FR2618671A1 - PROCESS FOR THE PREVENTIVE FIGHT AGAINST NUISANCE OF BLOOD SUCKING INSECTS - Google Patents

Abstract

A method of avoiding nuisance or sting from blood-sucking insects, which includes the use of 1-ethynyl-2-methyl-2-penten-2-yl chrysanthemum as the active ingredient. The active compound can also be used in combination with conventional insect repellants. The preventive effect of sucking blood is lasting.

Description

Preventive control against nuisance insects

  The present invention relates to a method of prevention against the harmful action of blood-sucking insects. said process comprising the use of chrysanthemate of ethynyl-1 methyl-2 penten-2 yle (hereinafter designated by Compose II]). represented by the formula C H

HC = C -3 C = C H

CH3 CH3

  5. alone. or a combination of Compose 1 [1 with at least one known insect repellant agent. Many insecticide agents are known for combating blood-sucking insects. these insecticide agents are used in spraying By spraying insecticide agents. the action of blood-sucking insects can be prevented to some extent. However, blood-sucking insects move from place to place to follow humans, cattle. domestic animals and others as targets to attack. so it is necessary to spray insecticidal agents in all affected areas. In particular, it is difficult to prevent bites or harmful insects

blood suckers outdoors.

  Furthermore. the use of known insect repellant agents is not necessarily satisfactory in order to avoid stings and nuisances. because their effectiveness is insufficient or the duration of their effectiveness turns out to be short, etc. Given this state of affairs, the present inventors have carried out in-depth research and have discovered that by using the Compound [II alone or in combination with at least one of the known insect repellants. the bites or nuisances of blood-sucking insects on humans and animals such as cattle can be effectively avoided. domestic animals, etc., for extended periods of time, and thus they have resulted in the present invention

  Compose 111 is an insecticidal compound described in patent US-4 IS 505.

  Examples of conventional insect repellents include N. Ndiethyl-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 .. Econ Entomol .. 44 813 (1951, etc 1 and other elms blood-sucking insects, the nuisance of which can be effectively prevented. We can mention mosquitoes such as Culex piopiens Aedes aeyvpti, Anopheles hyrcanus sinensis. Aedes albopictus Aedes togoi, etc. ,; flies such as Pulex irritans, Ctenoceohalides canis, Ctenocephalidae felis etc .; bedbugs such as Cimex hemipterus, Cimex pipistrelli, Cimex columbarius Cimex lectularius etc .; acarinas such as OrnithonYssu bacoti Ornithonyssus sylviarum, etc .; and blood-sucking flies such as stable flies, black flies such as Simulium aoki, etc. etc. Compose [I] has optical isomers and steric isomers. In the present invention, these active isomers may be used alone or in admixture with one another Examples of Compound II include the following compounds: Compound n Compound (1) d, l-cis, trans-chrysanthemate ethynyl- 1 methy l-2 pentén-2 yle (2) d-cis, trans-chrysanthemate of ethynyl-l methyl-2 pentén-2 yle - (3) d-trans-chrysanthemate of ethynyl-l methyl-2 pentén-2 yle In accordance with the present invention, the Compound [I] alone or in mixture with at least one of the conventional insect repellant agents can be used in the form of a composition obtained by formulation with an appropriate support (hereinafter designated by the present composition). which is used in preparation for example in liquid form such as a lotion, an aerosol. etc. .. an ointment or other. Examples of carriers used to prepare liquid preparations include water; alcohols such as methanol. ethanol. glycerin. polyethylene glycol, etc .; ethers such as tetrahydrofuran. dioxane etc .:

  aliphatic hydrocarbons such as hexane. kerosene, paraffin.

