl, 1-5-halogeno-C1-4-alkyl, C1-4-alkoxy, 1-5-halogeno-C1-4-alkoxy, C1-4-alkylthio, or 1-5-halogeno-C1-C4-alkylthio.

11. A collar according to claim 1 wherein the insect-development-inhibiting compound is selected from a group consisting of triazines of general formula (VI):

where R1 represents cyclopropyl or isopropyl;
R2 represents hydrogen, halogen, C1-C12-alkyl-carbonyl, cyclopropylcarbonyl, C1-C12-alkylcarbamoyl. C1-C12-alkylthiocarbamoyl or C2-C6-alkenylcarbamoyl; and R3 represents hydrogen, C1-C12-alkyl, cyclopropyl, C2-C6-alkenyl, C1-C12-alkylcarbonyl, cyclopropylcarbonyl, C1-C12-alkylcarbamoyl, C1-C12-alkylthiocarbamoyl or C2-C6-alkenylcarbamoyl, and their acid addition salts which are non-toxic to warm-blooded species.

12. A collar according to any one of claims 1 to 11 wherein the insect-development-inhibiting compound is mixed with a polymer selected from the group consisting of polyvinyl halides, polyacrylate or polymethacrylate esters, polyvinylbenzenes and polyurethanes to form a mixture which is molded to form the exposed surface layer of the collar.

13. A collar according to any one of claims 1 to 12 wherein the insect-development-inhibiting compound is present in an amount from 0.05 to 20% by weight of the surface layer.

14. A collar according to claim 13 wherein the insect-development-inhibiting compound is present in an amount from 0.1 to 5% by weight of the surface layer.

15. A collar according to claim 14 wherein the insect-development-inhibiting compound is present in an amount of approximately 1% by weight of the surface layer.

16. A collar according to any one of claims 1 to 15 wherein the surface layer additionally comprises one or more insecticides selected from the group consisting of an organophosphate, a carbamate and a pyrethroid.

17. A collar according to claim 16 wherein the insecticide is a carbamate.

18. A collar according to claim 17 wherein the carbamate is propoxur.

19. A collar according to claim 16 wherein the insecticide is an organophosphate.

20. A collar according to claim 16 wherein the insecticide is a pyrethroid

21. A collar according to claim 16 wherein the insecticide is cyfluthrin.

22. A collar according to claim 16 wherein the insecticide is flumethrin.

23. A method of combating fleas on, and in the surroundings of a domestic animal which comprises placing on the animal a collar according to any one of claims 1 to 22.