GB2207605A - Composition and method for deterring bloodsucking insects from bloodsucking - Google Patents

Abstract

A method for deterring bloodsucking insects from bloodsucking humans or animals comprises using 1-ethynyl-2-methyl-2-pentenyl chrysanthemate (I) as an effective ingredient. The active compound can also be used in combination with the conventional insect repellents. The bloodsucking prevention effect is durative. <IMAGE>

Description

METHOD FOR DETERRING BLOODSUCKING INSERTS FROM BLOODSUCKING The present invention relates to a method for preventing harm from bloodsucking insects which comprises using l-ethynyl-2-methyl-2-pentenyl chrysanthemate (hereinafter referred to as Compound [I]) represented by the formula:

alone or a combination of Compound [I] with at least one of known insect repellents.

Many insecticides are hitherto known. And, for preventing harm from bloodsucking insects, these insecticides are sprayed.

By spraying the insecticides, harm from blooksucking insects can be prevented to some extent.

However, bloodsucking insects transfer from place to place following humans, livestock, pets and the like as objectives to be injured, so that it is necessary to spray insecticides in all affected area. In particular, it is difficult to prevent plagues or harm from bloodsucking insects outdoors.

Furthermore, the use of known insect repellents is not necessarily guaranteed to be satisfactory for preventing plagues or harm, since their effectiveness is insufficient or the effective time period proves to be short, etc.

In view of such situations, the present inventors have made extensive investigations and as a result, have found that by using Compound [I] alone or Compound [I] in combination with at least one of known insect repellents, harm of human or animals such as livestock, pets, etc. can be effectively prevented from plagues or harm from bloodsucking insects over long periods of time, and the present invention has thus been reached.

Compound [I] is an insecticidal compound described in USP-4118505.

Examples of the conventional insect repellents include N,N-diethyl-m-toluamide, 2,3:4,5-bis(2-butylene)tetrahydro-2-furfural, di-n-propyl isocinchomeronate [described in Sine, C. et al., Farm Chemical Handbook C82, C170 and C171 (1987), respectively] , di-n-butyl succinate [described in Travis, B. et al., J. Econ.

Entomol., 44, 813 (1951), etc.] and the like.

As bloodsucking insects from which harm can effectively be prevented by the use of this composition, mention may be made of mosquitos such as Culex pipiens, Aedes aegypti, Anopheles hyrcanus sinensis, Aedes albopictus, Aedes togoi, etc.; fleas such as Pulex irritans, Ctenocephalides canis, Ctenocephalidae felis, etc.; bedbugs such as Cimex hemipterus, Cimex pipistrellit Cimex columbarius, Cimex lectularius, etc.; acarina such as Ornithonyssus bacoti, Ornithonyssus sylviarum, Trombicula akamushi, etc.; and bloodsucking flies such as stable flies, black -flies such as Simulium aoki, etc.; etc.

Compound [I] has optical isomers and steric isomers. In the present invention, these effective isomers can be used alone or as admixture thereof. Examples of Compound [I] include the following: Compound No. Compound (1) l-Ethynyl-2-methyl-2-pentenyl d,Q-cis,trans-chrysanthemate (2) 1-Ethnyl-2-methyl-2-pentenyl- d-cis ,trans-chrysanthemate (3) l-Ethynyl-2-methyl-2-pentenyl d-trans-chrysanthemate According to the present invention, Compound [I] alone or a mixture of Compound [I] and at least one of the conventional insect repellents can be used as a composition obtained by formulating them in an appropriate carrier (hereinafter referred to as the present composition), which is utilized by preparing into, for example, liquid forms such as a lotion, an aerosol, etc., an ointment form or the like.

Examples of carriers used to prepare liquid preparations include water; alcohols such as methanol, ethanol, glycerine, polyethylene glycol, etc.; ethers such as tetrahydrofuran, dioxan, etc.; aliphatic hydrocarbons such as hexane, kerosine, paraffin, petroleum benzine, etc.; esters such as ethyl acetate, etc.

