WO2008082028A1

WO2008082028A1 - Mosquito repellent comprising an esterified glycerol.

Info

Publication number: WO2008082028A1
Application number: PCT/KR2007/001340
Authority: WO
Inventors: Hyouk Il Kwoen; Kye Chung Park; Hyun Woo Oh
Original assignee: Bio & Hnt, Inc.
Priority date: 2006-12-28
Filing date: 2007-03-19
Publication date: 2008-07-10

Abstract

The present invention relates to a mosquito repellent comprises at least one or more selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof in an effective amount to repel mosquito.

Description

MOSQUITO REPELLENT COMPRISING AN ESTERIFIED

Technical Field

[1] The present invention relates to a mosquito repellent, and more particularly, to a new mosquito repellent composition comprising at least one compound selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof, which represent excellent mosquito repellent activity, as a mosquito repellent. Background Art

[2] Some insects are virulent and can cause harm, such as skin irritation, infection, and even disease, to people. In order to protect ourselves from such insects, various types of products have been developed. These products are developed to kill, suppress reproduction or proliferation, and debilitate sensory organs to maim perception.

[3] Among these developed products, debilitation of sensory organs is used for a

"repellent." In particular, the repellent is often used for protecting ourselves from mosquitoes. Such a mosquito repellent can paralyze sensory organs of a mosquito and prevent the mosquito from tracing carbon dioxide or odor generated frαn the skin of a mammal, such as human beings.

[4] Mosquito is a very harmful insect in view of hjgiene since it can carry dangerous bacteria for causing disease such as dengue, yellow fever, encephalitis, and malaria. Considering that millions of people die worldwide every year from malaria, it is difficult to ignore the fact that mosquito is a deadly, harmful insect. It is reported that malaria has resurfaced and has been affecting people again since 1993, and malaria infected patients have recently increased to reach several thousand patients every year in Korea alone. Notably, the infection rate of malaria has increased every year and as can be inferred from the discussion above, direct or indirect contact with mosquitoes can have potentially dangerous consequence.

[5] To combat mosquitoes, a mosquito repellent is preferably used because it is relatively free frαn harm to a human body. Various mosquito repellents are available. In particular, N,N-ctiethykn-toluanide (DEET) has been widely used owing to its excellent mosquito repellent effect. However, since the DEET has an unpleasant odor and strong penetration into the skin, it has been restricted from application on children, pregnant women, nursing mothers, hypotensive patients, people with sensitive skin, and so on. The United States restricts mosquito repellents containing more than 20% DEET from being manufactured. [6] In view of this, much efforts have been made to replace DEET. Although it is known that citronella, linalool, and lemongrass are effective in repelling mosquitoes, they are less effective than DEET. For this reason, a problem has been raised in practical use of mosquito repellents which contains the materials such as citronella, linalool, and lemongrass. [7] Accordingly, extensive studies and researches are made to develop new mosquito repellents derived from natural resources.

Disclosure of Invention

Technical Problem [8] An objective of the present invention is to provide a mosquito repellent composition having excellent mosquito repellent effect. [9] Another objective of the present invention is to provide a mosquito repellent composition derived frαn natural resources being harmless to a human body. [10] Above and other objectives of the present invention could be achieved by the present invention which will be described below.

Technical Solution [11] A mosquito repellent composition according to the present invention includes at least one compound selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof. [12] The mosquito repellent is used in more than 0.1 wt % with respect to the total amount of composition. [13] The present invention includes a method of repelling mosquito, which comprises applying the mosquito repellent composition to the skin. [14] The present invention also includes a method of repelling mosquito, which comprises the steps of mixing a composition with a liquid solution, wherein the composition comprises at least one mosquito repellent compound selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof in an effective amount to repel mosquito, and applying the nixed liquid solution to a skin. [15] Hereinafter, the present invention will be described in detail.

