Title of Invention

MOSQUITO COIL STICK OF INFECTIOUS DISEASE

Abstract A mosquito coil stick of infectious disease containing 0.01 to 0.5% by mass of an active ingredient in the form of 4-methoxymethyl-2,3,5/6-tetrafluorobenzyl 2,2,3,3-tetramethylcyclopropane carboxylate and incorporating an efficacy enhancer in the form of N-(2-ethylhexyl)-bicyclo[2,2,l]-hept-5-ene-2,3- dicarboxyimide preferably at 0.1 times or more, and more preferably at 0.2 times or more, the amount of the active ingredient, based on the object of providing a composition of a mosquito coil stick of infectious diseases that demonstrates outstanding effects against Aedes aegypti mosquitoes, southern house mosquitoes and Anopheles species mosquitoes, is capable of being produced inexpensively, and has superior safety with respect to humans and livestock.
Full Text FORM 2
THE PATENT ACT 1970 (39 of 1970)
&
The Patents Rules, 2 003 COMPLETE SPECIFICATION
(See Section 10, and rule 13)
TITLE OF INVENTION
MOSQUITO COIL STICK OF INFECTIOUS DISEASE

2. APPLICANT(S)
a) Name :
b) Nationality :
c) Address :

DAINIHON JOCHUGIKU CO., LTD.
JAPANESE Company
4-11, TOSABORI 1-CHOME,
NISHI-KU, OSAKA-SHI,
OSAKA
JAPAN

3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed : -

BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a mosquito coil stick of infectious diseases.
Description of the Related Art
There are numerous species of mosquitoes found around the world, and these mosquitoes not only bite and draw blood from humans, but also cause serious problems by serving as carriers of infectious diseases. In the tropical regions of Southeast Asia and Africa for example, malaria is known to be carried by Anopheles mosquitoes, Dengue fever by Aedes aegypti and Aedes albopictus mosquitoes, yellow fever by Aedes aegypti, filariasis by southern house mosquitoes and common house mosquitoes and Japanese encephalitis by Culex tritaeniorhynchus mosquitoes. In the current absence of a suitable vaccine, the first step to protecting oneself from these infectious diseases is not being bitten by these mosquitoes, and in the case of open-air residences in particular, the use of a mosquito coil stick is the optimum method. Although mosquito nets impregnated with pyrethroids are used, there are many problems with their use, including being able to use only while sleeping and becoming hot and uncomfortable during use.
The pyrethroid-based insecticide component, allethrin, has been used throughout the world as the active ingredient of mosquito coil sticks. There have recently been reports that in some parts of Southeast Asia, the efficacy of allethrin against major species of southern house mosquitoes has decreased, and southern house mosquitoes have generally been evaluated as being more resistant to drugs than Aedes aegypti mosquitoes.
However, during the course of a field test using Aedes aegypti mosquitoes collected outdoors in Thailand several years ago that underwent generational breeding in a research laboratory of the Department of Tropical Medicine at Thailand's Mahidol University, the inventors of the present invention found that this strain of Aedes

