Note: Descriptions are shown in the official language in which they were submitted.
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 -
0
0
.~C~HS
v C2H5 CH3
H5C2
GH3
-' ~ ~ i '°°'° ~ -O C H ~
~ CHI CH3
i so--H~C3
CH3 CH3 CH3 0
w.
H3C CH3
CHO i H3 I H3 ~~
H3C C\
~CH
CHI CH3 CH3 0 CHI
C H 3 0--w
o a 0
H3C CHI
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
R5
R1 ~ J R6
~ ' Ck3~ - CH' Cr'
N
R
R1 R3 R5 R6 Z
H H CHI H 0
H H CHI ~-C1 0
5-F H CH3 H 0
H H CFA H 0
H H CZHS H 0
H H H H 0
H H CH3 H CHI
H H CHI H C(CI9~)2
Z \_..-/ I R6
R3 o-CHZ-CH-a--(~~~
N
Ri Ft3 R5 R6 ~
H H CHI H 0
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
R3 R4
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
C 1
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
CH3
3 CH3
/ \ N
1 3_C1 -CH -CH- N_~,.N ~'~
S 2 2
CH3
IH3 ~CH3
- w~N 0
CHI 1.3-C12 -CH2-CH H
CH3
CH3 CH3
~
-CH- / \ N
H 0
0 H -C IJ~N ~"C
Z
CH3
CH3 I
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
0 0 CHI-CH2-0-CHI-CHI
0 S -CH2-CH- I
I e~
CHZ-F
S o -cH~-cH- r I
cH~-F
r
0 O °CHy CH-
I w
CfI2-F
r
CHI S -GH2-CH-
I w
CHI-F
IH3
0 p -CH2-CH-
w
7Le i~. 2 7 7 4 9 ° ~.7
0~5
~C Y a H~ ~
CHI
N-CH
AN
O 0 -CH2-CH- 3
~
CHI
~--N~O
O 0 - CH 2 CH ,
- N----N ~--(
I . CH3
CHZF
~ ~CI~~
~~
S 0 -CHZ-CH-
---N N-CH
I NN ~--J 'C 1-I ~
CHEF
CHI
CH 0 -CH -~~
-CH- ~--N~
2 I ,
I 0
~--
-
N
N
CF3 CHI
o O -cH~-cH-
--~~~---N o
i N.---N ~
CF3
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
3
4
0 1.3 C1~ -CH2-CHZ-0-CH~-CH- 3-NH2
CH3
iH3
S H -CHICH-0-CHZ-CH- 5-N~a
CH3
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
X R2 B R5
CH2 1.3-C1~ -CHI-CHZ-0-CH~CH2-0-CH~CH~-
3-NHS
CH2 H -CHI-CHI-O-CH2-CH 5-C~"3
CH3
CH3
0 H -CH2-~H-0-CHZ-iH- 5N~
CH3 CF3 CH3
S H CH~-iHO-CH~-CH2- 5-NON-CH3
CH2F
0 1.3-C1~ -CHZ-CHZ-0-CH2CH2-3-NH-C-NH f~_\ ~~\
~I
0
!H3 ~CH3
0 1.3-C12 -CHZ-CH-0-CH2CH2- 5-~N~O
CH3
CH3 CH3
~....~
S 1.3-C1~ -CHI-CH-0-CHZ-rH2-5-N~
CHI CH3
Le A 2? ?49 - 21 -
X F~'~ a R 5
iH3 ,~CH3
CHI 1.3-C1~ -CHI-CH-0-CH~CH~° 5-N~0
CH3
CH3
O H -CHI°CHZ-0-CH2CH2° 5°N~O
CH3
O 1.3°C1~ --CHZCI-1~0-CHZ°CH~- 3°NH-C-NH ~
ii
0 C1
-CH- H -CH2CH~°O°CNZCH~° 4°OCH3
i
CH3
i
O H 3°NH°C-NH ~
0
0 H -CH2CHZ°0°CHZCH2CH2° 4°NH°C-NH' F3
i ~l
0
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
CH3
H3 /~'~CH3
S 1 -CH ~~~~ --3J 0
3-C1 -CH
. 2 p,~'~"T~ ~.--
2
CH3
CHI CH3
~
CH2 1.3-C1~ _CH~-CH_ ! ~ N
0
H
CH3
CH3 CH3
0 H -CH ! ~ IJ~O
-CH-
2
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-
CH2-F
S 0 -CH2-iH-
CHI-F
0 0 -CH2-CH- °
CHc -~'
CHZ S -CH2-CH-
CH~_F
IH3
0 0 -CHZ-CH-
ri
Le A 27 749 - ~7 ~-
X Y ~~ Het
3
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
CF3
CH3
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):
R1
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'~
R2
- ~e :~ 27 749 - 29 -
R1 R2 R4
H C1 CFS
C1 C1 CF3
F F CFS
H F CF3
H C1 SCF3
F F SCFS
H F SCF3
H C1 OCF3
F F OCF3
H F OCFS
F F 0 ~~~ C1
F F 0 ~~~ CF3
F F 0 ~~.~ CF3
the ~triazines include compounds of the formula (VT)
-R1
N, IN (VI)
.
R2-HN NH-R3
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
H1 H2 H3
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)
R1 R2 R3
Cyclopropyl H C12H25 n
Cyclopropyl H CH2-CgH9-t
Cyclopropyl H CH2CH(CH3)C2H5
Cyelopropyl H CH2CH-CH2
Cyclopropyl C1
C2H5
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.
13
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
30
~ 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
CH3
~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
35
(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
3S
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
30
~e A 27 749 - 42 -
