CA1193191A - Method and compositions for repelling pests - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

What are disclosed are a method for repelling small blood feeding pests from the skin, hair, or fur of a mammal, which method comprises applying a pest repellant amount of a repellant which is cyano (3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl) benzeneacetate to said skin, hair, or fur and compositions for performing this method.

Description

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MET71r3D AN~) CC~MPOSITION~ FC)R RF,'PELI,ING PES~S

The present invention rela~es to a method for repelling small blood feedin~ pests from the skin, hair~ or fur of a mammal, and to repellant compositions for practicing said method.
More in particular, the present inventi~n relates to a method for repellinq pest~ ~uch as ticks, fleas, and m~squitoe~ from humans and animals ~uch as cats and dogs~
and to repellant compositions f or practicin~ such method~.
At present a number of composition~ are on the ~arket which are alleged to repel ~uch small bl~o~ ~ucking pests as ticks and fleas from household pets such a~ cats and dogs. The~e compositions, which may be t~picallv applied~ such as dip~ an~ sp~avs, or which mav be sv~temic, are in act insecticidal compo~itions having little or no rep~llant effect. Even though such compositions m~v in due course kill blood feeding pests such as ticks and fleas which are present on an animal, nevertheless they suffer the di~advantage that they permit, or even require, that the pests be pre~ent on the animal, at least ~or the time required for the in~ecticide to kill~ S~temic in~ecticides further have the ~i~ad~antage that, for efficacy, the pests mu~t feed on the anim~10 Pets are capable of developing allergic reactions to the en~mes excreted by the blood feeding pests to prevent coagulation of the blood on which they feed.

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The pro~lem thus exi~ted of fin~ing a compoxition, suitable to be applled to the skin, hair, or fur Of a mammal, for repelling ~mal~ blooa feeding pests ~f the type described above9 particularly ticks, fleas and mosquitoesv Cert~inly, effective repellants are known to the art. One of these, N,N-diethvl-m-toluamide (hereinafter DF,ET) is known to be excellently effective as a mosquito repellant. A number of compo~i~ion~ containin~ this material are commercially av~ilable f~r use as a repellant on humans and animals, f~r instance in a form of aerocol compositions~ Although ~ET is ~o effective as a repellant that it has been used in ~tudies reported later herein as a standard for testing re~ellancy, it has the dual disadvantage that it must be used in relatively hiqh concentrations and, more importantly, it is not effective for affording continuous pro~ection against pe.sts for ~re than about ~ix hoursO
Accordinq to the present invention, a method has now been f~und for repelling small bloo~-fee~ing pests from the skin~ hair, or fur of'a mammal by topically applying to the animal a repellant which is cyano (3-phenoxyphenyl3 methyl-4-chloro-alpha~ methylethyl)-benæeneacetate, of the following form~la:

Cl ~ C - COO~ CH

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The ac~ive compou~d is conveniently formulated into compositions which ar~ adaptable to topical application t~
the skin, hair, ~r fur of a mammal, an~ these composi~ions are ~lso a feature of the present invention~
The active compound mentioned ahove and methods for its preparation are known from Fu~imoto et al. ~.S.
Patent No. 4,062,968. ~he compound is one of many hundreds of suh~tituted acetate compounds of the general formulae Y - C~ - ~OOX

which are taught by the patent to be useful as pesticides~
particularly in insecticifles and miticides. The pestici~es axe taught as useful for controlling mosquitoes, flies~
cockroaches, gr~in inse~s such as the rice weevil, mites, agriculturally obnoxious insects such as plant-hopper~, green rice leafhoppers, ca~bage army ~orms, diamond-back moths, noctuidae, cab~age worm, rice stem borers, aphids, tortrixes, leaf-minersr ~nd the like. More specifically, the compounds are reported as havin~ selective or non-selective pesticidal activity on such orders as Coreoptera, Lepidoptera 9 Diptera, Orthoptera, Hemiptera, ~omoptera~ Acaru~, and other pests such as nematodan A number of the many pesticidal compounds disclosed in the aforementioned Fujimoto et alO patent are shown in Experim~ntal Example 3 of the patent t~ ha~e a ~q33~.~3~L

