WO2013122304A1

WO2013122304A1 - Composition for repelling insects comprising ir 3535 derivative as active ingredient

Info

Publication number: WO2013122304A1
Application number: PCT/KR2012/008991
Authority: WO
Inventors: 이삼빈; 이인선; 김배환; 유미희; 박성진; 이진호; 박민주; 김지은; 이지훈
Original assignee: 계명대학교 산학협력단
Priority date: 2012-02-17
Filing date: 2012-10-30
Publication date: 2013-08-22
Also published as: KR20130094945A; KR101386233B1

Abstract

The present invention relates to an insect-repelling composition comprising an IR 3535 derivative as an active ingredient. Also, the present invention provides an insect-repelling composition comprising an IR 3535 derivative and a cinnamon supercritical-based oil as active ingredients. The composition of the present invention exhibits a marked insect-repelling effect since the composition has outstanding aromatic properties and durability.

Description

- 【Specification】

[Name of invention]

Composition for avoiding stratum corneum containing IR 3535 derivative as an active ingredient

The present invention relates to a layered repellent composition, especially a mosquito repellent composition, comprising an IR 3535 derivative as an active ingredient.

Background Art

About 3,500 species of mosquitoes are known on the planet, and 9 genera and 55 species are recorded in Korea. The damage to these mosquitoes is inferred that the cause of the Australopithecus remains, found in Ethiopia, Africa in 1974, is malaria. Mosquitoes are generally vampireic to obtain proteins from animals to mature eggs of adult females after mating, and secrete saliva that causes allergy to the vampire. At this time, when the pathogenic virus bacteria in the salivary glands of the mosquitoes are latent, the disease is mediated to humans. The typical diseases are dengue hemorrhagic fever, encephal itis, and yellow fever. Malaria and dengue deaths affect more than one million people per year, killing more than 3,000 people a day, most of which are reported to be young children. Today, environmental pollution and the earth caused by the development of science

Due to warming, the period and frequency of occurrence of mosquitoes are increasing.

One of the methods used to control these mosquitoes from the living space is the repellent. Mosquito repellents are used to protect individuals instead of insecticides that are restricted for use outdoors. It is mainly used in the formulation of aerosols, liquids, or lotions. Representative repellents are divided into synthetic compounds and natural compounds. The main component of the mosquito repellents are organophosphate-based pesticides and Pierre droids and components and the most widely used worldwide DEETXN, N-diethyl- ntl- uamide) o This - the year 1964 - - ^o - the United States - Military It is used ^{as a} commodity. It is spread and used all over the world. But in different parts of the body When applied, the effective residual amount over time, high penetration rate through human skin, and oral toxicity have not yet proved stable in pregnant women and children. In order to supplement the problems with the chemical synthetic mosquito repellents, research on repellents using plant essential oils, which are natural ingredients, has been conducted. Throughout this specification, many papers and patent documents are referenced and their citations are indicated. The disclosures of cited papers and patent documents are incorporated herein by reference in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly explained.

[Content of invention]

[Problem to solve]

The present inventors have tried to develop insect repellents which are harmless to the human body and have high repellent activity against plows, especially mosquitoes. As a result, the present invention has been completed by confirming that the IR 3535 derivative is harmless to the human body and has an excellent pollinating effect, particularly mosquito repelling effect.

Accordingly, it is an object of the present invention to provide an insect repellent composition. It is another object of the present invention to provide a cosmetic composition for repelling nadir.

It is still another object of the present invention to provide a method for avoiding stagnation. Other objects and advantages of the present invention will become apparent from the following detailed description and claims.

[Measures of problem]

According to one aspect of the present invention, the present invention provides an insect repellent composition comprising the compound of formula 1 as an active ingredient:

The present inventors endeavored to develop a layered repellent which is harmless to the human body and has a high repellent activeol against the layered layer, particularly mosquito. As a result, the present invention was completed by confirming that the compound of Chemical Formula 1, which is an IR 3535 derivative, is harmless to the human body and has an excellent pollinating effect, particularly mosquito repelling effect.

According to a preferred embodiment of the present invention, the compound of Formula 1 as the IR 3535 derivative may be chemically synthesized from IR 3535.

Synthesis of the IR 3535 derivative can utilize various chemical synthesis methods known in the art. Preferably, IR 3535, a precursor, is treated with acetic acid chloride and pyridine, reacted under reduced pressure, and then purified by chromatography.

