U.S. patent application number 09/192499 was filed with the patent office on 2001-11-22 for method to control animal ecto-parasites.
Invention is credited to MORI, TATSUYA, SAKAMOTO, NORIYASU, SEMBO, SATOSHI.
Application Number | 20010044470 09/192499 |
Document ID | / |
Family ID | 18110960 |
Filed Date | 2001-11-22 |
United States Patent
Application |
20010044470 |
Kind Code |
A1 |
SEMBO, SATOSHI ; et
al. |
November 22, 2001 |
METHOD TO CONTROL ANIMAL ECTO-PARASITES
Abstract
The present invention provides a method to control
ecto-parasites of a host animals wherein
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-h-
exafluoropropoxy)phenyl]urea is applied to the said host animals.
By the method of the present invention, ecto-parasites of animals
can be controlled effectively for a long period of time.
Inventors: |
SEMBO, SATOSHI;
(TAKARAZUKA-SHI, JP) ; MORI, TATSUYA;
(TOYONAKA-SHI, JP) ; SAKAMOTO, NORIYASU;
(TOYONAKA-SHI, JP) |
Correspondence
Address: |
BIRCH STEWART KOLASCH & BIRCH
PO BOX 747
FALLS CHURCH
VA
22040-0747
US
|
Family ID: |
18110960 |
Appl. No.: |
09/192499 |
Filed: |
November 17, 1998 |
Current U.S.
Class: |
514/594 |
Current CPC
Class: |
A01N 47/34 20130101 |
Class at
Publication: |
514/594 |
International
Class: |
A01N 047/28 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 20, 1997 |
JP |
09-319503 |
Claims
What is claimed is:
1. The method to control ecto-parasites of a host animals wherein
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phen-
yl]urea is applied to the said host animals.
2. The method according to claim 1, wherein the amount of
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phen-
yl]urea applied to the host organism is from 0.1 mg to 500 mg per 1
kg of the host animals.
3. The method according to claim 1 or 2, wherein the host animals
are pets.
4. A method to inhibit flea eggs produced on host animals from
hatching wherein
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-hexafluoroprop-
oxy)phenyl]urea is applied to the said host animals.
5. Use of
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-hexafluoropro-
poxy)phenyl]urea for controlling ecto-parasites of animals.
6. A composition for controlling ecto-parasites which comprises
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phen-
yl]urea.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a method for controlling
ecto-parasites of animals. In detail, the present invention relates
to a method for controlling ecto parasites of animals wherein
1-(2,6-difluorobenzoyl)-3-[2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phen-
yl]urea (hereinafter, recited as Compound #1) is applied to the
said animals.
[0002] Ecto-parasites have been responsible for the transmission of
disease. Fleas have been a particular problem because of their
ability to completely infest an environment. The female flea lays
her eggs on the host animal after mating. The eggs are able to fall
off the host and be distributed to the host's environment. By this
mechanism, the eggs are able to cover a larger area.
[0003] It is disclosed in Japanese patent publication (laid-open)
No. 2-138247 that Compound #1 has an insecticidal activity. The
publication discloses that benzoylurea compounds including Compound
#1 in the publication are excreted as they are and therefore, can
control the larvae and eggs of such insects like houseflies that
breed in the excretion of domestic animals when they are applied to
the domestic animals orally.
[0004] It is disclosed in U.S. Pat. No. 4,089,975 that benzoylurea
compounds such as
1-(2,6-difluorobenzoyl)-3-(4-trifluoromethoxyphenyl)ure- a
(hereinafter, recited as Compound A) and
1-(2,6-difluorobenzoyl)-3-[4-(1-
,1,2,2-tetrafluoroethoxy)phenyl]urea (hereinafter, recited as
Compound B) can also be used for controlling insects which inhabit
in excretion of domestic animals.
