WO2017142368A2 - Composition for preventing and treating allergic or inflammatory skin disease - Google Patents

Composition for preventing and treating allergic or inflammatory skin disease Download PDF

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WO2017142368A2
WO2017142368A2 PCT/KR2017/001808 KR2017001808W WO2017142368A2 WO 2017142368 A2 WO2017142368 A2 WO 2017142368A2 KR 2017001808 W KR2017001808 W KR 2017001808W WO 2017142368 A2 WO2017142368 A2 WO 2017142368A2
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formula
allergic
composition
present
dermatitis
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PCT/KR2017/001808
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French (fr)
Korean (ko)
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WO2017142368A3 (en
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한명관
오유근
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전북대학교 산학협력단
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Priority claimed from KR1020170021592A external-priority patent/KR20170098182A/en
Publication of WO2017142368A2 publication Critical patent/WO2017142368A2/en
Publication of WO2017142368A3 publication Critical patent/WO2017142368A3/en

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  • the present invention relates to a composition for the prophylaxis or treatment of allergic or inflammatory skin diseases comprising NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • Itching is a dermatological symptom with severe pain that increases the feeling of scratching and is a representative symptom of atopic dermatitis, contact dermatitis, urticaria and various skin diseases. Severe itching in skin diseases, along with secondary exacerbations such as sleep disorders, emotional instability, and irritable stress reactions, not only have a significant effect on the quality of life of the same patients, but also lead to a vicious cycle of the disease itself. It also causes significant levels of social and psychological distress for those around them.
  • the skin is composed of three layers from the outside, epidermis, dermis and subcutaneous fat layer.
  • the skin is the largest organ in the body and is exposed outside, making it easy to recognize the itching caused by external stimuli or internal lesions on the skin.
  • keratinocytes which form one component of the epidermis, secrete various types of inflammatory cytokines, interleukin, TNF-a, interferon, and chemokine, which are known as immune response regulators. Reacts sensitively to stimuli. For this reason, various diseases accompanied by itching occur frequently on the skin.
  • Atopic dermatitis is a chronic inflammatory disease with aggravation and remission, which is caused by multifactorial factors such as immunological dysfunction and exposure to allergens.
  • Repeated scratching of skin lesions caused by the severe itching of atopic dermatitis worsens dermatitis with the collapse of the skin barrier. Therefore, controlling the scratching behavior due to itching or itching will be an important and effective treatment for atopic dermatitis. Itching is accompanied by a wound, which is accompanied by wounds caused by bacterial infection and secondary allergens caused by external allergens.
  • the present inventors have made efforts to develop a new drug which is excellent in preventing or treating allergic or inflammatory skin diseases without any side effects, and as a result, NED19, bromo-cyclic ADP-ribose, and emodine have a histamine dependency and a histamine ratio.
  • the present invention was completed by confirming that not only dependent itching but also an improvement effect on various allergic or inflammatory skin diseases such as itching by atopic dermatitis is excellent.
  • Another object of the present invention is to provide a method for preventing or treating allergic or inflammatory skin diseases, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
  • Still another object of the present invention is to provide a composition for alleviating or suppressing itching, including NED19, bromo-cyclic ADP-ribose, or emodine as an active ingredient.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • the present invention provides a skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • the present invention provides a health food composition for the prevention or improvement of allergic or inflammatory skin diseases comprising NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • the present invention also provides a method for preventing or treating allergic or inflammatory skin diseases, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
  • the present invention provides a cosmetic composition for alleviating or suppressing itching, including NED19, bromo-cyclic ADP-ribose, or emodine as an active ingredient.
  • the present invention also provides a method for alleviating or suppressing itching, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
  • NED19, bromo-cyclic ADP-ribose and emodine of the present invention are excellent in the prevention and treatment of various allergic or inflammatory skin diseases, including not only histamine-dependent and histamine-independent itch, but also itch caused by atopic dermatitis, It can be variously used as medicine, external skin preparation, food and cosmetics.
  • 1 is a diagram showing the effect of NED19 on the relief of histamine induced itch.
  • FIG. 2 is a diagram showing the effect of bromo-cyclic ADP-ribose on chloroquine induced itch relief.
  • FIG. 3 is a diagram showing the effect of emodin on the histamine induced itching relief.
  • FIG. 4 is a diagram showing the effect of emodine on chloroquine induced itch relief.
  • FIG. 5 is a diagram showing the effect of emodin on the itch relief by atopic dermatitis.
  • the present invention provides a composition for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • the composition includes a pharmaceutical composition, a topical skin composition and a nutraceutical composition.
  • the present invention also provides a method for preventing or treating allergic or inflammatory skin diseases, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
  • the present invention provides a pharmaceutical composition for the prophylaxis or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • the active ingredient NED19 includes both trans-NED19 or cis-NED19, but is not limited thereto.
  • the active ingredient NED19 ((1R, 3S) -1- [3-[[4- (2-Fluorophenyl) piperazin-1-yl] methyl] -4-methoxyphenyl] -2,3,4, 9-tetrahydro-1H-pyrido [3,4-b] indole-3-carboxylic acid) may be represented by the following Chemical Formula 1.
  • bromo-cyclic ADP-ribose (8-bromo-cyclic adenosine diphosphate ribose)
  • formula (2) the active ingredient bromo-cyclic ADP-ribose (8-bromo-cyclic adenosine diphosphate ribose)
  • the active ingredient emodin (emodin) may be represented by the following formula (3).
  • NED19, bromo-cyclic ADP-ribose, or emodine may be purchased commercially or directly synthesized, but are not limited thereto.
  • the compounds of the present invention can be prepared with pharmaceutically acceptable salts and solvates according to methods conventional in the art.
  • Pharmaceutically acceptable salts of the compounds of the invention include, but are not limited to, salts of acidic or basic groups that may be present in the compounds of the invention.
  • prevention means any action that prevents the disease by eliminating or early detecting the etiology of allergic or inflammatory skin disease.
  • treatment means all the actions that improve or beneficially change the symptoms caused by allergic or inflammatory skin diseases by the composition of the present invention.
  • allergy and inflammation are one of the defense reactions of biological tissues
  • the allergy is a sudden change in the ability to react in vivo when the organism comes in contact with any foreign substance, that is, the antigen antibody reaction occurs, the response It is said to be sensitive.
  • inflammation refers to complex lesions that involve three types: tissue degeneration, circulatory disorders and exudates, and tissue proliferation.
  • allergic or inflammatory skin diseases are atopic dermatitis, allergic dermatitis, contact dermatitis, acne. , Seborrheic dermatitis, sweat, urticaria or psoriasis, more preferably atopic dermatitis, contact dermatitis or itching, but the present invention is not limited thereto.
  • NED19, bromo-cyclic ADP-ribose and emodine of the present invention are excellent in the prevention and treatment of various allergic or inflammatory skin diseases, including not only histamine-dependent and histamine-independent itch, but also itch caused by atopic dermatitis, It can be variously used as medicine, external skin preparation, food and cosmetics.
  • the composition may further include one or more known active ingredients having an allergic or inflammatory skin disease prevention or treatment effect together with NED19, bromo-cyclic ADP-ribose, and emodine.
  • the composition may further comprise a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives are starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, hydrogen phosphate Calcium, lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, carnauba wax, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, white sugar and the like can be used.
  • the pharmaceutically acceptable additive according to the present invention is preferably included 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
  • the composition can be administered in various oral or parenteral dosage forms during actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used, or Excipients can be formulated and suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently, Mack Publishing Company, Easton PA.
  • diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used, or Excipients can be formulated and suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently, Mack Publishing Company, Easton PA.
  • Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, mineral oil and the like.
  • the solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or sucrose. It is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium styrate talc are also used.
  • the liquid preparations for oral administration include suspensions, solvents, emulsions, syrups, etc.
  • various excipients for example, wetting agents, sweeteners, fragrances, preservatives, etc. This may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the parenteral administration may be made using external skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection.
  • the term "administration" means providing a subject with a composition of the present invention in any suitable manner.
  • the preferred dosage of the composition depends on the condition and weight of the individual, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
  • the NED19, bromo-cyclic ADP-ribose and emodine of the present invention may be administered in an amount of 0.1 to 10000 mg / kg body weight per day.
  • Administration of the composition may be administered once a day, may be divided several times.
  • the composition can be administered to the subject by various routes. All modes of administration can be envisaged, for example, can be administered by oral, rectal or intravenous, intramuscular or subcutaneous injection, and can be administered by any route of application to the skin.
  • the composition may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of allergic or inflammatory skin diseases.
  • the present invention provides a skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • the composition may further contain one or more known active ingredients having a prophylactic or therapeutic effect of allergic or inflammatory skin diseases together with NED19, bromo-cyclic ADP-ribose or emimodine.
  • the composition is not particularly limited in its formulation according to the desired body part, it may be prepared in any formulation conventionally prepared with reference to the known art.