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aegypti mosquitoes demonstrated extremely low sensitivity to various pyrethroids in comparison with Aedes aegypti mosquitoes bred at a Thai national testing facility, thus making the new discovery that, in contrast to the aforementioned general evaluation, Aedes aegypti mosquitoes are more resistant to drugs than southern house mosquitoes. Aedes aegypti mosquitoes are carriers of Dengue fever and yellow fever, and countermeasures against them are extremely important in terms of protecting humans, and particularly residents of tropical regions in Southeast Asia and Africa, from the effects of infectious diseases. According to a presentation by Dr. Yuki Eshita, one of the most prominent experts in the field of Dengue fever, although Dengue fever was originally a disease of Southeast Asia, its infected area has expanded to include Africa and North and South America, while the breeding grounds for its mosquito carrier in the form of Aedes aegypti have also expanded, with roughly 90% of the mosquito species captured in residences located in northeastern Thailand being reported to be Aedes aegypti mosquitoes ("Seikatsu to Kankyo" (Life and Environment), Vol. 42 (1997) (Non-Patent Document 1)). This finding has posed a new serious problem in controlling infectious disease-carrying mosquitoes.
On the other hand, the development of new insecticide components is also progressing. For example, according to the literature (Biosci. Biotechnol. Biochem., 68(1) 170, 2004 (Non-Patent Document 2)), a mosquito coil stick containing the novel pyrethroid-based insecticide component, metofluthrin [4-methoxymethyl-2,3,5,6-tetrafluorobenzyl 2,2-dimethyl-3-(l-propenyl) cyclopropane carboxylate], is reported to have demonstrated knockdown effects nearly equal to those of d-allethrin mosquito coil sticks at a concentration equal to 1/40 to 1/20 that of d-allethrin. However, due to the complex synthesis process and high production cost of metofluthrin, when a mosquito coil stick is attempted to be obtained having insecticidal efficacy several times that of mosquito coil stick of d-allethrin repellant for mosquitoes, there is the disadvantage of being unable to provide such a mosquito coil stick inexpensively, thereby placing limitations on the concentration at which it is used. In addition, its efficacy against the aforementioned Aedes aegypti
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mosquitoes exhibiting decreased sensitivity has yet to be evaluated.
Under the present circumstances, searching for an insecticide component that demonstrates outstanding effects against Aedes aegypti mosquitoes, southern house mosquitoes, Anopheles mosquitoes and so forth that is also able to be produced inexpensively is an extremely effective means for countering infectious disease-carrying mosquitoes. As was clearly demonstrated for the first time in tests conducted by the inventors of the present invention, although there were determined to be considerably differences in sensitivity to drugs depending on the location where mosquitoes are captured, the cause of this cannot be concluded to be the development of resistance to a drug. In any case, since a drug-resistant population clearly exists among Aedes aegypti mosquitoes having the largest distribution rate as previously described, it is imperative to find an insecticide component that is effective against this population in particular. Consequently, it will only be possible to evaluate efficacy by actually conducting local insecticidal efficacy tests on Aedes aegypti mosquitoes, southern house mosquitoes and Anopheles mosquitoes.
The 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl 2,2,3,3-tetramethyl cyclopropane carboxylate focused on by the inventors of the present invention was disclosed as a known compound in Japanese Unexamined Patent Publication No. Sho 57-165343 (Patent Document 1), and a mosquito coil stick containing this compound is disclosed in Japanese Unexamined Patent Publication No. 2001-302591 (Patent Document 2). However, the mosquito coil stick of Patent Document 2 is merely disclosed as an example of a preparation and is not intended as a measure against infectious disease-carrying mosquitoes, and there are no separate studies regarding the incorporation of other drugs to further enhance efficacy.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a mosquito coil stick for controlling infectious disease-carrying mosquitoes that demonstrates outstanding effects against
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mosquitoes such as Aedes aegypti mosquitoes, southern house mosquitoes and Anopheles mosquitoes, can be produced inexpensively, and has superior safety with respect to humans and livestock.
In order to solve the aforementioned problems, the present invention employs the
basic composition described below.
(1) A mosquito coil stick for controlling infectious disease-carrying mosquitoes
comprising 0.01 to 0.5% by mass of an active ingredient in the form of 4-
methoxymethyl-2,3,5,6-tetrafluorobenzyl 2,2,3,3-tetramethyl cyclopropane
carboxylate represented by the following chemical formula:
[CHEMICAL 1]



The mosquito coil stick for controlling infectious disease-carrying mosquitoes described in (1), wherein N-(2-ethylhexyl)-bicyclo[2,2,l]-hept-5-ene-2,3-dicarboxyimide is incorporated as an efficacy enhancer at 0.1 times or more the amount of the active ingredient.
(2) The mosquito coil stick for controlling infectious disease-carrying mosquitoes described in (2), wherein N-(2-ethylhexyl)-bicyclo[2,2,l]-hept-5-ene-2,3-dicarboxyimide is incorporated as an efficacy enhancer at 2.0 times or more the amount of the active ingredient.
(3) The mosquito coil stick for controlling infectious disease-carrying mosquitoes described in (2) or (3), wherein a lower alkyl amine salt of an alkylbenzene sulfonic acid is incorporated as an assistant of the efficacy enhancer at 0.1 to 1.0 times the mass of the efficacy enhancer.
(4) The mosquito coil stick for controlling infectious disease-carrying mosquitoes described in any of (1), (2), (3) or (4), wherein the infectious disease-carrying mosquitoes are Aedes aegypti mosquitoes.




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DESCRIPTION OF THE PREFERRED EMBODIMENTS
The active ingredient serving as the base of the mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention is 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl 2,2,3,3-tetramethykyclopropane carboxylate (referred to as the subject compound).
This compound is already known, and can be prepared based on the synthesis method described in Patent Document 1 by reacting the cyclopropane carboxylic acid or reactive derivative thereof with 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol or a reactive derivative thereof.
Examples or reactive derivatives of carboxylic acids include acid halides, acid anhydrides, carboxylic acid lower alkyl esters, alkaline metal salts and salts of organic tertiary bases. On the other hand, examples of reactive derivatives of alcohols include chlorides, bromides and p-toluene sulfonic acid esters. The reaction is carried out in a suitable solvent in the presence of an organic or inorganic base or acid serving as a deoxidizer or catalyst as necessary and while heating as necessary.
Although the subject compound is a liquid at room temperature and ordinarily dissolves easily in organic solvents, the mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention is composed by mixing the subject compound dissolved in an organic solvent with a base material for mosquito coil stick such as wood chips.
In consideration of insecticidal efficacy on each type of infectious disease-carrying mosquito, economy and so forth, the content of the active ingredient in the mosquito coil stick is set to 0.01 to 0.5% by mass and preferably 0.03 to 0.2% by mass. The mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention preferably incorporates an efficacy enhancer in the form of N-(2-ethylhexyl)-bicyclo[2.2.1]-hept-5-ene-2,3- dicarboxyimide (to be referred to as


