WO2005007140A1

WO2005007140A1 - Pharmaceutical composition containing insect repellent

Info

Publication number: WO2005007140A1
Application number: PCT/KR2004/001774
Authority: WO
Inventors: Jong-Hoon Kim
Original assignee: Jong-Hoon Kim
Priority date: 2003-07-16
Filing date: 2004-07-16
Publication date: 2005-01-27
Also published as: KR20050009502A

Abstract

Disclosed is a pharmaceutical composition comprising (a) an insect repellent and (b) one or more components selected from the group consisting of an antihistamine, a topical anesthetic agent and an anti-inflammatory agent. The pharmaceutical composition has effects of repelling harmful insects and treating sites bitten by harmful insects.

Description

PHARMACETjπCAL COMPOSITION CONTAINING INSECT REPELLENT

Technical Field

The present invention relates, in general, to a pharmaceutical composition comprising an insect repellent and, more particularly, to a pharmaceutical composition for repelling haπnful insects and treating symptoms developed at sites bitten by harmful insects, which comprises (a) an insect repellent and (b) one or more components selected from the group consisting of an antMstamine, a topical anesthetic agent and an anu→nflammatory agent

Background Art

A wide spectrum of harmful insects (e.g., sucking insects, biting insects, mites, etc.), which bite people or suck their blood, inhabit the surroundings. To combat these harmful insects, insect repellents and therapeutic agents topically applied to sites bitten by harmful insects are used. The sucking insects include the common gnats (e.g., Aedes, Culex and Anopheles species), moth gnats (Phlebotomi), biting gnats (Culicoides species), sandflies (Simulium species), biting flies (e.g., Stomoxys calάtrans), tsetse flies (Glossina species), horseflies (Tabamis, Haematopota and Chγsops species), houseflies (e.g., Musca domestica and Fannia canicularis), flesh-flies (e.g., Sarcophaga camariά, myiasis-causing flies (e.g., Lucϊlia cuprina, Chysom ia chloropyga,

Hypodeπna bovis, Hypoderma lineatum, Dermatobia hominis, Oestrus ovis, Gasterophϊlus intestinalis, Cochliomyia hominivorax), bugs (e.g., Cimex lectulaήus, Rhodnius prolixus, Triatoma infestans), lice (e.g., Pediculus humanus, Haematopinus suis, Damalinia ovis), keds (e.g., Melophagus ovinus), fleas (e.g., Pulex iπitcms) and rat fleas (Xenopsylla cheopis). The biting insects include cockroaches (e.g., Blatteϊla gernianica, Periplcmeta americcma,

Blatta orientalis, S pella supellectiliwn), beetles (e.g., Sitophilus gi'anarius, Tenebήo molitor, Dermestes lardarius, Stegobiwn pcmiceum, Anobium puntaclum, Hylotrψes baj lus), termites (e.g., Reticulitermes luctfugus) and ants (e.g., Lasius niger). The mites include ticks (e.g., Oι iihodo"us moubata, Jxodes ricinus, Boophilus microplus, Amblyomma hebreum) and mites in the narrower sense (e.g., Sarcoptres scabiei, Dermanyssus gallinae). Insect repellents refer to compounds that function to prevent harmful insects from touching, and stinging and sucking or biting on surfaces to which they are attracted, for example, the external skin of animals and humans. Various compositions for repelling harmful insects have been developed so far, but are unpleasant when applied to the skin and inconvenient to use due to being used separately from cosmetics, thus limiting their applications to specific cases, such as long-term applications in outdoors where a large number of harmful insects inhabit. To accomplish convenient use of insect repellents, a composition with a different use (e.g., a cosmetic composition, U.S. Pat. No. 5,716,602) is supplemented with an insect repellent However, harmful insects (especially, mosquitoes) have a habit to attack someone sleeping at night rather than during the daytime, both outdoors and indoors. With regard to this habit of mosquitoes, conventional compositions for repelling insects are not suitable for use during the time when harmful insects substantially attack people in places where people spend most of their time. Therefore, there is a need for the development of compositions for repelling harmful insects, which are capable of being easily used during daily life (especially at home) regardless of time and place. On the other hand, many people carry therapeutic agents to be topically applied to sites that have been bitten by harmful insects. The insect-bitten sites develop symptoms including itching, edema and aching pain. In particular, when the sites are scratched due to the itching, blood and tissue fluids are stimulated to move to the sites while Mstamine production is stimulated, thereby causing irtflammation. To alleviate the itching and iriflairimation, therapeutic agents containing various antiMstamines, topical anesthetic agents and anti-inflammatory agents are used. However, since harmful insects have a habit of attacking one person several times, when the therapeutic agents are applied to insect bites immediately after the incidence of insect bites, they cannot stop the repeated incidences of insect bites.