  • liquids, ointments, creams, lotions, sprays, patches, oils, waxes, emulsions, suspensions, gels or aerosols may be used in the form, but is not limited thereto.
  • the composition may include conventional additives, for example, preservatives, solvents to aid the penetration of medicines, softeners in the case of ointments and creams, etc., may contain a conventional carrier such as ethanol or oleyl alcohol. have.
  • the composition is not limited to the above-described components, and may include other components blended with a conventional cosmetic composition or a pharmaceutical composition, if necessary.
  • a conventional cosmetic composition or a pharmaceutical composition for example, fats and oils, moisturizers, emollients, surfactants, organic or inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, blood circulation promoters, Coolants, limiting agents, purified water, and the like.
  • the present invention provides a dietary supplement for the prevention or improvement of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
  • health functional food refers to a food having a bioregulatory function, such as prevention and improvement of disease, biodefence, immunity, recovery from illness, and inhibition of aging, and should be harmless to the human body when taken in the long term. .
  • the NED19, bromo-cyclic ADP-ribose or emodine when the substance is used as a food additive, the NED19, bromo-cyclic ADP-ribose or emodine may be added as it is or may be used together with other food or food ingredients, and according to a conventional method. Can be used.
  • the mixed amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).
  • NED19, bromo-cyclic ADP-ribose or emodine is added in an amount of up to 15% by weight, preferably up to 10% by weight based on the raw material in the manufacture of food or beverage.
  • the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
  • the kind of the food there is no particular limitation on the kind of the food.
  • foods to which the substance may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, dairy products including gum, ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.
  • the composition may include various flavors or natural carbohydrates and the like as an additional component, as in the usual beverage.
  • the natural carbohydrates described above may be used as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame.
  • the proportion of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.
  • the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in the carbonated beverage.
  • the composition of the present invention may include a pulp for the production of natural fruit juice, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is usually selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
  • the present invention provides a cosmetic composition for alleviating or suppressing itching, including NED19, bromo-cyclic ADP-ribose, or emodine as an active ingredient.
  • the present invention also provides a method for alleviating or suppressing itching, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
  • the composition may further contain at least one known active ingredient having an itch relieving or suppressing effect together with NED19, bromo-cyclic ADP-ribose or emodine.
  • the itch is also called pruritus, an unpleasant sensation that causes a desire to scratch or rub the skin, which is a symptom commonly observed in skin diseases. Itching is not particularly limited in the cause or form of the cause, in particular, itching referred to in the present invention is atopic dermatitis, allergic dermatitis, contact dermatitis, dermatitis due to roughness of the skin, acne, seborrheic dermatitis, sweat band, erosion, It includes all of the itch caused by one or more from the group consisting of frostbite, urticaria and psoriasis.
  • the composition can improve the skin barrier by inducing skin moisturization or skin hyperkeratosis through the improvement of the itch, it is characterized by having a skin condition improvement effect accordingly.
  • the composition is in addition to NED19, bromo-cyclic ADP-ribose or emodine, in addition to fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, commonly used in cosmetic compositions, Suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes It may further contain auxiliaries commonly used in the field of cosmetics or dermatology, such as pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients conventionally used in cosmetics. In addition, the above components may be introduced in an amount generally used in the field of dermatology.
  • the composition may be prepared in the form of a general emulsion formulation and solubilized formulation.
  • Cosmetics of the emulsified formulations include nutrient cosmetics, creams, essences, etc., and cosmetics of the solubilized formulations are flexible cosmetics.
  • the cosmetic composition of the present invention is an emulsion, suspension, emulsion, microemulsion, microcapsules, microgranules or ionic (liposomes) obtained by dispersing an oil phase in a solution, gel, solid or pasty anhydrous product, aqueous phase.
  • ionic vesicle dispersants creams, skins, lotions, powders, sprays, pastes, packs, face washes, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, waxes, foundations or concealed sticks Can be provided. It may also be prepared in the form of a foam or in the form of an aerosol further containing a compressed propellant.
  • the carrier component is animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, oxidation Zinc and the like.
  • the carrier component may include lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, and the like, in particular, in the case of a spray, additionally chlorofluoro Propellants such as rohydrocarbon, propane / butane, dimethyl ether, and the like.
  • a carrier component may include a solvent, a solubilizer, an emulsifier, and the like, and specifically, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, Benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycols, fatty acid esters of sorbitan, and the like.
  • a carrier diluent such as water, ethanol, propylene glycol
  • Suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester
  • the formulation of the composition is a surfactant-containing cleansing
  • a carrier component an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, and sarcosy Acetates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, and the like.
  • the compounding component which may be added other than this is not limited to this, although any said component can be mix
  • NED19 represented by the following Chemical Formula 1 was purchased from Santa Cruz Biotechnology (Dallas, Texas, USA) (Cat. No. sc-362814).
  • Bromo-cyclic ADP-ribose represented by the following formula (2) was purchased from Sigma (Sigma, Catalog # B5416).
  • Emodine represented by the following formula (3) was purchased from Sigma (Sigma, Catalog # E7881).
  • mice All animal experiments were performed according to the guidelines of the Experimental Animal Steering Committee of Chonbuk National University. Balb / c mice, 6-8 weeks old, were purchased from Orient Laboratory Animals (Seoul, Korea). Mice were maintained in an environment of 21-24 ° C., repeated 12 hours light cycle, and freely supplied with water and diet.
  • NED19 had an excellent effect of alleviating the itching caused by histamine in a concentration-dependent manner.
  • Br-cADPR has an excellent effect of alleviating itch by chloroquine, that is, histamine-independent itch.
  • mice were placed in a chamber (11 cm x 11 cm, 18 cm high) and photographed by video, and the number of scratches was measured using the hind legs. The results are shown in FIG.
  • the emodine has an excellent effect of alleviating the itch caused by chloroquine, that is, the histamine-independent itch, in a concentration-dependent manner.
  • atopic dermatitis was induced in mice using DNCB. Specifically, the right ear was shaved to remove hair, and then 20 ⁇ l of a 1% solution of DNCB dissolved in olive oil: ethanol (1: 4 volume ratio) was applied to sensitization. After 7 days, 10 ⁇ l of 0.5% DNCB was applied to the same ear. Next, the emodine of Example 3 was dissolved in DMSO and physiological saline to prepare a concentration of 0.1-10 ⁇ M, and then 20 ⁇ l of each solution was applied to the right ear once after 10 minutes of the last DNCB treatment for 1 hour. The number of scratches was measured. For the negative control, physiological saline was applied. The results are shown in FIG.
  • emodine has an excellent effect of alleviating the itch caused by atopic dermatitis in a concentration-dependent manner, and thus can be used as a therapeutic agent for atopic dermatitis.
  • the NED19, bromo-cyclic ADP-ribose, and emodine of the present invention have a prophylactic and therapeutic effect against various allergic or inflammatory skin diseases such as histamine dependent and histamine independent itch, as well as itch caused by atopic dermatitis.
  • excellent bar it can be used in a variety of medicines, external skin preparations, food and cosmetics.
  • tablets were prepared by tableting according to a conventional method for producing tablets.
  • the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
  • Vitamin B6 0.5 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • Beta-1,3-Glucan 1.0%
  • Beta-1,3-Glucan 1.0%
  • Beta-1,3-Glucan 5.0%

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Abstract

The present invention relates to a composition for preventing or treating allergic or inflammatory disease, comprising an NED19, bromo-cyclic ADP-ribose or emodin as an effective ingredient. The NED19, bromo-cyclic ADP-ribose and emodin of the present invention have an excellent effect in preventing and treating various allergic or inflammatory skin diseases including histamine-dependent and histamine-independent itching and atopic dermatitis itching, and thus can be variously used in medicines, external skin preparations, foods, cosmetics, and the like.

Description

알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물Composition for preventing or treating allergic or inflammatory skin disease
본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prophylaxis or treatment of allergic or inflammatory skin diseases comprising NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
가려움증(pruritus)은 긁고 싶은 심정을 증가시켜 심한 고통을 동반하는 피부과적인 증상으로 아토피성 피부염, 접촉성 피부염, 두드러기 및 다양한 피부질환의 대표적 증상이다. 피부질환에서 발생하는 심한 가려움증은 수면장애, 정서적 불안정, 과민한 스트레스반응 등 이차적인 악화요인과 함께 같은 환자들의 삶의 질에 큰 영향을 끼칠 뿐 아니라, 질환 자체의 악순환을 초래하고 이로 인해 환자와 주변사람들에게도 상당한 수준의 사회심리적 고통을 야기시킨다. Itching (pruritus) is a dermatological symptom with severe pain that increases the feeling of scratching and is a representative symptom of atopic dermatitis, contact dermatitis, urticaria and various skin diseases. Severe itching in skin diseases, along with secondary exacerbations such as sleep disorders, emotional instability, and irritable stress reactions, not only have a significant effect on the quality of life of the same patients, but also lead to a vicious cycle of the disease itself. It also causes significant levels of social and psychological distress for those around them.