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efficacy enhancer A) at 0.1 times or more and preferably 2.0 time or more the amount of the active ingredient.
In the past, pyrethroid synergists such as piperonyl butoxide, N-(2-ethylhexyl)-bicyclo[2.2.1]-hept-5-ene-2,3- dicarboxyimide and N-(2-ethylhexyl)-l-isopropyl-4-methylbicyclo[2.2.2]-oct-5-ene-2,3-dicarboxyimide (referred to as synergist S) were frequently mixed into various preparations. Namely, although the aforementioned pyrethroid synergists did not themselves exhibit biological activity in the case of using in a liquid or powder, for example, they are known to enhance the efficacy of pyrethroids when mixed therewith. Furthermore, although octachlorodipropyl ether (S-421) is also included within the scope of pyrethroid synergists, since this substance itself exhibits biological activity and has been reported to be suspected of demonstrating mutagenicity, it is not suitable for use.
There are numerous reports describing the mechanism of synergists, and for example, are known to inhibit oxidative detoxifying metabolism of pyrethroids as a result of being subjected to metabolism and degradation within the insect body, or enhance the insecticidal efficacy of pyrethroids by promoting penetration of pyrethroids into the skin to facilitate their arrival at nervous system active sites. However, since the mechanism of action of these synergists is obviously largely dependent on the type of insect, synergistic effects of these synergists are typically only about 10 to 20%.
In contrast, as a result of conducting extensive studies on the action of certain formulations when in the form of stick, and incorporating the efficacy enhancer A into the subject compound, the inventors of the present invention unexpectedly found that the insecticidal efficacy of the mosquito coil stick increased two to three fold. This fact cannot be explained by the mechanism of synergists used in conventional pyrethroid preparations, namely the insect physiological mechanism described above, and a physical action is also thought to be contributing, such as a different factor in the form of a certain substance being involved in an increase in the

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vaporization rate of the active ingredient, thereby increasing the concentration of the active ingredient in the air, or a certain substance promoting dispersion of the vaporized active ingredient. Moreover, the vaporization rate of the subject compound has been experimentally confirmed to increase 5 to 10% as a result of adding the efficacy enhancer A to the subject compound.
Namely, the basic technical idea of the present invention is such that, in the case the subject compound is used in combination with a suitable amount of the efficacy enhancer A, when in the form of stick, it vaporizes most efficiently as a result of a type of steam distillation together with water contained in the stick and the efficacy enhancer A thereby promoting dispersion, and together with the efficacy enhancing effects attributable to insect physiology, is able to demonstrate remarkable synergistic effects, thus leading to a previously unknown, completely novel finding.
The quantitative ratio between the subject compound and the efficacy enhancer A is an important factor. Namely, although high efficacy enhancing effects in terms of knockdown effect as indicated by the indicator of the KT50 value is obtained if the incorporated amount of the efficacy enhancer A is within the range of 0.1 to 2.0 times the amount of the active ingredient, efficacy enhancing effects in terms of the KT90 value and kill rate tended to be observed to be comparatively low. Next, when the incorporated amount of the efficacy enhancer A was increased to 2.0 times or more the amount of the active ingredient, although the increase in terms of the KT50 value was not as great in proportion to the increase in the incorporated amount, efficacy enhancing effects in terms of the KT90 value and kill rate increased remarkably, thereby clearly demonstrating that the efficacy enhancer A is able to reliably and synergistically enhance both knockdown effect and lethal action. In this manner, although the incorporated amount of the efficacy enhancer A is preferably 2.0 times or more the amount of the active ingredient, it is obviously pointless to arbitrarily incorporate an excess amount of the efficacy enhancer A.
However, although the N-(2-ethylhexyl)-l-isopropyl-4-methylbicyclo[2.2.2]-oct-5-ene-2,3-dicarboxyimide (synergist S) has a similar structure to the structural