The liquid preparation may further contain a conventional emulsifier or dispersing agent, a spreading or wetting agent, a suspending agent, a preservative, a propellant, etc. In addition, conventional film forming agents may also be formulated in the liquid preparation.

Specific examples of the film forming agent include emulsifiers such as soaps; polyoxyethylene fatty acid alcohol ethers such as polyoxyethylene oleyl ether, etc.; polyoxyethylene alkyl aryl ethers such as polyoxyethylene nonyl phenyl ether, etc.; polyoxyethylene fatty acid esters, fatty acid glycerides, sorbitan fatty acid esters, sulfates of higher alcohols; alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate, etc.

spreading or wetting agents such as glycerine, polyethylene glycol, etc.; suspending agents such as casein, gelatin, alginic acid, carboxymethyl cellulose, gum arabic, hydroxypropyl cellulose, bentonite, etc.; preservatives such as methyl p-oxybenzoate, ethyl poxybenzoate, propyl p-oxybenzoate, butyl p-oxybenzoate, etc.; propellants such as dimethyl ether, chlorofluorocarbon, carbon dioxide gas, etc.; and various film forming agents such as cellulose derivatives, e.g., nitro cellulose, acetyl cellulose, acetylbutyryl cellulose, methyl cellulose, etc., vinyl resins such as vinyl acetate resins, etc., polyvinyl alcohol, etc.

As carriers used to prepare ointments, mention may be made of a mixture of beewax and vegetable oil, a mixture of white wax and white vaseline, etc. Examples of the vegetable oils are soybean oil, sesame oil, etc.

In addition, after preparing the composition into a microcapsule form, the microcapsules may further be prepared into a lotion, an aerosol, etc.

The composition may also be formulated with a synergist, an antioxidant and other additives, etc.

Examples of the synergist include piperonyl butoxide, isobornyl thiocyanate, lethane, S-421, etc.

Examples of the antioxidant are butylhydroxyanisol, dibutylhydroxytoluene, tocopherol, y-oryzanol, etc.

The addition amount of these additives is not critical but it is appropriate to incorporate up to an amount of 10 times, generally 1/50 to 10 times amount of Compound [I]. As other additives, there may be illustrated volatile antiseptic or antimold agents or coloring agents or flavors, for example, PCMX, d-BCA, salicylic acid, benzoic acid, sorbic acid, l-oxy-3methyl-4-isopropylbenzene, OPP, hinokitiol, etc. It is appropriate that the volatile antiseptic or antimold agents described above be added generally in an addition amount up to 70%, preferably in a range of 0.1 to 50%, in preparation forms thereof.

Next, preparation examples are given.

Preparation Example 1 In polyethylene glycol are dissolved 0.5 parts of Compound [I] to make 50 parts as a whole. The solution is filled in an aerosol container. Then, after a bulb is mounted to the container, 50 parts of Flon 12 (propellant) is filled up under pressure through the bulb portion to give an oil aerosol.

Preparation Example 2 In 66.5 parts of soybean oil are dissolved 0.5 parts of Compound [I]. The solution is thoroughly mixed with 33 parts of beewax to give an ointment.

Preparation Example 3 One part of Compound [I] is mixed with 2 parts of oleic acid and 1.5 parts of Atmos 300 z (emulsifier containing glycerol monooleate as a main ingredient, trademark registered by Atlas Chemical Co., Ltd.) to give an oil phase stock solution. Next, the oil phase stock solution described above is gradually poured carefully onto an aqueous phase stock solution obtained by mixing 0.5 parts of triethanolamine and 95 parts of distilled water. The mixture is mixed until emulsification is completed to make a homogeneous solution. Thus, a lotion is obtained.

Preparation Example 4 In polyethylene glycol are dissolved 0.5 parts of Compound [I] and 5 parts of each of N,N-diethyl-n-toluamide, 2,3:4 ,5-bis(2-butylene) tetrahydro-2-furfural, di-npropyl isoincomeronate and di-n-butyl succinate to make 50 parts as a whole. The solution is filled in an aerosol container. Then, -after a bulb is mounted to the container, 50 parts of Flon 12 (propellant) is filled up under pressure through the bulb portion to give an oil aerosol.