  petroleum ether. etc .: esters such as ethyl acetate. etc. The liquid preparation can also contain a conventional emulsifying or dispersing agent. a spraying agent or a wetting agent. a suspending agent. a preservative, a propellant, etc. In addition, conventional film-forming agents can also be formulated in liquid preparation. Specific examples of film-forming agents include emulsifiers such as soaps; polyoxyethylene fatty acid alcohol ethers such as polyoxyethylene oleyl ether. etc: alkyl aryl

  polyoxyethylene ethers such as nonyl phenyl ether of polyoxyethylene.

  etc .: polyoxyethylene fatty acid esters. fatty acid glycerides. sorbitan fatty acid esters. sulfates of higher alcohols; alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate. etc .: agents

  spreading agents or wetting agents such as glycerin. polyethylene glycol.

  etc .; suspending agents such as casein, gelatin, alginic acid. carboxymethylcellulose, gum arabic, hydroxypropyl cellulose, bentonite, etc .; preservatives such as methyl poxybenzoate,

  ethyl p-oxybenzoate. propyl p-oxybenzoate. butyl p-oxybenzoate.

  etc .; propellants such as dimethyl ether, a fluoro chlorine hydrocarbon. carbon dioxide, etc .; and various film-forming agents such as cellulose derivatives, for example nitrocellulose, acetylcellulose, acetylbutyryl cellulose, methylcellulose, etc .: vinyl resins such as vinyl acetate, etc .; polyvinyl alcohol, etc. As a support for the preparation of ointments, there may be mentioned a mixture of beeswax and a vegetable oil, a mixture of white wax and petrolatum

  white. etc. Examples of vegetable oils are soybean oil. sesame oil.

etc.

  Furthermore. after preparation of the composition in the form of microcapsules.

  these can be further transformed into a lotion, aerosol. etc. The composition can also be formulated with a synergy-enhancing agent, an antioxidant and other additives, etc. Examples of synergistic agents are piperonyl butoxide, isobornyl thiocyanate, lethane. S-421. etc. Examples of antioxidants are butylhydroxyanisol, dibutylhydroxytoluene. tocopherol, yoryzanol, etc. The added amount of these additives is not critical. but it is recommended to incorporate up to 10 times, generally 1/50 to 10 times, the amount of Compose 111 as other additives. there may be mentioned volatile antiseptic or anti-mold agents or coloring agents or flavors. for example the PCMX. d-BCA. salicylic acid. benzolque acid. sorbic acid. oxy-l methyl-3 isopropyl-4 benzene. The OPP. Hinokitiol. etc. It is recommended that the antiseptic or anti-mold agents described above are generally added in an amount of up to 70%, preferably in the range of 0.1 to

%. in preparative forms.

  Examples of preparation will be described below Example I of preparation In polyethylene glycol, 0.5 part of Compound 111 is dissolved to arrive

  in total 50 games. The solution is introduced into an aerosol container.

  Then, after a tank is mounted on the container, 50 parts of Freon 12 (propellant) are introduced under pressure through the tank part to

give an oily aerosol.

  Preparation Example 2 In 66.5 parts of soybean oil, 0.5 parts of Compound [II. The solution is mixed vigorously with 33 parts of beeswax to

produce an ointment.

  Preparation Example 3 A part of Compound [I] is mixed with 2 parts of oleic acid and 1.5 parts of Atmos 3000 (emulsifier containing glycerol monooleate as main ingredient. Trademark registered by Atlas Chemical Co., Ltd. ) to give an oily phase reserve solution Then. the oily phase reserve solution described above is gradually and carefully poured onto an aqueous phase reserve solution obtained by mixing 0.5 part of triethanolamine and X parts of distilled water. The mixture is stirred until complete emulsification to produce a homogeneous solution. We thus obtain

a lotion.

  Example 4 of separation In polyethylene glycol. 0.5 part of Compose 111I and 5 parts are dissolved

  each of N.N-diethyl-n-toluamide, 2.3. 4,5-bis (2-butylene) -

  tetrahydro-2-furfural, di-n-propyl isocinchomeronate and di-n-butyl succinate, so as to give 50 parts in total. The solution is introduced into

  an aerosol container. Then after a tank is mounted on the container.