피부는 바깥쪽부터 표피, 진피 및 피하지방층의 3개 층으로 구성되어 있다. 피부는 신체에서 가장 큰 장기이며 밖에 노출되어 있기 때문에 피부에 가해지는 외부자극이나 내부병변에 의해 나타나는 가려움증을 쉽게 인지할 수 있다. 표피의 한 성분을 이루고 있는 각질형성세포(keratinocyte)는 각질형성 외에도 면역반응 조절물질로 알려진 다양한 종류의 염증성 사이토카인(cytokine)인 인터루킨(interleukin), TNF-a, 인터페론, 케모카인 등을 분비하여 외부 자극에 민감하게 반응한다. 이러한 이유로 피부에는 가려움증을 동반하는 각종 질환이 빈번히 발생한다. The skin is composed of three layers from the outside, epidermis, dermis and subcutaneous fat layer. The skin is the largest organ in the body and is exposed outside, making it easy to recognize the itching caused by external stimuli or internal lesions on the skin. In addition to keratinogenesis, keratinocytes, which form one component of the epidermis, secrete various types of inflammatory cytokines, interleukin, TNF-a, interferon, and chemokine, which are known as immune response regulators. Reacts sensitively to stimuli. For this reason, various diseases accompanied by itching occur frequently on the skin.
한편, 아토피 피부염은 악화와 완화가 반복되며 심한 가려움증을 동반하는 만성질환으로 면역학적 기능 이상과 알레르기 항원의 노출과 같은 다인자적인 요인에 의해 발병하는 피부 염증성 질환이다. 이러한 아토피 피부염의 심각한 가려움증으로 인해 유발되는 피부병소를 반복하여 긁는 행위는 피부 장벽의 붕괴와 더불어 피부염을 더욱 악화시킨다. 그러므로 가려움증 또는 가려움증으로 인해 긁는 행위를 조절하는 것이 아토피 피부염에 있어서 중요하고 효과적인 치료법일 것이다. 가려움증을 동반하는 질환들은 자꾸 긁다 보면 상처가 나게 되고 이로 인해 세균감염 및 외부 알러젠에 의한 2차 감염에 따른 염증이 동반된다. 현재 가려움증에 사용되는 유일한 약물은 항히스타민제이나 가려움을 유발하는 물질은 히스타민 이외에도, IL-1을 비롯한 여러 사이토카인, 뉴로펩타이드(serotonin, acethycholine, substance P), 다양한 염증 물질(leukotrines, prostaglandins) 등, 많은 물질들이 관여하므로 항히스타민제의 효과가 제한적이며, 병변이 만성으로 진행되면 가려움을 나타내는 기작들이 더 복잡해져 더 많은 물질들이 관여하기 때문에 대부분의 만성 가려움증이 항히스타민제에 저항을 나타내게 된다. 따라서 히스타민 의존성 및 히스타민 비의존성 가려움증 모두를 예방, 개선 또는 치료할 수 있는 물질 개발이 절실히 요구되고 있다.Atopic dermatitis, on the other hand, is a chronic inflammatory disease with aggravation and remission, which is caused by multifactorial factors such as immunological dysfunction and exposure to allergens. Repeated scratching of skin lesions caused by the severe itching of atopic dermatitis worsens dermatitis with the collapse of the skin barrier. Therefore, controlling the scratching behavior due to itching or itching will be an important and effective treatment for atopic dermatitis. Itching is accompanied by a wound, which is accompanied by wounds caused by bacterial infection and secondary allergens caused by external allergens. Currently, the only drugs used for itching are antihistamines and other substances that cause itching, in addition to histamine, various cytokines such as IL-1, neuropeptides (serotonin, acethycholine, substance P), various inflammatory substances (leukotrines, prostaglandins), etc. Because of the involvement of many substances, the effectiveness of antihistamines is limited, and when the lesion progresses chronically, the mechanisms that indicate itching become more complex and most of the chronic itch is resistant to antihistamines because more substances are involved. Therefore, there is an urgent need for the development of substances capable of preventing, ameliorating or treating both histamine dependent and histamine independent itch.
이에 본 발명자들은 부작용이 없으면서도, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 효과가 우수한 새로운 약물을 개발하기 위하여 노력한 결과, NED19, 브로모-사이클릭 ADP-리보오스 및 에모딘이 히스타민 의존성 및 히스타민 비의존성 가려움증뿐만 아니라 나아가 아토피 피부염에 의한 가려움증 등 다양한 알레르기성 또는 염증성 피부질환에 대한 개선 효과가 우수함을 확인함으로써, 본 발명을 완성하였다. Accordingly, the present inventors have made efforts to develop a new drug which is excellent in preventing or treating allergic or inflammatory skin diseases without any side effects, and as a result, NED19, bromo-cyclic ADP-ribose, and emodine have a histamine dependency and a histamine ratio. The present invention was completed by confirming that not only dependent itching but also an improvement effect on various allergic or inflammatory skin diseases such as itching by atopic dermatitis is excellent.
본 발명의 목적은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물을 제공하는 것이다.It is an object of the present invention to provide a composition for the prevention or treatment of allergic or inflammatory skin diseases, comprising NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
본 발명의 다른 목적은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 방법을 제공하는 것이다. Another object of the present invention is to provide a method for preventing or treating allergic or inflammatory skin diseases, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
본 발명의 또 다른 목적은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는 가려움증 완화 또는 억제용 조성물을 제공하는 것이다.Still another object of the present invention is to provide a composition for alleviating or suppressing itching, including NED19, bromo-cyclic ADP-ribose, or emodine as an active ingredient.
본 발명의 또 다른 목적은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 가려움증 완화 또는 억제 방법을 제공하는 것이다. It is another object of the present invention to provide a method for alleviating or suppressing itching, comprising administering NED19, bromo-cyclic ADP-ribose or emodine to a subject in need thereof.
상기 목적을 달성하기 위하여, 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
또한 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 피부외용제를 제공한다.In another aspect, the present invention provides a skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
또한 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환의 예방 또는 개선용 건강식품 조성물을 제공한다.In another aspect, the present invention provides a health food composition for the prevention or improvement of allergic or inflammatory skin diseases comprising NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
또한 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 방법을 제공한다. The present invention also provides a method for preventing or treating allergic or inflammatory skin diseases, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
또한 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는 가려움증 완화 또는 억제용 화장료 조성물을 제공한다.In another aspect, the present invention provides a cosmetic composition for alleviating or suppressing itching, including NED19, bromo-cyclic ADP-ribose, or emodine as an active ingredient.
또한 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 가려움증 완화 또는 억제 방법을 제공한다. The present invention also provides a method for alleviating or suppressing itching, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
본 발명의 NED19, 브로모-사이클릭 ADP-리보오스 및 에모딘은 히스타민 의존성 및 히스타민 비의존성 가려움증뿐만 아니라 나아가 아토피 피부염에 의한 가려움증 등 다양한 알레르기성 또는 염증성 피부질환에 대한 예방 및 치료 효과가 우수한 바, 의약품, 피부외용제, 식품 및 화장품 등으로 다양하게 활용될 수 있다. NED19, bromo-cyclic ADP-ribose and emodine of the present invention are excellent in the prevention and treatment of various allergic or inflammatory skin diseases, including not only histamine-dependent and histamine-independent itch, but also itch caused by atopic dermatitis, It can be variously used as medicine, external skin preparation, food and cosmetics.
도 1은 NED19가 히스타민 유도 가려움증 완화에 미치는 영향을 나타낸 도이다. 1 is a diagram showing the effect of NED19 on the relief of histamine induced itch.
도 2는 브로모-사이클릭 ADP-리보오스가 클로로퀸 유도 가려움증 완화에 미치는 영향을 나타낸 도이다. 2 is a diagram showing the effect of bromo-cyclic ADP-ribose on chloroquine induced itch relief.
도 3은 에모딘이 히스타민 유도 가려움증 완화에 미치는 영향을 나타낸 도이다. 3 is a diagram showing the effect of emodin on the histamine induced itching relief.
도 4는 에모딘이 클로로퀸 유도 가려움증 완화에 미치는 영향을 나타낸 도이다.4 is a diagram showing the effect of emodine on chloroquine induced itch relief.
도 5는 에모딘이 아토피 피부염에 의한 가려움증 완화에 미치는 영향을 나타낸 도이다.5 is a diagram showing the effect of emodin on the itch relief by atopic dermatitis.
본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물을 제공한다.The present invention provides a composition for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
상기 조성물은 약학적 조성물, 피부 외용제 조성물 및 건강기능식품 조성물을 포함한다. The composition includes a pharmaceutical composition, a topical skin composition and a nutraceutical composition.
또한, 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 방법을 제공한다. The present invention also provides a method for preventing or treating allergic or inflammatory skin diseases, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
이하 본 발명에 대하여 보다 상세히 설명한다. Hereinafter, the present invention will be described in more detail.
