KR20160111769A - Composition for anti-itching effect comprising quinolone compounds - Google Patents

Abstract

The present invention relates to a composition for inhibiting or alleviating itchiness, comprising a quinoline-based compound and, more specifically, relates to a composition for preventing or treating various skin or systemic diseases accompanied with itchiness. The pharmaceutical composition for inhibiting or alleviating itchiness comprises a compound represented by chemical formula 1.

Description

[0001] The present invention relates to a composition for inhibiting or alleviating itching comprising a quinoline-based compound,

The present invention relates to a composition for inhibiting or alleviating an itch comprising a quinoline compound, and more particularly, to a composition capable of preventing or treating various skin or systemic diseases accompanied by itching by including the quinoline compound .

Itch is a sensation commonly associated with most skin disorders, along with pain, and is defined as an unpleasant sensation that causes the urge to scratch in the clinic (Yosipovitch et al, The Lancet, 361, pp. 690-93, 2003). Most of the causes except for biliary obstruction, kidney failure and parasitic phobia are confined to skin diseases (Sonja et al, Arch. Dermatol., 139, pp.1463-70, 2003). Examples of skin diseases that are particularly prone to itching include atopic dermatitis, urticaria, dry skin, seborrheic dermatitis, psoriasis and insect bites (Greaves et al, The Lancet., 348, pp.938-40, 1996). Among them, atopic dermatitis is a major cause of lowering the quality of life of patients with itching. In a study of atopic dermatitis patients, in severe atopic patients, about 15% of the sleep time is spent on scratching (Ebata et al, Br. J. Dermatol., 144, pp. 305-10, 2001). Therefore, there is a desperate need for a substance that inhibits the itching effectively while reducing toxicity and skin irritation.

Studies of itching and evaluation of itch inhibiting substances are mainly used in terms of ease of experimentation and management. Studies of itch with rodents have been accelerated, as Japanese researchers have found that itching-specific behavior, which is not easily observed in routine situations, is a scratching of the area injected with the itch inducer on the hind legs (Orito et al, Br. J. Dermatol., 150, pp. 33-8, 2004). It has also been shown that the intradermal injection method of injecting an itch-inducing drug between the epidermis and the dermis is most effective since the injected itching drug should not migrate from the injection site to another site or spread throughout the body (Kuraishi et al , Eur. J. Pharmacol., 275, pp. 229-23, 1995).

Examples of the itching inducing drugs used in the prior art include kallikrein, compound 48/80, serotonin, histamine, substance P (WO 2004/027413, JP2004-132794, JP 2003-313138, etc.) or a corrosive organic solvent (JP2001-321016) have been proposed. Of these, Compound 48/80 is less toxic and is more widely used for itching studies than other itching-inducing substances.

Corticosteroids, antihistamines, immunosuppressants, and capsaicin are used to treat itch, but these drugs have side effects in their own way. Adequate steroids can cause skin thinning, skin color change, or rash, and adverse effects can be suppressed by systemic side effects when used in large amounts over a long period of time. One-generation antihistamines are mainly used for systemic administration and have anti-parasympathetic effect, and the first-generation antihistamine, chlorpenilamine, did not inhibit the itching of patients with atopic dermatitis upon topical administration (Munday et al., Dermatology, 205, pp 40-45, 2002). Also, the use of topical antihistamines for atopic dermatitis is not recommended because of the risk of skin sensitization. Second-generation antihistamines without sedation Evastin and terfenadine can cause arrhythmias when taken with ketoconazole, erythromycin (Hey et al., Arzneimittelforschung, 46, pp159 -163, 1996). Cyclosporine, which is an immunosuppressant, may cause severe side effects such as hypertension, nephrotoxicity, drug interactions and the like when administered systemically.

Protocal (tacrolimus, FK506) and alldel (pimecrolimus), a calcineurin inhibitor developed recently as a topical formulation, have been shown to increase the incidence of leukemia in pediatric patients and, furthermore, (Gupta et al., JEADV, 16, pp. 100-114, 2002; Gupta and Chow, JEADV, 17, pp. 493-503, 2003). Capsaicin is widely known to be the most rapid and potent itching inhibitor, but its use is limited by strong skin irritation. Therefore, there is a need for more effective topical herbicide and skin irritation remedy that are safer without side effects.

The present invention provides a composition capable of inhibiting or alleviating itching caused by skin diseases or systemic diseases for various reasons.

