WO2002000021A2

WO2002000021A2 - Method and compositions for inhibiting the human and animal scent tracking ability of mosquitoes

Info

Publication number: WO2002000021A2
Application number: PCT/US2001/020254
Authority: WO
Inventors: James A. Nolen; Robert H. Bedoukian; Daniel L. Kline
Original assignee: Biosensory, Inc.; Bedoukian Research, Inc.; United States Of America, Represented By The Secretary Of Agriculture
Priority date: 2000-06-28
Filing date: 2001-06-26
Publication date: 2002-01-03
Also published as: AU7145401A; JP2004501168A; CN1444447A; WO2002000021A3

Abstract

The ability of mosquitoes to locate a target by olfactory emissions of the target is inhibited by dispensing into a spatial area an inhibiting effective amount of at least one inhibiting compound selected from the group consisting of esters of 1-alkene-3-ols of formula (I) and esters of 1-alkyn-3-ols of formula (II) wherein R is an alkyl group of from 1 to 4 carbon atoms, R?1 and R2¿ are each independently a saturated or unsaturated aliphatic hydrocarbon group containing from 1 to about 12 carbon atoms, and R¿3? or CH3.

Description

METHOD AND COMPOSITIONS FOR

INHIBITING THE HUMAN AND ANIMAL

SCENT TRACKING ABILITY OF MOSQUITOES

Field of the Invention

This invention relates to a method and compositions for inhibiting the ability of mosquitoes to locate or track a human or animal body by scent detection. More particularly, the invention relates to the use of certain compounds in compositions and apparatus to inhibit mosquitoes' ability to detect humans or animals by scent detection.

Background

Compounds, compositions and formulations for protecting human beings from being bitten by mosquitoes are known in the art. Generally, these compounds, compositions and formulations are based on their ability to persist on the skin of the person upon topical or surface application for a time sufficient to repel mosquitoes. Numerous adjuvant materials have been added to mosquito repellants to increase the persistence of the repellents to the skin of a person. However, despite the various attempts to improve the repelling activity of the known mosquito repellents, these attempts have generally not been successful, as almost anyone who has used such mosquito repellents can attest.

Thus, the art has been searching for new and more effective repellents against mosquitoes. However, the search for more effective mosquito repellents has not generally been met with success since most mosquito repellents have been found only to possess a limited degree of repeiiency and are generally not particularly effective. There is, therefore, a need for more effective means to deter mosquitoes from locating and biting humans and other targets such as livestock. Moreover, this need has recently become more acute and urgent because mosquitoes have been discovered to be carriers of significant diseases that can be passed on to a target by the mosquitoes biting the target. A further need is to be able to reduce the use of environmentally unfriendly pesticides.

Summary of the Invention

The inventors have discovered that compounds, compositions and formulations heretofore proposed as repellents for mosquitoes have lacked the necessary efficacy due to the ability of mosquitoes to locate and be drawn to the targets by olfactory emissions of the target. Thus, if a mosquito enters a zone or space where a potential target is located, the mosquito can be attracted to the target by olfactory emissions of the target and, this olfactory attraction is sufficient to overcome any repeiiency activity of the repellent compound, composition or formulation applied on the target. Therefore, the present invention provides compositions and formulations containing compounds usable in methods and apparatus for inhibiting the olfactory target tracking abilities of mosquitoes when an effective amount of the inhibiting compound(s) is/are dispersed in a three dimensional atmospheric space.

According to this invention, the ability of mosquitoes to locate a target is inhibited by dispensing into a spatial area an inhibiting effective amount of at least one inhibiting compound selected from the group consisting of lower alkyl esters of 1-alkene- 3-ols of the formula:

and lower alkyl esters of 1-alkyn-3-ols of the formula:

wherein R is or an alkyl group of from 1 to 4 carbon atoms, R¹ and R² are each independently a saturated or unsaturated aliphatic hydrocarbon group containing from 1 to about 12 carbon atoms, and R₃ is hydrogen or CH₃, preferably CH₃. Preferably, R is H or CH₃, R¹ and R² are C₆Hn, and R₃, is CH₃, i.e., formate and acetate esters of linalool.

The inhibiting compound can be dispensed into the three dimensional atmospheric space by any suitable means sufficient to provide an inhibiting effective amount of the inhibiting compound(s). Such dispensing means includes, for example, evaporation, atomization and ionic dispersion of the inhibiting compound from any suitable composition or formulation. Such composition or formulation will generally comprise a base vehicle containing at least one of the inhibiting compounds.