Preparation Example 5 In 61.5 parts of soybean oil are dissolved 0.5 parts of Compound [I] and 5 parts of N,N-diethyl-ntoluamide. The solution is thoroughly mixed with 33 parts of beewax to give an ointment.

Preparation Example 6 One part of Compound [I] is mixed with 10 parts of N,N-diethyl-n-toluamide, 2 parts of oleic acid and 1.5 parts of Atmos 300 z (emulsifier containing glycerol monooleate as a main ingredient, trademark registered by Atlas Chemical Co., Ltd.) to give an oil phase stock solution. Next the oil phase stock solution described above is gradually poured carefully onto an aqueous phase stock solution obtained by mixing 0.5 part of triethanolamine and 85 parts of distilled water. The mixture is mixed until emulsification is completed to make a homogeneous solution. Thus, a lotion is obtained.

The composition thus prepared as described above can be applied directly to the skin, etc. Further, the composition may also be used, after the composition is previously treated by coating, dipping, kneading, dropping, etc. onto appropriate base materials of sheet-like, film-like, net-like, bandage-like, etc., by covering exposed areas of the skin or clothes with the base materials. As materials of the base materials, mention may be made of synthetic fibers or resins such as polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, polyester, Vinylon, Nylon, etc.; animal and plant fibers such as silk, cotton, wool, etc.; inorganic fibers such as aluminum, etc. or a mixture thereof.In the case of using net-like base materials, it is preferred to use nets having a fine mesh and in general, nets having 16 mesh or less are sufficiently effective.

The amount of Compound [I] in the composition varies depending upon preparation form or application mode. In the case of using as liquid preparation such as a lotion, an aerosol, etc. or an ointment, etc., or in the case of incorporating into base materials, the amount of Compound [I] is 0.01 to 10 wt%, preferably 0.1 to 2 wt%.

An amount of the composition used for treatment is generally 0.04 mg or more, preferably 0.04 to 0.4 mg, per 1 cm of the skin area, when calculated as Compound [I] .

In case that Compound [I] is used as admixture with the conventional insect repellent, the formulating ratio of the conventional insect repellent such as N,Ndiethyl-m-toluamide, etc. to Compound [I] ranges from 1:1 to 99:1, preferably 4:1 to 19:1.

In this case, the amount of the composition used for treatment is generally 0.04 mg or more, preferably 0.04 to 0.4 mg, per 1 cm2 of area of the skin, when calculated as Compound [I]. The amount of the conven- tional insect repellent varies naturally depending upon the kind of Compound [I] but generally 0.04 mg or more, 2 preferably 0.04 to 0.76 mg, per 1 cm of the skin area.

Next, test examples are shown. Compound [I] used in the following tests is Compound No. (2) wherein a ratio of cis to trans is 2 : 8.

Test Example 1 In a glass tube of 4 cm in diameter and 12 cm in length, 20 female adult mosquitos (Anopheles stephansi) were released. Both ends of the glass tube were covered with nylon nets of 16 mesh. On the other hand, fur on the back of a rabbit (8 months after birth) was shaved off and several circles each having 4 cm in diameter were drawn there. A solution, 0.2 ml each, obtained by diluting Compound [I] or N,N-diethyl-m-toluamide with ethanol in a prescribed concentration was applied to the portion enclosed by the circle drawn on the back of the rabbit.

Two hours and 6 hours after the application, one end of the glass tube in which the mosquitos (Anopheles stephansi) described above had been released was brought into contact with the portion enclosed by the circle. One minute after, the number (A) of test mosquitos on the skin which were bloodsucking was counted and 3 minutes after, the number of mosquitos (B) whose abdomen was changed red by bloodsucking was counted. For the control, similar test was performed with the area applied with 0.2 ml of ethanol alone. The repellency rate and bloodsucking prevention rate were determined according to the equations defined below. Based on the test result of the control, the corrected repellency rate and corrected bloodsucking prevention rate were determined by applying to Abbott's correction equation. Table 1 shows the results.