In order to achieve the above object, the present invention provides a composition for inhibiting or reducing itching comprising a compound represented by the following formula (1): < EMI ID =

[Chemical Formula 1]

In Formula 1,

R ₁ and R ₂ are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, nitro, C ₁ to C ₄₀ alkyl, C ₃ to C ₄₀ cycloalkyl, C 3-40 heterocycloalkyl, C A group consisting of an aryl group having ₆ to ₆₀ carbon atoms, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkyloxy group, a C ₆ to C ₆₀ aryloxy group, and a C ₆ to C ₆₀ arylamine group ≪ / RTI >

The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyloxy, aryloxy and arylamine groups of R ₁ and R ₂ are each independently selected from the group consisting of deuterium, halogen, cyano, C ₁ to C ₄₀ An alkyl group, a C ₃ to C ₄₀ cycloalkyl group, a heteroaryl group having 3 to 40 nuclear atoms, a C ₆ to C ₆₀ aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkylox group, C ₆ ~ C ₆₀ aryloxy and C ₆ ~ may be unsubstituted or substituted by one substituent at least one selected from the group consisting of an aryl amine of the C ₆₀ of, when it is substituted with a plurality of substituents, these are equal to each other, or Can be different.

In one embodiment, R ₁ is preferably a substituted or unsubstituted C ₁ -C ₄₀ alkyl group, more preferably a substituted or unsubstituted methyl, ethyl, propyl, or butyl.

In one embodiment, R ₂ is preferably a substituted or unsubstituted 3 to 40 heterocycloalkyl group, more preferably a substituted or unsubstituted piperazine, piperidine, pyrrolidine or azetidine Can be Dean.

In one embodiment, the compound represented by Formula 1 may be contained in an amount of 0.1 to 10 μg / μl in the composition.

In one embodiment, the composition can be used for the prevention or treatment of skin or systemic diseases that cause itching. Wherein the itching may be serotonin or histamine-dependent, or may be non-specific, and is not particularly limited.

More specifically, the skin diseases may include eczematous dermatitis, urticaria, oto, insect bites, dry skin, or bacterial sarcoma. Examples of the systemic diseases include diabetes, chronic renal failure, chronic hemodialysis patients, , Anemia, malignant hematologic malignancies, intestinal parasitosis, hyperthyroidism, hypothyroidism or acquired immune deficiency syndrome, but it is not limited thereto and can be used for the prevention or treatment of various skin diseases or systemic diseases accompanied by itching .

One aspect of the present invention can be used as a pharmaceutical composition for inhibiting or alleviating itching.

Another aspect of the present invention may be used as a cosmetic composition for suppressing or alleviating itching.

Another aspect of the present invention can be used as a food composition for inhibiting or alleviating itching.

However, the term "itching" as used herein is a sensation commonly caused in most skin diseases, along with pain, which is defined as an unpleasant sensation which causes a urge to scratch in a clinic.

As used herein, the term " relief "includes the partial cure, improvement, and alleviation as well as the cure of the itch as described above.

The term "alkyl" as used herein means a monovalent substituent derived from a straight or branched saturated hydrocarbon having 1 to 40 carbon atoms. Examples thereof include, but are not limited to, methyl, ethyl, propyl, isobutyl, sec-butyl, pentyl, iso-amyl and hexyl.

As used herein, the term "alkenyl" means a monovalent substituent derived from a straight or branched chain unsaturated hydrocarbon having 2 to 40 carbon atoms and having at least one carbon-carbon double bond. Examples thereof include, but are not limited to, vinyl, allyl, isopropenyl, 2-butenyl, and the like.

As used herein, the term "alkynyl" means a monovalent substituent derived from a straight or branched chain unsaturated hydrocarbon having from 2 to 40 carbon atoms having at least one carbon-carbon triple bond. Examples thereof include, but are not limited to, ethynyl, 2-propynyl, and the like.

The term "aryl" as used herein means a monovalent substituent derived from a C6-C60 aromatic hydrocarbon in which a single ring or two or more rings are combined. Also, a form in which two or more rings are pendant or condensed with each other may be included. Examples of such aryl include, but are not limited to, phenyl, naphthyl, phenanthryl, anthryl, and the like.

