AU610906B2 - Method for preventing harm from bloodsucking insects - Google Patents

Description

ii 4

AUSTRALJIA

PATENTS ACT 2952 COMPLETE SPECIFICATION Form

(ORIGINAL)

FOR OFFICE USE Short Title: Int. Cl: Application Number: Lodged: 610906 a 0* Complete Specification-Lodged: Accepted: Lapsed: Published: Priority: Related Art: TO BE COMPLETED BY APPLICANT Name of Applicant: Address of Applicant: SUMITOMO CHEMICAL COMPANY,

LIMITED

15,

HIGASHI-KU

OSAKA

JAPAN

Actual Inventor: Address for Service: GRIFFITH HACK CO., 601 St. Kilda Road, Melbourne, Victoria 3004, Australia.

Complete Specification for the invention entitled: METHOD FOR PREVENTING HARM FROM BLOODSUCKING INSECTS The following statement is a full description of this invention including the best method of performing it known to me:-

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i t a 1 The present invention relates to a method for preventing harm from bloodsucking insects which comprises using 1-ethynyl-2-methyl-2-pentenyl chrysanthemate (hereinafter referred to as Compound Ye 5 represented by the formula: 0 C25\ CH 3 0 H CH 3 SH/CC\c 3 ,H CH-OC-CH-CH CH [I] C 3 HC CH CH 3 3 0 00 0 0 a o0 o' 0 alone or a combination of Compound with at least o one of known insect repellents.

Many insecticides are hitherto known. And, o00. for preventing harm from bloodsucking insects, these o0e S 0 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 reellents is not necessarily guaranteed to be satisfactory for 2 2 iLA

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rl 1 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 alone or Compound in combination with at least one of known insect repellents, harm of human or animals such as liveco0 0 stock, pets, etc. can be effectively prevented from 0 0 °o 10 plagues or harm from bloodsucking insects over long °o periods of time, and the present invention has thus been reached.

Compound is an insecticidal compound described in USP-4118505.

o oo 15 Examples of the conventional insect repellents o 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 0, 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 pipistrelli, Cimex columbarius, Cimex lectularius, etc.; acarina such 3 i I SIt 1 as Ornithonyssus bacoti, Ornithonyssus sylviarum, Trombicula akamushi, etc.; and bloodsucking flies such as stable flies, black flies such .as Simulium aoki, etc.; etc.

Compound has optical isomers and steric isomers. In the present invention, these effective isomers can be used alone or as admixture thereof. Examples of Compound include the following: Compound No. Compound 0 l-Ethynyl-2-methyl-2-pentenyl- S' 10 d,£-cis,trans-chrysanthemate l-Ethynyl-2-methyl-2-pentenylt d-cis,trans-chrysanthemate l-Ethynyl-2-methyl-2-pentenyld-trans-chrysanthemate o oo o 00 1 0 oo0 0 00 *o 15 According to the present invention, Compound alone or a mixture of Compound and at least 0 000 one of the conventional insect repellents can be used as oo0. a composition obtained by formulating them in an ooo I Soo appropriate carrier (hereinafter referred to as the o 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.

-4 J 1 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 0os. include emulsifiers such as soaps; polyoxyethylene fatty 0 0.°0 acid alcohol ethers such as polyoxyethylene oleyl ether, 0 0 10 etc.; polyoxyethylene alkyl aryl ethers such as polyoxy- S 0oo 0 0o ethylene nonyl phenyl ether, etc.; polyoxyethylene Q 0 0"",00 fatty acid esters, fatty acid glycerides, sorbitan fatty acid esters, sulfates of higher alcohols; alkyl aryl 0oo" sulfonates such as sodium dodecylbenzene sulfonate, etc.; °C0 15 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.; 0000 oo o 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, 1 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.

6oV Examples of the synergist include piperonyl 0900 00. 0 butoxide, isobornyl thiocyanate, lethane, S-421, etc.

0 9 10 Examples of the antioxidant are butylhydroxyanisol, dibutylhydroxytoluene, tocopherol, y-oryzanol, etc.

ine 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 o o' 15 of Compound As other additives, there may be o 0 illustrated volatile antiseptic or antimold agents or coloring agents or flavors, for example, PCMX, d-BCA, 00 salicylic acid, benzoic acid, sorbic acid, l-oxy-3- 000 o0. methyl-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 in preparation forms thereof.

Next, preparation examples are given.