Best Mode for Carrying Out the Invention [16] In the present invention, it has been confirmed whether various plant materials that can be obtained from nature have mosquito repellent effect. As a result, it has been found that one or more chemical compounds selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid, and derivatives thereof have repellency against mosquito. [17] The one or more compounds selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid, and derivatives thereof are harmless to a human body and have high repellent activity against mosquitoes. [18] It is known that monoolein, tributyrin, tricaproin, triolein and tripropionin of the above compounds exist in a very small amount in vegetable oil and certain animal fat.

Moreover, citronellic and geranic acid have a similar chemical structure and exist in a certain amount in various essential oils such as lemongrass oil and so on. These two compounds can be used as food additives and perfume. [19] Monoolein, which is used in the present invention, can be expressed as a molecular formula, i.e., C H O , and can have a following Chemical Structure 1.

21 40 4

[20] [Chemical Structure 1]

[21]

[22] Other names of monoolein include glycerol monooleate; 1-oleoyl-sn-glycerol;

9-octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol; glyceryl oleate; and glyceyl oleate. [23] Monoolein has been known to have been used in food additives or can be used as an emulsifying agent for cosmetic composition. [24] Tributyrin used in the present invention has a molecular formula, i.e., C H O , and

15 26 6 can have a following Chemical Structure 2. [25] [Chemical Structure 2]

[26]

[27] Other names of tributyrin include tri-n-butyrin; 1,2,3-propanetriyl tributyrate; butanoic acid, 1,2,3-ρropanetxiyl ester; glycerol tributyrate; glyceryl tributyrate; and tributanoylglycerol.

[28] It is known that tributyrin can exist in vegetable oil and butter, and can be used as food additives. [29] Tricaproin used in the present invention is represented as a molecular formula, i.e., C H O , and has a following Chemical Structure 3.

21 38 6

[30] [Chemical Structure 3] [31]

[32] Other names of tricaproin include tricaprioylglycerol; 1,2,3-propanetriyl tri- hexanoate; tricaprϋn; tricaprioylglycerol; and tri-n-caproin. [33] Triolein used in the present invention can be represented as a molecular formula, i.e., C H O , and has a following Chemical Structure 4.

57 104 6

[34] [Chemical Structure 4] [35]

[36] Other names of triolein include 9-octadecenoic acid (Z)-, 1,2,3-propanetriyl ester; 1,2,3-propanetriyl tri-((E)-9-octadecenoate); 9-octadecenoic acid (Z)-, 1,2,3-propanetriyl ester; glyceryl trioleate- 1-13C); olein; and trioleoylglycerol.

[37] Triolein is known compound as a solvent, viscosity controlling agent or eraulsifier for cosmetic composition. [38] Tripropionin used in the present invention can be represented as a molecular formula, i.e., C H O , and has a following Chemical Structure 5.

12 20 6

[39] [Chemical Structure 5] [40]

[41] Other names of tripropionin include 1,2,3-propantriol, tripropanoate; 1,2,3-propanetriyl tripropionate; glyceryl tripropanoate; tripropanoin; tripropanoylglycerol; and tripropionyl glycerol.

[42] Tripropionin can be known as food additives. [43] Citronellic acid, which is used in the present invention, can be expressed as a molecular formula, i.e., C H O , and can have a following Chemical Structure 6.

10 18 2

[44] [Chemical Structure 6] [45]

[46] Other names of citronellic acid include (+/-)-citronellic acid; and

3,7-dimethyl-6-octanoic acid. [47] Citronellic acid can be known as a natural compound which exists in a plant like lemon tree and can be used as food additives. [48] Geranic acid, which is used in the present invention, can be expressed as a molecular formula, i.e., C H O , and has a following Chemical Structure 7.

10 16 2

[49] [Chemical Structure 7]

[50]

[51] Geranic acid is known to exist as a natural plant compound in tea trees, tomatoes, wine or the like. Furthermore, it has been used as food additives and used for preparing perfume.

[52] The chemical structures of the aforementioned monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid and geranic acid can be modified to manufacture a derivative for a new repellent which represents high repellent activity to mosquitoes.