[0005] On the other hand, Japanese patent publication (laid-open)
No. 63-72631 discloses a method for defending dogs or cats from
re-infection of fleas by applying juvenile hormone like chemical
compounds, triazine derivatives that regulate the growth of fleas
and benzoylurea derivatives (specifically,
N-3-(5-trifluoromethylpyridin-2-yl)phenyl-N'-benzoylurea
derivatives) that regulate the growth of fleas to dogs or cats.
However, the effectiveness of the method generally do not last a
sufficient amount of time.
SUMMARY OF THE INVENTION
[0006] The present invention relates to a method for systemic
control of ecto-parasites of animals.
[0007] More specifically, the present invention relates to a method
that effectively controls ecto-parasites for a comparably long
period of time by applying Compound #1 to the host animal. The
propagation of ecto-parasites is prevented by applying an effective
amount of Compound #1 to the host animal and letting the
ecto-parasites feed thereon.
DETAILED DESCRIPTION OF THE INVENTION
[0008] Compound #1, employed in the present invention, may be
produced by employing Japanese patent publication (laid-open) No.
2-138247 (recited above).
[0009] The objective ecto-parasites of the present invention are
pests that live externally to the host animal but necessitate blood
from the host animal to achieve normal reproductive abilities. More
specifically, the objective ecto-parasites of the present invention
are not only limited to the kinds of mites and/or ticks (Acarina)
such as Boophilus microplus and Haemaphxalis longicornis; Pulicidae
(fleas) such as Ctenocephalides felis (cat fleas), Ctenocephalides
canis (dog fleas), and Xenopsylla cheopis; and Anoplura (lice) such
as Haematopinus eurysternus and Damalinia ovis that live external
to the host organism but, may include blood sucking Dipthera
insects such as Tabanus chrysurus, Culicoides oxystoma, and
Simulium iwatens.
[0010] The objective host animals for the present invention are
warm-blooded animals whose blood will permit an ecto-parasite to
achieve normal reproductive capabilities. More specifically, the
objective host animals include pet animals such as dogs, cats,
mice, rats, hamsters, squirrels, rabbits, ferrets, and birds (for
example, pigeons, parrots, minas, java sparrows, love birds, and
canaries) but, are not limited to the kinds of domestic animals
such as cattle, horses, swine, sheep, ducks, drakes, and
poultry.
[0011] The manner which Compound #1 is administered as an
efficacious dosage may vary. Compound #1 may be administered to the
host animals at a rate from about 0.01 mg to about 1000 mg per each
kilogram of the host animal (i.e. 0.01-1000 mg of Composition #1/kg
of the host animal), and preferably at the rate from about 0.1 mg
to about 500 mg per each kilogram of the host animal (i.e., 0.1-500
mg Composition #1/kg of the host animal). The preferred dosage for
controlling a given ecto-parasite is determined individually, but
it is generally necessary to have an efficacious amount of Compound
#1 present in the bloodstream of the treated host animal to control
the given ecto-parasite. The systemic control of ecto-parasites is
achieved by having the ecto-parasites ingest blood from the treated
host animal so that the said ecto-parasite is exposed to an
efficacious amount of Compound #1. As used herein, "efficacious
amount" means an amount that leads to a reduced rate of the
hatching of eggs and/or to the inability to fertilize.
[0012] Compound #1 is may be applied in pure form, but preferably
in the form of a composition which comprises Compound #1 in an
amount of 0.1% to 99% by weight in the composition.
[0013] Compound #1 may be applied to host animals by oral or
non-oral application.
[0014] In oral application, examples of the form of the composition
includes tablets, liquids, capsules, wafers, biscuits, emulsifiable
concentrates, and/or so on. The oral application includes a method
to apply the composition and a method to apply the mixture of
Compound #1 or the composition with feed for the host animals. To
prevent hydrolysis or degradation by constituents of animal feed,
Compound #1 may previously be formulated in a protective matrix
such as gelatin, and be further protected by formulation with
preservatives and anti-oxidents such as sodium benzoate, parabens,
BHT (butylated hydroxytoluene), and BHA (butylated
hydroxyanisole).