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formula of the efficacy enhancer A, in the case of combining with the use of the stick of the subject compound, efficacy enhancing effects were extremely low. A possible factor for this is that the transpiration of the synergist S in the presence of heated smoke is considerably lower than that of the efficacy enhancer A, and can be evaluated as test results in support of the intimate involvement of transpiration properties of active ingredients and formulations in insecticidal efficacy when in the form of incense stick.
As one embodiment of the present invention, a lower alkyl amine salt of an alkylbenzene sulfonic acid may be further incorporated as efficacy enhancer assistant in addition to the efficacy enhancer A. Here, the alkyl group of the alkylbenzene sulfonic acid has about 8 to 14 carbon atoms, while the lower alkyl group of the alkyl amine salt has about 2 to 4 carbon atoms, typical examples of which include dodecylbenzene sulfonic acid isopropyl amine salt and dodecylbenzene sulfonic acid ethyl amine salt.
The ratio of the lower alkyl amine salt of an alkylbenzene sulfonic acid to the efficacy enhancer A is suitably within the range of 0.2 to 1.0 times the amount of the efficacy enhancer A.
Examples of base materials for a mosquito coil stick include combustion promoters and binders, with examples of the former including plant powders such as wood chips, powdered pyrethrum extraction residue, powdered citrus skin and powdered coconut shell, and carbon powder such as powdered charcoal and fly ash. In addition, examples of the latter binder include banyan powder, starch, methyl cellulose and carboxymethyl cellulose.
The mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention may also contain, for example, a pigment, preservative or stabilizer as necessary. Examples of pigments include organic dyes such as malachite green, while typical examples of preservatives include acids such as sorbic


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acid, dehydroacetic acid or p-hydroxybenzoic acid and salts thereof. In addition, examples of stabilizers include, but are not limited to, 2,6-di-tertiary-butyl-4-methylphenol (BHT) and 2,2'-methylenebis(4-ethyl-6-tertiary-butylphenol).
Moreover, other insecticide and insect control components including conventional pyrethroid-based insecticides such as pyrethrin, allethrin, prallethrin, furamethrin, transfluthrin, metofluthrin or empenthrin, bactericides, disinfectants and repellants, as well as fragrances or deodorizers can be mixed provided they do not inhibit the action and effects of the present invention to obtain a multipurpose composition having superior efficacy.
Known production process can be used to prepare the mosquito coil stick of infectious disease of the present invention without requiring any extraordinary techniques. For example, a mosquito coil stick can be produced by adding water to a mixture of a premixed powder (containing the active ingredient, efficacy enhancer and so forth in a portion of a combustion promoter) and the remainder of the mosquito coil stick base material and kneading, followed by molding with an extruder or press and drying. In addition, after molding using only the base material for a mosquito coil stick a solution containing the active ingredient and so forth may be sprayed or coated.
Although the mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention specifically demonstrates outstanding efficacy against Aedes aegypti mosquitoes, southern house mosquitoes, Anopheles mosquitoes, Aedes albopictus mosquitoes, common house mosquitoes and other infectious disease-carrying mosquitoes, it is particularly useful against Aedes aegypti mosquitoes carrying Dengue fever having decreased sensitivity. The present invention is naturally also effective against other species of mosquitoes, flies, cockroaches, house dust mites and other insects posing potential health threats, and has an extremely high level of practicality in such applications.
The following provides a more detailed explanation of the mosquito coil

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stick of infectious disease of the present invention based on specific examples thereof.
Example 1
After uniformly mixing 0.1% by mass of the subject compound, 0.2% by mass of the
efficacy enhancer A and 99.7% by mass of mosquito coil stick base materials such as
powdered pyrethrum extraction residue, wood chips and starch, water containing
pigment and preservative was added to obtain the mosquito coil stick for controlling
infectious disease-carrying mosquitoes of the present invention according to known
methods.
Example 2
After mixing 0.05% by mass of the subject compound, 0.15% by mass of the efficacy enhancer A, 0.08% by mass of dodecylbenzene sulfonic acid isopropyl amine salt and 0.1% by mass of 2,6-di-tertiary-butyl-4-methylphenol, 99.62% by mass of base materials of a mosquito coil stick such as powdered coconut shell, wood chips, banyan powder and starch were uniformly mixed in followed by the addition of water containing preservative to obtain the mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention according to known methods.
Example 3
[Measurement of Effective Ingredient Vaporization Rate uring Stick Burning] Two traps for capturing vaporized substances (inner diameter: 25 mm, length: 10 cm) were connected in series to the upper portion of an evacuation bell having an internal volume of 1.5 liters followed by connecting to a suction pump. 2 g of test mosquito coil stick were placed on a stick stand, the stick stand was placed in the center of the bottom of the evacuation bell, and samples of the vaporized substance were collected by aspirating the air at the rate of 8 Hters/min after igniting the stick. After the stick finished burning, the vaporized substances captured in the traps and the vaporized substances adhered to the inside of the evaporation bell were washed
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off and collected followed by analyzing the amount of active ingredient contained therein by gas chromatography. The active ingredient vaporization rate was calculated from the amount of active ingredient recovered relative to the theoretical amount of active ingredient contained in 2 g of the test mosquito coil stick.
[Table 1]