Disclosure of the Invention

An object of the present invention is to provide a pharmaceutical composition having effects on both of repelling harmful insects and treating sites bitten by harmful insects. More particularly the present invention aims to provide a pharrnaceutical composition which is capable of repelling harmful insects when applied prior to the incidence of insect bites, alleviating itohing, aching pain and iriflarnmation at a bitten site when applied after insect bites, and preventing repeated biting of riarmrul insects. On the other band, based on the fact that insect repellents have a molecular structure that does not chemically react with other therapeutically active components, thus not causing a reduction in therapeutic effects of the therapeutically active components and other side effects, and being approved to be safe to humans when used for a prolonged time, the present inventors added an insect repellent to a therapeutic agent carried by people and applied to sites bitten by harmful insects, and found that the resulting pharmaceutical composition has an effect of repelling riarmful insects. In an aspect, the present invention provides a pharmaceutical composition for repelling haimful insects and treating symptoms developed at sites bitten by hamiful insects, which comprises (a) an insect repellent and (b) one or more components selected from the group consisting of an antiMstarrώie, a topical anesthetic agent and an anti-inflammatory agent In another aspect, the present invention provides a method of repelling harmful insects by applying the pharmaceutical composition to the external skin or clothing.

Best Mode for Carrying Out the Invention The pharmaceutical composition according to the present invention may comprise an insect repellent known in the art. Non-limiting examples of the insect repellent include N-N-detfryl toluamide, N,N-diethyl benzamide, p-menthane-3,8-diol, lS,3S,4S,6R-carene-3,4-diol (granted to Sumitomo Chemical Company, U.S. Pat No. 5,130,136), 1-piperidinecarboxylic acid, 2-(2- hydroxyethyl)-l-methylpropylester, l-(3-cyclohexene-l-ylcarbonyl)-2-methylpiperidine, l-(3-cyclohe xene-1-ylcarbonyl) piperidine, N^-diethyl mandelamide, isopulegol hydrate, ethyl-3-[N-n-butyl-N- acetyl] aminopropionate, dϋsopropyladipate, alpha biasabal, spearmint oil, benzyl alcohol, N-N- dielhylphenylacetamide, 3-acetyl-2-(2-,6-dimethyl-5-heptenyl) oxa∞lidine, (2-hydroxymethylcyclohe xyl) acetic acid lactone, and eucalyptol. Preferably, the pliarrnaceutical composition according to the present invention comprises N,N-diethyl toluamide as an insect repellent. Each of the insect repellents may be used singly or in combinations of two or more. The insect repellents may be used in an amount of 1 wt% to 50 wt%, preferably 5 wt% to 30 wt%, and most preferably 10 wt% to 25 wt%, based on the total weight of the pharmaceutical composition of the present invention. In addition to an insect repellent to prevent hamiful insects from biting as described above, the pharmaceutical composition according to the present invention may comprise a component to alleviate or treat "symptoms developed at sites bitten by baπriful insects (e.g., itehing, aching pain, inflammation and edema)". The component includes anti stamines, topical anesthetic agents and anti- inflarrrmatory agents. The pharmaceutical composition according to the present invention includes at least one selected from among the components. Hereinafter each of the components will be described in detail. The pharmaceutical composition according to the present invention may comprise an antihistamine known in the art. Non-limiting examples of the antihistamine include acrivastine, astemizole, azatadine, azelastine, bromo&phenhydramine, brompheriiramine, carbinoxamine, cetirizine, c oφheriiramine, cyproheptadine, dexbrompheniramine, dexc oφhemramine, dphenhydramine, mepyramine, promethazine, ebastine, ketotifen, lodoxamide, loratidine, levocuvastine, mequitazine, oxatomide, pyrilamine, phenindarnine, phenyltoloxamine, setastine, taztfylline, temelastine, terfenadine, tripelennamine, and pharmaceutically acceptable salts thereof. Preferably, the pharmaceutical composition according to the present invention comprises dphenhydramine as an antihistamine. Each of the antiMstamines may be used singly or in combinations of two or more. The antitastamines may be used in an amount of 0.05 wt% to 10 wt%, preferably 0.1 wt% to 5 wt%, and most preferably 0.5 wt% to 2.5 wt%, based on the total weight of the pharmaceutical composition of the present invention. The pharmaceutical composition according to the present invention may comprise a topical anesthetic agent known in the art Non-limitii g examples of the topical anesthetic agent include dibucaine hydrochloride, benzocaine, butamben, piperocaine hydrochloride, oxybuprocaine hydrochloride, tetracaine hydrochloride, lidocaine hydrochloride, cinchocaine hydrochloride, oxetacaine, propirocaine hydrochloride, bupivacaine hydrochloride, mepivacaine hydrochloride, dyclonine hydrochloride, fomocaine hydrochloride, quinisocaine hydrochloride, polydocanol, and pharmaceutically acceptable salts thereof. Preferably, the pharmaceutical composition according to the present invention comprises dibucaine hydrochloride as a topical anesthetic agent. Each of the topical anesthetic agents may be used singly or in combinations of two or more. The topical anesthetic agents may be used in an amount of 0.01 wt% to 5 wt%, preferably 0.05 wt% to 2.5 wt%, and most preferably 0.1 wt% to 1 wt%, based on the total weight of the pharmaceutical composition of the present invention. The pharmaceutical composition according to the present invention may comprise an anti- Mammatory agent known in the art. The anti-Mammatory agent includes steroidal and non- steroidal anti-inflammatory agents. Non-limiting examples of the steroidal anti- ammatory agent include 21- acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, triamcinolone, clobetasol, hydrocortisone, fludrocortisone, flurandrenolide, cortisone, desonide, methylprednisolone, fluocinonide, medrysone, desoximetasone, dexamethasone, hexacetonide, fluorometholone, diflorasone, flunisolide, prednisone, paramethasone, benetonide, halcinonide, prednisolone, and pharmaceutically acceptable salts thereof. Non-limiting examples of the non-steroidal anti-inflammatory agent include acetylsalicylic acid, glycyrrhetic acid, ii domethacin, suprofen, phenylbutazone, sulindac, ibuprofen, naproxen, ketoprofen, flurbiprofen, piroxicam, diclofenac, and phannaceutically acceptable salts thereof.

