Note: Descriptions are shown in the official language in which they were submitted.
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TOPICAL ORGANIC ECTOPARASITICIDAL FORMULATIONS
This invention relates to topical organic ectoparasiticidal formulations.
Ectoparasites such as fleas, blowflies, lice, ticks and mites can seriously
affect
productivity in the domesticated animal industries. Further, such parasites
cause
disease and discomfort for pets and other companion animals. Ectoparasites are
often
controlled by topically applying an insecticide or mixture of insecticides
onto the
animal. Topical ectoparasite control agents are usually applied in liquid
formulations.
The formulations can be applied by spot-on application, plunge or spray
dipping,
10. jetting with a hand held spray or in a race, or as a back-line spray or
pour-on.
A particular problem with topical formulations is poor migration from
the site of application. In the sheep industry, for example, treatment for
ectoparasites
is commonly carried out in the early season within 24 hours after shearing,
or, less
frequently, later in the season when the wool is longer. Especially with early
season
treatments, when the topical formulation is applied along the dorsal midline
or back-
line of the animal, the insecticide component of currently available
commercial
formulations migrates very poorly from the application site. Typically less
than 10%
of the applied insecticide diffuses away from the application site within the
first 10
days. Thus, extensive areas of the animal's skin and/or hair may receive
sublethal
concentrations of the insecticide. These areas remain susceptible to damaging
invasion by ectoparasites.
To overcome the inadequate control caused by poor migration of the
insecticide, it has become common in the industry to apply relatively large
amounts of
insecticide. This practice introduces unwelcome costs, results in the presence
of
insecticide residues in certain animal products (such as wool and wool
byproducts)
and increases the potential of environmental pollution. It also increases the
risk of
unwanted and unnecessary exposure to pesticides to animal handlers and farmers
treating the animals.
Solvent-based formulations have received attention in recent times in
the search for greater insecticide mobility that would allow the same
insecticidal
effect to be achieved with less insecticide in the formulations. Up to the
present, there
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has been little success in identifying a solvent that materially enhances the
spread of
insecticides that are applied using a spot-on or pour-on method.
This invention provides insecticidal formulations that can be applied
topically to animals and that have the advantage of permitting the active
ingredient to
spread over the surface of the skin and/or hair of the treated animal, thereby
providing
more extensive coverage of the insecticide. These formulations, therefore,
provide
greater inhibition or eradication of ectoparasites with smaller amounts of
insecticide.
The topical ectoparasiticidal formulations of this invention comprise an
ectoparasiticide, a spreading agent and optionally a miscibilizing agent. More
. . specifically, the invention relates to a topical ectoparasiticidal
formulation comprising
from about 0.1 to about 25 weight percent of an ectoparasiticide, from about
25 to
about 99.9 weight percent of a (C3-C6) branched alkyl (C,o-C2o) alkanoate
spreading
agent, and optionally up to about 70 weight percent of a miscibilizing agent
compatible with organic solvent systems.
An exemplary topical ectoparasiticidal formulation of this invention is
one wherein the ectoparasiticide is a spinosyn, or a physiologically
acceptable
derivative or salt thereof.
This invention also encompasses a method of controlling an
ectoparasite infestation on a small ruminant or companion animal, comprising
topically applying to the hair and/or skin of the animal a formulation
comprising from
about 0.1 to about 25 weight percent of a spinosyn, or a physiologically
acceptable
derivative or salt thereof, from about 25 to 99.9 weight percent isopropyl
myristate,
and from 0 to about 70 weight percent of a miscibilizing agent compatible with
organic solvent systems.
The invention also relates to an article of manufacture, comprising
packaging material and a topical formulation for controlling an ectoparasite
infestation on a small ruminant or companion animal contained within said
packaging
material, wherein said formulation comprises
a topical unit dose of a formulation comprising 0.1 to about 25 weight
percent of an ectoparasiticide, from about 25 to about 99.9 weight
percent of a (C3-C6) branched alkyl (C,o-CZO) alkanoate spreading
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agent, and optionally up to about 70 weight percent of a miscibilizing
agent compatible with organic solvent systems; and,
wherein said packaging material comprises a label or package insert with
instructions
for topically administering the dose to the animal.