[53] In the present invention, compounds used as the aforementioned mosquito repellent can be used alone or nixed with a well-known solvent to manufacture a mosquito repellent composition. The well-known solvent means either a solvent used for a general repellent composition or a doping material applied to the skin of a human body, having a type of a cream, a liquid phase, a spray, and a gel. In this case, the monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof are used alone or in combination. In this case, monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof are used in an amount of more than 0.1 wt % with respect to a weight of the total amount of mosquito repellent composition. If used less than 0.1 wt %, repellent activity may be insufficient.

[54] The mosquito repellent composition according to the present invention is preferably used in such a manner that it is applied to the skin in a type of a cream, a lotion, a spray, a spreader, or an ointment. The mosquito repellent composition is used in a place where mosquitoes inhabit. The expression, "applied to the skin" includes "applied to a path of a mosquito for contact to the skin, such as clothes and door," as well as "directly applied to the skin." Furthermore, it is expected that the mosquito repellent composition can be used as a repellent for arthropod of various species in addition to mosquito.

[55] The present invention will be embodied by the following embodiment, and the following embodiment is only a detailed exemplary of the present invention and is not intended to restrict or limit the protection scope of the present invention. Mode for the Invention

[56] Preparation of sample

[57] Monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid and geranic acid which are used in the present invention, are cαimercially available or can directly be synthesized. In this embodiment, products of TCI America (product names respectively called Glycerol monooleate, Glycerol tri-n-butyrate, Glycerol trioleat) were purchased and used as monoolein, tributyrin and tricaproin. For triolein, tripropionin, citronellic acid and geraninc acid, products of Aldich (product names respectively called Glycerol tripropionat, Glycerol tri-n-hexanoat, Citronellic acid, Geranic acid) were purchased and used.

[58] Purities of the above seven compounds were examined using a gas chromatograph

(GC) and a gas chromatograph-mass spectrometry (GC-MS). The compounds having purity of 99.5 % or greater were only used. Respective ingredients of the above compounds were added to isopropyl alcohol of 91 % to make test samples consisting of a solution in the concentration of 2 %, 5 % and 10 % respectively. The samples were used for mosquito repellent efficacy experiments.

[59] The seven test samples manufactured as above underwent repellent effective experiments with respect to Aedes, Culex and Anopheles which are three main mosquito groups attacking human.

[60] Examination test mosquitoes used in the experiments

[61] In this embodiment, Aedes aegypti, Culex pipiens pallens and Anopheles sinensis were used as test mosquitoes. The Aedes aegypti was supplied from Korea Research Institute of Bioscience and Biotechnology and reared indoor from generation to generation. The Culex pipiens pallens was supplied from Korea Research Institute of Chemical Technology and also reared indoor from generation to generation. The Anopheles sinensis was collected in the field near Ccnrainity Hall, Kyehwa-ri, Kyehwa^ityon, Buan-gun, Chollanatn-do, Republic of Korea and was used for the experiments.

[62] The larvae of the Aedes aeqypti were reared in a plastic container of 22x14x7 an containing distilled water with a one to one mixture of chicken feed and yeast. Mosquito pupae were transferred into a paper cup and then placed in a rearing cage to emerge as adults. Here, the rearing cage was constructed with metal net. Males and females of the adult mosquitoes at one to one ratio were put in a rearing cage for two or three days for mating. The female mosquitoes were then used for repellency tests. Eight percent (8 %) sugar water supplied for the adult mosquitoes. The following rearing conditions were maintained: light condition of 16h:8h (day:night), temperature of 27+2°C, and relative humidity of 80+10 %.

[63] Examination of repellent activity using skin test

[64] In order to examine effectiveness of the mosquito repellent of the prepared sample solutions, one (1) ml of a sample solution was uniformly applied, using a metal rod, on a forearm of a volunteer human test subject between a wrist and an elbow. Thereafter, the arm treated with the test solution was inserted in a bioassay cage, constructed with Plexiglass of 50x50x50 cm containing approximately 100 mated female mosquitoes. The number of mosquitoes trying to bite was recorded for three minutes in every thirty minutes for up to 4 hours. The time required to get the arm bitten by two cumulative mosquitoes was regarded as effective repellency duration. A net window of 40x40 cm was present at each side and top of the Plexiglass bioassay cage to allow air ventilation. A 15x15 an hole was prepared at the front side of the Plexiglass bioassay cage and a long net sleeve was attached to the hole so that the test arm could be put into the cage for repellency test.