According to a preferred embodiment of the present invention the compound of formula 1 of the present invention exhibits a remarkable mosquito repellent effect (Table 3) and does not cause skin irritation or skin sensitization when applied to the skin (Tables 19 and 24).

According to a preferred embodiment of the present invention, the content of the compound of Chemical Formula 1 is 0.1-30% by weight, preferably 0.1-25% by weight, and more preferably, based on the total weight of the insect repellent composition of the present invention. 1-20% by weight), still more preferably 1-15% by weight, most preferably 1-10% by weight.

According to a preferred embodiment, the goncheung of the invention mosquitoes, flies, ants, bees, crickets, norinjae, fan worms, fleas, beetles, and mole or cockroaches, preferably mosquitoes, ^■ flies, ants, bees, Fanworms or fleas, more preferably mosquitoes, flies, ants or bees, most preferably mosquitoes.

₇ ——The invention—of the invention—according to this invention's—desirable—implementation—contains additionally one super-critical oil. Cinnamon supercritical oil included in the composition of the present invention may be prepared by a supercritical fluid extraction process. Cinnamomum verum, a raw material for supercritical extraction, is crushed to form a powder of a suitable size. Supercritical that can be used in the method of the present invention

5 The extraction vessel can be controlled in temperature and pressure, and is not particularly limited as long as it is a vessel configured to be in contact with the extraction raw material and the supercritical fluid.

The supercritical fluid used in the present invention includes various supercritical fluids commonly used in the art, and preferably water or carbon dioxide is used.

10 The co-solvent used with the supercritical fluid includes a polar solvent commonly used in the art, preferably alcohol, water, ethylene glycol, polyethylene glycol, propylene carbonate, formic acid, acetic acid, aceto Nitrile, chlorodifluoromethane or mixtures thereof, more preferably methane, ethanol, propanol, 1-

15 is an alcohol selected from the group consisting of nucleanol, 2-methoxyethanol and combinations thereof, even more preferably methanol or ethanol, most preferably ethane.

According to a preferred embodiment of the invention, the pressure in the supercritical extraction is 100-500 bar, more preferably 200-400 bar, most preferably 20 300-400 bar.

According to another preferred embodiment of the invention, the temperature in the supercritical extraction is 10-10CTC, more preferably 30 ^° C-70 ^° C, even more preferably 30-50 ^° C, most preferably 30-40 ^° C.

According to a preferred embodiment of the present invention, the cinnamon supercritical oil is obtained by supercritical extraction of 25 cinnamon at a temperature of 30-40 ^° C and a pressure of 200-400 bar.

According to a preferred embodiment of the present invention, the content of cinnamon supercritical oil with respect to the total weight of the insect repellent composition of the present invention is 0.1-25% by weight, preferably 0.1-20% by weight, more preferably 1 -20 wt%, even more preferably wt _% , most preferably wt _%

According to another aspect of the invention, the present invention provides a composition for insect repellent Cosmetically effective amount; And a cosmetically acceptable carrier.

Ingredients included in the cosmetic composition of the present invention as an active ingredient includes components commonly used in cosmetic compositions in addition to the mosquito repellent composition, for example, conventional supplements such as stabilizers, solubilizers, vitamins, pigments and flavors, and Carrier.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing It may be formulated as an oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

When the formulation of the present invention is a paste, cream or gel, the carrier components include animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. Can be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, and in particular, in the case of spray, additionally chlorofluorohydrocarbon, Propellant such as propane / butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizer or an emulsifier is used as the carrier component, for example, water, ethane, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil and glycerol are aliphatic esters, polyethylene glycols or fatty acid esters of sorbitan.

When the formulation of the present invention is a suspension, the carrier component is water, ethanol or a liquid diluent such as propylene glycol, ethoxylated isostearal-alcohol, polyoxyethylene sorbide ester and polyoxyethylene sorbitan. Suspending agents such as esters, microcrystalline cellulose, aluminum metahydroxy bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.

According to another aspect of the present invention, the present invention provides a tomb layer avoidance method comprising the step of applying the insect repellent cosmetic composition of the present invention to the skin.

According to still another aspect of the present invention, the present invention provides a method for avoiding insects, comprising applying the insect repellent composition composition of the present invention to a region to obtain a barrier effect.