This article of manufacture or kit is particularly appropriate when the
companion animal is a dog or a cat. The timing of administering the doses will
generally be every 30 days. Each kit typically contains a sufficient number of
doses
to control the ectoparasite infestation for a period of several months.
This invention further provides a topical formulation for controlling an
ectoparasite infestation on a small ruminant or companion animal comprising a
spinosyn, or a derivative or salt thereof, and a spreading agent substantially
as
hereinbefore described with references to any one of the Examples.
Examples of small ruminant animals are a sheep, a goat or a camellid.
The term "companion animal" includes dogs, cats, horses and other
1 S pets owned and maintained in close association with humans as part of the
human-
animal bond.
The term "controlling" as used herein refers to either ameliorating or
eliminating a current infestation or preventing an infestation in a
susceptible host.
Many insecticidal agents are useful in the formulations of this
invention. Indeed, any ectoparasiticidal compound that is soluble in a (C3-C6)
branched alkyl (C,o-Czo) alkanoate vehicle and is useful for topical
application can be
incorporated as the insecticidal component of these formulations. Typically,
the
insecticidal agent is active against a broad spectrum of pest species,
including
acaricides, antiparasitic agents, insect growth regulators and compounds that
inhibit or
kill flies, flying pests and other "temporary" pests that only alight
momentarily on
domesticated animals.
Examples of useful classes of insecticides are spinosyns,
organophospates, organochlorines, carbamates, and pyrethrins. Specific useful
insecticidal compounds include tetraethyl pyrophosphate (TEPP), mevinphos,
disulfoton, azinphosmethyl, parathion, methylparathion, chlorfenvinphos,
cichlorvos,
diazinon, dimethoate, trichlorfon, chlorothion, malathion, ronnel, abate,
baygon,
carbaryl, mobam, temik, zectran, methoxychlor, aldrin, dieldrin, endrin,
heptachlor,
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chlordane, lindane, mirex, nicotine, rotenoids, pyrethrums, spinosyns and
synthetic
pyrethroids, including cypermethrin.
Preferred insecticides useful in these formulations are spinosyns or a
pyrethroid such as cypermethrin.. Spinosyns are especially preferred.
The spinosyns (also known as A83453 factors) are agricultural
insecticides that have shown activity against southern armyworm and other
insects in
the order Lepidoptera, and cotton aphid and other members of the order
Homoptera.
(See, for example, U.S. Patent No. 5,571,901).
The spinosyns were also known to have some ectoparasiticidal activity,
- i.e., they had in vitro activity against mosquito larvae, black blowfly
larvae and adult
stable flies, which are members of the insect order Diptera, and transient
systemic
activity against larval blowfly and adult stable fly in guinea pigs and sheep.
For these
tests, the spinosyns were administered in aqueous polyvinylpyrrolidone or in
polyethylene glycol (see U.S. Patent No. 5,571,901, col. 26-32).
The spinosyns are naturally-derived macrolides produced by
fermentation of Saccharopolyspora spinosa. The fermentation produces multiple
factors, including spinosyn A and spinosyn D (also called A83543A and A8354D).
Spinosyn A and spinosyn D are the two spinosyns that are most active as
insecticides.
An agricultural product comprised mainly of these two spinosyns is available
commercially under the name "spinosad".
Spinosyn A was the first spinosyn isolated and identified from the
fermentation broth of Saccharopolyspora spinosa. Subsequent examination of the
fermentation broth revealed that S. spinosa produced a number of spinosyns
that have
been called spinosyns A to H and J. Additional spinosyns, denominated K to W,
have been identified from various strains of S. spinosa. The various spinosyns
are
characterized by differences in the substitution patterns on the amino group
of the
forosamine, at selected sites on the tetracyclic ring system and on the
2N,3N,4N-(tri-
O-methyl)rhamnose group.
Boeck et al. described spinosyns A-H and J (which they called A83543
factors A, B, C, D, E, F, G, H and J), and salts thereof, in U.S. Patent Nos.