일 태양으로서, 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 약학적 조성물을 제공한다.In one aspect, the present invention provides a pharmaceutical composition for the prophylaxis or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
본 발명에 있어서, 유효성분인 NED19는 trans-NED19 또는 cis-NED19를 모두 포함하며, 이에 제한되지 않는다. In the present invention, the active ingredient NED19 includes both trans-NED19 or cis-NED19, but is not limited thereto.
본 발명에 있어서, 유효성분인 NED19((1R,3S)-1-[3-[[4-(2-Fluorophenyl)piperazin-1-yl]methyl]-4-methoxyphenyl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid)는 하기 화학식 1로 표시될 수 있다. In the present invention, the active ingredient NED19 ((1R, 3S) -1- [3-[[4- (2-Fluorophenyl) piperazin-1-yl] methyl] -4-methoxyphenyl] -2,3,4, 9-tetrahydro-1H-pyrido [3,4-b] indole-3-carboxylic acid) may be represented by the following Chemical Formula 1.
[화학식 1][Formula 1]
Figure PCTKR2017001808-appb-I000001
Figure PCTKR2017001808-appb-I000001
본 발명에 있어서, 유효성분인 브로모-사이클릭 ADP-리보오스(8-bromo-cyclic adenosine diphosphate ribose)는 하기 화학식 2로 표시될 수 있다. In the present invention, the active ingredient bromo-cyclic ADP-ribose (8-bromo-cyclic adenosine diphosphate ribose) may be represented by the following formula (2).
[화학식 2][Formula 2]
Figure PCTKR2017001808-appb-I000002
Figure PCTKR2017001808-appb-I000002
본 발명에 있어서, 유효성분인 에모딘(emodin)은 하기 화학식 3으로 표시될 수 있다. In the present invention, the active ingredient emodin (emodin) may be represented by the following formula (3).
[화학식 3][Formula 3]
Figure PCTKR2017001808-appb-I000003
Figure PCTKR2017001808-appb-I000003
본 발명에 있어서, NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘은 시판중인 것을 구입하거나 직접 합성하여 사용할 수 있으며, 이에 제한되지 않는다. In the present invention, NED19, bromo-cyclic ADP-ribose, or emodine may be purchased commercially or directly synthesized, but are not limited thereto.
본 발명의 화합물은 당해 기술 분야에서 통상적인 방법에 따라 약학적으로 허용 가능한 염 및 용매화물로 제조될 수 있다. 본 발명의 화합물의 약학적으로 허용 가능한 염은, 달리 지시되지 않는 한, 본 발명의 화합물에 존재할 수 있는 산성 또는 염기성기의 염을 포함하며, 이에 제한되지 않는다. The compounds of the present invention can be prepared with pharmaceutically acceptable salts and solvates according to methods conventional in the art. Pharmaceutically acceptable salts of the compounds of the invention include, but are not limited to, salts of acidic or basic groups that may be present in the compounds of the invention.
본 발명에 있어서, 용어 "예방"은 알레르기성 또는 염증성 피부질환의 병인을 제거하거나 조기 발견하여 해당 질환을 막는 모든 행위를 의미한다.In the present invention, the term "prevention" means any action that prevents the disease by eliminating or early detecting the etiology of allergic or inflammatory skin disease.
본 발명에 있어서, 용어 "치료"는 본 발명의 조성물에 의해 알레르기성 또는 염증성 피부질환에 의한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.In the present invention, the term "treatment" means all the actions that improve or beneficially change the symptoms caused by allergic or inflammatory skin diseases by the composition of the present invention.
본 발명에 있어서, 알레르기와 염증은 생체조직의 방어반응에 하나로, 상기 알레르기는 생물체가 어떤 외래성 물질과 접하게 될 때 생체 내에서 급격한 반응 능력의 변화, 즉 항원항체반응이 발생하게 되는 데, 상기 반응이 과민하게 반응하는 경우를 말한다. 아울러, 염증은 조직 변질, 순환장애와 삼출, 조직 증식의 세 가지를 병발하는 복잡한 병변을 지칭한다. In the present invention, allergy and inflammation are one of the defense reactions of biological tissues, the allergy is a sudden change in the ability to react in vivo when the organism comes in contact with any foreign substance, that is, the antigen antibody reaction occurs, the response It is said to be sensitive. In addition, inflammation refers to complex lesions that involve three types: tissue degeneration, circulatory disorders and exudates, and tissue proliferation.
이와 같은 증상들을 수반하여 피부에서 발생하는 질환을 알레르기성 또는 염증성 피부질환이라 하며, 구체적으로 본 발명에서 지칭하는 알레르기성 또는 염증성 피부질환이라 함은 아토피성 피부염, 알레르기성 피부염, 접촉성 피부염, 여드름, 지루성 피부염, 땀띠, 두드러기 또는 건선일 수 있으며, 보다 바람직하게는 아토피성 피부염, 접촉성 피부염 또는 가려움증이나, 이에 본 발명이 제한되는 것은 아니다.Diseases that occur in the skin with such symptoms are called allergic or inflammatory skin diseases. Specifically, allergic or inflammatory skin diseases referred to in the present invention are atopic dermatitis, allergic dermatitis, contact dermatitis, acne. , Seborrheic dermatitis, sweat, urticaria or psoriasis, more preferably atopic dermatitis, contact dermatitis or itching, but the present invention is not limited thereto.
본 발명의 NED19, 브로모-사이클릭 ADP-리보오스 및 에모딘은 히스타민 의존성 및 히스타민 비의존성 가려움증뿐만 아니라 나아가 아토피 피부염에 의한 가려움증 등 다양한 알레르기성 또는 염증성 피부질환에 대한 예방 및 치료 효과가 우수한 바, 의약품, 피부외용제, 식품 및 화장품 등으로 다양하게 활용될 수 있다. NED19, bromo-cyclic ADP-ribose and emodine of the present invention are excellent in the prevention and treatment of various allergic or inflammatory skin diseases, including not only histamine-dependent and histamine-independent itch, but also itch caused by atopic dermatitis, It can be variously used as medicine, external skin preparation, food and cosmetics.
본 발명에 있어서, 상기 조성물은 NED19, 브로모-사이클릭 ADP-리보오스 및 에모딘과 함께 알레르기성 또는 염증성 피부질환 예방 또는 치료 효과를 가지는 공지의 유효성분을 1종 이상 더 포함할 수 있다. In the present invention, the composition may further include one or more known active ingredients having an allergic or inflammatory skin disease prevention or treatment effect together with NED19, bromo-cyclic ADP-ribose, and emodine.
본 발명에 있어서, 상기 조성물은 약학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니톨, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말셀룰로오스, 히드록시프로필셀룰로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당 등이 사용될 수 있다. 본 발명에 따른 약학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 내지 90 중량부 포함되는 것이 바람직하나 이에 한정되는 것은 아니다.In the present invention, the composition may further comprise a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives are starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, hydrogen phosphate Calcium, lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, carnauba wax, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, white sugar and the like can be used. The pharmaceutically acceptable additive according to the present invention is preferably included 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
본 발명에 있어서, 상기 조성물은 실제 임상투여시에 경구 또는 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제할 수 있으며, 당해 기술 분야에 알려진 적합한 제제는 문헌 (Remington's Pharmaceutical Science, 최근, Mack Publishing Company, Easton PA)에 개시되어 있는 것을 이용하는 것이 바람직하다. 상기 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 올리고당, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트, 광물유 등이 있다.In the present invention, the composition can be administered in various oral or parenteral dosage forms during actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used, or Excipients can be formulated and suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, mineral oil and the like.
상기 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트(Calcium carbonate), 수크로스 (Sucrose) 또는 락토오스(Lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 또한, 상기 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. The solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or sucrose. It is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. In addition, the liquid preparations for oral administration include suspensions, solvents, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. This may be included.
상기 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 상기 비경구투여는 피부 외용 또는 복강 내 주사, 직장 내 주사, 피하주사, 정맥주사, 근육 내 주사 또는 흉부 내 주사 주입방식을 사용하여 이루어질 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used. The parenteral administration may be made using external skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection.
본 발명에 있어서, 용어 "투여"는 임의의 적절한 방법으로 개체에게 소정의 본 발명의 조성물을 제공하는 것을 의미한다.In the present invention, the term "administration" means providing a subject with a composition of the present invention in any suitable manner.
본 발명에 있어서, 상기 조성물의 바람직한 투여량은 개체의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 예를 들어, 바람직한 효과를 위해서, 본 발명의 NED19, 브로모-사이클릭 ADP-리보오스 및 에모딘은 1일 0.1 내지 10000 mg/kg(체중)의 양으로 투여할 수 있다. 상기 조성물의 투여는 하루에 한 번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다. In the present invention, the preferred dosage of the composition depends on the condition and weight of the individual, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. For example, for the desired effect, the NED19, bromo-cyclic ADP-ribose and emodine of the present invention may be administered in an amount of 0.1 to 10000 mg / kg body weight per day. Administration of the composition may be administered once a day, may be divided several times.