【Effects of the Invention】

The features and advantages of the present invention are summarized as follows:

(i) The present invention provides an insect repellent composition comprising a compound of Formula 1 as an active ingredient as an IR 3535 derivative.

(iii) The present invention provides a tonic layer avoiding composition comprising the compound of formula 1 and cinnamon supercritical oil as an active ingredient.

(iii) The composition of the present invention has excellent fragrance and sustainability, and exhibits a remarkable ≤ excess layer avoiding effect.

(iv) The present invention provides a tortilla-repellent cosmetic composition.

(V) The present invention provides a method for evacuating a stratum layer comprising applying a stratum layer avoidance cosmetic composition to the skin.

(vi) The present invention provides a method for avoiding insects, comprising applying to the area to obtain a layering effect. [Brief Description of Drawings]

1 is a schematic diagram of a kennel produced to confirm the mosquito repelling effect of the test substance.

Figure 2 is a diagram showing the chemical structural formula of the IR 3535 derivative (LJH-1-58) which is a compound of formula 1 of the present invention.

Figure 3 is a diagram showing the eye drops and cleaning process of the test material in the eye irritation test for the test material.

Figure 4 is a diagram showing the eye film stimulation test results for the test substance. 5 is a diagram showing the treatment procedure in the skin primary stimulation test for the test substance.

Figure 6 is a diagram showing the skin primary stimulation test results for the test substance. 7 is a diagram showing the procedure of treatment in the skin sensitization test for the test substance.

8 is a diagram showing a skin sensitization test result for a test substance.

[Specific contents 1 to carry out invention

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention more specifically, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. . EXAMPLE

Materials and methods

Test insect

The mosquitoes used in this experiment were collected and prepondered oil layers of Aedes albopictus and Cx. Pi pi ens pal lens. The temperature was 25-28 ^° C, the humidity was 75-95%, the light condition was 16: 8 (L: D), and 10% sugar water was supplied, and SD rats (4 weeks old) were supplied for vampire blood, and the egg mass was 10 The mosquitoes were collected by dividing them into small boxes of X 10 X 10 cm, supplied with distilled water daily to increase the diet by distinguishing the larvae at each growth stage. The pupa was delivered daily and raised in a stratified breeding ground (40 × 30 × 20) (FIG. 1). The stratification was separated by mating according to the growth cycle to maintain vampire force. Bio assay (Arm—in—cage test)

Avoidance experiment was made to expose only part of the arm and protect the rest of the hand by connecting a cloth to a box of 40, 30 and 30 cm in height. Evasion test was performed by spinning 50 mated females over 5 days of age in the evacuation box, and fasting by stopping 10% sugar water supply 6-8 hours before the experiment. The white beetle mosquito is a species that can absorb 24 hours, but the most active time was observed at 10 am and 8 pm, respectively. The experiment was conducted using only red illumination, a wavelength that mosquitoes could not recognize. During the experiment, the temperature was 27 ± 1 ^° C, the relative humidity was 75 ± 5%, and the exposed areas were exposed for 5 minutes for each sample, and 1 mL of the sample was evenly applied to the exposed areas. The mosquitoes were changed every time according to the sample, and the experiment was repeated three times, and 24% DEET was used as a control. The number of bites was counted for 5 seconds or more landing mosquito bites.

Synthesis of 3- (butylamino) propanoic acid methyl ester

Methyl acrylate (2.40 g, 2.73 X 10 ^"2 moL) was dissolved in 5 mL of acetonitrile, and n-butylamine (1 g, 1.36 X 10 ^{" 2} moL) was added thereto at 120 ^° C and 70 W. The microwave reaction was allowed for 30 minutes. The solvent was removed by distillation under reduced pressure to obtain 3- (butylamino) propanoic acid methyl ester in 96.4% yield (2.06 g).

Synthesis of 3- (N-butylacetamino) propanoic acid methyl ester (UH ′ 1-58)

3- (Butylamino) propanoic acid methyl ester (2.06 g, 1.29 X 10 ^"2 moL) was dissolved in 30 mL of dichloromethane (DCM), followed by acetic acid chloride (1.83 mL, 2.58 X 10 ^'2 moL), pyridine 3.21 mL, 3.87 X 10 ^"2 moL) was added and stirred at room temperature for 1 hour. The filtrate obtained by filtration under reduced pressure was washed with water and 5% citric acid solution, and then the DMC layer was treated with anhydrous sodium sulfate to remove water. Solvent After distillation under reduced pressure, the residue was purified by column chromatography using nucleine and ethyl acetate (1: 2) to give 3- (N-butylacetamino) propanoic acid methyl ester (FIG. 2) in a yield of 72.3% (1.88 g). .