5,362,634
(issued Nov. 8, 1994); 5,496,932 (issued March 5, 1996); and 5,571,901 (issued
Nov. 5, 1996). Mynderse et al. described spinosyns L-N (which they called
A83543
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factors L, M and N), their N-dimethyl derivatives, and salts thereof, in U.S.
Patent
No. 5,202,242 (issued Apr. 13, 1993); and Turner et al. described spinosyns Q-
T
(which they called A83543 factors Q, R, S and T), their N-dimethyl
derivatives, and
salts thereof, in U.S. Patent Nos. 5,591,606 (issued January 7, 1997) and
5,631,155
(issued May 29, 1997). Spinosyns K, O, P, U, V, W and Y are described, for
example, by Carl V. DeAmicis, James E. Dripps, Chris J. Hatton and Laura I.
Karr in
American Chemical Society's Symposium Series: Phytochemicals for Pest Control,
Chapter 11, "Physical and Biological Properties of Spinosyns: Novel Macrolide
Pest-
Control Agents from Fermentation", pages 146-154 (1997).
. The spinosyns can be isolated in the form of salts that are also useful in
the formulations of this invention. The salts are prepared using standard
procedures
for salt preparation. For example, spinosyn A can be neutralized with an
appropriate
acid to form an acid addition salt. Representative suitable acid addition
salts include
salts formed by reaction with either an organic or inorganic acid, for
example,
sulfuric, hydrochloric, phosphoric, acetic, succinic, citric, lactic, malefic,
fumaric,
cholic, pamoic, mucic, glutamic, camphoric, glutaric, glycolic, phthalic,
tartaric,
formic, lauric, stearic, salicylic, methanesulfonic, benzenesulfonic, sorbic,
picric,
benzoic, cinnamic and like acids.
The term a "spinosyn or a derivative thereof ' as used herein refers to
an individual spinosyn factor (spinosyn A, B, C, D, E, F, G, H, J, K, L, M, N,
O, P, Q,
R, S, T, U, V, W or Y), an N-dimethyl derivative of one or more spinosyn
factor, or a
combination thereof. For convenience, the term "spinosyn component" as used
means
an individual spinosyn or a physiologically acceptable derivative or salt
thereof, or a
combination thereof. "Spinosad" as used herein refers to a mixture of
spinosyns
comprised mainly of spinosyns A and D.
The spinosyns are known to have excellent human and animal safety
and toxicological profiles. Because of their low toxicity to animals and
humans,
spinosyns are considered to be environment-friendly, "green" insecticides. It
is
desirable to formulate spinosyns to maintain this "green" profile.
Spinosyns have recently been found to be useful in the eradication or
control of ectoparasites on sheep and companion animals. Thus, formulations of
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spinosyns with low toxicity and increased stability are potentially valuable
in
combating ectoparasites and the diseases such pests often carry.
The present formulations further comprise a (C3-C6) branched alkyl
(C,o-Czo) alkanoate. This component is an organic solvent that acts as a
spreading
agent. Spreading agents increase the spreading of, and aid in substantially
equalizing
the distribution of, the active ingredient over the hair and/or skin surface
area of the
animal over time. The spreading agent solvent system should be safe, non-
toxic,
environment-friendly and non-flammable.
The branched alkyl portion of the (C3-C6) branched alkyl (C,o-Czo)
alkanoate includes all branched chain isomers of C3-C6 alkyl groups. Examples
are
isopropyl, isobutyl, isopentyl, and isohexyl. The (C,~-Czo) alkanoate moiety
includes
all C,o-Czo fatty alkanoate groups, including but not limited to, decanoate
(C,o),
hendecanoate (C"), dodecanoate (CIZ), tridecanoate (C,3), tetradecanoate
(C,4),
pentadecanoate (C,5), hexadecarioate (C,6), heptadecanoate (C,~),
octadecanoate (C,8),
and eicosanoate (Czo). Preferably, the spreading agent is a (C3-C6) branched
alkyl
(C,z-C,~) alkanoate. Of these solvents, C3- branched alkyl-C,4 alkanoates are
especially useful. A preferred spreading agent is isopropyl myristate (IPM).