본 발명에 있어서, 상기 조성물은 개체에게 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육 또는 피하 내 주사에 의해 투여될 수 있으며, 피부에 도포되는 방식이라는 어떤 경로로든지 투여될 수 있다. In the present invention, the composition can be administered to the subject by various routes. All modes of administration can be envisaged, for example, can be administered by oral, rectal or intravenous, intramuscular or subcutaneous injection, and can be administered by any route of application to the skin.
본 발명에 있어서, 상기 조성물은 알레르기성 또는 염증성 피부질환의 예방 및 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.In the present invention, the composition may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of allergic or inflammatory skin diseases.
또한, 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 피부외용제를 제공한다.In another aspect, the present invention provides a skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
본 발명에 있어서, 상기 조성물은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘과 함께 알레르기성 또는 염증성 피부질환의 예방 또는 치료 효과를 갖는 공지의 유효성분을 1종 이상 더 함유할 수 있다.In the present invention, the composition may further contain one or more known active ingredients having a prophylactic or therapeutic effect of allergic or inflammatory skin diseases together with NED19, bromo-cyclic ADP-ribose or emimodine.
본 발명에 있어서, 상기 조성물은 목적하는 신체 부위에 따라 그 제형이 특별히 한정되지 않으며, 당업계의 공지기술을 참조하여 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있다. 예를 들어, 액제, 연고제, 크림제, 로션제, 스프레이제, 패취제, 오일제, 왁스제, 유탁액제, 현탁액제, 겔제 또는 에어로졸제 등 형태로 사용될 수 있으나, 이에 한정되는 것은 아니다. In the present invention, the composition is not particularly limited in its formulation according to the desired body part, it may be prepared in any formulation conventionally prepared with reference to the known art. For example, liquids, ointments, creams, lotions, sprays, patches, oils, waxes, emulsions, suspensions, gels or aerosols may be used in the form, but is not limited thereto.
본 발명에 있어서, 상기 조성물은 통상적인 첨가제, 예를 들어 보존제, 의약 침투를 보조하는 용매, 연고 및 크림의 경우 연화제 등을 포함할 수 있으며, 에탄올 또는 올레일 알코올과 같은 통상적 담체를 함유할 수 있다.In the present invention, the composition may include conventional additives, for example, preservatives, solvents to aid the penetration of medicines, softeners in the case of ointments and creams, etc., may contain a conventional carrier such as ethanol or oleyl alcohol. have.
본 발명에 있어서, 상기 조성물은 상술한 성분에 한정되지 않고, 필요에 따라 통상의 화장료 조성물 또는 약학 조성물에 배합되는 다른 성분을 포함할 수 있다. 예를 들어, 유지 성분, 보습제, 에몰리엔트제, 계면활성제, 유기 또는 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한제, 정제수 등을 포함할 수 있다.In the present invention, the composition is not limited to the above-described components, and may include other components blended with a conventional cosmetic composition or a pharmaceutical composition, if necessary. For example, fats and oils, moisturizers, emollients, surfactants, organic or inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, blood circulation promoters, Coolants, limiting agents, purified water, and the like.
또한, 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 개선용 건강기능식품을 제공한다.In another aspect, the present invention provides a dietary supplement for the prevention or improvement of allergic or inflammatory skin diseases, including NED19, bromo-cyclic ADP-ribose or emodine as an active ingredient.
본 발명에 있어서, "건강기능식품"이란, 질병의 예방 및 개선, 생체방어, 면역, 병후의 회복, 노화 억제 등 생체조절 기능을 가지는 식품을 말하는 것으로, 장기적으로 복용하였을 때 인체에 무해해야 한다. In the present invention, "health functional food" refers to a food having a bioregulatory function, such as prevention and improvement of disease, biodefence, immunity, recovery from illness, and inhibition of aging, and should be harmless to the human body when taken in the long term. .
본 발명에 있어서, 상기 물질을 식품 첨가물로 사용할 경우, 상기 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조 시에 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘은 원료에 대하여 15 중량% 이하, 바람직하게는 10 중량% 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.In the present invention, when the substance is used as a food additive, the NED19, bromo-cyclic ADP-ribose or emodine may be added as it is or may be used together with other food or food ingredients, and according to a conventional method. Can be used. The mixed amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, NED19, bromo-cyclic ADP-ribose or emodine is added in an amount of up to 15% by weight, preferably up to 10% by weight based on the raw material in the manufacture of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, it may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
본 발명에 있어서, 상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.In the present invention, there is no particular limitation on the kind of the food. Examples of foods to which the substance may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, dairy products including gum, ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.
본 발명에 있어서, 상기 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 포함할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토오스, 수크로오스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml 당 일반적으로 약 0.01 내지 10 g, 바람직하게는 약 0.01 내지 0.1 g 이다.In the present invention, the composition may include various flavors or natural carbohydrates and the like as an additional component, as in the usual beverage. The natural carbohydrates described above may be used as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in the carbonated beverage. In addition, the composition of the present invention may include a pulp for the production of natural fruit juice, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is usually selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
또한, 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 유효성분으로 포함하는, 가려움증 완화 또는 억제용 화장료 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for alleviating or suppressing itching, including NED19, bromo-cyclic ADP-ribose, or emodine as an active ingredient.
또한 본 발명은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘을 이를 필요로 하는 개체에 투여하는 단계를 포함하는, 가려움증 완화 또는 억제 방법을 제공한다. The present invention also provides a method for alleviating or suppressing itching, comprising administering NED19, bromo-cyclic ADP-ribose, or emodine to a subject in need thereof.
본 발명에 있어서, 상기 조성물은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘과 함께 가려움증 완화 또는 억제 효과를 갖는 공지의 유효성분을 1종 이상 더 함유할 수 있다.In the present invention, the composition may further contain at least one known active ingredient having an itch relieving or suppressing effect together with NED19, bromo-cyclic ADP-ribose or emodine.
본 발명에 있어서, 상기 가려움증은 소양증이라고도 하며, 피부를 긁거나 문지르고 싶은 욕망을 일으키는 불쾌한 감각으로, 피부질환에서 흔히 관찰되는 증상이다. 가려움증은 유발 원인 또는 형태가 특별히 제한되지 않으나, 구체적으로 본 발명에서 지칭하는 가려움증은 아토피성 피부염, 알레르기성 피부염, 접촉성 피부염, 살갗의 거칠어짐으로 인한 피부염, 여드름, 지루성 피부염, 땀띠, 진무름, 동상, 두드러기 및 건선으로 이루어진 군으로부터 하나 이상에 의해 유발된 가려움증을 모두 포함한다. In the present invention, the itch is also called pruritus, an unpleasant sensation that causes a desire to scratch or rub the skin, which is a symptom commonly observed in skin diseases. Itching is not particularly limited in the cause or form of the cause, in particular, itching referred to in the present invention is atopic dermatitis, allergic dermatitis, contact dermatitis, dermatitis due to roughness of the skin, acne, seborrheic dermatitis, sweat band, erosion, It includes all of the itch caused by one or more from the group consisting of frostbite, urticaria and psoriasis.
본 발명에 있어서, 상기 조성물은 가려움증의 개선을 통해 피부 보습 증진 또는 피부 과각질화 방지를 유도함으로써 피부 장벽을 개선시킬 수 있으며, 이에 따른 피부 상태 개선 효과를 가지는 것이 특징이다. In the present invention, the composition can improve the skin barrier by inducing skin moisturization or skin hyperkeratosis through the improvement of the itch, it is characterized by having a skin condition improvement effect accordingly.
본 발명에 있어서, 상기 조성물은 NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 외에 추가로 화장료 조성물에 통상적으로 사용되는 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속 이온 봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품학 또는 피부 과학 분야 에서 통상적으로 사용되는 보조제를 추가로 함유할 수 있다. 또한, 상기의 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다. In the present invention, the composition is in addition to NED19, bromo-cyclic ADP-ribose or emodine, in addition to fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, commonly used in cosmetic compositions, Suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes It may further contain auxiliaries commonly used in the field of cosmetics or dermatology, such as pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients conventionally used in cosmetics. In addition, the above components may be introduced in an amount generally used in the field of dermatology.