[0015] In non-oral application, examples of the form of the
composition includes a water soluble suspension, oily suspension,
implants comprising of resins and soluble/erodible materials and/or
so on. The non-oral application includes parenteral applications
such as subcutaneous, intravenous, and intramuscular injection;
percutaneous applications such as spot-on and pour-on application;
implants application.
[0016] The tablet formulation for oral application generally
employs sugars such as lactoses, sucroses, mannitols, and
sorbitols; excipien agents such as celluloses and calcium
phosphates; binders such as powdered starches, gelatins, gum
arabic, tragacanth, methylcelluloses, agars, alginic acids, and
alginic acid salts; lubricants such as silicas, talcs, stearic
acids, and stearic acid salts; Dragee cores such as polyvinyl
pyrrolidones, polyethylene glycols, and titanium dioxides; and/or
so on in addition to Compound #1. Coloring agents and food
additives may also be employed when necessary.
[0017] The capsule formulation for oral application may be a
dry-filled capsule comprising of gelatins, a soft capsule
comprising of gelatins and plasticisers such as glycerins,
sorbitols, and so on. The said dry-filled capsule, may include
excipien agents such as lactoses, binders such as powdered
starches, lubricants such as talc and stearic acid salts,
stabilizers, and so on. The soft capsule formulation generally
comprises Compound #1 dissolved or suspended in a suitable solvent
such as fatty oils, parraffin oils, liquid polyethylene glycols,
and so on. In addition, the soft capsule formulation may also
comprise of a stabilizer when necessary.
[0018] The composition for a non-orally applied injection may be
water-soluble suspensions or oily suspensions which comprise
animal/plant oils such as sesame oils; esters of fatty acids such
as ethyl oleates; triglycerides; thicking agent such as sodium
carboxymethylcellulose, sorbitol, and dextran; and so on in
addition to Compound #1.
[0019] The composition for percutaneous application may be a
spot-on formulation or a pour-on formulation which comprises
Compound #1 dissolved or suspended in esters such as
polyoxyethylene hardened castor oil, esters of stearic acid, fatty
acid coconut oil diethanolamide, methyl oleate and ethyl oleate;
fatty acids such as lauric acid and oleic acid; alcohols such as
myristyl alcohol, palmityl alcohol and polyoxyethylene
polyoxypropylene glycol; ethers such as dipropyleneglycol
monomethyl ether; and/or so on.
EXAMPLES
[0020] Hereinafter, the present invention is explained more
specifically with the examples and is compared to Compound A
disclosed in U.S. Pat. No. 4,089,975; Compound B, also disclosed in
U.S. Pat. No. 4,089,975; and
1-(2,6-difluorobenzoyl)-3-[3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)p-
henyl]urea (hereinafter, recited as Compound C), disclosed in
Japanese patent publication (laid-open) 63-72631, but does not
limit the present invention in any way.
1TABLE 1 Compound #1 1 Compound A 2 Compound B 3 Compound C 4
Example 1
[0021] An each predetermined amount of compound #1, Compound A,
Compound B and Compound C was dissolved in corn oil to be a
composition so that a dose of 20 milligrams per kilogram body
weight of the mouse would ultimately be applied. By using an
appropriate sonde for the mouse, oral application to the mouse was
performed at the rate of about 10 mL of the composition per
kilogram body weight of the mouse. The said mouse was then
stabilized with a wire netting, and was placed in a plastic
container (depth 15 cm.times.width 15 cm.times.height 60 cm).
Thirty (10 male and 20 female) starved adult cat fleas
(Ctenocephalides felis) were freed into the said plastic container
and the produced f lea eggs were retrieved f ive days later. A
suitable amount (about 60 eggs) was transferred to a plastic dish
and, preserved under the conditions wherein the temperature was
26.degree. C. and the humidity was at 90%. After 2 days of
preservation, the hatching conditions were observed.