The formulations can optionally contain a miscibilizing agent. The
miscibilizing agent aids in solubilizing the active ingredient and must be
compatible
with organic solvent systems. The phrase "compatible with organic solvent
systems"
means that the miscibilizing agent does not form more than one phase when
mixed
with the (C3-C6) branched alkyl (C,o-Czo) alkanoate component.
Suitable miscibilizing agents for use in these formulations generally
are (C,-C3o) organic acids. Typically, such organic acids are straight-chain
saturated
fatty acids, but they can also be low molecular weight organic acids such as
formic
acid, acetic acid, propionic acid and benzoic acid.
The choice of miscibilizing agent will vary depending on the insecticide in
the
formulation. When the insecticide component is a spinosyn, examples of
suitable
miscibilizing agents are formic acid, acetic acid, propionic acid, butyric
acid, valeric
acid, caproic acid, benzoic acid, enanthic acid, caprylic acid, pelargonic
acid, capric
acid, undecylic acid, lauric acid, tridecylic acid, myristic acid,
pentadecylic acid,
palmitic acid, margaric acid, stearic acid, oleic, arachidic acid, behenic
acid,
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lignoceric acid, cerotic acid, montanic acid, triacontanoic acid, psyllic
acid, and
ceroplastic acid. Other useful miscibilizing agents are (C,-C3o) alkyl
sulfuric acids,
(C,-C3o) alkyl phosphoric acids, and (C,-C3o) alkyl sulfonic acids.
In formulations containing a spinosyn solubilized in isopropyl
myristate, for example, oleic acid is a particularly useful miscibilizing
agent because
it aids in solubilizing the spinosyn (thus allowing for the formation of
solvent
solutions containing relatively high concentrations of active ingredient), and
it is
compatible with the isopropyl myristate component.
Compounds other than (C1-C3o) organic acids can also be useful
miscibilizing agents in the formulations of this invention. In general, a
miscibilizing
compound useful for these formulations: 1) is compatible with the selected
organic
solvent component, and 2) solubilizes the active ingredient without
substantially
altering the spreading properties of the formulation.
When insecticide is a spinosyn and the spinosyn component is
spinosyn D or spinosad (i.e., a mixture of spinosyns A and D), it is
especially
important that the miscibilizing agent is able to solubilize the spinosyn D
sufficiently.
In technical grade spinosad, factor D is generally the factor that causes
solubility
problems when preparing spinosad-containing formulations. Examples of
miscibilizing agents that are useful for spinosad-containing ectoparasiticidal
formulations of the present invention include, but are not limited to, benzyl
alcohol,
ethylene glycol phenyl ether, D-limonene, N-methyl-2-pyrrolidinone, and
methylated
soybean oils and soybean oil methyl esters, such as SOYGOLD 1000 (AG
EnvironW ental Products LLC).
The present formulations can also contain other optional ingredients,
such as: antioxidants, UV-absorbing compounds or photostabilizers, viscosity-
modifying agents, antimicrobial agents, dyes, perfumes, deodorants and
physiologically or dermatologically acceptable carriers, diluents, excipients
or
adjuvants. Such agents are known in the art.
For example, one or more antioxidants can be added to the
formulations in an amount effective to retard oxidation of the formulation
components
and the ensuing degradative effects. Potentially useful antioxidants include
primary
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antioxidants that are radical scavengers, such as hindered phenolics and
secondary
amines, and secondary antioxidants, such as phosphites and thioesters that
function as
peroxide decomposers. Preferred antioxidants for use in these formulations are
blends
of primary and secondary antioxidants, including particularly blends of
phenolic and
phosphite antioxidant compositions.
There are many commercially available antioxidants products designed
for polymer stabilization, including antioxidant formulations comprising
synergistic
combinations of primary and secondary antioxidants. Examples of commercially
available antioxidants useful in the formulations of this invention include
the
Irganox~ antioxidants available from Ciba Geigy, Vanox~ antioxidants from R.T.
Vanderbilt, and the Naugard~ antioxidants available from Uniroyal Chemicals.
When the formulations include an antimicrobial component, it should
be present in an amount effective to prevent the growth of microorganisms in
the
formulation.
1 S Generally, the formulations of this invention can be prepared by
blending the components with adequate mixing or stirring. For example, a
useful
spinosad formulation is one having a final concentration of 2 mg of spinosad
per mL.