본 발명에 있어서, 상기 조성물은 일반적인 유화 제형 및 가용화 제형의 형태로 제조할 수 있다. 유화 제형의 화장품으로는 영양화장수, 크림, 에센스 등이 있으며, 가용화 제형의 화장품으로는 유연화장수가 있다. 보다 구체적으로, 본 발명의 화장료 조성물은 용액, 겔, 고체 또는 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 유탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는 이온형(리포좀), 비이온형의 소낭 분산 제의 형태, 크림, 스킨, 로션, 파우더, 스프레이, 페이스트, 팩, 세안제, 비누, 계면활성제 함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스, 파운데이션 또는 콘실 스틱의 형태로 제공될 수 있다. 또한, 포말 (foam)의 형태 또는 압축된 추진제를 더 함유한 에어로졸의 형태로도 제조될 수 있다.In the present invention, the composition may be prepared in the form of a general emulsion formulation and solubilized formulation. Cosmetics of the emulsified formulations include nutrient cosmetics, creams, essences, etc., and cosmetics of the solubilized formulations are flexible cosmetics. More specifically, the cosmetic composition of the present invention is an emulsion, suspension, emulsion, microemulsion, microcapsules, microgranules or ionic (liposomes) obtained by dispersing an oil phase in a solution, gel, solid or pasty anhydrous product, aqueous phase. In the form of ionic vesicle dispersants, creams, skins, lotions, powders, sprays, pastes, packs, face washes, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, waxes, foundations or concealed sticks Can be provided. It may also be prepared in the form of a foam or in the form of an aerosol further containing a compressed propellant.
본 발명에 있어서, 상기 조성물의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크, 산화아연 등이 포함될 수 있다. In the present invention, when the formulation of the composition is a paste, cream or gel, the carrier component is animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, oxidation Zinc and the like.
본 발명에 있어서, 상기 조성물의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트, 폴리아미드 파우더 등이 포함될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄, 디메틸 에테르 등의 추진체를 포함할 수 있다. In the present invention, when the formulation of the composition is a powder or a spray, the carrier component may include lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, and the like, in particular, in the case of a spray, additionally chlorofluoro Propellants such as rohydrocarbon, propane / butane, dimethyl ether, and the like.
본 발명에 있어서, 상기 조성물의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로 용매, 용해화제, 유탁화제 등이 포함될 수 있고, 구체적으로 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프 로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜, 소르비탄의 지방산 에스테르 등이 포함될 수 있다. In the present invention, when the formulation of the composition is a solution or emulsion, a carrier component may include a solvent, a solubilizer, an emulsifier, and the like, and specifically, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, Benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycols, fatty acid esters of sorbitan, and the like.
본 발명에 있어서, 상기 조성물의 제형이 현탁액인 경우에는 담체 성분으로 물, 에탄올, 프로필렌글리콜 등의 액상 희석제; 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르, 폴리옥시에틸렌 소르비탄 에스테르 등의 현탁제; 미 소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가, 트라칸트 등이 포함될 수 있다. In the present invention, when the formulation of the composition is a suspension, a carrier diluent such as water, ethanol, propylene glycol; Suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester; Microcrystalline cellulose, aluminum metahydroxy, bentonite, agar, tracant and the like.
본 발명에 있어서, 상기 조성물의 제형이 계면활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시 네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄 올아미드, 식물성유, 라놀린유도체, 에톡실화 글리세롤 지방산 에스테르 등이 포함될 수 있다.In the present invention, when the formulation of the composition is a surfactant-containing cleansing, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, and sarcosy Acetates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, and the like.
또한, 이외에 첨가해도 되는 배합 성분은 이에 한정되는 것은 아니며, 상기 어느 성분도 본 발명의 목적 및 효과를 손상시키지 않는 범위 내에서 배합 가능하지만, 총 중량에 대하여 바람직하게는 0.01-10 %중량 백분율, 보다 바람직하게는 0.01-5 %중량 백분율로 배합된다.Moreover, the compounding component which may be added other than this is not limited to this, Although any said component can be mix | blended within the range which does not impair the objective and effect of this invention, Preferably it is 0.01-10% weight percentage with respect to a total weight, More Preferably 0.01 to 5% by weight.
중복되는 내용은 본 명세서의 복잡성을 고려하여 생락하며, 본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술분야에서 통상적으로 사용되는 의미를 갖는 것이다.Duplicate content is omitted in consideration of the complexity of the present specification, terms not otherwise defined herein have a meaning commonly used in the art to which the present invention belongs.
이하 본 발명을 실시예 및 실험예에 의해 상세히 설명한다. 하기 실시예 및 실험예는 본 발명을 예시하기 위한 것일 뿐 본 발명이 하기 실시예 및 실험예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by Examples and Experimental Examples. The following Examples and Experimental Examples are only for illustrating the present invention and the present invention is not limited by the following Examples and Experimental Examples.
실시예Example 1.  One. NED19의Of NED19 수득 purchase
하기 화학식 1로 표시되는 NED19는 Santa Cruz Biotechnology (Dallas, Texas, USA)에서 구입하였다(Cat. No. sc-362814).NED19 represented by the following Chemical Formula 1 was purchased from Santa Cruz Biotechnology (Dallas, Texas, USA) (Cat. No. sc-362814).
[화학식 1][Formula 1]
Figure PCTKR2017001808-appb-I000004
Figure PCTKR2017001808-appb-I000004
실시예Example 2.  2. 브로모Bromo -- 사이클릭Cyclic ADP-리보오스(Br- ADP-Ribose (Br- cADPRcADPR )의 수득Obtain
하기 화학식 2로 표시되는 브로모-사이클릭 ADP-리보오스는 시그마 사로부터 구입하였다 (Sigma, Catalog # B5416). Bromo-cyclic ADP-ribose represented by the following formula (2) was purchased from Sigma (Sigma, Catalog # B5416).
[화학식 2][Formula 2]
Figure PCTKR2017001808-appb-I000005
Figure PCTKR2017001808-appb-I000005
실시예Example 3.  3. 에모딘(emodin)의Of emodin 수득  purchase
하기 화학식 3으로 표시되는 에모딘은 시그마 사로부터 구입하였다 (Sigma, Catalog # E7881). Emodine represented by the following formula (3) was purchased from Sigma (Sigma, Catalog # E7881).
[화학식 3][Formula 3]
Figure PCTKR2017001808-appb-I000006
Figure PCTKR2017001808-appb-I000006
실시예Example 4.  4. 실험 동물의Experimental animals 준비 Preparations
이하 모든 동물 실험은 전북대학교의 실험동물운영위원회의 가이드라인에 따라 수행하였다. 6~8 주령의 Balb/c 마우스는 오리엔트 사(Orient Laboratory Animals)에서 구입하였다 (Seoul, Korea). 마우스는 21∼24℃가 유지되고, 12시간 명암 주기가 반복되는 환경에서 유지하였으며, 물 및 식이를 자유롭게 공급하였다. All animal experiments were performed according to the guidelines of the Experimental Animal Steering Committee of Chonbuk National University. Balb / c mice, 6-8 weeks old, were purchased from Orient Laboratory Animals (Seoul, Korea). Mice were maintained in an environment of 21-24 ° C., repeated 12 hours light cycle, and freely supplied with water and diet.
실험예Experimental Example 1.  One. NED19에On NED19 의한 가려움증 완화 효과 검증 Itching effect verification
먼저, 히스타민 200 ㎍을 0.1 ㎖의 PBS에 용해시켜 마우스의 오른쪽 귀 뒤쪽의 피하에 주사하여 가려움증을 유발시켰다. 실험군의 경우, 상기 실시예 1의 NED19를 1-100 μM의 농도로 제조한 후, 히스타민과 혼합하여 주사하였으며, 30 분 동안 긁는 횟수를 측정하였다. 이를 위해 마우스를 챔버(11 cm x 11 cm, 18 cm 높이)에 넣고 비디오로 촬영하였으며, 뒷다리를 이용하여 긁는 횟수를 측정하였다. 그 결과를 도 1에 나타내었다. First, 200 μg of histamine was dissolved in 0.1 ml of PBS and injected subcutaneously in the back of the right ear of the mouse to cause itching. For the experimental group, NED19 of Example 1 was prepared at a concentration of 1-100 μM, injected with a mixture of histamine, and the number of scratches was measured for 30 minutes. To this end, the mice were placed in a chamber (11 cm x 11 cm, 18 cm high) and photographed by video, and the number of scratches was measured using the hind legs. The results are shown in FIG.
도 1에 나타낸 바와 같이, NED19가 농도 의존적으로 히스타민에 의한 가려움증을 완화하는 효과가 우수함을 확인하였다. As shown in FIG. 1, it was confirmed that NED19 had an excellent effect of alleviating the itching caused by histamine in a concentration-dependent manner.
실험예Experimental Example 2.  2. 브로모Bromo -- 사이클릭Cyclic ADP-리보오스(Br- ADP-Ribose (Br- cADPRcADPR )에 의한 가려움증 완화 효과 검증Verification of itching effect by
먼저, 클로로퀸 400 ㎍을 0.1 ㎖의 PBS에 용해시켜 마우스의 오른쪽 귀 뒤쪽의 피하에 주사하여 가려움증을 유발시켰다. 실험군의 경우, 상기 실시예 2의 Br-cADPR을 1 μM의 농도로 제조한 후, 클로로퀸과 혼합하여 주사하였으며, 30 분 동안 긁는 횟수를 측정하였다. 이를 위해 마우스를 챔버(11 cm x 11 cm, 18 cm 높이)에 넣고 비디오로 촬영하였으며, 뒷다리를 이용하여 긁는 횟수를 측정하였다. 그 결과를 도 2에 나타내었다. First, 400 μg of chloroquine was dissolved in 0.1 ml of PBS and injected subcutaneously behind the right ear of the mouse to cause itching. For the experimental group, Br-cADPR of Example 2 was prepared at a concentration of 1 μM, mixed with chloroquine and injected, and the number of scratches was measured for 30 minutes. To this end, the mice were placed in a chamber (11 cm x 11 cm, 18 cm high) and photographed by video, and the number of scratches was measured using the hind legs. The results are shown in FIG.