[0022] Afterwards, the treated mouse was allowed to inhabit a
standard pet cage with food and water. Ten days after the
application, the mouse was stabilized, placed in a plastic
container, and was exposed to cat fleas in the same way as stated
above. The produced flea eggs were then retrieved 14 days after the
application, preserved in the conditions stated above, and had the
hatching conditions observed.
[0023] Twenty-six days after the application, the mouse was
stabilized, placed in a plastic container, and was exposed to cat
fleas in the same way as stated above. The produced flea eggs were
then retrieved 30 days after the application of the composition,
preserved in the conditions stated above, and had the hatching
conditions observed.
[0024] The same procedure was repeated without the application of
the composition.
[0025] The percentages of hatching for applied mouse "T" and the
percentage of hatching for non-applied mouse "C" were derived from
the equation, respectively:
T=(the amount of hatched eggs).div.(the amount of retrieved
eggs).times.100
C=(the amount of hatched eggs).div.(the amount of retrieved
eggs).times.100
[0026] The acquired values of "T" and "C" were used to determine
the adjusted percentage concerning the loss of hatchings by
employing equation 1.
[0027] The results are given in table 2.
Equation 1
[0028] The acquired values of "T" and "C" were utilized in the
following equation:
The adjusted percentage concerning the loss of hatchings
(%)=(C-T).div.C.times.100
[0029] to determine the adjusted percentage concerning the loss of
hatchings (hereinafter, recited as APH). As used herein, "APH" is
the adjusted comparison between "T" and "C" which measures the
effect Compound #1 was able to enforce upon a given group of
retrieved eggs. In other words, "APH" looks at the amount of eggs
that were unable to hatch rather than the amount of eggs that were
able to hatch.
2 TABLE 2 Application adjusted percentage concerning the loss
amount of hatchings (%) (mg/kg) 5 days after 14 days after 30 days
after Compound 20 100 100 93 #1 Compound A 20 0 0 Compound B 20 83
0 Compound C 20 96 77 11
[0030] As given in the results of the table above, it was not
effective for this method to control fleas with the aid of blood of
mouse by using Compound A and Compound B which were used for method
to control housefly larvae and the like living in excretions of
domestic animals by applying to the domestic animals as disclosed
in U.S. Pat. No. 4,089,975. In addition, it was effective to the
flea eggs 5 days after production but, was not effective to the
flea eggs 30 days after production for this method by using
Compound C which was usable for preventing re-infection of fleas by
applying to dogs and cats as disclosed in Japanese patent
publication (laid-open) No. 63-72631. To the contrary, Compound #1
used for the method of the present invention, which was disclosed
in Japanese patent publication (laid-open) No. 2-138247 to be
usable for the method to control housefly larvae and the like
living in excretion of domestic animals by applying to the domestic
animals (said method was a similar method disclosed in U.S. Pat.
No. 4,089,975), showed an extraordinary inhibition of hatchings
such flea eggs that are not only 5 days but 30 days after
production.
Example 2
[0031] Each of four cats (a cross between the Abyssinian cat and
the European type household cat; weight, about 2.2-2.9 kg) was
infested with 100 adult cat fleas (Ctenocephalides felis) and then
was placed in a steel cage wherein the steel cage comprised of a
removable bottom tray, had the dimensions of 760 mm
(width).times.540 mm (depth).times.610 mm (height), and had a
supply of solid feed and water. Seven days after infestation, the
weights of two cats of were measured and Compound #1 was applied
orally to each of said two cats in an amount of 20 mg per one
kilogram of the weight of the cat by incorporating Compound #1 into
cat feed and having the cat to eat it. After application, the cats
were placed in said steel cages.