One such formulation is prepared to contain 99.1 weight percent IPM, 0.6
weight
percent oleic acid, and 0.3 weight percent spinosad technical (89% active
ingredient).
This formulation is made by adding the appropriate amount of spinosad to the
IPM
solvent with mixing or stirnng, blending the oleic acid into the IPM/spinosad
mixture,
and continuing the mixing or stirnng until the spinosad has completely
solubilized to
form the final formulation product. An optional additional step is to filter
the final
formulation to remove any impurities or extraneous materials.
The formulations of this invention are applied to the animal topically.
Topical control protocols include spot-on or pour-on treatments wherein the
formulation is placed directly onto a discreet skin and/or hair surface area
of the
animal and allowed to spread over the remainder of the animal's skin or hair
surface
area. Generally, spot-on or pour-on protocols involve initially placing the
formulation
on the dorsal midline (i.e., the head, neck, shoulders or back) of the animal.
Placement typically occurs on a dorsal midline surface area that constitutes
less than
10% of the animal's entire surface area. For example, a typical pour-on
treatment
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protocol involves applying about 4 to about 50 mL of a liquid
ectoparasiticidal
formulation in a narrow strip along the backline of an animal, from the
withers to the
tail or rump.
For spot-on or pour-on treatment to control ectoparasites, such as lice,
which are present over the whole surface of an animal, the ectoparasiticidal
active
ingredient must spread from the narrow strip at the backline to cover the
entire surface
of the animal. The present formulations have this advantageous spreading
effect. Of
course, they can be applied to areas of skin that constitute greater than 10%
of the
surface area of the animal, but such applications limit the advantage offered
by these
. formulations. Another advantage of these formulations is that they offer
extended
ectoparasiticidal coverage and need not be applied more than weekly or
biweekly at
most.
Example 1
Wetting Tests for Various Solvent Systems
To determine organic solvents that are useful spreading agents, solvent
systems that are capable of solubilizing at least 1 % spinosad by weight
percent were
screened for hair wetting by applying about 1 mL of the solvent system
(solvents were
screened without active ingredient), dropwise, to a tanned rabbit pelt that
was at an
angle of about 45 °. Solvent systems that wet the rabbit hair and did
not run off before
wetting the hair were considered to pass the screen. Table I describes the
ability of
selected organic solvents to wet the rabbit hair.
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Table I. Ability of Solvents and Aqueous Surfactant
Systems to Wet Rabbit Hair on Tanned Rabbit Pelts.
Organic Solvent
Wet Well Did Not Wet
isopropyl myristate triacetin
methyl laurate N-methyl pyrrolidone
dipropylene glycol methyl ether propylene glycol
butyl lactate
methyl caprate
methyl oleatP
octanoic acid
limonene
hexanol
ethyl oleate
As Table I shows, water immiscible, nonpolar solvents generally wet
well, although dipropylene glycol methyl ether is water miscible and did wet
the hair
very well.
~xamnle 2
Formulation Spreadin _ Tests
Further studies were conducted to determine the abilities of various
solvents to aid in spreading of active ingredient.
International Patent Application WO 9524219 teaches that wool grease
fraction (F1) provides superior spreading of pyrethroid insecticides on sheep
when
compared to organic solvent spreading agents. Tests were conducted to compare
the
spreading properties of formulations containing the F 1 wool grease fraction
and
various organic solvents. The amount and rate of diffusion of '4C-labeled zeta-
cypermethrin from the dorsal midline of sheep were determined when applied in
F1
wool grease fraction and a range of test excipients. Four formulations
containing 10
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mg/mL zeta-cypermethrin spiked with 100 uCi ['4C] zeta-cypermethrin were
prepared
in the following vehicles: wool grease fraction F1, isopropyl myristate, octyl
stearate
and glyceryl tricaprylate/caprate. A dose of 1 mL/Skg body weight of each
formulation was applied to the backline of 3 sheep. Wool was collected and
pooled 1,
2, 4, 8, 11 and 14 days after treatment from three 12 x 12 mm squares chosen
at
random, along meridian lines drawn 2, 7.5 and 15 cm down the side of each
sheep
from the backline. The clipped areas were also swabbed. At day 14 after
treatment
the wool at the site of application was collected, and back and perirenal fat
samples
were collected. The quantity of zeta-cypermethrin in each sample was measured
by
liquid scintillation counting.