¾ NMR (CDC13, 400MHz): δ 3.70 (m, 3H), 3.59 (m, 2H), 3.28 (m, 2H), 5 2.62 (m, 2H), 2.09 (m, 3H), 1.55 (m, 2H ), 0.95 (m, 3H)

¹² C NMR (CDC13, 400 MHz): Preparation of δ 176.68, δ 175.37, δ 49.29, δ 48.13, 546.27, δ 36.37, δ 34.86, δ 24.98, 523.83, δ 17.53 Cinnamon Supercritical Oil

10 Supercritical extraction includes the supercritical extraction unit Waters AD-RC 08 (Waters CO.,

Mil ford, MA, USA). 300 g of the sample was placed in the extraction vessel, and the carbon dioxide (C0 ₂ ) flow rate: co-solvent flow rate = 47.5 g / min: 2.5 g / min. HPLC solvent ethyl alcohol (JT Baker Co., Phi 11 ipsburg, NJ, USA) was used.

15 was used. The extraction temperature was fixed at 35 ^° C., extraction time was 120 minutes, and the pressure was set to 200, 300, 400 bar and extracted under three different conditions. The rare extract was concentrated in a rotary vacuum concentrator (EYELA Co., Tokyo, Japan) at 40 ^° C and used for the experiment.

20 Experiment Results

Example 1 ： mosquito evasion test (Semi—field test)

Mosquito evasion experiment

Mosquito Experiment with Cinnamon Supercritical Extract A rectangular acrylic box of 180 x 60 x 60 cm (width x height x height) was fabricated to provide

Three boxes of the same size were divided into cages A, cage B, and cage C using 25 (FIG. 1). Cage B has holes with a diameter of 20 cm on each side to allow mosquitoes to move in cage A and cage C. Place a mixture of cinnamon supercritical extract, IR 3535, IR 3535 derivatives in cage A, and place a control (70% EtOH) in cage C. Evenly smell. 30 minutes after opening a partition in B, the number of mosquitoes in each cage was measured. Mosquito repellent effect of LJH-1-58

Table 1 shows the results of observation of repellent activity on the LJH-1-58 at 5% and 10% concentration of DEET at 24%. After 1-2 minutes, 1OT of LJH-1-58 showed high repelling force, and it was confirmed that repelling force persisted even after 4-5 minutes. The similarity of 10% UH-1-58 and 24% DEET avoidance suggests that LJH-1-58 could be used as a novel compound of IR 3535 to replace DEET. In addition, white-row mosquitoes showed about 90% repellency (Table 2). LJH-1-58 can be applied to both mosquitoes.

[Table 1]

Respiratory Effect of IR 3535 Derivative (LJH-l-58)

^1} Repelling effect = 100 X (bited from control)

Mosquito bites) / number of mosquito bites in the control group

2 ⁾ 24% Diethyl Toluamide (DEET)

Table 2

IR 3535 derivative (LJH-1-58) avoids white mosquitoes

Mosquito Repellent Effects of LJH-1-58 and Cinnamon Supercritical Oil

1 5 The results of the fragrance experiments of 10% cinnamon supercritical oil and 1% cinnamon supercritical oil, 10% IR 3535 mixture, 1% cinnamon supercritical oil, and 10% LJH-1-58 mixture are shown in Table 3. . Mosquitoes that migrated from cage Β to cage A with cinnamon supercritical oil for 30 minutes after spinning mosquitoes decreased their total number of grains to 20¾> 18.75% and 8.57% as the oil concentration increased. In addition, respiratory activity was observed in the cinnamon supercritical oil of 1) and 10% of IR 3535 and LJH-1-58, respectively, and the total number of mars of mosquitoes transferred to cage A was 12.9% in the IR 3535 mixture. The LJH-1-58 mixture showed a level of 7.4%, indicating that the mixture of cinnamon supercritical oil and LJH-1-58 had a very good activity in fragrance and mosquito repellent effects.