Mosquito coil stick (mass %) Active ingredient vaporization rate(%)
Active ingredient Efficacy enhancer
1 Subject compound 0.1 - 84.7
2 Subject compound 0.1 Efficacy enhancer A 0.2 89.1
As a result of this test, although the active ingredient vaporization rate of the mosquito coil stick containing 0.1% of the subject compound was 84.7%, as a result of incorporating the efficacy enhancer A at twice the amount of the subject compound, the vaporization rate of the active ingredient was experimentally confirmed to increase by about 5%. Thus, the use of the inexpensive efficacy enhancer A is extremely useful in terms of enhancing the insecticidal efficacy of the mosquito coil stick containing the subject compound.
Example 4
[Basic Efficacy Test Using Mosquito coil stick]
A basic efficacy test was conducted at this testing facility using adult Aedes aegypti mosquitoes and adult southern house mosquitoes that underwent generational breeding at a Thai national testing facility. Namely, 0.5 g of the mosquito coil stick for controlling infectious disease-carrying mosquitoes of the present invention obtained in compliance with Example 1 or Example 2 were ignited and placed in a glass chamber measuring 70 x 70 x 70 cm, and after the stick had finished burning, 20 test mosquitoes consisting of adult Aedes aegypti mosquitoes and adult southern house mosquitoes were released into the chamber. After exposing the mosquitoes for 20 minutes, the numbers of test mosquitoes that fell to the ground and rolled over were counted over the course of time to determine the KT90 values as
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shown in Table 2.
[Table 2]

Mosquito coil stick (mass %) KT90 Value
Active Ingredient Efficacy Enhancer AedesaegyptiMosquitoes SouthernHouseMosquitoes
Present Invention 1 Subject compound 0.1 - 4'07" 11'02"
2 Subject compound 0.01 Efficacy enhancer A 0.03 519" 10'43"
3 Subject compound 0.1 Efficacy enhancer A 0.03 3'24" 6'36"
4 Subject compound 0.1 Efficacy enhancer A 0.2 2'06" 312"
5 Subject compound 0.1 Efficacy enhancer A 0.4 Assistant 0.1 2'01" 3'07"
6 Subject compound 0.1 Synergist S 0.3 3'53" 10'44"
7 Subject compound 0.2 Efficacy enhancer A 0.5 1'37" 2*30"
Comparative Examples 1 Subject compound0.005 - >10' >20'
2 dl,d-T80-allethrin0.225 - 8'21" 17'28"
3 dl,d-T80-allethrin 0.3 Efficacy enhancer A 0.7 Assistant 0.3 5'44" 11'20"
4 Metofluthrin 0.0075 - 816" ir02"
• Efficacy enhancer A: N-(2-ethylhexyl)-bicyclo[2.2.1]-hept-5-ene-2,3-dicarboxyimide
• Assistant: Dodecylbenzene sulfonic acid isopropyl amine salt
• Synergist S: N-(2-ethylhexyl)-l-isopropyl-4-methylbicyclo[2.2.2]-oct-5-ene-2,3-dicarboxyimide
The Aedes aegypti mosquitoes used in this test were obtained by generational breeding at a Thai national testing facility, and consisted of a strain that was highly sensitive to pyrethroids. Thus, in the results of this test, the KT90 values for Aedes aegypti mosquitoes were much lower than those for southern house
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mosquitoes for all of the test mosquito coil sticks.
The mosquito coil sticks of the present invention containing 0.01% by mass or more of the subject compound and preferably incorporating efficacy enhancer A as an efficacy enhancer {N-(2-ethylhexyl)-bicyclo[2.2.1]-hept-5-ene-2/3- dicarboxyimide} demonstrated superior knockdown effects. In particular, those mosquito coil sticks in which the incorporated amount of the efficacy enhancer A was two or more times the amount of the subject compound demonstrated remarkable enhancing effects, with knockdown effects being enhanced by about 2.0 times with respect to Aedes aegypti mosquitoes and by about 3.5 times with respect to southern house mosquitoes. Furthermore, as indicated in the compound 6 of the present invention, even though synergist S{N-(2-ethylhexyl)-l-isopropyl-4-methylbicyclo[2.2.2]-oct-5-ene-2,3-dicarboxyimide} has a similar chemical structure to the efficacy enhancer A and has been conventionally been commonly used as a pyrethroid synergist, its efficacy enhancing effects were low in the form of mosquito coil stick of the present invention combined with the subject compound.
Thus, in consideration of the extremely low cost of the efficacy enhancer A as compared with the subject compound, it is clear that the mosquito coil stick of the present invention used in combination with the efficacy enhancer A is an extremely useful mosquito coil stick for controlling infectious disease-carrying mosquitoes.
In contrast, a mosquito coil stick in which the content of the subject compound was less than 0.01% by mass (Comparative Example 1) demonstrated inferior knockdown effects. In addition, the dl,d-T80-allethrin demonstrated inferior knockdown effects against both Aedes aegypti mosquitoes and southern house mosquitoes despite being incorporated at 2 to 3 times the levels of compound 1 of the present invention as shown in Comparative Examples 2 and 3. Similarly, the knockdown effects of the metofluthrin stick (Comparative Example 4) were also inadequate.
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Example 5
[Practical Field Efficacy Test in 25 m3 Room]
Although the efficacy test of Example 4 was carried out in a 70 x70 x 70 cm (0.343 m3)
glass chamber, since this is only 1/73 the volume of a 25 m3 room in which mosquito
coil sticks are actually used, a considerably higher concentration is reached as
compared with concentrations during actual use. A practical field efficacy test
was therefore conducted in a 25 m3 room to evaluate the performance of the
mosquito coil stick under conditions that more closely matched the conditions of
actual use.
Namely, after releasing 100 adult common house mosquitoes into a closed 25 m3 room, a burning test of mosquito coil stick (prepared in compliance with Example 1 or Example 2) was placed in the center of the room. After exposing the mosquitoes for 2 hours, the numbers of common house mosquitoes that fell to the ground and rolled over were counted over the course of time to determine the KT50 values, KT90 values and kill rates as shown in Table 3.
[Table 3]