For the majority of the measurements taken, isopropyl myristate gave
the greatest spread of zeta-cypermethrin and the wool grease fraction F 1
provided the
least spreading. When the vehicle was the F1 wool grease fraction, only the 2-
cm
meridian showed increased concentration of zeta-cypermethrin over time after
initial
application. When the vehicle was isopropyl myristate, the quantity of zeta-
cypermethrin measured at all meridians increased with time following
administration.
Octyl stearate and glyceryl tricaprylate/caprate gave modest spread, but not
as great
as the spread provided by the IPM formulations. Tissue residues were similar
amongst formulations except the glyceryl tricaprylate/caprate formulation
appeared to
cause the highest residue levels.
After two weeks it was determined that F1 was a comparatively poor
spreading agent, octyl stearate and glyceryl tricaprylate/caprate provided
better
spreading properties, and isopropyl myristate gave the best spread of zeta-
cypermethrin.
Example 3
Ectonarasiticidal Efficacy Tests of Wool Grease and IPM Formulations
Tests were conducted to compare the efficacy of formulations of
spinosad in F1 wool grease fraction versus those in isopropyl myristate
against lice on
sheep. Two F1 formulations containing spinosad at 2 mg/mL and 10 mg/mL, and
one
formulation containing 2 mg/mL spinosad in isopropyl myristate were made as
follows:
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a) F1 Formulation (2 mg/mL)
81.11 % F1
18.62 % solvent (50/50 petroleum ether/acetone)
0.27 % spinosad technical that was 89% active
100 % (w/w)
Formulation density = 0.84 g/mL
b) F1 Formulation (10 m,.~)
80.26 % F1
18.42 % solvent (50/50 petroleum ether/acetone)
1.32 % spinosad technical that was 89% active
100
Formulation density = 0.84 g/mL
c) IPM Formulation (2 mg/mL)
99.123 % IPM
0.613 % oleic acid
0.264 % spinosad technical that was 89% active
100
Formulation density = 0.85 g/mL
Each formulation was administered to sheep as a pour-on application
immediately after shearing. Spinosad/F1 formulations were tested at doses of 0
(i.e.,
vehicle alone), 0.4 and 2 mg/kg, while the spinosad/IPM formulation was tested
at a
lose of 0.4 mg/kg. The 2 mg/kg dose orspinosadlFl was administered using the
10
mg/mL formulation, while the 0.4 mg/kg doses were administered using the 2
mg/mL
formulations. Lice counts were taken on the sheep at sites all over the
animal,
including the head and neck. These lice counts were taken before treatment and
on or
about weekly for the following eight weeks. The results of this study are
summarized
in Table II.
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Table II: Comparison of Ectoparasiticidal Efficacy of
Spinosad in F1 and IPM Formulations in Sheep
Lice Counts (mean)
Week
of
Study
Day U _1 _2 _3 _4 _5 _6 _7 _8
lice count
F1 Only 643 428 328 350 237 245 159 156 145
0.4 mg/kg 622 391 213 211 159 118 103 69 68
Spinosad/F
1
2 mg/kg 582 146 86 48 2 13 4 3 2
Spinosad/F1
,
0.4 mg/kg 575 ~ 138 81 68 47 32 13 25 21
Spinosad/IPM
As the results summarized in Table II show, spinosad in IPM at a dose
of 0.4 mg/kg was superior in lice control to spinosad in F1 at 0.4 mg/kg, and
was
almost equal in efficacy to spinosad in Fl at 2 mg/kg. Spinosad in IPM gave
outstanding control of lice on sheep, including control of lice on the head
and neck,
which indicated that IPM potentiated the spreading of spinosad from the dorsal
midline to the head, neck and other body surface regions.