Preferably, the pharmaceutical composition according to the present invention comprises glycyrrhetic acid as an anti-inflammatory agent Each of the anti-ύiflammatory agents may be used singly or in combinations of two or more. The anti-inflammatory agents may be used in an amount of 0.05 wt% to 5 wt%, preferably 0.01 wt% to 1 wt%. and most preferably 0.05 wt% to 0.5 wt%, based on the total weight of the pharmaceutical composition of the present invention. In addition to the aforementioned antihistamines, topical anesthetic agents and anti- inflammatory agents, the pharmaceutical composition according to the present invention may further comprise other components known in the art to alleviate symptoms developed at sites bitten by harmful insects (e.g., antipruritic agents or cool-feeling agents). The pharmaceutical composition of the present invention preferably comprises an antipruritic agent to rapidly alleviate itching. Non-limiting examples of the antipruritic agent include crotamiton, methdilazine, trimeprazine, and pharmaceutically acceptable salts thereof. Each of the antipruritic agents may be used singly or in combinations of two or more. The antipruritic agents may be used in an amount of 0.1 wt% to 20 wt%, preferably 0.5 wt% to 15 wt%, and most preferably 1 wt% to 10 wt%, based on the total weight of the pharmaceutical composition of the present invention. In addition, the pharmaceutical composition of the present invention preferably comprises a cool-feeling agent to impart a refreshing feeling by local stimulation when applied to a bitten site of the skin. Examples of the cool-feeling agent include menthol, camphor, borneol, cineol, thymol, eucalyptus, menthane, glycosyl-mono-menthyl-oacetate, 3-l-menthoxypropane-l-2-diol_s menthyl malonate, l-menthyl-3-hydroxybutyrate, menthyl salicylate, piperitone, peppermint, beta-pinene and spearmint Each of the cool-feeling agents may be used singly or in combinations of two or more. The cool-feeling agents may be used in an amount of 0.1 wt% to 20 wt%, preferably 0.5 wt% to 10 wt%, and most preferably 1 wt% to 5 wt%, based on the total weight of the pharmaceutical composition of the present invention. The pharmaceutical composition according to the present invention is preferably formulated to a topically admirEStrable form. The formulation for topical aάtøirustration includes ointments, gels, creams, liniments and lotions. This formulation may be prepared according to a guidebook known in the art: Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042 (Chapter 87: Blaug, Seymour). In an aspect, the pharmaceutical composition according to the present invention may be formulated to an ointment, which is prepared by suitably combining and processing ointment base materials, active components, additives typically contained in other ointments, etc. The ointment base materials are selected from among those known in the art, such as higher fatty acids or esters thereof (e.g., adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipic acid esters, myristic acid esters, palmitatic acid esters, dimethyl sebacate, hexyl laurate, cetyl isooctanate, etc.), waxes (e.g., spermaceti, beeswax, cerecine, etc.), surfactants (e.g., polyoxyethylene alkylether phosphate esters, etc.), higher alcohols (e.g., cetanol, stearylalcohol, cetostearylalcohol, etc.), silicon oils (e.g., dimethyl polysiloxanes, methylphenyl polysiloxanes, glycol methyl polysiloxanes, silicon glycol copolymers, etc.), hydrocarbons (e.g., hydrophilic petrolatum, white petiolatum, purified lanolin, liquid paraffin, etc.), water, humectants (e.g., glycerin, propylene glycol, butylene glycol, sorbitol, etc.), and infection inhibitors. In another aspect, the pharmaceutical composition according to the present invention may be formulated to a gel, which is prepared by suitably combύiing and processing gel base materials, active components, additives typically contained in other gels, etc. The gel base materials are selected