Detailed Summary of the Invention

The inventors have discovered that if an effective amount of at least one inhibiting compound selected from the group consisting of the lower alkyl esters of 1- alkene-3-ols of the formula:

and the lower alkyl esters of 1-alkyn-3-ols of the formula:

R₃

R— C — C≡CH

I O-C-R

II O

wherein R is an alkyl group of from 1 to 4 carbon atoms, R¹ and R² are each independently a saturated or unsaturated aliphatic hydrocarbon group containing from 1 to about 12 carbon atoms, and R₃ is hydrogen or CH₃ is dispensed into the atmosphere of a three dimensional environmental space, the ability of mosquitoes to locate and track a target, such as humans or livestock, by the target's olfactory emissions is inhibited.

Any suitable lower alkyl esters of 1-alkene-3-ols or 1-alkyn-3-ols of the formulas may be employed in the method, compositions and apparatus of this invention. Preferred suitable inhibiting compounds are the formate and acetate esters of nerolidol, 3-methyl-1-octen-3-ol, linalool and dehydrolinalool. Depending on the particular mosquito species, either the esters of 1-alkyn-3-ols or the esters of 1-alkene-3-ols are better inhibitors than the other class of components and will be preferred for that species of mosquito. The inhibiting compounds may be utilized singly or as mixtures of two or more of such compounds.

Any suitable inhibiting effective amount of the inhibiting compound(s) may be employed. Such inhibiting effective amounts can include amounts, based on the square footage of land or base surface area of the environmental area to be treated, within the range of from about 0.000005 g/hr/ft² to about 0.004 g/hr/ft², preferably amounts within the range of from about 0.00015 g/hr/ft² to about 0.0002 g/hr/ft², and especially an amount of about 0.00016 g/hr/ft².

The inhibiting compounds for use in this invention may be provided in an essentially pure form of the inhibiting compounds or as a component of a natural essential oil having a concentration of an inhibiting compound sufficient to make it practical and feasible to dispense an inhibiting effective amount of inhibiting compound. Generally, the essential oil will contain a concentration of the inhibiting compound of at least about 2%, preferably at least about 5%, and especially at least about 50% by weight. For example, the inhibiting compound can be provided as a synthetically produced, essentially pure compound or as a component of an essential oil such as basil oil, ho wood oil and the like.

The inhibiting compounds of this invention may be employed in any formulation suitable for dispensing inhibiting effective amounts of the compounds. The compounds will generally be employed in formulations comprising a suitable vehicle containing the inhibiting compounds. For example, the inhibiting compound can be formulated in a specially formulated waxy medium or vehicle engineered to release desired amounts of vaporous inhibiting compound at ambient temperatures, such as those mediums or vehicles available from Koster Keunen of Watertown, Connecticut. An example of such a waxy medium available from Koster Keunen is known as Insect Repellent Wax Bar No. 9, which is a blend of waxes having the following general composition: fatty acids ranging in carbon chain length of from C-ι₆ to C₂₂, fatty alcohols ranging in carbon chain length of from Cι₆ to C₂2, paraffinic hydrocarbons ranging in carbon chain length of from C₁₉ to C ₇, branched hydrocarbons ranging in carbon chain length of from C₂₃ to Cβg, beeswax and other natural waxes such as candelilla and carnauba. The wax mixture will generally be formulated with concentrations of the inhibiting compounds of this invention ranging from about 20% to 60% and the formulation has a congealing point which may vary from about 75°C to about 45°C. Alternatively, the inhibiting compound can be formulated in a porous medium or vehicle suitable for releasing effective amounts of the inhibiting compound. As an example of such porous medium or vehicle is a polyester membrane material having micropores encasing a block of inhibiting compound saturated fibers that gradually releases the inhibiting compound so that it permeates the microporous membrane and is released to the environment. Such porous membrane known as World of Fragrance™ cups is available from Waterbury Companies, Inc. of Waterbury, Connecticut. The formulations can be placed in any suitable container or device for dispensing the inhibiting compound. For example, the formulations can be placed in a suitable fan-equipped device so that one can obtain, for example, fan-driven evaporation of the inhibiting compound from a porous medium or wax-like medium containing the inhibiting compound. As examples of such fan-equipped devices, there can be mentioned the devices disclosed in US Patent 5,370,829 of Waterbury Companies, Inc. and the apparatus disclosed in US Patent 5,799,436 of Biosensory Insect Control Corporation, each of said patents being incorporated herein by reference thereto.