As used herein, the term "heteroaryl" means a monovalent substituent derived from a monoheterocyclic or polyheterocyclic aromatic hydrocarbon having 5 to 40 nuclear atoms. Wherein at least one of the carbons, preferably one to three carbons, is replaced by a heteroatom such as N, O, S or Se. In addition, a form in which two or more rings are pendant or condensed with each other may be included, and further, a condensed form with an aryl group may be included. Examples of such heteroaryls include 6-membered monocyclic rings such as pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, phenoxathienyl, indolizinyl, indolyl indolyl), purinyl, quinolyl, benzothiazole, carbazolyl, and heterocyclic rings such as 2-furanyl, N-imidazolyl, 2- , 2-pyridinyl, 2-pyrimidinyl, and the like, but are not limited thereto.

As used herein, the term "aryloxy" means a monovalent substituent group represented by RO-, and R means an aryl group having 5 to 60 carbon atoms. Examples of such aryloxy include, but are not limited to, phenyloxy, naphthyloxy, diphenyloxy, and the like.

As used herein, the term "alkyloxy" means a monovalent substituent group represented by R'O-, wherein R 'represents an alkyl having 1 to 40 carbon atoms and may be linear, branched or cyclic cyclic structure. Examples of alkyloxy include, but are not limited to, methoxy, ethoxy, n-propoxy, 1-propoxy, t-butoxy, n-butoxy and pentoxy.

The term "arylamine" as used herein refers to an amine substituted with aryl having 6 to 60 carbon atoms.

The term "cycloalkyl" as used herein refers to a monovalent substituent derived from a monocyclic or polycyclic non-aromatic hydrocarbon having from 3 to 40 carbon atoms. Examples of such cycloalkyls include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl, adamantine, and the like.

The term " heterocycloalkyl ", as used herein, refers to a monovalent substituent derived from 3 to 40 non-aromatic hydrocarbons having from 3 to 40 nuclear atoms, wherein at least one carbon, preferably one to three carbons, O, S, or Se. Examples of such heterocycloalkyl include, but are not limited to, morpholine, piperazine, and the like.

The composition provided by the present invention can be used for prevention or treatment of various skin diseases or systemic diseases which have an excellent effect in inhibiting or alleviating itching and furthermore, it causes itching.

FIG. 1 shows the results of confirming the effect of suppressing or alleviating the itching of the composition according to an embodiment of the present invention.
FIG. 2 is a graph showing the inhibition or relaxation effect of alpha methylotonin-induced itching of the composition according to an embodiment of the present invention.
FIG. 3 shows the inhibition or relaxation effect of histamine-induced itching in a composition according to an embodiment of the present invention.
4 (a) and 4 (b) show the results of confirming the mechanism of action of the composition according to an embodiment of the present invention.
5 (a) and 5 (b) show the results of confirming the mechanism of action of the composition according to one embodiment of the present invention.

Hereinafter, preferred embodiments of the present invention will be described. However, the embodiments of the present invention can be modified into various other forms, and the scope of the present invention is not limited to the embodiments described below. Further, the embodiments of the present invention are provided to more fully explain the present invention to those skilled in the art.

The inventors of the present invention have found that quinoline-based compounds represented by the following formula 1 can effectively inhibit or alleviate itching caused by various skin diseases or systemic diseases, leading to the present invention.

Specifically, the present invention provides a composition for inhibiting or ameliorating itching comprising a compound represented by the following formula (1).

[Chemical Formula 1]

In Formula 1,

R ₁ and R ₂ are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, nitro, C ₁ to C ₄₀ alkyl, C ₃ to C ₄₀ cycloalkyl, C 3-40 heterocycloalkyl, C A group consisting of an aryl group having ₆ to ₆₀ carbon atoms, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkyloxy group, a C ₆ to C ₆₀ aryloxy group, and a C ₆ to C ₆₀ arylamine group ≪ / RTI >

The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyloxy, aryloxy and arylamine groups of R ₁ and R ₂ are each independently selected from the group consisting of deuterium, halogen, cyano, C ₁ to C ₄₀ An alkyl group, a C ₃ to C ₄₀ cycloalkyl group, a heteroaryl group having 3 to 40 nuclear atoms, a C ₆ to C ₆₀ aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkylox group, C ₆ ~ C ₆₀ aryloxy and C ₆ ~ may be unsubstituted or substituted by one substituent at least one selected from the group consisting of an aryl amine of the C ₆₀ of, when it is substituted with a plurality of substituents, these are equal to each other, or Can be different.