from among those known in the art, such as lower alcohols (e.g., ethanol, isopropyl alcohol, etc.), water, gelling agents (e.g., carboxyvinyl polymers, hydroxyethyl cellulose, ethyl cellulose, carboxymethyl cellulose, propylene lycol alginate esters, etc.), neutralizing agents (e.g., triethanolamine, αϊsopropanolamine, sodium hydroxide, etc.), surfactants (e.g., sorbitane sesquioleate, sorbitane trioleate, sorbitane monooleate, sorbitane monostearate, sorbitane monolaurate, polyethylene glycol monostearate, polyoxyethylene nonyl phenylether, polyoxyethylene laurylethα, etc.), and infection inhibitors. In a further aspect, the pharmaceutical composition according to the present invention may be formulated to a cream, which is prepared by suitably combining and processing cream base materials, active components, additives typically contained in other creams, etc. The cream base materials are selected from among those known in the art, such as higher fatty acid esters (e.g., myristic acid esters, palmitic acid esters, dimethyl sebacate, hexyl laurate, cetyl isooctanate, etc.), lower alcohols (e.g., ethanol, isopropanol, etc.), carbohydrates (e.g., liquid paraffin, squalane, etc.), multivalent alcohols (e.g., propylene glycol, 1,3-butylene glycol, etc.), higher alcohols (e.g., 2-hexyldecanol, cetanol, 2- octyldecanol, etc.), emulsifying agents (e.g., polyoxyethylene alkyletfiers, fatty acid esters, polyethylene glycol fatty acid esters, etc.), antiseptics (e.g., paraoxybenzoic acid esters, etc.), and infection inhibitors. In still another aspect, the pharmaceutical composition according to the present invention may be formulated to a Hniment, which is prepared by suitably combining and processing an active component with alcohols (e.g., monovalent alcohols such as ethanol, propanol and isopropanol, multivalent alcohols such as polyethylene glycol, propylene glycol and butylene glycol, etc.), water, fatter acid esters (e.g., various esters of adipic acid, sebacic acid, myristic acid, etc.), surfactants (e.g., polyoxyethylene alkylethers, etc.), if desired, in combination with ultraviolet absorbers, antioxidants, neutralizers for contiolling pH, viscosity controlling agents (e.g., methyl cellulose, carboxyvinyl polymers, hydroxypropyl cellulose, etc.), and infection inhibitors. In still another aspect, the pharmaceutical composition according to the present invention may be formulated to an aerosol, which is prepared using a liquid or a suspension of an active component and a propellant The liquid or suspension may be prepared using a diluting agent typically used in the art or used in the preparation of injectable preparations. Typically used propellants may be used, such as liquefied gas propellants including chlorofluoromethane, such as freon-12 (cMorodifluoromethane) and freon-123 (tiifluoroαichloroethane), and compressed gas propellants including nitrogen and carbon dioxide gases. An aerosol may include a solution adjuvant and a buffering agent, which are typically used in the art, and, if desired, may further include a colorant, a preservative, an aromatic and a flavoring agent Daily dosage of the pharmaceutical composition according to the present invention may vary depending on patients' age, sex and skin condition, application sites, application frequency, formulation types, adjuvant types, etc, but typically ranges from 0.01 mg to 10 mg, preferably 0.05 mg to 5 mg, and most preferably 0.5 mgto 1 mg. The present invention provides a method of repelling harmful insects by applying the pharmaceutical composition to the skin or clothing. In particular, in case of applying prior to any incidence of insect bites, the pharmaceutical composition is preferably applied to clothing rather than the skin. This is because the temperature of clothing is lower than body temperature, resulting in delayed evaporation of an insect repellant A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as the limit of the present invention.