repellant effect against spider mites (Tetranychus telarius) as tested on seed]ings of mottled kidney beans treated with an emulsifiable concentrate prepared by blending the compound tested with xylene and "Sorpol SM~200" (trade mark), presumably an emulslfying agent. The compounds tested Eor repellancy against spider mites do not include the compound used according to the present invention, the common name of which is fenvalerate and which is commercially available under the trade mark "Pydrin" and the trade mark "Ectrin". The active compound will be identified hereinafter as "FV" for sake of convenience.
Thus, although FV is known in the art as a pesticide, and compounds related to FV have been shown to have repellant activity for spider mites on plants, one skilled in the art would not have expected from such teachings that FV would have outstanding properties as a repellant for small blood feeding pests such as ticks, fleas, and mosquitoes, particularly the long lasting actlvity which is observed.
Many well known insecticides have no effective repellant properties; conversely, many materials recognized as repellants do not have any pesticidal effect.
In discovering the unique repellant properties of FV, approximately ~0 known compollnds were tested, of which all were known to have some repellancy for fleas or mosquitoes and over half of which were known to exhibit a, _ 3~

repellancy activity comparable to or better than that of DEET against hiting fleas and/ox mosquitoes.
Because of the magnitude ~f the testing effort, the compounds were first tested for repellant efficacy by an in _tro technique employing the brown dog tick, Rhipice~halus sanguineus1 Ticks were used for the assay because thev are more resistant ~o pes~icides and repellants than are other pests such as fleas or mo~qui~oes~ because they are less mobile ~han fleas or mosqui~oes, and ~ec~us~
they neea blood feeding three times in their life cvcle.
The in vitro test procedure involved weighing each material to be tested and dissolving it in ethanol. Next, 0.15 ml of the test solution was ap~lied to a disk~ ~.9 c~
in diameter, Cllt from No. 3 Whatm~n filter p~per. Th~
treated di~ks were kept under a hood and ~llowed to drv ~or 24 hours.
~ ach txeated disk was then mounted in a drilled-out vial cap that the treated side face~ down when the cap was placed on a seven dram polvstvrene vi~l (25 X 52 mm~ which served as a test chamber. In each case, an untreated filter paper disX was also glued on the drilled out bottom of the vial. In each cas~, fifteen holes were punched in both disXs when in position on the ehamber.
Next, twenty unfed adult brown dog ticks ~ten ~ale and ten fem~le~, sorted 24 hours ~efore use, were placed in each test chamber. The cham~ers w~re held with the treated end upright under a hood. Four h~urs l~ter 7 when the ti~ks ~3~

had cea~ed wandering~ the chamber wa~ ob~rved and the number of ticks on the treated top surface of the chamher were coun~ed. Because of the known tendency of ticks to climb, the presence o~ ticks on the treated upper surface of the test chamber indicated a lack of repellancy. In each case t non-treated, standard-treated, and solvent~tre~ted disks w~re included in the ~est.
q~7enty-.six of 81 compound~ tested were ini~ia~v tested at an area ooncentration of l.0 mg/cm2 and then again at lower ~evels if activi~y was obsexved. ReplicA ~esting was conducted on all but one of these compoun~ in order better to validate the assav. Subsequent compounfl~ were tested at a lower initial test level of 0.44 mg/cm2, Compounds highly active at this level would be clearlv superior to DF,ET and Indalone (bu~yl 3,4 dihvdro-2,2-dimethyl-4-oxo-2H-pyran-6-carboxylate~ used as stan~ards of repellancy. In general, the best conventional repell~nts lapart from the material of the present invention~ were rhodanine and oxo-rhodanine compounds, of which seven compounds tested were more than 75% active at a level of 0.29 mg/cm2 or less~ 3-ethyl,5-n-hexyl rhodanine and 3 me~.hyl, 5-n-hexyl rhodanine were found to be 100%
repellant at a concentration of 0.13 mg/cm~. In cOmpari~Qn, FV shows comparable high repellant activi.ty ~own to a level of only 0.005 mg/cm2.
FV was next tested in vivo in an animal host to determine whether the in vitro effect reported above was in ~3~