Preparation Example 1 In polyethylene glycol are dissolved 0.5 parts of Compound to make 50 parts as a whole. The -6 PoI 1 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 .oo 0.5 parts of Compound The solution is thoroughly b o 0oo°,, mixed with 33 parts of beewax to give an ointment.

o q o r 0 Preparation Example 3 One part of Compound is mixed with 2 parts of oleic acid and 1.5 parts of Atmos 300® (emulsifier 0°o containing glycerol monooleate as a main ingredient, 0o00 trademark registered by Atlas Chemical Co., Ltd.) to o 0 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 0-0 Oo 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 and 5 parts of each of N,N-diethyl-n-toluamide, 2,3:4,5-bis(2-butylene)tetrahydro-2-furfural, di-npropyl isoincomeronatt and di-n-butyl succinate to make parts as a whole. The solution is filled in an aerosol 7 1 container. Then, after a bulb is mounted to the container, parts of Flon 12 (propellant) is filled up under pressure through the bulb portion to give an oil aerosol.

Preparation Example In 61.5 parts of soybean oil are dissolved parts of Compound and 5 parts of N,N-diethyl-naosa toluamide. The solution is thoroughly mixed with 33 00 oparts of beewax to give an ointment.

oo 00 o 04 0 Sr on Preparation Example 6 10 One part of Compound is mixed with parts of N,N-diethyl-n-toluamide, 2 parts of oleic acid oo and 1.5 parts of Atmos 3 00 (emulsifier containing o 00 0oo 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 00,0 solution described above is gradually poured carefully 0 o BO o onto an aqueous phase stock solution obtained by mixing 0 00 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, i dropping, etc. onto appropriate base materials of 8 1 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, t 10 it is preferred to use nets having a fine mesh and in 000 "general, nets having 16 mesh or less are sufficiently 0006 effective.

The amount of Compound in the composition 0 00 varies depending upon preparation form or application oo0 15 mode. In the case of using as liquid preparation such as boo a lotion, an aerosol, etc. or an ointment, etc., or in o oa the case of incorporating into base materials, the amount of Compound is 0.01 to 10 wt%, preferably 0.1 IS to 2 wt%.

An amount of the composition used 'or treatment I is generally 0.04 mg or more, preferably 0.04 to 0.4 mg, per 1 cm 2 of the skin area, when calculated as Compound In case that Compound is used as admixture with the conventional insect repellent, the formulating ratio of the conventional insect repellent such as N,N- i diethyl-m-toluamide, etc. to Compound ranges from i 1:1 to 99:1, preferably 4:1 to 19:1. I 9 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 cm 2 of area of the skin, when calculated as Compound The amount of the conventional insect repellent varies naturally depending upon the kind of Compound but generally 0.04 mg or more, preferably 0.04 to 0.76 mg, per 1 cm of the skin area.

eoo. Next, test examples are shown. Compound [I] o00 used in the following tests is Compound No. wherein 0 o' 10 a ratio of cis to trans is 2 8.

00t o o cc"'1 Test Example 1 In a glass tube of 4 cm in diameter and 12 cm in length, 20 female adult mosquitos (Anopheles stephansi) o 00 o 0o were released. Both ends of the glass tube were covered "o 15 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 oo0o o o were drawn there. A solution, 0.2 ml each, obtained by diluting Compound 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 of test i 10 f 1 mosquitos on the skin which were bloodsucking was counted and 3 minutes after, the number of mosquitos 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 oD0p test result of the control, the corrected repellency rate 0ooo o o and corrected bloodsucking prevention rate were deter- 10 mined by applying to Abbott's correction equation. Table 0 1 shows the results.

00aC Repellency 100 A x 100 0, rate Number of all mosquitos tested S0 0 o o 0 0 0 00 0o Bloodsucking pre- B x 100 vention rate Number of all mosquitos tested o 00 .*00 0 0 0 9 o o a 0 0 0 11 o 0 0 00 a 0 '0 0 0 o0 00 C 00 0 TQable I 1

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2 Hours AfterI 6 Hours after Chemical Tested and Concentration Corrected Repellency Rate Corrected Bloodsucking prevention :te Corrected Repellency Rate Corrected Bloodsucking prevention.Rcte 57 96 28 78 Compound 1.0% 70 9454 57 100 67 91 N,N-Diethyl- 2.5% B3 75 4 31 m-toluamide: 10% 100 1032 39 *I I 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.

:o Test Example 2 A Nylon net (25 x 25 cm 2 of 16 mesh was dipped in 1% ethanol solution of Compound 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, female adult mosquitos (Aedes aegypti) were released.

The upper part of the glass tube was covered ith 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%.

13 L_ wIq 0 0 a 9 9 a a 9 99 9 0 099 9 9 9 9999 0 4 9 9*9 9 9 9 9 OS 9 9 0 *9 9 9 9 *9* Table 2 Reettin1 Hour After 4 Hours After 7 Hours After N.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 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. sees. secs. secs. sees, sees. sees. sees, sees.