EXAMPLE Preparation of a liniment containing an insect repellent

Active components were dissolved in 38 g of ethanol according to the amounts listed in Table

1, below. 12 g of propylene glycol, 0.8 g of methylcellulose and 3.0 g of diethylsebacate were added to the solution and sufficiently dispersed with stirring. To this solution, 0.07 g of sodium hydroxide dissolved in purified water was added with stirring. The solution was stirred until it was homogenously mixed, thus generating a linimen

TABLE 1 Components of a liniment and their contents

COMPARATIVE EXAMPLE Another lbiment not containing an insect repellent was prepared according to the same method as the above Example except that diethyl toluamide in the components listed in the above Table 1 was not used.

EXPERIMENTAL EXAMPLE 1 Assay for insect repelling effect of liniments in guinea pigs Test animal: Aedes aegypti Test mosquitoes number: about 1,000 Guinea pigs were shaved on the back over an area of about 50 cm², and were put into a narrow box to allow mosquitoes to access only the shaved area of guinea pig. At the state of being placed in the box, guinea pigs were put into a cage of 60x60x60cm, which contained mosquitoes fed with only sugared water. After 10 min, guinea pigs were taken out from the cage, and sites bitten by mosquitoes were counted and recorded. In a group, the pharmaceutical composition prepared in Example was applied to the bitten sites of guinea pigs. In another group, the pharmaceutical composition prepared in Comparative Example was applied to the bitten sites of guinea pigs. Then, guinea pigs were put into the cage. After two hours, guinea pigs were taken out from the cage, and sites bitten by mosquitoes were counted and recorded. Guinea pigs were again put into the cage, and, after two hours, were taken out from the cage, followed by counting the number of mosquitoes' bites. This step was repeated twice more, until efficacy of the insect repellent was maintained.