Another suitable means of dispensing the inhibiting compound is by atomization and/or ionic dispersion of the compound as suitable-sized, positively- charged droplets from a suitable atomization or ionic dispersing apparatus, such as the Ionic Wind™ device, available from Brandenburg, Ltd. of Brierery Hill, United Kingdom.

The inhibiting compounds of this invention are effective against mosquitoes, such as for example, Aedes taeniorhyncus (Black Salt Marsh mosquito),

Culex nigripalpus, Aedes aegypti, Aedes albopictus (Asian Tiger mosquito), Culex pipiens (common house mosquito), Culex quinquefasciatus, Anopheles gambiae and the like.

The use of this invention is illustrated by the following non-limited examples.

Example 1

A triple cage, dual-port olfactometer, illustrated and described in detail by Posey et al. J. Med. Entomol. 35(3), 330-334 (1998), was used to study the responses of 6 to 8 day old, laboratory-reared adult female Aedes aegypti mosquitoes. This system allows mosquitoes to choose between two different stimuli. The olfactometer is constructed of clear acrylic, comprises three test chambers in a tiered configuration, has paired removable sleeves, and mosquito traps on each chamber, and is equipped with a filtered external air supply system that allows precise temperature (+/- 0.5°C) and relative humidity (+/- 2%) control. Only one chamber at a time was used for the tests. Outside air was conditioned prior to entry through the choice ports, the mosquito trap, and the olfactometer by passing through a series of charcoal filters and then heated and humidified, if necessary.

One hour before initiation of tests, about 70 to about 93 female Ae. aegypti about 6-8day old mosquitoes were aspirated into the olfactometer chamber and allowed to acclimatize for that one hour before testing. Test compounds were placed into test ports upwind of the traps and olfactometer chamber. A completely randomized design was used for cage position.

Competitive tests were conducted. In these competitive tests, the inhibiting compound was placed into one of the ports (treatment port); the second port (check port) had the same apparatus but no chemical inhibiting compound. In these tests, 250 μL inhibiting compounds were presented in glass Pyrex petri dishes (60 x 15 mm) that had been cleaned and sterilized in a vacuum oven and then handled only with gloves to minimize any chance of contamination and placed into one port (Treatment Port) along with another petri dish containing 500 μL of Clara Sludge (CS), a synthetic human attractant. The other port (Check Port) contained an untreated petri dish with no inhibiting compound and a second petri dish containing 500 μL CS. A concentration of 250 μL of the test compounds were used in these tests. Each test was conducted for a period of 3 minutes; the number of mosquitoes trapped in the baited ports, and those remaining in the cage, were counted. The data are then presented as a percentage of total mosquitoes in the cage that were attracted to each port and the percentage of mosquitoes remaining in the cage (i.e., not attracted to either port).

Results of the competitive tests are set forth in the following Table 1. Table 1 Competitive Tests

With the foregoing description of the invention, those skilled in the art will appreciate that modifications may be made to the invention without departing from the spirit thereof. Therefore, it is not intended that the scope of the invention be limited to the specific embodiments illustrated and described.

Claims

WE CLAIM:

1. A method of inhibiting the ability of mosquitoes to sense a target by olfactory sensing of the target within a three dimensional environmental space having a land or base surface area, the method comprising dispensing into the atmosphere of the three dimensional environmental space an inhibiting effective amount of at least one inhibiting compound selected from the group consisting of esters of 1-alkene-3-ols of the formula:

and esters of 1-alkyn-3-ols of the formula:

wherein R is an alkyl group of from 1 to 4 carbon atoms, R¹ and R² are each independently a saturated or unsaturated aliphatic hydrocarbon group containing from 1 to about 12 carbon atoms, and R₃ is hydrogen or CH₃.

The method according to Claim 1 , wherein the inhibiting effective amount ranges from about 0.000005 g/hr/ft² to about 0.004 g/hr/ft² based on the square footage of the land or base surface area of the environmental space.

3. The method according to Claim 1 , wherein the inhibiting effective amount ranges from about 0.00015 g/hr/ft2 to about 0.0002 g/hr/ft² based on the square footage of the land or base surface area of the environmental space.

4. The method according to Claim 1 wherein R₃ is CH₃.

5. The method according to Claim 1 , wherein the at least one inhibiting compound is selected from the group consisting of formate and acetate esters of nerolidol, 3- methyl-1-octen-3-ol, linalool and dehydrolinalool.