In one embodiment, R ₁ is preferably a substituted or unsubstituted C ₁ -C ₄₀ alkyl group, more preferably a substituted or unsubstituted methyl, ethyl, propyl, or butyl.

In one embodiment, R ₂ is preferably a substituted or unsubstituted 3 to 40 heterocycloalkyl group, more preferably a substituted or unsubstituted piperazine, piperidine, pyrrolidine or azetidine Can be Dean.

In the present invention, the above composition can be used for the prevention or treatment of a skin disease or systemic disease causing itching. Wherein the itching may be serotonin or histamine-dependent, or may be non-specific, and is not particularly limited.

More specifically, the skin diseases may include eczematous dermatitis, urticaria, oto, insect bites, dry skin, or bacterial sarcoma. Examples of the systemic diseases include diabetes, chronic renal failure, chronic hemodialysis patients, , Anemia, malignant hematologic malignancies, intestinal parasitosis, hyperthyroidism, hypothyroidism or acquired immune deficiency syndrome, but is not limited thereto and can be used for the prevention or treatment of various skin diseases or systemic diseases accompanied by itching .

In the present invention, the compound represented by the formula (1) contained in the composition may be contained in the composition in an amount of 0.1 to 10 μg / μl, preferably 0.1 to 5 μg / μl, or 0.1 to 3 μg / Or 0.2 to 2 μg / μl, or 0.2 to 1 μg / μl, and most preferably 0.2 to 0.4 μg / μl.

Meanwhile, one aspect of the present invention is to use the above composition as a pharmaceutical composition for inhibiting or alleviating itching.

Here, the pharmaceutical composition of the present invention may contain an appropriate solvent together with the compound of formula (1). The type of the solvent is not particularly limited. For example, water, saline, dimethyl sulfoxide DMSO) or a combination thereof.

In addition, the pharmaceutical composition of the present invention may further comprise an appropriate carrier, excipient or diluent according to a conventional method. Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate But are not limited to, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In addition, the pharmaceutical composition according to the present invention may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like, oral preparation, suppository or sterilized injection solution, Can be used. More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like. Such solid preparations can be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances and preservatives . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

In another aspect, the composition of the present invention can be used as a cosmetic composition for inhibiting or alleviating itching.

The cosmetic composition comprising the composition of the present invention as an active ingredient can be used as a skin lotion, a nutritional lotion, a nutrition essence, a massage cream, a cosmetic bath additive, a body lotion, a body milk, a bath oil, a baby oil, Skin lotions, skin creams, sunscreen cosmetics, cleansing milks, hair removal products, cosmetics, face and body lotions, face and body creams, skin whitening creams, hand lotions, hair lotions, Soap, facial wash, whole body cleanser, scalp cleanser, hair rinse, cosmetic soap, toothpaste, cosmetic cream, jasmine oil, bath soap, water soap, beauty soap, shampoo, hand cleanser Bleaching gel, toothpaste, and the like. To this end, the composition of the present invention may further comprise a solvent commonly used in the production of a cosmetic composition, or a suitable carrier, excipient or diluent.

For example, water, saline solution, DMSO, or a combination thereof may be used. Examples of the carrier, excipient or diluent include purified water, oil, wax But are not limited to, fatty acids, fatty acid alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, chelating agents, buffers, lower alcohols and the like. Further, if necessary, it may contain a whitening agent, a moisturizing agent, a vitamin, an ultraviolet screening agent, a perfume, a dye, an antibiotic, an antibacterial agent, and an antifungal agent.

As the oil, hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, palm oil, jojoba oil and avocado oil may be used. Examples of the wax include wax, wax, carnauba, candelilla, montan, ceresin, liquid paraffin, Can be used.

As the fatty acid, stearic acid, linoleic acid, linolenic acid and oleic acid may be used. As the fatty acid alcohol, cetyl alcohol, octyldodecanol, oleyl alcohol, panthenol, lanolin alcohol, stearyl alcohol and hexadecanol may be used As fatty acid esters, isopropyl myristate, isopropyl palmitate, and butyl stearate may be used. As the surfactant, a cationic surfactant, an anionic surfactant and a nonionic surfactant known in the art can be used, and a surfactant derived from a natural material is preferably used.

In addition, it may contain a hygroscopic agent, a thickening agent, an antioxidant and the like widely known in the field of cosmetics, and the kind and amount thereof are well known in the art.

In another aspect, the composition of the present invention can be used as a food composition for inhibiting or alleviating itching.