TABLE 2 Insect repelling effect of the pharmaceutical composition according to the present invention in relation to time

As shown in Table 2, in guinea pigs topically treated with the pharmaceutical composition of Comparative Example, mosquitoes' bites increased rapidly in relation to time. In contrast, in guinea pigs topically treated with the pharmaceutical composition of Example, mosquitoes' bites increased slightly in relation to time, indicating that the pharmaceutical composition according to the present invention has the effect of repelling harmful insects. In addition, when the bitten sites of guinea pigs were observed with the naked eye, inflammation and edema were alleviated in guinea pigs topically treated with the pharmaceutical composition of Example. That is, the pharmaceutical composition of the present invention alleviated symptoms developed at bitten sites, as well as displaying the effect of repelling harmful insects. In addition, diethyl toluamide, contained in the pliarmaceutical composition of the present invention, maintained its insect repelling effect for a certain period of time similar to that known in the art, indicating that diethyl toluamide maintains its activity even when mixed with other components.

EXPERIMENTAL EXAMPLE 2 Clinical tests Test subject: a present inventor Test period: 17 days The test subject, a present inventor, had a physical constitution sweating profusely and being likely to be bitten by mosquitoes. The subject was bitten with various frequencies of three to ten times daily. Clinical tests were perforated with the liniment prepared in Example, as follows.

Test l After the subject was bitten on the right foot, the liniment of Example was applied once to the bitten site (the first bite). Until the next morning, additional application of the liniment was not performed. - Total bites: six (including the first bite) - Two bites on hands; and three bites on arms

Test 2 After the subject was bitten on the right hand, the liniment of Example was applied once to the bitten site. Until the next morning, additional application of the liniment was not performed. - Total bites: six (including the first bite) - One bite on the fleshy inside of the thigh; three bites on feet; and one bite on the left hand

Test 3 After the subject was bitten on the right hand, the liniment of Example was applied once to the bitten site and a certain area of the left hand (the "certain area", as used herein, refers to an area that is not bitten by mosquitoes but substantially treated with the liniment of Example, and, hereinafter, the term "certain area" has the same meaning). Until the next morning, additional application of the liniment was not performed. - Total bites: three (including the first bite) -Two bites on feet

Test 4 After the subject was bitten on the left foot, the liriiment of Example was applied once to the bitten site and a certain area of the right foot. Until the next moming, additional application of the liniment was not performed. - Total bites: five (including the first bite) - Two bites on arms; and two bites on face

Test5 After the subject was bitten on the left hand, the Imiment of Example was applied once to the bitten site and certain areas of the right arm, the left foot and the right foot. Until the next morning, additional application of the liniment was not performed. - Total bites: two (including the first bite) - One bite on face Test 6 After the subject was bitten on the left hand, the liniment of Example was applied twice to the bitten site and certain areas of the right arm, the left foot and the right foot. Until the next morning, additional application of the liniment was not performed. - Total bites: one (including the first bite)

Test 7 Prior to any incidence of mosquitoes' bites to the subject, the liniment of Example was applied twice to both hands and both feet of the subject Until the next morning, additional application of the liniment was not performed. - No bites

Test 8 Prior to any incidence of mosquitoes' bites to the subject, the liniment of Example was applied twice to both hands and both feet of the subject. Until the next morning, additional application of the liniment was not performed. -No bites

Test 9 Prior to any incidence of mosquitoes' bites to the subject, the liniment of Example was applied twice to a lower part of each of an upper nightshirt and knee trousers. Until the next morning, additional application of the liniment was not perfomied. -Total bites: One - One bite on the right foot Test 10 Prior to any incidence of mosquitoes' bites to the subject, the liniment of Example was applied twice to a lower part of each of an upper nightshirt and knee trousers and both feet. Until the next morning, additional application of the liniment was not performed. -No bites

As apparent from data of the tests 1 to 6, when applied to sites bitten by harmful insects, the pharmaceutical composition according to the present invention alleviated itching, aching pain and inflammation, as well as preventing repeated insect bites. In addition, the tests 7 to 10 revealed that, in case of applying prior to any incidence of insect bites, the present composition is effective in repelling hamiful insects. These results indicate that the pharmaceutical composition of the present invention can prevent people from being bitten by liarmful insects when applied to the skin or clothing.

