Synergistic ectoparasiticidal methods and compositions

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S450000

Reexamination Certificate

active

06479537

ABSTRACT:

BACKGROUND OF THE INVENTION
Although insecticidal agents have been developed to control insect and acarid pests such as agrohorticultural pests, animal ectoparasites or hygienic pests, and in practice have been used as a single or a mixed agent, economically efficient and ecologically safe control agents are still being sought. Insecticides or acaricides which allow for reduced effective dosage rates, increased environmental safety and lower the incidence of resistance are highly desirable.
Examples of such agents are found in U.S. Pat. No. 4,916,154, which discloses the anthelmintic, insecticidal, ectoparasiticidal, nematicidal and acaricidal activity of macrocyclic lactones, and in U.S. Pat. No. 5,455,263, which teaches that a broad spectrum of arylpyrrole compounds is known to be useful for the control of endo- and ectoparasites on warm-blooded mammals.
The rotational application of control agents having different modes of action may be adopted for good pest management practice, but this approach does not necessarily give satisfactory control. Combinations of control agents have been studied, but these do not always exhibit high synergistic action. Obtaining a composition which demonstrates no cross-resistance to existing agents, no toxicity problems and little negative impact on the environment is extremely difficult.
Therefore it is an object of this invention to provide novel methods for synergistic ectoparasite control and protecting animals from infestation and attack by insects, ticks and mites.
It is another object of this invention to provide novel synergistic ectoparasiticidal compositions.
Other objects and advantages of the present invention will be apparent from the disclosure below and the attached claims.
SUMMARY OF THE INVENTION
The present invention provides a method for the control of insects, mite and ticks which comprises contacting said insects or their host, habitat, breeding area, or food supply with a synergistically effective amount of a combination of the macrocyclic lactone moxidectin having the formula I
and an arylpyrrole compound of formula II
wherein R is hydrogen or C
1
-C
4
alkoxymethyl;
X is Cl or Br, and
L, M, and Q are each independently hydrogen, Cl, Br, I, F or C
1
-C
4
haloalkyl.
Also provided are methods of protecting animals from infestation and attack by insects, ticks and mites which comprises administering to the animals a synergistically effective amount of said combination.
The present invention further provides a synergistic ectoparasiticidal composition which comprises a synergistically effective amount of a combination of moxidectin and said arylpyrrole.
DETAILED DESCRIPTION OF THE INVENTION
When two or more substances in combination demonstrate unexpectedly high biological activity, for example, insecticidal activity, the resulting phenomenon may be referred to as synergism. The mechanism of synergism is not fully understood, and quite possibly may differ with different combinations. However, the term “synergism” as used in this application designates a cooperative action encountered in a combination of two or more biologically active components in which the combined activity of the two or more components exceeds the sum of the activity of each component alone.
Surprisingly, it has now been found that combinations of the macrocyclic lactone moxidectin having formula I
and an arylpyrrole of formula II
wherein R, X, L, M, and Q are defined as above, provide superior control at lower levels of the combined active agents than may be achieved when moxidectin or the arylpyrrole is applied alone. Preferred arylpyrrole compounds are those of formula II
wherein
X is Br;
R is hydrogen or ethoxymethyl;
L and Q are hydrogen; and
M is 4-Cl or 4-Br.
Among the formula II arylpyrrole compounds particularly useful in the method of the invention is 4-bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile, commonly known as chlorfenapyr.
The present invention also provides methods for the protection of animals from infestation and attack by insects and acarids. Important agronomic and companion animals such as cattle, sheep, horses, pigs, goats, water buffalo, llamas, deer, cats, dogs, rabbits, and the like, are prone to attack and infestation by biting and sucking insects, such as Diptera, Phthiraptera and Siphonáptera, and parasitic Acarina such as mites and ticks. In particular, Diptera: Muscidae such as
Musca autumnalis
(face flies),
Haematobia irritans
(horn flies),
Stomoxys calcitrans
(stable flies), heel flies, tsetse flies, and the like, are breeders of filth and vectors of disease and are serious pests of animals such as cattle, horses and sheep. Further, Diptera: Hippoboscidae (louse flies) such as
Melophagus ovinus
(sheep ked), which is a serious parasite of sheep, are problematic in animal production.
Among the Phthiraptera families known to be parasites of animals are: Trichodectidae such as
Bovicola bovis
(important cattle-biting louse) or
B. equi
(horse-biting louse); Haematopinidae such as
Haematopinus suis
(hog louse), or
H. asini
(horse sucking louse); Linognathidae such as
Linognathus stenopsis
(goat sucking louse) or
L. vitali
(long-nosed cattle louse); and the like.
One of the Siphonaptera families known to infest companion animals is Pulicinae such as Archaeopsyllinae (cat and dog fleas), Spilopsyllinae (rabbit fleas), and the like.
From the order of the Acarina, for example, Argas spp., Omithodoros spp.,
Dermanyssus gallinae
, Boophilus spp., Rhipicephalus spp., Amblyomma spp., Dermacentor spp., Hyalomma spp., Ixodes spp., Psoroptes spp., Choriopes spp., Sarcoptes spp., are some of the ticks and mites known to infest domesticated animals and birds.
The methods and compositions of this invention may be used for combating and preventing infestation of many of the aforementioned pests.
The effective amount of the synergistically effective combination of the macrocyclic lactone moxidectin (formula I) and an arylpyrrole of formula II to be used in the method of this invention will vary according to the specific arylpyrrole compound used, the mode of application, the insect pest to be controlled, the degree of infestation, the extent of the insect population, the nature of the target host, the weather conditions, and the like. Effective dosages may range from about 0.001 mg/kg to 10.0 mg/kg, preferably about 0.01 mg/kg to 10.0 mg/kg.
The present invention also provides a synergistic ectoparasiticidal composition comprising an acceptable carrier and a synergistically effective amount of a combination of the macrocyclic lactone moxidectin and an arylpyrrole of formula II. It has been found that the active ingredients of the invention are highly synergistic when present at a ratio of moxidectin to arylpyrrole of about 1:5 to 1:20.
In practice, a synergistically effective amount of a combination of moxidectin and an arylpyrrole of formula 11 may be applied to the animal as a dip, spray, pour-on, backrubber, oiler, dustbag, powder, lotion or the like; or as an ear-tag or collar; or as an oral drench, bolus, pill, implant, capsule, feed or drinking water additive or the like; or as a parenteral injection; or by any other methods suitable for administering drugs to animals.
Advantageously, moxidectin may be formulated with an arylpyrrole of formula II, and such a formulation may then be dispersed in a solid or liquid diluent for application to the ectoparasite, its host, food supply, breeding ground or habitat, as a dilute spray or as a solid dust or dust concentrate. Customary formulation adjuvants as well as additional nontoxic pharmaceutically acceptable active ingredients may be added and are within the scope of the invention.
The active ingredients of the inventive composition may also be formulated separately as a wettable powder, emulsifiable concentrate, aqueous or liquid flowable, suspension concentrate or any one of the conventional formulations used for ectoparasite control. The separately formulated compositions may be applied sequentially to achieve a synergistic res

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