[65] At the beginning of each repellency test, an arm treated with no solvent was placed in the bioassay cage containing mosquitoes, in order to examine blood feeding activity of the mated female test mosquitoes. This test with the bioassay cage carried out only when the arm was bitten by at least two mosquitoes for initial three minutes.

[66] Result of examination of repellent activity of each ingredient

[67] Repellent activities against three mosquito species were examined in accordance with the aforementioned method using the samples which respectively contain monoolein, tributyrin, tricaproin, triolein or tripropionin. The obtained result was shown in Table 1 and Table 2. In these tables, "Ae" stands for Aedes aegypti, "Cx" for Culex pipiens pallens and "An" for Anopheles sinensis. [68] Table 1

[69] In Table 1, "NA" means that the test was not carried out. [70] Table 1 indicates effective repellency duration of each compound at the concentration of 5 %, represented as protection time until the arm was bitten by two cumulative mosquitoes. In this case, the dose amount of the concentration of 5 % corresponds to 0.125 mg/αn .

[71] Table 2

[72] Table 2 indicates repellent efficiency measured at every 30 minutes after test solution was applied onto an arm at the concentration of 5 % and 10 %. In this case, the dose amount of the concentration of 5 % corresponds to 0.125 mg/αn , and 10 % to 0.25 mg/cm³.

[73] Meanwhile, repellent activity against Aedes was examined in accordance with the aforementioned method using the samples which respectively contain citronellic acid and geranic acid. Furthermore, mosquito repellent activity was measured with solutions which contain DEET or Picadirin. The DEET and Picadirin are corrmercially available mosquito repellents which are currently recommended by the Center for Disease Control of the United States. The obtained results were shown in Table 3 to Table 6.

[74] Table 3

[75] Table 3 indicates effective repellency duration of each compound at the concentration of 2 %, represented as protection time until the arm was bitten by two cumulative mosquitoes. In this case, the dose amount of the concentration of 2 % corresponds to 0.05 mg/cm .

[76] Table 4

[77] Table 4 indicates effective repellency duration per compound at the concentration of 10 %, represented as protection time until the arm was bitten by two cumulative mosquitoes. In this case, the dose amount of the concentration of 10 % corresponds to 0.25 mg/αn³.

[78] Table 5

[79] Table 5 indicates a repellent efficiency measured every 30 minutes after test solution was applied on an arm at the concentration of 2 %. In this case, the dose amount of the concentration of 2 % corresponds to 0.05 mg/αn .

[80] Table 6

[81] Table 6 indicates a repellent efficiency measured every 30 minutes after test solution was applied on an arm at the concentration of 10 %. In this case, the dose

3 amount of the concentration of 10 % corresponds to 0.25 mg/αn . [82] In Table 2, Table 5 and Table 6, the repellent efficiency was calculated using the following Equation 1. [83] [Equation 1]

[84]

(number of mosquitoes of control example - number of mosquitoes of experiment example)

Repellent efficiency (%) = _; ^■ X 100 number of mosquitoes of control example

[85] Based on the results of Table 1 and Table 2 above, monoolein, tributyrin, tricaproin, triolein and tripropionin indicated strong repellent efficiency of over 90 % for 30 minutes at the level of 0.125 mg/αn . Moreover, the results indicated high repellent effect of 50 % or greater even after lapse of 2 hours.

[86] As shown in Table 4 above, the effective repellency duration of citronellic acid and geranic acid lasted for 240 minutes at the level of 0.25 mg/cm . It is noted that citronellic acid and geranic acid have greater mosquito repellent effect than that of DEET or Picadirin. More specifically, the effective repellency duration of DEET lasted for 218 minutes and the effective repellency duration of Picadirin lasted for 158 minutes. In the meantime, as shown in Table 3, the effective repellency duration of geranic acid lasted for 195 minutes at the level of 0.05 mg/cm while that of DEET lasted for 70 minutes at the same concentration.