  Freon 12 (thruster) parts are introduced under pressure through the

  part of tank to give an oily aerosol.

  Preparation Example 5 In 61.5 parts of soybean oil, 0. 5 parts of Compound [I] and 5 parts of N.N-diethyl-n-toluamide are dissolved. The solution is stirred vigorously with 33 parts

  beeswax to get 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 15 parts of Atmos 300 (emulsifier containing glycerol monooleate as main ingredient , registered trademark by Atlas Chemical Co., Ltd.) to give an oily phase reserve solution. Then, the oily phase reserve solution described above is gradually and carefully poured onto an aqueous phase reserve solution obtained by mixing 0.5 part of triethanolamine and parts of distilled water. The mixture is stirred until complete emulsification

  to produce a homogeneous solution. This gives a lotion.

  The composition thus prepared and described above can be applied directly to the skin, etc. In addition, the composition can also be used, after having been treated by coating, immersion, kneading. draining, etc., of suitable base materials of the sheet, film type. net, bandage, etc., covering exposed areas of skin or clothing with base materials. As basic materials, mention may be made of - fibers or resins

26 18671

  b synthetics such as polyethylene, polypropylene, polyvinyl chloride. polyvinylidene chloride. polyester. Vinylon, Nylon. etc .; animal and vegetable fibers such as silk. cotton, wool. etc .; inorganic fibers such as aluminum. etc., or a mixture of these products. In the case where basic materials of the net type are used. it is preferable to use fine mesh nets and in general nets with a mesh opening of 16

  or less are effective enough.

  The amount of Compose 111 in the composition varies depending on the form of preparation or the mode of application. When using a liquid preparation such as a lotion, an aerosol, etc. or an ointment, etc., or when incorporated into basic materials. the amount of Compose [It is 0.01 to

  % in weight. preferably 0.1 to 2% by weight.

  The amount of composition used for the treatment is generally 0.04 mg or more, preferably 0.04 to 0.4 mg, for I cm2 of the surface of the skin, calculated as Compound [I1 When Compound [l] is used in combination with a conventional insect repellant. the formulation ratio of the conventional insect repellant such as, for example, N, N-diethyl-m-toluamide, etc. aul Compound [It is in the range of I1 1 to 99: 1. preferably 4: 1 to 19 1 In this case, the amount of composition used for treatment is generally 0.04 mg or more, preferably 0.04 to 0.4 mg, for I cm2 of the surface of the skin, calculated as Compound [II. The amount of conventional insect repellant naturally varies depending on the type of Compose [II], but generally it is 0.04 mg or more, preferably 0.04 to 0.76 mg, for I cm2 of the surface of the skin Test examples will be shown below. Compound [II used in the following test examples is Compound n '(2) in which the ratio of cis to trans is 2: 8 Example I of test In a glass tube 4 cm in diameter and 12 cm long, 20 adult female mosquitoes (Anooheles steohansi) were released. The two ends of the

  glass were covered with nylon nets having a mesh opening of 16.

  On the other hand, the back of a rabbit was shaved (8 months after birth) and several circles, each 4 cm in diameter, were drawn there. A solution, 0.2 ml each, obtained by diluting Compound 111 or N, N-diethyl-m-toluamide with

261 867 1

  ethanol in a prescribed concentration, was applied to the part surrounded by the circle drawn on the back of the rabbit Two hours and six hours after application, an extramite from the glass tube in which the mosquitoes described above ( Anooheles steohansi) were released, was put in contact with the part included in the circle A minute later, the number (A) of mosquitoes on the skin sucking blood was counted, and 3 minutes later, we counted the number of mosquitoes whose abdomen became red from sucked blood. As a control, a similar test was carried out on the area having received only the application of 0.2 ml of ethanol. The repulsion rate and the rate of prevention of blood suction were determined according to the defined equations. below. Based on control test results, repulsion rates and prevention of blood sucking rates

  Corrected were determined by applying the Abboti correction equation.