fact valia. A~o, it was ne~e~sary to determine whether the repellancy effect also occurred a~ong fle~s~ the other main ectoparasite affecting househo7d pet~. Because of the ~obility ~f fleas, it was not possi~le to develop an in vitro evaluation method for these insects.
For in vivo testing, six adult short-haire~
beagle-sized conditioned monqrel dogs were u~ed as tes~
animals. Two dogs, one ~reated with a test ~ero~l and one treated with a control aer~sol, are used to evaluate each test material. After treatmen~, the dogs are released ~o vut~oor runs, all~we~ t~ ~ry for approximatelv four hours, and then are brought into the testing roomO
The testing room i~ 11.5 x 11.5 ft. in size with a

2.5 x 6.5 ft. ~o~ run on two opposit~ ~ides of the room.
One run is used to house the do~ treated with the test material; the control dog is in the second run. ~nfe~ adult cat fleas (Ctenocephalides felis~, which are the principal parasitic flea for dogs, were released in the center of the roo~ and 75 unfed a~ult brown dog ti~ks were released at the si~e of each run. The room was sealed and the doqs werP
left in the test chamber overnightO The next morning, ~h~
room was washed and all parasites were removed from the dogs and counted. If a test material wa~ active~ the dog~ were returned to outdoor runs and rechallenged at periodic interva~ following the intial treatment~

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Initial trials were made with the active ingredient at a concentrati~n of 0.005 my/cm2. Since the bo~y surface of the animals tested was approximately

4,000 cm2, approximately 20 m~ of FV were applied per dog using an ethanol solution of the chemical and applying ~ h an atomizer. The results are shown in Table 1 belowD

Table 1 In Vivo ~valuation ~ mg/cm2 (20 mg/dog~
24 Hour 48 ~our 8 Days T F T F T
EtOH 2 60 37 53 31 57 FV 0 4 ~ 5 0 26 T = Ticks; F = Fleas; Numbers signifv live parasites observedO
Thus, repellancy effect expected with ticks from the in vitro experiments was, in fact, obser~Ted also in vivo together with a significantlY effective repellan~v effect against fleas.
However~ to improve the effect and make it lon~er lasting9 the tests were r~peated and a concentration of OoOl mg/cm2 ~40 mg FV/dog~ and again at 0~0~ mg/cm2. The results of the latter experiment are shown below in Table 2, from which it will e~ident that there is almost complete repellancy of ticks for a period of 22 davs as well as more than 80% rep~llancy of fleas at the end of the same period~

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~able 2 .
24 ~ours 48 Hours 6 Da~s 9 Da~S 16 DaYS 22 D~YS
T F T F T T F T F T F
EtOH 13 32 33 1~2 32 115 60 126 19 81 41 50 Xn a further test t~ improve upon flea repellancv, the concentrat-on of FV was increa~ed tO OOQ4 mq/cm2 or 160 mg of FV per dog. In Table 3 bel~w, the results are shown together with the results of crossover tests in which the doqs and treatments were reversed in order to eliminate animal bias. Tha~ is, the dog treated with ethanol a~ a control received the active ingredient in ethanol solution during the crossover experiment, while the doq which had previ~usly received the active ingre~ient was treated with ethanol in the crosso~er.

