Insecticidal combination to control mammal fleas, in...

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Biocides; animal or insect repellents or attractants

Reexamination Certificate

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C514S407000, C514S875000, C514S341000

Reexamination Certificate

active

06685954

ABSTRACT:

The present invention relates to an improvement to the processes for controlling mammal fleas and in particular fleas on cats and dogs. The invention also relates to a novel composition for this use, based on a synergistic combination of parasiticides which are already known. Lastly, the invention relates to the use of such already-known parasiticides for the preparation of such a composition.
A novel class of 1-N-arylpyrazole-based 1(insecticides has been described in patents EP-A-295,217 and EP-A-352,944. The compounds of the classes defined in these patents are highly active, and one of these compounds
1-[2,6-Cl
2
4-CF
3
phenyl]3-CN 4-[SO—CF
3
]5-NH
2
pyrazole, whose common name is fipronil, has proven to be particularly effective not only against crop parasites but also against mammal ectoparasites and in particular, but not exclusively, fleas, ticks, flies and myiases.
Compounds with an ovicidal and/or larvicidal effect on the immature stages of various ectoparasites are already known, for example from patent U.S. Pat. No. 5,439,924. Among these compounds are featured insect growth regulator compounds (IGR) which act either by blocking the development of the immature stages (eggs and larvae) into adult stages, or by inhibiting the synthesis of chitin.
Patent FR-A-2,713,889 is moreover known, which generally describes the combination of at least one compound of IGR (insect growth regulator) type, comprising compounds with juvenile hormone activity and chitin synthesis inhibitors, with at least one of three N-aryldiazole compounds, in particular fipronil, to control many harmful insects belonging to very varied orders.
The compositions may be used in very diverse forms, although the applications, for example veterinary, healthcare or plant-protection applications, for which these different forms are designed are not specified, nor are the parasites for which they are respectively intended.
The only application which may be thought to be veterinary is associated with the example of the manufacture of a pesticidal collar which is a slow-release formulation.
The invention proposes to improve the processes for controlling fleas in small mammals, and in particular in cats and dogs.
The object of the invention is, in particular, to use already-known parasiticides in order to prepare a composition which is highly active against the fleas of these animals.
Lastly, the object of the invention is a novel composition thus prepared and intended, in particular, to control fleas.
For the purposes of the present invention, the term flea is understood to refer to all the usual or accidental species of parasitic flea of the order Siphonaptera, and in particular the species Ctenocephalides, in particular
C. felis
and
C. canis
, rat fleas (
Xenopsylla cheopis
) and human fleas (
Pulex irritans
).
The very high efficacy of the process and of the composition according to the invention implies not only high immediate efficacy but also very long-lasting efficacy after the animal has been treated.
The subject of the invention is a process for controlling the fleas of small mammals, and in particular cats and dogs, over a long period, characterized in that the animal is treated by locally depositing on the skin, preferably localized over a small surface area (spot-on application), in parasiticidally effective doses and proportions, on the one hand at least one compound (A) belonging to formula (I),
in which:
R
1
is CN or methyl or a halogen atom;
R
2
is S(O)
n
R
3
or 4,5-dicyanoimidazol-2-yl or haloalkyl;
R
3
is alkyl or haloalkyl;
R
4
represents a hydrogen or halogen atom; or a member of a group consisting of NR
5
R
6
, S(O)
m
R
7
, C(O)R
7
, C(O)O—R
7
, alkyl, haloalkyl, OR