  Table I collates the Ax 100 results

Repulsion rate (%) = 100 -

  number of all mosquitoes tested Prevention rate of B x-

blood suction (%) = 100 -

  number of all mosquitoes tested

TABLE 1

2 hrs after 6 hrs

I -

  Chemical product.tdr Prevention rate- Response rate Prevention rate

  tests and its puCsion tion of suction suction of tion cora concentration corrected blood corrected blood

0.5% 57 96 28 78

ornposà1, 0% 70 94 54 85 [I]:

2.0% 57 100 67 91

NN-dithy-2 5% 83 75 4 31

N, N- dithyl-

  m-toluamide: 10% 100 100 32 39 ce Table I clearly shows that the composition possesses not only repellent properties with respect to insects, but also properties which can be attributed to a blood suction prevention agent. . The composition also has efficacy characteristics which are maintained for a long period of time. Exemole 2 for testing nylon thread linen (25 x 25 cm2) having a mesh opening of 16. has been

  immersed in a 1% solution of Compound [II in ethanol for 5 minutes.

  The prevention effect of the net against sucking blood was examined 1, 4 and 7 hours after treatment. as follows. In a glass tube 4 cm in diameter and 12 cm long. 10 adult female mosquitoes (Aedes aegvoti) were released. The upper part of the glass tube was covered with gauze and the open lower end was brought into contact with a human arm, through the net described above which was placed on the arm. The duration of selection was measured. by the mosquito from a bite area. the length of time he stayed in this area and the length of time he moved to a suction position through the net. The test was repeated three times Table 2 brings together the results Table 2 clearly shows that no mosquito maintained a sucking position within 5 minutes and that the prevention rate of blood sucking was

2) 0 of 100%.

TABLE 2

  * Reptii 1 hour after 4 hours after 7 hours after No. 1 2 3 1 2 3 1 2 3 More More More More More More More More More More Composed of 5 of 5 of 5 of 5 of 5 of 5 of 5 of 5 of 5

  OmpOSe <p? mii in u- min nu- mi nu- - inu- i nu- ì nu- "inu-

s are your your your your your your

31 17 22 21 20 8 36 30 37

Intact

  dry. dry. dry. dry. dry. dry. dry. dry. dry.

  o -.4 I1 Example 3 of an test An aerosol containing I part of Compose [I] 5 parts of NN-diethyl-m-toluamide or 10 parts of NN-diethyl-mtoluamide as active ingredients was sprayed intermittently for approximately 5 seconds between the knee and ankle of the left leg of a volunteer, at a distance of 15 cm from the skin. After spraying, the sprayed area was rubbed

  with both hands to distribute the chemical evenly.

  After a rest of predetermined duration. blood sucking from flies (Simulium aolki) was observed, the right leg serving as a control. Two hours after spraying, the observation was made in the same way. The rate

  The prevention of suction has been determined by the following equation.

  number of blood sucking flies Prevention rate of on the treated area blood sucking (o) = 100 x100 number of blood sucking flies on the virgin treatment area The aerosol used in this test was prepared by dissolving the active ingredients in trichloro- 1, l, lethane in a proportion of 60% by weight and introduction of Freon 12 to 40% by weight under pressure

  The results are collated in Table 3.

Table 3

  Aerosol preparation Suction prevention rate (%) active ingredient% by weight Immediately Two hours after treatment after voluntary N.N-diethylmetoluamide A) 10 100 56

Compound II / N.N-diethyl-

  -toluamide (voluntary B) 1/5 100 100 2 61867 l Table 3 shows that the two ingredients have an excellent preventive action for sucking blood immediately after spraying; however, approximately 2 hours after spraying. the action of the aerosol containing 10 parts

  N.N-diethyl-m-toluamide was already significantly reduced.