[0032] The flea eggs collected onto the removable bottom tray were
retrieved 6 and 14 days after the date of application. About 60
eggs were chosen from each batch of retrieved eggs. They were
transferred to a plastic dish and then preserved under the
conditions wherein the temperature was 26.degree. C. and the
humidity was at 90%. After 5-7 days of preservation, the eggs were
observed about hatching.
[0033] The same procedure was repeated with another two cats except
that cat feed comprising no Compound #1 was applied.
[0034] The percentages of hatching for applied cats "T" and the
percentage of hatching for non-applied cats "C" were derived from
the equation, respectively:
T=(the amount of hatched eggs).div.(the amount of retrieved
eggs).times.100
C=(the amount of hatched eggs).div.(the amount of retrieved
eggs).times.100
[0035] The obtained values of "T" and "C" were then used to
determine the APH by employing the equation 1 mentioned above
Example 1.
[0036] The average APH for Compound #1 was 81.9% after 6 days and
was 79.6% after 14 days.
Example 3
[0037] Each of six dogs (beagle dog; weight, 9-10 kg) was infested
with 100 adult cat fleas (Ctenocephalides felis) and then was
placed in a steel cage comprised of a removable bottom tray, had
the dimensions of 760 mm (width).times.540 mm (depth).times.610 mm
(height), and had a supply of solid feed on the market and water.
One day after infestation, the weights of three dogs were measured
and Compound #1 was applied orally to each of said three dogs in an
amount of 10 mg per one kilogram of the weight of the dog by
incorporating Compound #1 into dog feed and having the dog to eat
it. After application, the dogs were placed in said steel
cages.
[0038] The flea eggs collected onto the removable bottom tray were
retrieved 4 and 5 days after the application. About 60 eggs were
chosen from each batch of retrieved eggs. They were transferred to
a plastic dish and then preserved under the conditions wherein the
temperature was 26.degree. C. and the humidity was at 90%. After
5-7 days of preservation, the eggs were observed about
hatching.
[0039] The same procedure was repeated with another three dogs
except that dog feed comprising no Compound #1 was applied. The
percentages of hatching for applied dogs "T" and the percentage of
hatching for non-applied dogs "C" were derived from the equation,
respectively:
T=(the amount of hatched eggs).div.(the amount of retrieved
eggs).times.100
C=(the amount of hatched eggs).div.(the amount of retrieved
eggs).times.100
[0040] The obtained values of "T" and "C" were then used to
determine the APH by employing the equation 1 mentioned above
Example 1.
[0041] The average APH was 86.5% after 4 days and was 76.6% after 5
days.
[0042] Compound #1 was disclosed in Japanese patent publication
(laid-open) No. 2-138247 as a compound that can control insects
breeding in excretion but, was also able to exceed the
effectiveness of Compound A, B, and C when employed in a systemic
method. Table 1 exhibits the superior effectiveness Compound #1
sets forth on the 30.sup.th day after application. Compounds A and
B could not exhibit any effectiveness past the 14.sup.th day after
application and Compound C was only able to exhibit a low 11% APH
on the 30.sup.th day after application. Compound #1 showed its
superior effectiveness by being able to provide 93% APH on the
30.sup.th day.
[0043] In addition, Compound #1 was able to provide exceptional
results when applied to a cat or dog. The cat had a surprisingly
high APH of 80% on the 14.sup.th day after application while the
dog was also able to provide high APH of 77% on the 5.sup.th day
after application.
[0044] Compound A and Compound B are disclosed in U.S. Pat. No.
4,089,975 as a compound that controls excretion-breeding insects
but, neither Compound A nor Compound B effectively control
ecto-parasites when employed in a systemic method. Compound C is
disclosed in Japanese Laid-open Patent No. sho63-72631-A as a
compound that avoids re-infection by being applied to cats or dogs
but, was not effective against flea eggs 30 days after application.
The present invention was effective after a long period of time
when employed in a systemic method.
* * * * *