Table 3 -?-4 Hour.s 7 naYs 14 Davs ~1 Davs T F T F T F T F
EtOH 3 45 7 B5 11 ~ 68 ~ 0 ~ ~ l 13 Cross over same rate EtOR 4 892 66 12 123 7 47 FV 0 0 0 1 0 13 0 lS

~g_ For sake of tllorouyhnes~, tw~ ad~iti~nal procluct lots of FV were evaluated by the ln vivo tests described above: a similar effect wa 6 observed.
From other studies done at the same time, it was determined th~t the amount of a spray product normally applied to an average size household pet for full coverage is 50-75 gm. ~hus, such a product should contain approximately 0.2~ of active ingredient in order to deposi~
100-150 mg onto the pet. The active ingredient should be included within a carrier suitable for topical application to the skin, hair or fur of the animal~ Thus, the product to be applied should contain approximately 0.2% of active ingredient. An aerosol spray formula containing this level of the active inyredient was developed and was shown to be highly effective. The composition of the aerosol product and the results obtained therewith on beagle-~ized dogs are given below in Table 4.

I O -~abl _ Formula prepared 0.2% FV
61.7~ Ethanol 13.-1% CH2Cl 25.n~ Prope~lent A--46 ( PL OPa ne/lsobutane) Results:
24 Hours 7 Days 14 ~ys 21_~ays T F T F T F T F
EtOH 35 20 43 86 24 B2 2~ 30 FV Sample #~511 0 0 1 7 2 ~ 21 ~6 The _ vivo tests reported above were all performed using indoor kennel facilities. As a ~inal test of the efficacy of FV, comparable outdoor test faci].ities were employed at a location in north Texas using the same product and A similar protocol. The area was selected because its climate is particularly accomodatin~ to fleas and ticks. The results of the outdoor -tests are shown below in Table 5.

~ble S
24 ~rs. 3 Da~s 6 D~ys 9 Days 13 D~y~ 20 ~ays T F T F T F T F ~ F T F
No Treat26 24 32 27 108 34 125 22 36 44 16 27 FV Sam-ple 4901 1 5 0 2 0 S 0 6 3 38 2 27 3~

Finally, to permit an evalua~ion of the in vivo result~ u~ing FV versus the effects of known repellants, an in vivo test of type described above was undertaken indoo~s using the known repellant DEET at a concentration.of lB~.
As a control, a placebo free of any repellant material was employed. The results, given in Table 6 below, show that D~T does show early effectiveness against fleas and ticks at this high concentration~ but that the effect is not residual.

TA~ 6 24 Hours~ Days 14 Davs 21 Days T F T F T F T F
DEET 4 B1~ 64 33 178 Placebo 18 323 54 13 18 All of the in vivo results reported earlier herein involve tests in which the parasites (ticks and fleas~
relea.sed had a choice of migration to a treated or to an untreated dog. That is~ a host was alwaYs available which might be more attractive to the parasites. As a further evaluation, in v1vo te.sts were performea u~ing ~ssentiallv the same protocol but in whih both test ~ogs were treated with the FV pro~uct at a concen~ration o~ 0.2%. ~he results are shown in Ta~le 7.

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Table 7 Day 10 Day 14 T F T F T ~ T F

Sa~ple FV 5002 Dog 1 O O O O O O O
~og 2 0 0 0 0 0 1 ~ 3 As is eviden~ from ~he Table, neither dog beca~e infested under ~hese test conditio~s. Tha~ is, parasi~es faced with ~ choice between two treated doqs di~ not migrate to either animal D
To te~t the e~ficacy of ~V as a repellant for mosquitoes, approxima~ely 25 to 50 unfed female mosquitoes, newly hatched from larvae, were placed for each test in a screen cage and applied to the shaved a~domen of a ~uinea pig a fixed interval of time after the shaved skin of the test animal had been treated with a given concen~ra~ion of FV in an ethanol solution. Several hours after the completion of each test (to permit determination of mosquito mortality), the living anA dead mosquitoes were crushed to ascertain i~ they had had a blood meal. The number of mosquitoes fed was used as a measure o~ repellancy. The num~er of mosquitoes killed was used as a measure of insectici~al activity. The resu~ts are reported below in Table 8 ~3~