Table 3

Changes in mosquito numbers after exposure of cinnamon supercritical oil and a combination of IR 3535 or LJH-1-58

Cinnamon supercritical oil (400 bar, 35 ^° C).

Cinnamon supercritical oil (400 bar, 35 ^° C) 1% + 10% IR 3535.

Λ supercritical oil (400 bar, 35 ^° C) 1% + 10% LJH-1-58. Example 2: Evaluation of Skin Stability (Single Oral Dose Toxicity Test)

summary

In this study, in order to assess whether the repellent (LJH-1-58) is safe when applied to the skin, the screening of functional cosmetics, etc. Regulations pertaining to the KFDA Notification No. 2009-166) and

In accordance with the Non-Clinical Study Control Criteria, experiments were conducted to determine whether single-dose toxicity, primary skin irritation and ocular mucosal irritation were caused. Test system

Six-week-old ICR mice were obtained (Hyochang Science, Korea) and administered at seven weeks of age. A total of 18 animals (9 males and 9 females) were used for the experiments, and they had a weekly quarantine and adaptation period, and were observed daily during this period, and only healthy animals were used for the test. Test Methods

Animals were screened based on body weight during quarantine and red-eye periods, and then groups were constructed so that the average weight of each group was as evenly as possible by random method based on body weight on the day of group separation. The number of digits per group was assigned to three male and female experiments. Individual identification was by tail labeling and 3 animals per cage were housed. After fasting (about 14-16 hours) the day before administration, the test substance was orally administered using sonde.

Table 4

Composition of test group

Observation and Inspection Items

On the day of dosing, every 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours after the administration was observed every hour. Changes in general condition, intoxication symptoms and mortality by drugs were observed. Body weights were measured immediately prior to dosing, 1 day, 3 days, 7 days after dosing and immediately before autopsy (14 days). Test result

The group administered 100% of the repellent showed no abnormality on the day of administration, but all died 1 day after administration. The repellent group and the solvent-administered group did not show any specific clinical symptoms or died animals during the experiment (Table 5-10).

In the present test conditions repellents are hayeoteumeuro when administered with, 50% dilution 10 ml / kg was our both when administered as a 100% stock solution toxicity test danhui orally administered 10 ml / kg, all survived, LD ₅₀ of the test substance Value is estimated at 5-10 ml / kg based on 100% stock solution.

Table 5

Test result

Table 6

Mortality of ICR Mice Administered Orally with Test Substance

Table 7

Weight Change in ICR Mice Orally Administered with Test Substance

* All values are expressed as standard deviation (士 S.D.).

^ Group Hi water ^ was-3 —. Table 8

Clinical Findings of ICR Mice (Men) with oral PEG-400

Table 9

Clinical Findings of ICR Mice (Magnetic) Orally Administered with 50% Repellent (LJH-1-58)

Example 3: Evaluation of Skin Stability (Eye Membrane Stimulation Test)

Test system

Three-month-old NZ white rabbits (Samtaco Korea) were purchased and had a week-long quarantine and acclimatization period during which daily observations were used to test only healthy animals. Test Methods

On the basis of weight during the quarantine and red-eye period, animals with no abnormalities in the eye such as corneal damage are selected after eye examination, and healthy animals with no abnormalities in clinical and weight gain and healthy condition are determined by weight and age on the day of group separation. On the basis of the random method, groups were composed so that the average weight of each group was equal. Two out of four eyes were given the test substance in the right eye, and the left eye was left untreated. The other two eyes were given the test group after the instillation of the test substance in the right eye and PEG-400, the left eye in the control group. (FIG. 3).

Table 11

Composition of test group

Test Substance Concentration and Dosage

Test substance was diluted in PEG-400 and administered 0.1 ml per eye at 10% concentration. Washing eyes were thoroughly washed with warm physiological saline 30 seconds after eye drops. Observation and Inspection Items

General symptoms and deaths were observed daily during the test period. Observation site of applied area was observed at 1 hour, 24 hours, 48 hours, 72 hours and 4 days, 7 days after instillation of the test substance. According to the rating. Interpretation of results

Judgment of the results by response evaluation followed the commonly used Draize eye irritation table.