The food composition containing the composition of the present invention as an active ingredient may be prepared in the form of various foods such as beverage, gum, tea, vitamin complex, powder, granule, tablet, capsule, . Since the food composition of the present invention is composed of a plant extract having little toxicity and side effects, it can be safely used for prolonged use even for prophylactic purposes.

When the composition of the present invention is contained in the food composition, the amount thereof may be added in a proportion of 0.1 to 50% of the total weight.

Here, when the food composition is prepared in a beverage form, there are no particular limitations other than those containing the food composition at the indicated ratios and may contain various flavors or natural carbohydrates such as ordinary beverages as an additional ingredient. That is, natural carbohydrates include monosaccharides such as glucose, disaccharides such as fructose, sucrose and the like and sugar sugars such as polysaccharide, dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol can do. Examples of the above-mentioned flavors include natural flavors (such as tau martin and stevia extract (for example, rebaudioside A and glycyrrhizin) and synthetic flavors (for example, saccharine and aspartame).

In addition, the food composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated drink, and the like.

These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0.1 to about 50 parts by weight per 100 parts by weight of the composition of the present invention.

Example

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention, and it is to be understood by those skilled in the art that the present invention is not limited thereto It will be obvious.

[Preparation Examples 1 to 3]

DMSO and sterile physiological saline were prepared as a solvent, and then 4-methyl-2- (1-piperidinyl) -quinoline represented by the following formula 2 was added to each of 0.2 μg / μl, 0.4 μg / μl and 0.8 μg / μl ≪ / RTI >

(2)

[Experimental Example 1] Confirmation of inhibitory or mitigating effect of serotonin-induced itching

In order to confirm the effect of inhibiting or alleviating the itching of the composition according to the present invention, an itch-induced animal behavior model experiment was conducted as follows. This was accomplished by developing the method described in Kuraishi et al. (Kuraishi et al., 1995). Specifically, 10 male BL6 / C57 mice weighing 20 to 23 g were housed under temperature control at 23 to 25 ° C , Food and water were freely available. To induce itching in these mice, histamine and serotonin (alpha methyl serotonin), which are known to cause a sense of itching in humans, are used as shown below. First, 10 mice were mixed with zolethyl and rumpun at a volume ratio of 1: 4, and the mice were anesthetized by dosing with 1 ml / kg of each mouse. X-length was 2 cm x 2 cm in a square shape. After 24 hours, 100 μl of the composition prepared in Preparation Examples 1 to 3 was applied to the back of the neck of the epilated head. After 30 minutes, serotonin (10 μg / site ) Was injected intradermally, and as a control, only a mixed solvent of DMSO and sterilized physiological saline was applied. Thereafter, the movement of the mouse was observed for 30 minutes, and the number of scratches on the area injected with the hind leg was measured. The results are shown in FIG. However, the graph is obtained by calculating and analyzing the mean and standard deviation with respect to the number of scratches, and the statistical difference of the mean values is determined using a student t-test.

As shown in FIG. 1, when the composition of the present invention was applied, it was confirmed that the itching reaction was reduced compared with the control group. Furthermore, when the compositions of Preparative Examples 2 and 3 containing the compound of Formula 2 at a concentration of 0.4 μg / μl and 0.8 μg / μl were used, it was confirmed that the itching reaction was markedly decreased as compared with the control, This was the most effective.

[Experimental Example 2] Confirmation of inhibition or mitigation effect of alpha methylotonin-induced itching

100 μl of the composition prepared in Preparative Example 2 was applied to the back of the neck of the depilated mouse, and 50 μl of alpha methyl serotonin (10 μg / site) instead of serotonin was administered as the itching inducer And the number of times of scraping the area injected with the hindlimb of the mouse for 30 minutes was measured. The results are shown in FIG. 2.

As shown in FIG. 2, when the composition of Preparation Example 2 according to the present invention was applied, it was confirmed that the itching reaction was significantly reduced as compared with the control group.

[Experimental Example 3] Confirmation of suppression or mitigation effect of histamine-induced itching

100 μl of the composition prepared in Preparative Example 2 was applied to the back of the mouse neck of the epilated mouse, and 50 μl of histamine (500 μg / site) was injected intramuscularly instead of serotonin as an itching inducer. And the number of scratching of the area injected with the hindpaw for 30 minutes was measured. The results are shown in FIG.