도 2에 나타낸 바와 같이, Br-cADPR이 클로로퀸에 의한 가려움증, 즉, 히스타민 비 의존성 가려움증을 완화하는 효과가 우수함을 확인하였다. As shown in FIG. 2, it was confirmed that Br-cADPR has an excellent effect of alleviating itch by chloroquine, that is, histamine-independent itch.
실험예Experimental Example 3.  3. 에모딘(emodin)에In emodin 의한 가려움증 완화 효과 검증 Itching effect verification
3-1. 히스타민에 의한 가려움증 완화 효과 검증3-1. Verification of itching effect by histamine
먼저, 히스타민 100 ㎍을 0.1 ㎖의 생리식염수에 용해시켜 마우스의 피하에 주사하여 가려움증을 유발시켰다. 실험군의 경우, 상기 실시예 3의 에모딘을 0.1 - 10 μM의 농도로 제조한 후, 히스타민과 혼합하여 마우스의 피하에 주사하였으며, 1 시간 동안 긁는 횟수를 측정하였다. 이를 위해 마우스를 챔버(11 cm x 11 cm, 18 cm 높이)에 넣고 비디오로 촬영하였으며, 뒷다리를 이용하여 긁는 횟수를 측정하였다. 그 결과를 도 3에 나타내었다. First, 100 μg of histamine was dissolved in 0.1 ml of saline solution and injected subcutaneously of the mouse to cause itching. For the experimental group, the emodine of Example 3 was prepared at a concentration of 0.1-10 μM, and then mixed with histamine and injected subcutaneously in the mouse, and the number of scratches was measured for 1 hour. To this end, the mice were placed in a chamber (11 cm x 11 cm, 18 cm high) and photographed by video, and the number of scratches was measured using the hind legs. The results are shown in FIG.
도 3에 나타낸 바와 같이, 에모딘이 농도 의존적으로 히스타민에 의한 가려움증을 완화하는 효과가 우수함을 확인하였다. As shown in FIG. 3, it was confirmed that emodine has an effect of alleviating the itching caused by histamine in a concentration-dependent manner.
3-2. 3-2. 클로로퀸에Chloroquine 의한 가려움증 완화 효과 검증 Itching effect verification
먼저, 클로로퀸 200 ㎍을 0.1 ㎖의 생리식염수에 용해시켜 마우스의 피하에 주사하여 가려움증을 유발시켰다. 실험군의 경우, 상기 실시예 3의 에모딘을 0.1 - 10 μM의 농도로 제조한 후, 클로로퀸과 혼합하여 마우스의 피하에 주사하였으며, 1 시간 동안 긁는 횟수를 측정하였다. 이를 위해 마우스를 챔버(11 cm x 11 cm, 18 cm 높이)에 넣고 비디오로 촬영하였으며, 뒷다리를 이용하여 긁는 횟수를 측정하였다. 그 결과를 도 4에 나타내었다. First, 200 μg of chloroquine was dissolved in 0.1 mL of physiological saline and injected subcutaneously of the mouse to cause itching. For the experimental group, the emodine of Example 3 was prepared at a concentration of 0.1-10 μM, and then mixed with chloroquine and injected subcutaneously in the mouse, and the number of scratches was measured for 1 hour. To this end, the mice were placed in a chamber (11 cm x 11 cm, 18 cm high) and photographed by video, and the number of scratches was measured using the hind legs. The results are shown in FIG.
도 4에 나타낸 바와 같이, 에모딘이 농도 의존적으로 클로로퀸에 의한 가려움증, 즉, 히스타민 비 의존성 가려움증을 완화하는 효과가 우수함을 확인하였다. As shown in FIG. 4, it was confirmed that the emodine has an excellent effect of alleviating the itch caused by chloroquine, that is, the histamine-independent itch, in a concentration-dependent manner.
3-3. 아토피 피부염에 의한 가려움증 완화 효과 검증3-3. Verification of itching effect by atopic dermatitis
아토피 피부염에 의한 가려움증 완화 및 치료 효과를 확인하기 위하여, DNCB를 이용하여 마우스에 아토피 피부염을 유발하였다. 구체적으로 마우스 오른쪽 귀를 면도하여 털을 제거한 후 올리브유:에탄올(1:4 부피비)에 녹인 DNCB 1% 용액 20 ㎕ 를 발라 감작 (sensitization)시켰다. 7일 후 동일한 귀에 0.5%의 DNCB 10 ㎕을 발라주었다. 다음으로, 상기 실시예 3의 에모딘을DMSO 및 생리 식염수에 용해시켜 0.1 - 10 μM의 농도로 제조한 후, 각 용액 20 ㎕을 DNCB 마지막 처리 10 분 후에 1회에 걸쳐 오른쪽 귀에 바르고 1 시간 동안 긁는 횟수를 측정하였다. 음성 대조군의 경우 생리 식염수를 발라주었다. 그 결과를 도 5에 나타내었다. In order to confirm the itch relief and treatment effect by atopic dermatitis, atopic dermatitis was induced in mice using DNCB. Specifically, the right ear was shaved to remove hair, and then 20 μl of a 1% solution of DNCB dissolved in olive oil: ethanol (1: 4 volume ratio) was applied to sensitization. After 7 days, 10 μl of 0.5% DNCB was applied to the same ear. Next, the emodine of Example 3 was dissolved in DMSO and physiological saline to prepare a concentration of 0.1-10 μM, and then 20 μl of each solution was applied to the right ear once after 10 minutes of the last DNCB treatment for 1 hour. The number of scratches was measured. For the negative control, physiological saline was applied. The results are shown in FIG.
도 5에 나타낸 바와 같이, 에모딘이 농도 의존적으로 아토피 피부염에 의한 가려움증을 완화하는 효과가 우수하며, 이를 통해 아토피 피부염에 대한 치료제로 이용될 수 있음을 확인하였다. As shown in FIG. 5, it was confirmed that emodine has an excellent effect of alleviating the itch caused by atopic dermatitis in a concentration-dependent manner, and thus can be used as a therapeutic agent for atopic dermatitis.
종합적으로, 본 발명의 NED19, 브로모-사이클릭 ADP-리보오스 및 에모딘은 히스타민 의존성 및 히스타민 비의존성 가려움증뿐만 아니라 나아가 아토피 피부염에 의한 가려움증 등 다양한 알레르기성 또는 염증성 피부질환에 대한 예방 및 치료 효과가 우수한바, 의약품, 피부외용제, 식품 및 화장품 등으로 다양하게 활용될 수 있다. Overall, the NED19, bromo-cyclic ADP-ribose, and emodine of the present invention have a prophylactic and therapeutic effect against various allergic or inflammatory skin diseases such as histamine dependent and histamine independent itch, as well as itch caused by atopic dermatitis. Excellent bar, it can be used in a variety of medicines, external skin preparations, food and cosmetics.
이하 본 발명의 상기 조성물을 함유하는 약학적 조성물, 식품 조성물 및 화장료 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, the preparation examples of the pharmaceutical composition, food composition and cosmetic composition containing the composition of the present invention, but the present invention is not intended to limit it, but only to explain in detail.
제제예Formulation example 1. 약학적 조성물의 제조 1. Preparation of pharmaceutical composition
1- 1. 1-1. 산제의Powder 제조 Produce
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 2 g2 g NED19, Bromo-cyclic ADP-ribose or Emodine
유당 1 g1 g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in airtight cloth to prepare a powder.