8
and —N═C(R
9
)(R
10
);
R
5
and R
6
independently represent a hydrogen atom or an alkyl, haloalkyl, C(O)alkyl, alkoxycarbonyl or S(O)
r
—CF
3
radical; or R
5
and R
6
may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms such as oxygen or sulphur;
R
7
represents an alkyl or haloalkyl radical;
R
8
represents an alkyl or haloalkyl radical or a hydrogen atom;
R
9
represents an alkyl radical or a hydrogen atom;
R
10
represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or a member of the group consisting of OH, —O-alkyl, S-alkyl, cyano and alkyl;
R
11
and R
12
represent, independently of each other, a hydrogen or halogen atom, or possibly CN or NO
2
;
R
13
represents a halogen atom or a haloalkyl, haloalkoxy, S(O)
q
CF
3
or SF
5
group;
m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2
X represents a trivalent nitrogen atom or a radical C—R
12
, the other three valency positions of the carbon atom forming part of the aromatic ring
with the proviso that when R
1
is methyl, either R
3
is haloalkyl, R
4
is NH
2
, R
11
is Cl, R
13
is CF
3
and X is N; or R
2
is 4,5-dicyanoimidazol-2-yl, R
4
is Cl, R
11
is Cl, R
13
is CF
3
and X is ═C—Cl;
and, on the other hand at least one compound (B), of IGR (insect growth regulator) type, in a fluid 10 vehicle which is acceptable for the animal and suitable for local application on the skin.
Preferably, one uses at least one compound (A) belonging to the formula (I) in which:
R
1
is CN or methyl
R
2
is S(O)
n
R
3
R
3
is alkyl or haloalkyl
R
4
represents a hydrogen or halogen atom; or a radical NR
5
R
6
, S(O)
m
R
7
, C(O)R
7
, alkyl, haloalkyl or OR
8
or a radical —N═C(R
9
) (R
10
)
R
5
and R
6
independently represent a hydrogen atom or an alkyl, haloalkyl, C(O)alkyl or S(O)
r
—CF
3
radical; or R
5
and R
6
may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms such as oxygen or sulphur
R
7
represents an alkyl or haloalkyl radical
R
8
represents an alkyl or haloalkyl radical or a hydrogen atom
R
9
represents an alkyl radical or a hydrogen atom
R
10
represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, —O-alkyl, S-alkyl, cyano or alkyl
R
11
and R
12
represent, independently of each other, a hydrogen or halogen atom
R
13
represents a halogen atom or a haloalkyl, haloalkoxy, S(O)
q
CF
3
or SF
5
group
m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2
X represents a trivalent nitrogen atom or a radical C—R
12
, the other three valency positions of the carbon atom forming part of the aromatic ring
with the proviso that when R
1
is methyl, then R
3
is haloalkyl, R
4
is NH
2
, R
1
is Cl, R
13
is CF
3
and X is N.
Compounds of formula (I) in which R
1
is CN will be selected most particularly. Compounds in which R
2
is S(O)
n
R
3
, preferably with n=1, R
3
preferably being CF
3
or alkyl, for example methyl or ethyl, or alternatively n=0, R
3
preferably being CF
3
, as well as those in which X=C—R
12
, R
12
being a halogen atom, will also be selected. Compounds in which R
11
is a halogen atom and those in which R
13
is haloalkyl, preferably CF
3
, are also preferred. Within the context of the present invention, compounds which combine two or more of these characteristics will advantageously be selected.
A preferred class of compounds of formula (I) consists of compounds such that R
1
is CN, R
3
is haloalkyl, R
4
is NH
2
, R
11
and R
12
are, independently of each other, a halogen atom, and/or R
13
is haloalkyl. Preferably also, X is C—R
12
.
In these compounds, R
3
preferably represents CF
3
or ethyl.
In the present invention, the alkyl radicals may contain generally from 1 to 6 carbon atoms. The ring formed by the divalent alkylene radical representing R
5
and R
6
, as well as the nitrogen atom to which R
5
and R
6
are attached, may be generally a 5-, 6- or 7-membered ring.
A compound of formula (I) which is most particularly preferred in the invention is 1-[2,6-Cl
2
4-CF
3
phenyl]3-CN 4-[SO—CF
3
] 5—NH
2
pyrazole, the common name of which is fipronil.
The two compounds which differ f

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