Mosquito coil Stick (mass %) Insecticidal Efficacy Against Common House Mosquitoes
Active Ingredient Efficacy Enhancer KT50Value(min) KT90Value(min) Kill rate(%)
Present Invention 1 Subject compound 0.1 15.7 44.7 46
2 Subject compound 0.1 Efficacy enhancer A0.01 11.6 35.0 54
3 Subject compound 0.1 Efficacy enhancer A0.1 11.2 23.1 73
4 Subject compound 0.1 Efficacy enhancer A0.2 10.8 17.7 90
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5 Subject compound 0.1 Efficacy enhancer A0.5 10.5 16.5 92
Comparative Examples 1 dl,d-T80-aUethrin0.5 20.8 >120 28
2 Metofluthrin0.007 5 93.3 >120 13
3 Metofluthrin0.015 - 26.5 82 39
As a result of testing against common house mosquitoes, the mosquito coil stick of the present invention containing 0.01% by mass or more of the subject compound, and preferably incorporating the efficacy enhancer A {N-(2- ethylhexyl)-bicyclo[2.2.2]-hept-5-ene-2,3-dicarboxyimide} at 0.1 times or more the amount of the subject compound, demonstrated superior insecticidal efficacy. As indicated in the compounds 2 and 3 of the present invention, mosquito coil stick incorporating the efficacy enhancer A at 0.1 or 1.0 times the amount of the subject compound were observed to enhance knockdown effects as indicated by KT50 values. In addition, mosquito coil sticks incorporating the efficacy enhancer A at 2.0 to 5.0 times the amount of the subject compound (compounds 4 and 5 of the present invention) exhibited remarkable efficacy enhancement in terms of knockdown effects and kill rates as indicated by KT90 values, and were observed to be able to demonstrate more reliable and stable insecticidal efficacy. Thus, in consideration of the cost of the efficacy enhancer A being extremely low as compared with the subject compound, it is clear that the present invention in the case of incorporating the efficacy enhancer A provides a mosquito coil stick of infectious disease that is extremely useful as described in (2) above. In contrast, as indicated in the comparative examples, dl,d-T80-allethrin stick demonstrated efficacy that was inferior to that of the present invention even if the active ingredient is incorporated at a high concentration equal to roughly twice the ordinary concentration, while the metofluthrin 0.015% stick was inferior in terms of knockdown effects and lethal effects.
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Example 6
[Practical Field Efficacy Test in a 25 m3 Room]
A practical field efficacy test was conducted in compliance with the aforementioned
Example 5 at the research laboratory of the Department of Tropical Medicine at
Thailand's Mahidol University. The test mosquitoes consisted of Aedes aegypti
mosquitoes, southern house mosquitoes and Anopheles dims mosquitoes collected
outdoors in Thailand several years ago that underwent generational breeding at the
research laboratory of this university. The results obtained for Aedes aegypti
mosquitoes and southern house mosquitoes are shown in Table 4.
[Table 4]