Claims

1. A pharmaceutical composition for repelling liarmful insects and treating symptoms developed at sites bitten by harmful insects, which comprises (a) an insect repellent and (b) one or more components selected from the group consisting of an antihistamine, a topical anesthetic agent and an anti-iriflarnmatory agent.

2. The pharmaceutical composition according to claim 1, wherein the insect repellent is selected from the group consisting of N,N-cliethyl toluamide, N,N-diethyl benzamide, p-menthane-3,8- diol, 1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-l-methylpropylester, l-(3-cyclohexene-l- ylcarb nyl)-2-methylpiperidine, l-(3-cyclohexene-l-ylcarbonyl) piperidine, N,N-diethyl mandelamide, isopulegol hydrate, ethyl-3-[N-n-butyl-N-acetyl] aminopropionate, diisopropyladipate, alpha biasabal, spearmint oil, benzyl alcohol, N-N-diethylphenylacetamide, 3-acetyl-2-(2-,6-dimethyl-5-heptenyl) oxazolidine, (2-hydroxymethylcyclohexyl) acetic acid lactone, and eucalyptol.

3. The pharmaceutical composition according to claim 1 or 2, wherein the insect repellent is contained in an amount of 1 wt% to 50 wt% based on the total weight of the composition.

4. The ptarmaceutical composition according to claim 1, wherein the antiMstamine is selected from the group consisting of acrivastine, astemizole, azatadine, azelastine, bromodiphenhydramine, brompheriiramine, carbinoxamine, cetirizine, cMoφheriiramine, cyproheptadine, dexbrompheriiramine, dexcMoφheriirarnine, ώpherihydramine, mepyramine, promethazine, ebastine, ketotifen, lodoxamide, loratidine, levocuvastine, mequitazine, oxatomide, phenindamine, phenyltoloxamine, pyrilamine, setastine, tazifylline, temelastine, teifenadine, tripelemiamine, and pharmaceutically acceptable salts thereof.

5. The pharmaceutical composition according to claim 1 or 4, wherein the antiMstarnine is contained in an amount of 0.05 wt% to 10 wt% based on the total weight of the composition.

6. The pharmaceutical composition according to claim 1, wherein the topical anesthetic agent is selected from the group consisting of dibucaine hydrochloride, benzocaine, butamben, piperocaine hydrochloride, oxybuprocaine hydrochloride, tetracaine hydrochloride, Hdocaine hydrochloride, cinchocaine hydrochloride, oxetacaine, propirocaine hydrochloride, bupivacaine hydrochloride, mepivacaine hydrochloride, dyclonine hydrochloride, fomocaine hydrochloride, quimsocaine hydrochloride, polydocanol, and pharmaceutically acceptable salts thereof

7. The pharmaceutical composition according to claim 1 or 6, wherein the topical anesthetic agent is contained in an amount of 0.01 wt% to 5 wt% based on the total weight of the composition.

8. The pharmaceutical composition according to claim 1, wherein the anti-inflammatory agent is selected from the group consisting of 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone. betamethasone, clobetasol, hydrocortisone, cortisone, desonide, desoximetasone, dexamethasone, diflorasone, fludrocortisone, flunisolide, prednisone, benetonide, fluocinonide, fluorometholone, flurandrenolide, halcinonide, methylprednisolone, medrysone, paramethasone, prednisolone, triamcinolone, hexacetonide, acetylsalicylic acid, glycynhetic acid, indomethacin, suprofen, phenylbutazone, sulindac, ibuprofen, naproxen, ketoprofen, flurbiprofen, piroxicam, diclofenac, and pharmaceutically acceptable salts thereof.

9. The pha naceutical composition according to claim 1 or 8, wherein the anti-inflammatory agent is contained in an amount of 0.05 wt% to 5 wt% based on the total weight of the composition.

10. The pharmaceutical composition according to claim 1, further comprising an antipruritic agent or a cool-feeling agent.

11. A method of repelling liarmful insects by applying the pliarmaceutical composition according to any one of claims 1 to 10 to the skin or clothing.