Example 4
Lfficac~f Spinosad in Various Organic Solvents vs. Lice in Sheep
Further lice efficacy studies on sheep were conducted to compare the
efficacy of IPM as a spreading agent to that of other organic solvent systems
containing blends of organic solvents. The formulations tested had the
following
compositions:
a) IPM Formulation:
99.12 % IPM
0.61 % oleic acid
0.27 % spinosad technical (89% active)
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10
b) OP/IPM Formulation
79.78% octyl palmitate (OP)
19.95% IPM
0.27% spinosad technical (89% active)
c) GTCC/OP Formulation
79.78% glyceryl tricaprylate/caprate (GTCC)
19.95% octyl palmitate
0.27% spinosad technical (89% active)
d) GTCC/IPM/CAP Formulation
69.81 % glyceryl tricaprylate/caprate
14.96% IPM
14.96% cetearyl octanoate (CAP)
0.27% spinosad technical (89% active)
e) OP/IPM/OSU Formulation
69.81 % octyl palmitate
14.96% IPM
14.96% dioctyl succinate (OSU)
0.27% spinosad technical (89% active)
f) TPM/LWG/GTCC Formulation
59.84% tripropylene glycol methyl ether (TPM)
19.95% liquid wool grease (LWG)
19.95% glyceryl tricaprylate/caprate
0.27% spinosad technical (89% active)
g) TPM/OSU Formulation
79.78% tripropylene glycol methyl ether
19.95% dioctyl succinate
0.27% spinosad technical (89% active)
Lice counts were taken on the sheep at sites all over the animal,
including the head and neck. These lice counts were taken before treatment and
on or
about weekly for the following twelve weeks. The results of this study
summarized in
Table III.
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Table III: Efficiacy of Spinosad in Organic Solvent Formulations vs. Lice in
Sheen
Lice Count (mean)
Weeks
Treatment 1 2 4 6 8 12
Pretreatment
lice count
Control 253 197 128 163 206 162 204
IPM 268 33 23 18 20 18 18
OP/IPM 271 71 51 83 90 71 184
GTCC/OP 257 32 28 40 52 46 106
GTCC/IPM/CAP 278 28 16 24 25 22 33
OP/TPM/OSU 259 33 19 23 22 19 40
TM/LWG/GTCC 267 53 29 39 34 27 48
TPM/OSU 259 58 38 64 62 66 119
As Table III shows, spinosad in IPM alone was the most effective treatment of
the 7 formulations tested. A strong correlation exists between the results of
the
spreading experiments and those of the field efficacy experiments. Spinosad
formulations in IPM exhibited excellent spreading characteristics and
demonstrated
outstanding long-term protective and inhibitory effects against
ectoparasiticidal
infestation in sheep.
Examples 5-11 illustrate various formulations of this invention.
Example 5: Spinosad/IPM/acetic acid Formulation
5.65% spinosad (88.5% active)
3% acetic acid
91.35% IPM
Example 6: Spinosad/IPM/octanoic acid Formulation
5.65% spinosad (88.5% active)
7.5% octanoic acid
86.85% IPM
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10
20
Example 7: Spinosad/IPM/lauric acid Formulation
5.65% spinosad (88.5% active)
10.15% lauric acid
84.2% IPM
Example 8: Spinosad/IPM/oleic acid Formulation
5.65% spinosad (88.5% active)
16.5% oleic acid
77.85% IPM
Example 9: Spinosad/IPM/benzoic acid Formulation
5.65% spinosad (88.5% active)
3.76% benzoic acid
90.59% IPM
Example 10: Spinosad/IPM/NMP Formulation
5.65% spinosad (88.5% active)
40.0% 1-methyl-2-pyrrolidinone (NMP)
54.35% IPM
Example 11: Zeta-cypermethrin/IPM Formulation
1.18% zeta-cypermethrin (84.7% active)
98.82% IPM
The formulations of Examples 5-10 can be prepared by weighing the
spinosad into a suitable container, adding the IPM and stirring to create a
slurry, and
then adding the final component and stirring until a clear solution is
achieved. In
preparing the formulation of Example 11, the zeta-cypermethrin is an oily
liquid that
';,quires gentle heating (approximately 4v-50°C) to allow for proper
mixing into the
organic solvent phase. No separation of phases is evident upon cooling.