Table ~
7 ~irs. 24 ~lrs. 48 Hrs.
Fed % Dead ~ Fed ~ ~ead % Fed ~ ~ead _ _ _ EtOH 64 0 43 0 60 n 1% FV 18 53 15 46 56 54 0.1% FV 20 15 42 0 - -o01~ FV 70 0 52 0 - -The Table shows that the repellant properties of FV persist at low concentrations at which insecticidal activity is reduced. However, the repellant effect for mosquitoes is more fugitive than for fleas or ticks~ at least under the test protocol employed.
As mentioned earlier herein, the active ingre~lient found to be so highly effective as a repellant accor~linq to the present invention can be incorporated in any carrier suitable for application to the skin, hair, or fur of a mammal, particularly household pets ~nd humans.
Thus, a further aerosol product was formulated to decrease flammability and to provide a co~smetically acceptable spray pattern. The composition of the aerosol product is given below in Table 9. It is noted that vitamin E may be added to the composition as a skin emol]ient, if dcsired.

, , -Ta~le Inc3redients 0.2 FV Vitamin E may 37.7 C~ Cl also be added as 200q Mineral Spirits skin e~ollient.
8.4 Isopropanol l.0 Propylene Glycol 0.3 Perfume _2. n Propellent A-46 (Propane/~obutane) 100 . O
Alternatively, the active ingredient may be dispensed in the form of a powdered pro~uct in an appropriate carrier, for example. A numb~r of compositions containinq the active ingreAient ~t various levels are reported belo~ in Table lO, Table lO
A ~%) B ~%~ C ~ D (%~
_ FV l.0 5.0 1.0 5.0 Isopropanol ~. n 3 . n Calcium Carbonate 48.541~n Diatomaceous Earth 49.04005 Colloidal Silica 005' 075 ~.5 0.5 Talc ~ ~ 9~5 94-5 Finally, Table lO below qives a formulatic)n which can be convenien~ly di~pensed from A pu~p-spray uni~. It is noted that perfume, propylene g1ycol, color, ancl emollients and conclitioners may be addecl to the composition if desired~

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~ble 11 ~ Pum~_Spray Repeilent Isopropanol 50.0 water 49.8 It should be clear that the exemplified aero~ol, powder, ~r pump-~pray formulations specifically report~d herein are merely typical ~f others which can ~e ~ormulated (e~g. towlettes, foams, creams, etc.~ and that the present invention inclu~es still other formulations, or formulations of the type shown wherein the nature ~f the ingredien~
and/or their concentration, including the concentr~ion of the active ingredient, may be varied if de~ired to confor~
the product to particular needs.

Claims (12)

WHAT IS CLAIMED IS:

1. A method for repelling small blood feeding pests from the skin, hair, or fur of a mammal, which method comprises applying a pest repellant amount of a repellant which is cyano (3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl) benzeneacetate to said skin, hair, or fur.

2. A method as in Claim 1 wherein said small blood feeding pest is a tick or flea.

3. A method as in Claim 1 wherein said small blood feeding pest is a mosquito.

4. A method as in Claim 1 wherein said repellant is applied to said skin, hair, or fur as an aerosol composition.

5. A method as in Claim 1 wherein said repellant is applied to said skin, hair, or fur as a powder composition.

6. A method as in Claim 1 wherein said repellant is applied to said skin, hair, or fur as a liquid composition.

7. A method as in Claim 1 wherein said repellant is applied to said skin, hair, or fur at a minimum area concentration of about 0.005 mg/cm2.

8. A method for repelling ticks or fleas from a dog or cat; which method comprises applying to said dog or cat a repellant amount of a repellant which is cyano (3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl) benzeneacetate.

9. A method as in Claim 8 wherein said repellant amount is at least about 0.005 mg/cm2.

10. A method as in Claim 8 wherein said repellant amount is at least about 0.02 mg/cm2.

11. A method as in Claim 8 wherein said repellant amount is at least about 0.04 mg/cm2.

12. A composition for repelling small blood feeding pests from the skin, hair, or fur of a mammal, said composition comprising a pest repellant amount of cyano (3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl) benzeneacetate and a carrier therefor, said carrier being adaptable to topical application to skin, hair, or fur.