[87] In addition, the results of Table 5 and Table 6 above indicate that citronellic acid showed strong repellent efficiency of 100 % for 30 minutes and geranic acid for 120 minutes at the level of 0.05 mg/αn . The citronellic acid and geranic acid showed greater repellent activity than that of DEET at the same level and even after 30 and 60 minutes respectively. Further, citronellic acid indicated strong repellent efficiency of 100 % for 150 minutes and geranic acid for 210 minutes at the level of 0.25 mg/cm . The citronellic acid and geranic acid showed even greater repellent activity than that of DEET whose repellent efficiency of 100 % for 120 minutes at the same level or that of picadirin for less than 30 minutes.

[88] It will be apparent to those skilled in the art that the present invention can be embodied in other specific forms without departing from the spirit and essential characteristics of the invention. Industrial Applicability

[89] The present invention can be used as a mosquito repellent.

Claims

[1] A mosquito repellent composition comprising at least one mosquito repellent compound selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof in an effective amount to repel mosquito.

[2] The composition as defined in claim 1, wherein the monoolein has a following

Chemical Structure 1:

[Chemical Structure 1]

[3] The composition as defined in claim 1, wherein the tributyrin has a following Chemical Structure 2: [Chemical Structure 2]

[4] The composition as defined in claim 1, wherein the tricaproin has a following Chemical Structure 3: [Chemical Structure 3]

[5] The composition as defined in claim 1, wherein the triolein has a following Chemical Structure 4: [Chemical Structure 4]

[6] The composition as defined in claim 1, wherein the tripropionin has a following Chemical Structure 5: [Chemical Structure 5]

[7] The composition as defined in claim 1, wherein the citronellic acid has a following Chemical Structure 6 [Chemical Structure 6]

[8] The composition as defined in claim 1, wherein the geranic acid has a following

Chemical Structure 7. [Chemical Structure 7]

[9] The composition as defined in any one of claims 1 to 8, wherein the mosquito repellent compound is used more than 0.1 wt % with respect to the total amount of composition.

[10] A method of repelling mosquito, which comprises applying mosquito repellent composition according to any one of claims 1 to 9.

[11] The method as defined in claim 10, wherein the composition is applied to the skin in a type of a cream, a lotion, a spray, a spreader, or an ointment.

[12] A method of repelling mosquito, which comprises the steps of: mixing a composition with a liquid solution, wherein the composition comprises at least one mosquito repellent compound selected from the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof in an effective amount to repel mosquito; and applying the nixed liquid solution to a skin.

[13] The method as defined in claim 12, wherein the monoolein a following Chemical

Structure 1: [Chemical Structure 1]

[14] The method as defined in claim 12, wherein the tributyrin has a following Chemical Structure 2: [Chemical Structure 2]

[15] The method as defined in claim 12, wherein the tricaproin has a following Chemical Structure 3: [Chemical Structure 3]

[16] The method as defined in claim 12, wherein the triolein has a following Chemical Structure 4: [Chemical Structure 4]

[17] The method as defined in claim 12, wherein the tripropionin has a following Chemical Structure 5: [Chemical Structure 5]

[18] The method as defined in claim 12, wherein the citronellic acid has a following Chemical Structure 6 [Chemical Structure 6]

[19] The method as defined in claim 12, wherein the geranic acid has a following Chemical Structure 1. [Chemical Structure 7]

[20] The method as defined in any one of claims 12 to 19, wherein the mosquito repellent compound is used more than 0.1 wt % with respect to the total amount of composition. [21] The method as defined in claim 20, wherein the composition is applied to the skin in a type of a cream, a lotion, a spray, a spreader, or an ointment. [22] A use of at least one compound selected frαn the group consisting of monoolein, tributyrin, tricaproin, triolein, tripropionin, citronellic acid, geranic acid and derivatives thereof as a mosquito repellent.