Repellency = 100 - A x 100 rate (%) 100 Number of all mosquitos tested Bloodsucking pre- = 100 - B x 100 invention rate (%) 100 Number of all mosquitos tested Table 1

2 Hours After 6 Hours after Chemical Tested and Concentra- Corrected Corrected Corrected Corrected tion Repellency Bloodsucking Repellency Bloodsucking Rate Prevenion Rate Rate Prevention Rate 0.5% 57 96 28 78 Compound 1.0% 70 94 54 85 [I] : 2.0% 57 100 67 91 N, N-Diethyl- 2.5% 83 75 4 31 m-toluamide : 10% 100 100 32 39 Table 1 clearly demonstrates that the composition possessed not only an insect repellent properties but also properties that should be termed a bloodsucking prevention agent. The composition also possessed a characteristic that the effectiveness is maintained particularly over a long period of time.

Test Example 2 A Nylon net (25 x 25 cm2) of 16 mesh was dipped in 1% ethanol solution of Compound [11 for 5 minutes.

The bloodsucking prevention effect of the net was examined 1, 4 and 7 hours after the treatment as follows.

In a glass tube of 4 cm in diameter and 12 cm in length, 10 female adult mosquitos (Aedes aegypti) were released.

The upper part of the glass tube was covered with a gauze and the open lower end was brought into contact with a human arm through the above-described net placed thereon. A time period was measured from the mosquito's selecting a stinging area, remaining still over that area and shifting to a bloodsucking pose through the net. The test was repeated three times. Table 2 shows the results.

Table 2 clearly demonstrates that no mosquito showed bloodsucking pose within 5 minutes and the bloodsucking prevention rate was 100%.

Table 2

1 Hour After 4 Hours After 7 Hours After Repetition No. 1 2 3 1 2 3 1 2 3 more more more more more more more more more Treated with than than than than than than than than than Compound [I] 5 5 5 5 5 5 5 5 5 mins. mins. mins. mins. mins. mins. mins. mins. mins.

Intact 31 17 22 21 20 8 36 30 37 secs. secs. secs. secs. secs. secs. secs. secs. secs.

Test Example 3 An aerosol containing 1 part of Compound [I], 5 parts of N,N-diethyl-m-toluamide or 10 parts of N,N-diethyl-m-toluamide as effective ingredients was intermittently sprayed for about 5 seconds between the knee and the malleolus of a volunteer's left leg, at a distance of 10 to 15 cm apart from the skin. After spraying, the sprayed region was rubber with both hands to uniformly spread the chemical.

After standing for a prescribed ime period bloodsucking of flies (Simulium aoki) was observed with.

the right leg as a control. Two hours after spraying, observation was made again in the same manner. The bloodsucking prevention rate was determined by the following equation.

Number of bloodsucking flies at the treated Bloodsucking pre- = 100 - region vention rate (%) Number of bloodsucklr.g flies at the intact region The aerosol used in this test was prepared by dissolving the effective ingredients in 1,1,1trichloroethane in ó0 wt% and filling Flon 12 in 4 wt% under pressure.

Table 3 shows the results.

Table 3

. Bloodsucking Prevention Aerosol Preparation Rate (%) Immediately 2 Hours Effective Ingredient wtt After Treatment After N,N-Diethyl-m-toluamide 10 100 56 (volunteer A) Compound tI]/N,N-Diethyl- 1/5 100 100 m-toluamide (volunteer B) Table 3 demonstrates that both ingredients gave excellent bloodsucking prevention effects immediately after the spraying; however, about 2 hours after the spraying, the effect of the aerosol containing 10 parts of N,N-diethyl-m-toluamide was already greatly reduced.

On the other hand, the combined aerosol containing 1 part of Compound [I] and 5 parts of N,N-diethyl-m-toluamide showed an excellent bloodsucking prevention effect equal to the effect immediately after the spraying.