As shown in FIG. 3, when the composition of Preparation Example 2 according to the present invention was applied, it was confirmed that the itching reaction was significantly reduced as compared with the control group.

[Experimental Example 4] The mechanism of action of the composition according to the present invention

The occurrence of serotonin-induced pruritus is caused by peripheral nerve stimulation. Thus, it was confirmed how the peripheral nerve activity induced by serotonin (or alphamethylserotonin) was blocked by the composition according to the present invention. To measure peripheral nerve excitement, skin-centric neural tissue was prepared. Specifically, the posterior legs of the BL6 / C57 mice were detached and the replica nerves were detached from the skin of the tissue. After the recording electrode was placed on the replica nerve, the activity of the single nerve was separated from the various nerve activity levels caused by skin stimulation and then measured. After securing the recording of single nerve activity in the skin-spinal nerve preservation tissue as described above, administration of alpha methyl serotonin and the composition prepared in Preparation Example 2 to the soles of the feet and instability frequency according to time, And the results are shown in the graphs of FIGS. 4 (a) and 4 (b).

As shown in FIG. 4 (a), the frequency of single neuronal activity after administration of alphamethyl serotonin was increased, and the activity by alpha methyl serotonin was blocked by the composition prepared in Preparation Example 2. The activity of each single nerve fiber was shown in FIG. 4 (b), and the neuronal activity by alphamethylserotonin was statistically significantly increased, and it was also confirmed by the composition prepared in Preparation Example 2 that it decreased significantly Respectively. As a result, Preparation Example 2 according to the present invention showed that the increase of the neural activity by the alpha methyl acts directly on the nerve fiber and blocks the activity.

[Experimental Example 5] The action mechanism of the composition according to the present invention

It was confirmed whether the composition according to the present invention directly blocked the excitability of the peripheral nerve by serotonin at the cellular level. Specifically, the spinal cord proximal ganglion cells of the mouse were separated and primary cultured, and these cells were administered with alpha methyl serotonin. Then, the composition prepared in Preparation Example 2 was administered, and the ganglion late ganglion cells Electrophysiological characteristics were recorded. The electrophysiological method was performed as follows. The recording electrode was made using a PC-10 puller (Narishige Co., Tokyo, Japan) with a glass capillary having an outer diameter of 1.5 mm (Harvard apparatus Ltd., Edenbridge, Kent, UK) -6 MΩ. The composition (mM) of the intracellular solution was 136 K-Gluconate, 10 NaCl, 1 MgCl2, 10 EGTA, 2 Mg-ATP and 0.1 Na- Was 140 NaCl, 2 CaCl2, 1 MgCl2, 5 KCl, 10 HEPES, 10 D-Glucose and the pH was adjusted to 7.4 with NaOH. The perfusion of the drug used in the examples was controlled using a manual valve and each drug was perfused at a rate of 10 ml / min for 3 seconds. The currents measured in the spinal ganglion ganglion cells were recorded using a membrane voltage clamped signal amplifier (EPC10 USB amplifier, HEKA electronik, Lambrecht, Germany) and analyzed using the PULSE program (HEKA electronik, Lambrecht, Germany) (21-23 < 0 > C). The results are shown graphically in Figs. 5 (a) and 5 (b).

As shown in Figs. 5 (a) and 5 (b), it was confirmed that alpha methylotenotin generated an inward current and this current was blocked by the composition of Preparation Example 2. [ Therefore, it can be seen that serotonin generates an inward current in peripheral nerve cells, and the composition according to the present invention has a characteristic of specifically blocking the above composition.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, It will be obvious to those of ordinary skill in the art.

Claims (13)

A pharmaceutical composition for inhibiting or treating itching comprising a compound represented by the following formula (1):
[Chemical Formula 1]