Table 12

Eye stimulation result judgment table

a ⁾ AOI (Acute ocular irritation index): maximum value of mean ocular irritation index

b ⁾ Mean ocular irritation index (MOI): Total score / number of experimental animals ^c) 7 days 1.0.1. (Individual ocular irritation index): score of each animal on day 7 Test result

No animals showed unusual clinical symptoms or died during the study. Repellent (LJH-1-58) 10% of non-cleansing group stimulation index (A.0.1) was 'virtually non-irritating' with 2, and the facial cleansing group was 'non-irritating' with 0. The stimulus index (A.0.1) of PEG-400 used as a solvent was 3, indicating 'virtually non-irritating'. The non-eye washing group stimulation of 10% of the repellent disappeared after 24 hours, and redness of the solvent PEG-400 remained, but recovered after 48 hours (FIG. 4).

Table 13

Test result

As a result of this test, 10% of repellents do not induce ocular mucosal irritation because acute mucosal irritation index is 5 or less. The initial mild stimulus is believed to be the effect of PEG-400 used as solvent.

Table 14

Eye irritation test results of repellent (LJH-1-58)

Ϊ66800 / ΖΪ0ΖΗΜ / Χ3 <1 Example 4 Skin Stability Assessment (Skin Primary Stimulation Test)

Test system

Three-month-old NZ white rabbits (Samtaco Korea) were purchased and had a week-long quarantine and red-eye period during which daily observations were used to test only healthy animals. Test Methods

Based on body weight during the quarantine and adaptation periods, animals with good skin condition at the back of the epilator were randomized to the test group. Two of the four animals received 10% repellent (LJH-1-58) and two 50% repellent.

Table 15

Composition of test group

Test substance treatment

After shaving the hair on the back of the rabbit to be more than about 10 cm in length, the experiment was conducted on the left side of the test substance application site and the right side of the control material application site. The test substance was prepared at an appropriate concentration, 0.5 ml of each site was applied, and closed patch for 24 hours (FIG. 5). Observation and Inspection Items

General condition and death were observed daily, and body weight was measured at group separation and at 72 hours. The site of application of the test substance is observed at 24 hours and 72 hours after application. `` Toxicity Test Standards for Drugs '' (Notice of KFDA)

The evaluation was performed according to the evaluation criteria of skin reaction.

Table 16

Evaluation criteria of skin reaction

Interpretation of results

The skin primary stimulation index (Ρ.Ι.Ι.) was calculated by erythema and edema grade at 24 hours and 72 hours after application of test substance. The mean of erythema score and edema score were calculated for each of the abrasion site and the non-brain site, and the results were judged by the skin primary stimulation index based on the skin primary stimulation index as the average value of the results at 24 hours and at 72 hours. It was.

Table 17

Skin Primary Stimulation Result Determination Table

Test result

No animals showed unusual clinical symptoms or died during the study. P.I.I. of 10% repellent is 0.13 and can be used because it falls within the non-irritating range. P.I.I. of 50% repellent is 0.13 and can be used because it falls within the non-irritating range (Tables 19-21). Some mild hemorrhage was observed at the scratch and site of the test substance and solvent treatment site at 24 hours, but it was judged to be a temporary stimulus by physical stimulus and immediately recovered to normal (FIG. 6).

Table 18

Test result

Above results, under the test conditions, the experimental period

No animals were seen or died, 10% repellent

We believe it is a safe raw material.

Table 19

Repellent (LJH-1-58) 10% primary stimulation test results

_■纏 0 0 1 0 0 0 .0 0 0 0 1 0 ο. 0 0 0 圖 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0

0 0 0.5 0 0 0 0 0 0 0 0.5 0 0 0 0 0

0.5 0 0.5

0. 13 0. 13

Table 20

50% primary irritation test results of repellent (LJH-1-58)

Example 5 Skin Sensitization Test Using Guinea Pigs (GPMD)

Test system

Hartley albino guinea pigs weighing 250-300 g were purchased (Samtaco Korea). Healthy animals with a week-long quarantine and red-eye period during which weight gain and general symptoms were not removed were used for the test. After removing the quarantine and adaptation period, the back of the animal is epilated to select healthy animals with good skin condition. Based on the weight on the day of separation, the groups were configured so that the average body weight was as even as possible. Test Methods