Mosquito Coil Stick (mass %) KT90 Value (min)
Active Ingredient Efficacy Enhancer AedesaegyptiMosquitoes SouthernHouseMosquitoes
Present Invention 1 Subject compound 0.1 - 117 33
2 Subject compound 0.1 Efficacy enhancer A 0.2 67 18
3 Subject compound 0.15 - 60 20
4 Subject compound 0.15 Efficacy enhancer A 0.3 47 15
Comp. Examples 1 dl,d-T80-allethrin 0.5 - 170 72
2 Metofluthrin 0.0075 173 74
The adult Aedes aegypti mosquitoes used in this test had extremely low sensitivity to pyrethroids as compared with the Aedes aegypti mosquitoes used in Example 4 (strain bred at the Thai national testing facility), and the KT50 values were times higher than southern house mosquitoes in contrast to Example 3. Furthermore, the Anopheles dims mosquitoes demonstrated extremely high sensitivity to pyrethroids, and the KT50 values were 1/2 to 1/6 those of southern house mosquitoes.
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As a result of this test, the mosquito coil stick of infectious disease of the present invention containing the subject compound demonstrated high knockdown effects against not only Aedes aegypti mosquitoes and Anopheles dims mosquitoes in the same manner as common house mosquitoes, but also against Anopheles dims mosquitoes having decreased sensitivity. In addition, as a result of incorporating the efficacy enhancer A in mosquito coil stick containing the subject compound at 2.0 times the amount of the subject compound, knockdown effects against Aedes aegypti mosquitoes and southern house mosquitoes were observed to be enhanced by about 1.5 to 2 times.
In contrast, as indicated in the comparative examples, stick containing 0.5% dl,d-T80-allethrin (twice the concentration used during actual use) and stick containing metofluthrin were virtually ineffective against Aedes aegypti mosquitoes, and the mosquito coil stick containing the subject compound is currently the only mosquito coil stick to be found capable of demonstrating outstanding effects against Aedes aegypti mosquitoes inhabiting outdoor environments.
As explained in the section on the Description of the Related Art, although Dengue fever was originally a disease found in Southeast Asia, its infected area has expanded to include Africa and North and South America, while the breeding grounds for its mosquito carrier in the form of Aedes aegypti have also expanded, with roughly 90% of the mosquito species captured in residences located in northeastern Thailand being reported to be Aedes aegypti mosquitoes. Thus, in consideration of the carrying of Dengue fever and yellow fever by Aedes aegypti mosquitoes and the urgency of deploying countermeasures against them, the usefulness of the mosquito coil stick of infectious disease of the present invention is clear.
The mosquito coil stick of infectious disease of the present invention demonstrates outstanding effects for eradicating Aedes aegypti mosquitoes, southern house mosquitoes and Anopheles species of mosquitoes, can be produced inexpensively,


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and demonstrates superior safety with respect to humans and Hvestock, thereby having an extremely high degree of practicality.
The present invention can also be used in the fields of manufacturing and sales of mosquito coil sticks.

WE CLAIM:
1. A mosquito coil stick of infectious disease comprising 0.01 to 0.5% by mass of an active ingredient in the form of 4-methoxymethyl-2,3/5,6-tetrafluorobenzyl 2,2,3,3-tetramethylcyclopropane carboxylate represented by the following chemical formula:
[CHEMICAL 1]

2. The mosquito coil stick of infectious disease according to claim 1, wherein N-(2-ethylhexyl)-bicyclo[2/2,l]-hept-5-ene-2/3-dicarboxyimide is incorporated as an efficacy enhancer at 0.1 times or more the amount of the active ingredient.
3. The mosquito coil stick of infectious disease according to claim 2, wherein N-(2-ethylhexyl)-bicyclo[2,2/l]-hept-5-ene-2,3- dicarboxyimide is incorporated as an efficacy enhancer at 2.0 times or more the amount of the active ingredient.
4. The mosquito coil stick of infectious disease according to claim 2 or 3,
wherein a lower alkyl amine salt of an alkylbenzene sulfonic acid is incorporated as an assistant of the efficacy enhancer at 0.1 to 1.0 times the weight of the efficacy enhancer.
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5. The mosquito coil stick of infectious disease according to any of claims 1 to 4,
wherein the infectious disease-carrying mosquitoes are Aedes aegypti mosquitoes.
Dated this 12th day of June, 2007

HIRAL CHANDRAKANT JOSHI
AGENT FOR
DAINIHON JOCHUGIKU CO., LTD.
21

ABSTRACT

A mosquito coil stick of infectious disease containing 0.01 to 0.5% by mass of an active ingredient in the form of 4-methoxymethyl-2,3,5/6-tetrafluorobenzyl 2,2,3,3-tetramethylcyclopropane carboxylate represented by the following chemical formula:
[CHEMICAL 1]


and incorporating an efficacy enhancer in the form of N-(2-ethylhexyl)-bicyclo[2,2,l]-hept-5-ene-2,3- dicarboxyimide preferably at 0.1 times or more, and more preferably at 0.2 times or more, the amount of the active ingredient, based on the object of providing a composition of a mosquito coil stick of infectious diseases that demonstrates outstanding effects against Aedes aegypti mosquitoes, southern house mosquitoes and Anopheles species mosquitoes, is capable of being produced inexpensively, and has superior safety with respect to humans and livestock.