Test Example 4 An aerosol containing 1 part of Compound Zit 5 parts of N,N-diethyl-m-toluamide, 1 part of Compound [I] and 5 parts of N,N-diethyl-m-toluamide, 0.5 part of Compound [I] and 5 parts of N,N-diethyl-m-toluamide or 0.25 parts of Compound [I] and 5 parts of N,N-diethyl-m-toluamide, as effective ingredients, respectively, was intermittently sprayed for about 6 seconds between the knee and the malleolus of a volunteer's left leg, at a distance of 10 to 15 cm apart from the skin. After spraying, the sprayed region was rubbed with both hands to uniformly spread the chemical.

After about 100 female adult mosquitos (Aedes albopictus) were released in a large room (3 x 4x2.5 m3), bloodsucking of the mosquitos was observed for 20 minutes in the large rocm with the right leg as a control. Four hours after the spraying, observation was made in the same manner.

The aerosol used in this test was prepared by dissolving the effective ingredients in isopropanol in 60 wt% and filling LPG gas in 40 wt% under pressure.

Number o bloodsucking Bloosucking mosquitos at the treated prevention = 100 - ###### ## ############ x 100 rate ######### ## ### ###### region Table 4 shows the results.

Table 4

Aerosol Preparation Bloodsucking Prevention Rate (%) Immediately 4 Hours Effective Ingredient wt% After After Spraying Compound [I] 1 100 33 N, N-Diethyl-m-toluamide 5 100 60 Compound [I]/N,N Diethyl-m-toluamide 0.25/5 100 100 Compound [I]/N,N Diethyl-m-toluamide 0.5/5 100 100 Compound [I]/N,N Diethyl-m-toluamide 1/5 100 100 Table 4 demonstrates that both ingredients showed excellent bloodsucking prevention effect immediately after the spraying; however, about 4 hours after the spraying, the effect of the aerosol containing 1 part of Compound [I] and 5 parts of N,N-diethyl-mtoluamide was already greatly reduced. On the other hand, the combined aerosol containing 1 part of Compound [I] and 5 parts of N,N-diethyl-m-toluamide showed an excellent bloodsucking prevention effect equal to the effect immediately after the spraying.

Claims (15)

1. Use, for deterring bloodsucking insects from bloodsucking a human or animal, of a composition comprising a compound represented by the formula:

and a carrier.

2. Use according to Claim 1, wherein the composition additionally comprises at least one known insect repellent.

3. Use according to Claim 2, wherein the said known insect repellent is selected from N,N-diethyl-m-toluamide, 2,3:4,5bis(2-butylene)-tetrahydro-2-furfural, di-n-propyl isocianchomaeronate and di-n-butyl succinate.

4. Use according to Claim 3, wherein the said known insect repellent is N, N-diethyl-m-toluamide.

5. Use according to Claim 2, wherein the mixing ratio of the compound of the formula (I] to the known insect repellent is from 50 : 1 to 1 : 10.

6. Use according to Claim 1 or 2, wherein said composition is a liquid preparation or an ointment.

7. Use according to Claim 1 or 2, wherein said composition is applied to the skin.

8. Use according to Claim 1 or 2, wherein the skin is covered with a base material treated with said composition.

9. Use according to Claim 8, wherein the base material is clothing.

10. Use according to Claim 8, wherein the base material is a material covering exposed areas of clothing.

11. A method for treating the skin of a human or animal, or a material covering areas of skin otherwise exposed to attack by insects, in order to deter bloodsucking insects from bloodsucking, which method comprises administering to the skin or the said material a composition comprising a compound of the formula (I), given and defined in Claim 1, and a carrier.

12. A composition comprising a compound of the formula [I], given and defined in Claim 1, and a carrier for use in deterring bloodsucking insects for bloodsucking a human or animal.

13. A composition capable of deterring bloodsucking insects from bloodsucking a human or animal, which composition comprises a compound of the formula (I], given and defined in Claim 1, and a dermatologically acceptable carrier.

14. A composition according to Claim 13, which is an ointment or a lotion.

15. Use, for deterring bloodsucking insects from bloodsucking a human or animal, of a compound of the formula (I], given and defined in Claim 1.