Induction was performed using the upper part of the back (the upper part of the shoulders) at 3 x 3 cm hair removal 4 hours before the test. The hair was removed to a size of 4 × 6 cm and used after removing the remaining hair with an electric razor on the test day. Primary induction was intradermal injection of 0.1 ml of sample, FCA, and sample + FCA into the guinea pig scapula in each test group. Secondary induction is a week after depilation of the same site of FCA injection, 10% SLS (solvent: petrolatum) is applied to the injection site, and after 24 hours, a patch of 1.5 X 1.5 cm in diameter in which 0.1 ml of the test substance is administered to the same site. 0.1 ml was applied to four and closed patched for 48 hours. Challenge 10 days after the last induction, the skin was closed for 24 hours at 2 concentrations each left and right at concentrations without primary stimulation of the skin to observe the skin growth and edema (Fig. 7). Test Group Configuration 【Table 21】

Composition of test group

Observation and Inspection Items

Clinical symptoms and death were observed during the trial. After challenge with the test substance, it was determined whether there was irritation such as hemorrhage and edema reaction at 24 and 48 hours after removing the test substance patch. If necessary, hair removal was performed using an electric razor, and when hair removal was performed, an examination was performed after about 1 hour (within 2 hours).

The evaluation of the response in each compartment was determined using the Toxicology Test Standards (Notification No. 2005-60 of the Korea Food and Drug Administration) (Table 23). In addition, the determination of skin sensitization potential was based on Kligman's rating (Table 24). Grades I and II of the skin sensitization criteria table were made available and grades III and above were made unusable.

Table 22

Evaluation standard of skin reaction Toxicity standard of medicine

81-100 V `` Severe sensitizer test results not available

Nothing unusual was observed in clinical symptoms and body weight changes during the trial. As a result of the sensitization of the repellent, sensitization was observed at 0% when caused by 10% and 50% concentrations, corresponding to the test substance available range "Grade Γ. 24 hours and 48 at 0,5% concentrations of the DNCB group. All of them corresponded to "Class V" in the range of non-use of the test substance on Kligman's sensitization criteria table at 100 hours, and 100% and 75% at 24% and 48 hours at 0.1% concentration, respectively. Corresponding to the substance unusable range, “grade V.” No negative stimulation was observed in the negative control group after sensitization with solvent and caused by 50% repellent and 0.5% DNCB (FIG. 8).

Table 24

Challenge result

No abnormal animals were observed during clinical trials. Repellents 50 and 10% rated the outcome positive for the challenge category. DNCB 0.5 and 0.1% was used as positive control substance showed a high ^steam-right. Table 25

Fatality rate after challenge

Table 26

Challenge Results (Group Data)

As described above, a specific part of the present invention has been described in detail. For those skilled in the art, the specific technology is merely a preferred embodiment, and it is obvious that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the invention will be defined by the appended claims and equivalents thereof.

Claims

Claims Claim 1 An insect repel lent composition comprising the compound of formula 1 as an active ingredient:

[Formula 1]

[Claim 2]

According to claim 1, wherein the compound of formula (1) characterized in that the topping layer avoiding composition, characterized in that contained in 0.1 to 25% by weight based on the total composition.

[Claim 3]

The method of claim 1, wherein the insects are mosquitoes, flies, ants, bees, crickets, stink bugs, fan beetle, fleas, scarabs, warts or cockroaches.

[Claim 4]

4. The dope avoidance composition of claim 3, wherein the dope is a mosquito.

[Claim 5]

The insect repellent composition of claim 1, wherein said composition further comprises cinnamon supercritical oil.

[Claim 6]

6. The method according to claim 5, wherein the cinnamon supercritical oil is characterized in that the cinnamon is characterized in that the cinnamon is extracted at a temperature of 30-40 ^° C at a pressure of 200-0α—bar-—supercritical—based—extracted—obtained. ^ ^ᅵ Chungcheong avoidance composition.

[Claim 7]

6. The tortilla repellent composition of claim 5, wherein the cinnamon supercritical oil is contained in an amount of 0.1 to 20% by weight based on the total composition.

[Claim 8]

(a) a cosmetically effective amount of the composition of any one of the preceding claims; And (b) a pharmaceutically acceptable cosmetic composition comprising a cosmetically acceptable carrier.

[Claim 9]

An insect repelling method comprising applying the composition of claim 1 to the skin.

[Claim 10]

Claims 1 to 7 of claim 1 comprising applying the composition of any one of the claims to the area to obtain a barrier effect.