In Formula 1,
R ₁ and R ₂ are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, nitro, C ₁ to C ₄₀ alkyl, C ₃ to C ₄₀ cycloalkyl, C 3-40 heterocycloalkyl, C A group consisting of an aryl group having ₆ to ₆₀ carbon atoms, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkyloxy group, a C ₆ to C ₆₀ aryloxy group, and a C ₆ to C ₆₀ arylamine group ≪ / RTI >
The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyloxy, aryloxy and arylamine groups of R ₁ and R ₂ are each independently selected from the group consisting of deuterium, halogen, cyano, C ₁ to C ₄₀ An alkyl group, a C ₃ to C ₄₀ cycloalkyl group, a heteroaryl group having 3 to 40 nuclear atoms, a C ₆ to C ₆₀ aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkylox group, C ₆ ~ C ₆₀ aryloxy and C ₆ ~ may be unsubstituted or substituted by one substituent at least one selected from the group consisting of an aryl amine of the C ₆₀ of, when it is substituted with a plurality of substituents, these are equal to each other, or Can be different. The method according to claim 1,
Wherein said R ₁ is a substituted or unsubstituted C ₁ -C ₄₀ alkyl group. 3. The method of claim 2,
Wherein said R < ₁ > is methyl, ethyl, propyl or butyl. The method according to claim 1,
Wherein said R < ₂ > is a substituted or unsubstituted 3 to 40 heterocycloalkyl groups. The method of claim 3,
Wherein said R < _{2 >} is piperazine, piperidine, pyrrolidine or azetidine. The method according to claim 1,
Wherein the compound represented by Formula 1 is contained in an amount of 0.1 to 10 占 퐂 / 占 퐇. The method according to claim 1,
The composition can be used for the treatment and / or prophylaxis of eczematous dermatitis, urticaria, acne, insect bites, dry skin, bacterial sarcoma, diabetes, chronic kidney failure, chronic hemodialysis patients, biliary obstructive disease, anemia, malignant hematologic malignancy, intestinal parasitosis, Dyslipidemia, acquired immunodeficiency syndrome, and a prophylactic or therapeutic agent for itch. A cosmetic composition for suppressing or treating itching comprising a compound represented by the following formula (1):
[Chemical Formula 1]

In Formula 1,
R ₁ and R ₂ are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, nitro, C ₁ to C ₄₀ alkyl, C ₃ to C ₄₀ cycloalkyl, C 3-40 heterocycloalkyl, C A group consisting of an aryl group having ₆ to ₆₀ carbon atoms, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkyloxy group, a C ₆ to C ₆₀ aryloxy group, and a C ₆ to C ₆₀ arylamine group ≪ / RTI >
The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyloxy, aryloxy and arylamine groups of R ₁ and R ₂ are each independently selected from the group consisting of deuterium, halogen, cyano, C ₁ to C ₄₀ An alkyl group, a C ₃ to C ₄₀ cycloalkyl group, a heteroaryl group having 3 to 40 nuclear atoms, a C ₆ to C ₆₀ aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkylox group, C ₆ ~ C ₆₀ aryloxy and C ₆ ~ may be unsubstituted or substituted by one substituent at least one selected from the group consisting of an aryl amine of the C ₆₀ of, when it is substituted with a plurality of substituents, these are equal to each other, or Can be different. 9. The method of claim 8,
Wherein the R ₁ is a substituted or unsubstituted C ₁ -C ₄₀ alkyl group. 9. The method of claim 8,
Wherein R ₂ is a substituted or unsubstituted 3 to 40 heterocycloalkyl group. A food composition for suppressing or alleviating itching comprising a compound represented by the following formula (1): < EMI ID =
[Chemical Formula 1]

In Formula 1,
R ₁ and R ₂ are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, nitro, C ₁ to C ₄₀ alkyl, C ₃ to C ₄₀ cycloalkyl, C 3-40 heterocycloalkyl, C A group consisting of an aryl group having ₆ to ₆₀ carbon atoms, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkyloxy group, a C ₆ to C ₆₀ aryloxy group, and a C ₆ to C ₆₀ arylamine group ≪ / RTI >
The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyloxy, aryloxy and arylamine groups of R ₁ and R ₂ are each independently selected from the group consisting of deuterium, halogen, cyano, C ₁ to C ₄₀ An alkyl group, a C ₃ to C ₄₀ cycloalkyl group, a heteroaryl group having 3 to 40 nuclear atoms, a C ₆ to C ₆₀ aryl group, a heteroaryl group having 5 to 60 nuclear atoms, a C ₁ to C ₄₀ alkylox group, C ₆ ~ C ₆₀ aryloxy and C ₆ ~ may be unsubstituted or substituted by one substituent at least one selected from the group consisting of an aryl amine of the C ₆₀ of, when it is substituted with a plurality of substituents, these are equal to each other, or Can be different. 12. The method of claim 11,
Wherein the R ₁ is a substituted or unsubstituted C ₁ -C ₄₀ alkyl group. 12. The method of claim 11,
Wherein said R < ₂ > is a substituted or unsubstituted 3 to 40 heterocycloalkyl group.

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