  On the other hand. the combined aerosol containing I part of Compose [1] l and 5 parts of N.N-diethyl-m-toluamide has an excellent preventive action against

  blood sucking, equivalent to the action immediately after spraying.

  Test example 4 Aerosols containing (i) I part of Compose 111, (ii) 5 parts of NN-diethyl-m-toluamide. (iii) I part of Compose [I] and 5 parts of N.N-diethyl-m-toluamide. (iv) 0.5 part of Compose [1] and 5 parts of N.N-diethyl-m-toluamide. and (v) 0.25 part of Compound I1] and 5 parts of N.N-diethyl-m-toluamide, as active ingredients. respectively. were sprayed intermittently for approximately 6 seconds between the knee and ankle of the volunteers' left leg, at a distance of approximately 10 to 15 cm from the skin. After spraying. the sprayed area was rubbed with both hands to spread the chemical evenly After approximately 100 adult female mosquitoes (Aedes albopictus) were released in a large room (3 x 4 x 2.5 m3). mosquito blood sucking was observed for 20 minutes in the large room. the right leg serving as a witness. Four hours after spraying, the observation was carried out in the same way. The aerosols used in this test were prepared by dissolving the active ingredients in isopropanol in a proportion of 60% by weight. and

  introduction of LPG gas in a proportion of 40% by weight under pressure.

  number of mosquitoes sucking blood Prevention rate of on the treated area the sucking of blood = 100 1 100 number of mosquitoes sucking blood on the virgin area of treatment

  The results are collated in Table 4.

Table 4

  Aerosol preparation Suction prevention rate (%) of the blood Active ingredient% by weight Immediately 4 hours after spraying after Compound [Il I 100 33 N, N-diethyl-m-toluamide 5 10t 60

Compose [I] / N.N-diethyl-

m-toluamide 0.25 / 5 100 100

Compound [I] f N.N-diethyl-

m-toluamide 0.5 / 5 100 100

Compound 111 i N, N-diethyl-

  m-toluamide 1/5 100 100l Table 4 shows that the two ingredients have an excellent action

  preventive of blood sucking immediately after spraying: however.

  about 4 hours after spraying. the effect of aerosols containing either I part

  of Compound [It is 5 parts of N, N-diethyl-m-toluamide was markedly reduced.

  On the other hand, the combined aerosol containing I part of Compound [I] and 5 parts of N, N-diethyl-m-toluamide had an excellent suction prevention effect

  blood, equivalent to that immediately after spraying.

Claims (8)

  1. Method for preventing the nuisance of blood-sucking insects. which comprises the use of a composition comprising a compound represented by the formula: CH H CH3 C2H5 \ / CH3 O H / \ CH-OC-CH-CH / CH3 [I] CC HCt f / \ HC CH3 CH   and a support 2 Method for preventing the nuisance of blood sucking insects which comprises the use of a composition comprising a compound represented by the formula C H H CH 2 5 \ / CH3 o / 3 \ CH-OC-CH-CH CH3 X / CH3 [1 HCc HC '/ C CH3 CH3 3 3   at least one known insect repellant and one support.   3. The method of claim 2. wherein said insect repellant is selected from the group consisting of N, N-diethyl-mtoluamide, 2,3: -bis (2-butylene) -tetrahydro-2-furfural , di-n-propyl isocinchomeronate or di-n-butyl succinate.   4. The method of claim 3, wherein said insect repellant is N, N-diethyl-m-toluamide.   5. The method of claim 2, wherein the mixing ratio of   compound of formula [III the known insect repellant is 50: 1 to: 10.   - 6. Method according to claim I or 2. wherein said composition is a liquid preparation or ointment.   7. Method according to claim 1 or 2. wherein said composition is applied to the skin 8. Method according to claim I or 2. wherein the skin is covered with a   base material treated with said composition.