To,
The Controller of Patents,
The Patent Office,
Mumbai

22

Documents:

1117-MUM-2007-ABSTRACT(24-2-2012).pdf

1117-MUM-2007-ABSTRACT(GRANTED)-(14-6-2012).pdf

1117-mum-2007-abstract.doc

1117-mum-2007-abstract.pdf

1117-MUM-2007-CANCELLED PAGE(24-2-2012).pdf

1117-MUM-2007-CHINA DOCUMENT(13-6-2012).pdf

1117-MUM-2007-CLAIMS(AMENDED)-(13-6-2012).pdf

1117-MUM-2007-CLAIMS(AMENDED)-(24-2-2012).pdf

1117-MUM-2007-CLAIMS(GRANTED)-(14-6-2012).pdf

1117-MUM-2007-CLAIMS(MARKED COPY)-(13-6-2012).pdf

1117-mum-2007-claims.doc

1117-mum-2007-claims.pdf

1117-MUM-2007-CORRESPONDENCE(24-2-2012).pdf

1117-MUM-2007-CORRESPONDENCE(26-3-2010).pdf

1117-MUM-2007-CORRESPONDENCE(9-1-2009).pdf

1117-MUM-2007-CORRESPONDENCE(IPO)-(14-6-2012).pdf

1117-mum-2007-correspondence-received.pdf

1117-mum-2007-descripiton (complete).pdf

1117-MUM-2007-DESCRIPTION(GRANTED)-(14-6-2012).pdf

1117-MUM-2007-ENGLISH TRANSLATION(24-2-2012).pdf

1117-MUM-2007-EP DOCUMENT(13-6-2012).pdf

1117-MUM-2007-FORM 1(24-2-2012).pdf

1117-MUM-2007-FORM 2(GRANTED)-(14-6-2012).pdf

1117-MUM-2007-FORM 2(TITLE PAGE)-(24-2-2012).pdf

1117-MUM-2007-FORM 2(TITLE PAGE)-(GRANTED)-(14-6-2012).pdf

1117-MUM-2007-FORM 26(13-6-2012).pdf

1117-MUM-2007-FORM 3(24-2-2012).pdf

1117-mum-2007-form-1.pdf

1117-mum-2007-form-18.pdf

1117-mum-2007-form-2.doc

1117-mum-2007-form-2.pdf

1117-mum-2007-form-3.pdf

1117-mum-2007-form-5.pdf

1117-MUM-2007-MALAYSIAN DOCUMENT(13-6-2012).pdf

1117-MUM-2007-MALAYSIAN DOCUMENT(24-2-2012).pdf

1117-MUM-2007-MARKED COPY(24-2-2012).pdf

1117-MUM-2007-OTHER DOCUMENT(24-2-2012).pdf

1117-MUM-2007-OTHER DOCUMENT(9-1-2009).pdf

1117-MUM-2007-PETITION UNDER RULE-137(24-2-2012).pdf

1117-MUM-2007-REPLY TO EXAMINATION REPORT(24-2-2012).pdf

1117-MUM-2007-REPLY TO HEARING(13-6-2012).pdf

1117-MUM-2007-SPECIFICATION(AMENDED)-(24-2-2012).pdf


Patent Number 253006
Indian Patent Application Number 1117/MUM/2007
PG Journal Number 24/2012
Publication Date 15-Jun-2012
Grant Date 14-Jun-2012
Date of Filing 13-Jun-2007
Name of Patentee DAINIHON JOCHUGIKU CO., LTD.
Applicant Address 4-11, TOSABORI 1- CHOME, NISHI-KU, OSAKA-SHI, OSAKA
Inventors:
# Inventor's Name Inventor's Address
1 YOSHIO KATSUDA C/O RESEARCH AND DEVELOPMENT LABORATORY, DAINIHON JOCHUGIKU CO., LTD., 1-11, DAIKOKU-CHO 1- CHOME, TOYONAKA-SHI, OSAKA.
2 TSUTOMU KANZAKI C/O RESEARCH AND DEVELOPMENT LABORATORY, DAINIHON JOCHUGIKU CO., LTD., 1-11, DAIKOKU-CHO 1-CHOME, TOYONAKA-SHI, OSAKA.
PCT International Classification Number A01N25/18
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 JP2006-185048 2006-07-05 Japan
2 JP2006-304879 2006-11-10 Japan