9 1 Test Example 3 An aerosol contai ing 1 part of Compound 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 rubbed with both hands 0 0 00 to uniformly spread the chemical.

o a 10 After standing for a prescribed time period, r bloodsucking of flies (Simulium aoki) was obserbed with the right leg as a control. Two hours after spraying, observation was made again in the same manner. The o0.. bloodsucking prevention rate was determined by the 0 o o o0 15 following equation.

Number of bloodsucking flies at the treated Bloodsucking pre- 100 region x 100 vention rate Number of bloodsucking or, flies at the intact p.aoo. region o pi The aerosol used in this test was prepared by dissolving the effective ingredients in 1,1,1trichloroethane in 60 wt% and filling Flon 12 in 40 wt% under pressure.

Table 3 shows the results.

i I 15 4V Table 3

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S. Bloodsucking Prevention Aerosol Preparation Rt Rate Immediately 2 Hours Effective Ingredient wt% After After Treatment N,N-Diethyl-m-toluamide 10 100 56 (volunteer A) Compound [I]/N,N-Diethyl- 1/5 100 100 m-toluamide (volunteer B) o 0 0 0 o 0 0 0 0 OQ 0 00 *o 0 0 0 0 1 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 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 parts of N,N-diethyl-m-toluamide, 1 part of Compound and 5 parts of N,N-diethyl-m-toluamide, 0.5 part of Compound and 5 parts of N,N-diethyl-m-toluamide or 0.25 parts of Compound and 5 parts of 16 16 1 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 o 4x 2.5 m 3 bloodsucking of the mosquitos was observed 0 10 for 20 minutes in the large room with the right leg as Pa 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 0 00 o oo 15 in 60 wt% and filling LPG gas in 40 wt% under pressure.

do Number of bloodsucking Blg mosquitos at the treated Bloodsuckingion oprevention 100 region prevention 00 Number of bloodsucking x 100 rate mosquitos at the intact region Table 4 shows the results.

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Table 4 Bloodsucking Prevention Aerosol Preparation Rate Immediately 4 Hours Effective Ingredient wt% After After Spraying Compound 1 100 33 N,N-Diethyl-m-toluamide 5 100 Compound 0.25/5 00 100 Diethyl-m-toluamide Compound 0.5/5 100 100 Diethyl-m-toluamide Compound 1/5 100 100 Diethyl-m-toluamide 0 0 00 0 0 0 0 0 6 o o 0-4k .0 00 0 0 o 00 a oo o 0 0 0 0 00 1 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 and 5 parts of N,N-diethyl-mtoluamide was already greatly reduced. On the other hand, the combined aerosol containing 1 part of Compound and 5 parts of N,N-diethyl-m-toluamide showed an excellent bloodsucking prevention effect equal to the effect immediately after the spraying.

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Claims (3)

1. 4- a. 19 THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. A method for preventing harm from bloodsucking insects which comprises applying a composition comprising a compound represented by the formula, CH H CH /CH 0 3 I /C=C H CH-OC-CH-CH CH 3 C3 3 CH C1 3 '3 0.O 0* e o co 0 06 *C *0 i and a carrier to the skin. 2. A method for preventing harm from bloodsucking insects which comprises using a composition comprising a compound represented by the formula: CH H ,CB O C=C 3 1 SCH-OC-CH-CH C C HC CH CH 3 3 C=C CH 3 XCH 00 o o 0 0 0 Go$ at least one of a known insect repellents and a carrier. 3. A method according to Claim 2, wherein said insect repellent is selected from the group consisting of N,N-diethyl-m-toluamide, 2,3:4,5-bis(2-butylene)- tetrahydro-2-furfural, di-n-propyl isocianchomaeronate or di-n-butyl succinate. 4. A method according to Claim 3, wherein said insect repellent is N,N-diethyl-m-toluamide. i: 20 A method according to Claim 2, wherein a mixing ratio of the compound of the formula to the known insect repellent is 50 1 to 1
2. 6. A method according to Claim 1 or 2, wherein said composition is a liquid preparation or an ointment.
3. 7. The method of Claim 1, which comprisec directly applying the composition to the skin. 7 The method of Claim 1, wherein the application of the composition to the skin includes the steps of applying the composition to a base material as hereinbefore defined e¢ by coating, dipping, kneading, dropping etc; and covering a the skin with the base material treated with the composition. 0000 0 a DATED THIS 7TH DAY OF NOVEMBER 1990 o00. 000 0o. 0 SUMITOMO CHEMICAL COMPANY LTD -4&p By its Patent Attorneys: GRIFFITH HACK CO. Fellows Institute of Patent Attorneys of Australia. 0 0 00 -7 i 1 zi j