6. The method according to Claim 1 , wherein the at least one inhibiting compound comprises a linalyl ester selected from the group consisting of linalyl acetate and linalyl formate and 1-octen-3-yl acetate.

7. The method according to Claim 1 , wherein the at least one inhibiting compound comprises linalyl acetate.

8. The method according to Claim 1 , wherein the dispensing of the at least one inhibiting compound comprises dispensing by a method selected from volatilization, evaporation, atomization and ionic dispersion of the at least one inhibiting compound from a formulation comprising a vehicle containing the at least one inhibiting compound.

9. The method according to Claim 8, wherein the dispensing comprises fan-driven evaporation of the at least one inhibiting compound from a formulation in which the vehicle is a porous medium.

10. The method according to Claim 8, wherein the dispensing comprises fan-driven evaporation of the at least one inhibiting compound from a formulation in which the vehicle is a waxy solution.

11. The method according to Claim 6, wherein the linalyl ester is dispensed by fan- driven evaporation of linalyl ester from a formulation of a porous medium containing linalyl ester.

12. The method according to Claim 6, wherein the linalyl ester is dispensed by fan- driven evaporation of linalyl ester from a formulation of a waxy solution containing linalyl ester.

13. The method according to Claim 6, wherein the linalyl ester is dispensed by atomization of linalyl ester from a formulation of a vehicle and linalyl ester.

14. The method according to Claim 6, wherein the linalyl ester is dispersed by ionic dispersion of linalyl ester from a formulation of a vehicle and linalyl ester.

15. A composition for inhibiting the ability of mosquitoes to sense a target by olfactory sensing of the target within a three dimensional environmental space having a land or base surface area, the composition comprising at least one inhibiting compound selected from the group consisting of esters of 1-alkene-3-ols, other than linalyl acetate, of the formula:

and esters of 1-alkyn-3-ols of the formula: R3

0 '

R— C -C≡CH

I O— C-R

II O

wherein R is an alkyl group of from 1 to 4 carbon atoms , R¹ and R² are each independently a saturated or unsaturated aliphatic hydrocarbon group containing from 1 to about 12 carbon atoms, and R₃ is hydrogen or CH₃ in a base formulation of a vehicle and the at least one inhibiting compound capable of permitting sufficient dispersion from the formulation of the at least one inhibiting compound by at least one of evaporation, volatilization, atomization or ionic dispersion sufficient to provide an inhibiting effective amount of said at least one inhibiting compound in an atmosphere of the three dimensional environmental space.

16. The composition according to Claim 15, wherein the composition is sufficient to provide an inhibiting effective amount of the at least one inhibiting compound ranging from about 0.000005 g/hr/ft² to about 0.004 g/hr/ft² per square footage of the land or base surface area of the three dimensional environmental space.

17. The composition according to Claim 15, wherein the composition is sufficient to provide an inhibiting effective amount of the at least one inhibiting compound ranging from about 0.00015 g/hr/ft2 to about 0.0002 g/hr/ft² per square footage of the land or base surface area of the three dimensional environmental space.

18. The composition according to Claim 15, wherein the at least one inhibiting compound is selected from the group consisting of esters of nerolidol, 3-methyl-1- octen-3-ol, linalool and dehydrolinalool.

19. The composition according to Claim 15, wherein the at least one inhibiting compound comprises a linalyl ester selected from the group consisting of linalyl formate and 1-octen-3-yl acetate.

20. The composition according to Claim 15, wherein the composition is able to dispense the at least one inhibiting compound by a method selected from volatilization, evaporation, atomization and ionic dispersion of the at least one inhibiting compound.

21. The composition according to Claim 15, wherein the composition is dispensable by fan-driven evaporation of the at least one inhibiting compound and the vehicle is a porous medium.

22. The composition according to Claim 15, wherein the composition is dispensable by fan-driven evaporation of the at least one inhibiting compound and the vehicle is a waxy solution.

23. The composition according to Claim 19, wherein the linalyl ester is dispensable by fan-driven evaporation of linalyl ester and the vehicle is of a porous medium containing linalyl ester.

24. The composition according to Claim 19, wherein the linalyl ester is dispensable by fan-driven evaporation of linalyl ester and the vehicle is of a waxy solution containing linalyl ester.

25. The composition according to Claim 19, wherein the linalyl ester is dispensable by atomization of the linalyl ester.

26. The composition according to Claim 19, wherein the linalyl ester is dispersible by ionic dispersion of the linalyl ester.