1- 2. 정제의 제조1-2 Preparation of Tablets
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 100 mgNED19, Bromo-cyclic ADP-ribose or Emodine 100 mg
옥수수전분 100 mg Corn starch 100 mg
유당 100 mg Lactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
1-3. 캡슐제의 제조1-3. Preparation of Capsule
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 100 mgNED19, Bromo-cyclic ADP-ribose or Emodine 100 mg
옥수수전분 100 mg Corn starch 100 mg
유당 100 mg Lactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
제제예Formulation example 2. 식품 조성물의 제조 2. Preparation of Food Composition
2-1. 건강기능식품의 제조2-1. Preparation of health functional food
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 100 mgNED19, Bromo-cyclic ADP-ribose or Emodine 100 mg
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 μg 70 μg of Vitamin A Acetate
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 μg 0.2 μg of vitamin B12
비타민 C 10 mg Vitamin C 10 mg
비오틴 10 μg Biotin 10 μg
니코틴산아미드 1.7 mgNicotinamide 1.7 mg
엽산 50 μg Folic acid 50 μg
판토텐산 칼슘 0.5 mgCalcium Pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 mgFerrous Sulfate 1.75 mg
산화아연 0.82 mgZinc Oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mg15 mg potassium monophosphate
제2인산칼슘 55 mgDicalcium Phosphate 55 mg
구연산칼륨 90 mgPotassium Citrate 90 mg
탄산칼슘 100 mg Calcium Carbonate 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
제제예Formulation example 3.  3. 화장료Cosmetics 조성물의 제조 Preparation of the composition
3-1. 유연화장수(스킨로션)의 제조3-1. Preparation of Soft Cosmetics (Skin Lotion)
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 0.5 %NED19, Bromo-cyclic ADP-Ribose or Emodine 0.5%
베타-1,3-글루칸 1.0 %Beta-1,3-Glucan 1.0%
부틸렌글리콜 2.0 %Butylene Glycol 2.0%
프로필렌글리콜 2.0 %Propylene Glycol 2.0%
카르복시비닐폴리머 0.1 %Carboxy vinyl polymer 0.1%
피이지-12 노닐페닐에테르 0.2 %Fiji-12 nonylphenyl ether 0.2%
폴리솔베이트 80 0.4 % Polysorbate 80 0.4%
에탄올 10.0 %Ethanol 10.0%
트리에탄올아민 0.1 %Triethanolamine 0.1%
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 %Purified water to 100%
2. 영양화장수(2. Nutritional Cosmetics ( 밀크로션Milk Croissant )의 제조Manufacturing
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 0.5 %NED19, Bromo-cyclic ADP-Ribose or Emodine 0.5%
베타-1,3-글루칸 1.0 %Beta-1,3-Glucan 1.0%
밀납 4.0 %Beeswax 4.0%
폴리솔베이트 60 1.5 % Polysorbate 60 1.5%
솔비탄세스퀴올레이트 1.5 %Sorbanthesquioleate 1.5%
유동파라핀 0.5 %Liquid paraffin 0.5%
카프릴릭/카프릭트리글리세라이드 5.0 %Caprylic / Capric Triglycerides 5.0%
글리세린 3.0 %Glycerin 3.0%
부틸렌글리콜 3.0 %Butylene Glycol 3.0%
프로필렌글리콜 3.0 %Propylene Glycol 3.0%
카르복시비닐폴리머 0.1 %Carboxy vinyl polymer 0.1%
트리에탄올아민 0.2 %Triethanolamine 0.2%
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 %Purified water to 100%
3. 영양크림의 제조3. Preparation of nutrition cream
NED19, 브로모-사이클릭 ADP-리보오스 또는 에모딘 1.0 %NED19, Bromo-cyclic ADP-Ribose or Emodine 1.0%
베타-1,3-글루칸 5.0 %Beta-1,3-Glucan 5.0%
밀납 10.0 %Beeswax 10.0%
폴리솔베이트 60 1.5 % Polysorbate 60 1.5%
피이지 60 경화피마자유 2.0 % Sebum 60 Cured Castor Oil 2.0%
솔비탄세스퀴올레이트 0.5 %Solbitan Sesquioleate 0.5%
유동파라핀 10.0 %Liquid paraffin 10.0%
스쿠알란 5.0 %Squalane 5.0%
카프릴릭/카프릭트리글리세라이드 5.0 %Caprylic / Capric Triglycerides 5.0%
글리세린 5.0 %Glycerin 5.0%
부틸렌글리콜 3.0 %Butylene Glycol 3.0%
프로필렌글리콜 3.0 %Propylene Glycol 3.0%
트리에탄올아민 0.2 %Triethanolamine 0.2%
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 %Purified water to 100%

Claims (9)

  1. 화학식 1 내지 3 중 어느 하나의 화합물을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for the prophylaxis or treatment of allergic or inflammatory skin diseases comprising the compound of any one of Formulas 1 to 3 as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2017001808-appb-I000007
    Figure PCTKR2017001808-appb-I000007
    [화학식 2][Formula 2]
    Figure PCTKR2017001808-appb-I000008
    Figure PCTKR2017001808-appb-I000008
    [화학식 3][Formula 3]
    Figure PCTKR2017001808-appb-I000009
    Figure PCTKR2017001808-appb-I000009
  2. 제1항에 있어서, The method of claim 1,
    상기 피부질환은 아토피성 피부염, 알레르기성 피부염, 접촉성 피부염, 여드름, 지루성 피부염, 땀띠, 두드러기 및 건선으로 이루어진 군으로부터 하나 이상 선택되는 것을 특징으로 하는, 약학적 조성물.The skin disease is characterized in that at least one selected from the group consisting of atopic dermatitis, allergic dermatitis, contact dermatitis, acne, seborrheic dermatitis, sweat, urticaria and psoriasis.
  3. 화학식 1 내지 3 중 어느 하나의 화합물을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 피부외용제.Skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases comprising the compound of any one of Formulas 1 to 3 as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2017001808-appb-I000010
    Figure PCTKR2017001808-appb-I000010
    [화학식 2][Formula 2]
    Figure PCTKR2017001808-appb-I000011
    Figure PCTKR2017001808-appb-I000011
    [화학식 3][Formula 3]
    Figure PCTKR2017001808-appb-I000012
    Figure PCTKR2017001808-appb-I000012
  4. 화학식 1 내지 3 중 어느 하나의 화합물을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 개선용 건강식품 조성물.Health food composition for the prevention or improvement of allergic or inflammatory skin diseases comprising the compound of any one of Formulas 1 to 3 as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2017001808-appb-I000013
    Figure PCTKR2017001808-appb-I000013
    [화학식 2][Formula 2]
    Figure PCTKR2017001808-appb-I000014
    Figure PCTKR2017001808-appb-I000014
    [화학식 3][Formula 3]
    Figure PCTKR2017001808-appb-I000015
    Figure PCTKR2017001808-appb-I000015
  5. 화학식 1 내지 3 중 어느 하나의 화합물을 유효성분으로 포함하는, 가려움증 완화 또는 억제용 화장료 조성물.Cosmetic composition for alleviating or suppressing itching comprising a compound of any one of Formulas 1 to 3 as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2017001808-appb-I000016
    Figure PCTKR2017001808-appb-I000016
    [화학식 2][Formula 2]
    Figure PCTKR2017001808-appb-I000017
    Figure PCTKR2017001808-appb-I000017
    [화학식 3][Formula 3]
    Figure PCTKR2017001808-appb-I000018
    Figure PCTKR2017001808-appb-I000018
  6. 제5항에 있어서,The method of claim 5,
    상기 가려움증은 아토피성 피부염, 알레르기성 피부염, 접촉성 피부염, 살갗의 거칠어짐으로 인한 피부염, 여드름, 지루성 피부염, 땀띠, 진무름, 동상, 두드러기 및 건선으로 이루어진 군으로부터 하나 이상에 의해 유발된 것을 특징으로 하는, 화장료 조성물.The itching is caused by one or more from the group consisting of atopic dermatitis, allergic dermatitis, contact dermatitis, skin roughness dermatitis, acne, seborrheic dermatitis, sweat band, erosion, frostbite, urticaria and psoriasis Cosmetic composition.
  7. 제5항에 있어서,The method of claim 5,
    상기 화장료 조성물은 피부 보습 증진 또는 피부 과각질화 방지 효과를 갖는 것을 특징으로 하는, 화장료 조성물.The cosmetic composition is characterized in that it has a skin moisturizing enhancement or skin hyperkeratosis preventing effect.
  8. 제5항에 있어서,The method of claim 5,
    상기 화장료 조성물은 용액, 겔, 고체, 반죽 무수 생성물, 에멀젼, 현탁액, 유탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구, 리포좀, 비이온형의 소낭 분산제, 크림, 스킨, 로션, 파우더, 스프레이, 페이스트, 팩, 세안제, 비누, 오일, 왁스, 콘실스틱 또는 에어로졸인 것을 특징으로 하는, 화장료 조성물.The cosmetic composition may include solutions, gels, solids, pasty anhydrides, emulsions, suspensions, emulsions, microemulsions, microcapsules, microgranules, liposomes, nonionic vesicle dispersants, creams, skins, lotions, powders, sprays, pastes. , A pack, a face wash, soap, oil, wax, a conceal stick or an aerosol, cosmetic composition.
  9. 화학식 1 내지 3 중 어느 하나의 화합물을 이를 필요로하는 개체에 투여하는단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료방법.A method for preventing or treating allergic or inflammatory skin diseases, comprising administering a compound of any one of Formulas 1 to 3 to a subject in need thereof.
    [화학식 1][Formula 1]
    Figure PCTKR2017001808-appb-I000019
    Figure PCTKR2017001808-appb-I000019
    [화학식 2][Formula 2]
    Figure PCTKR2017001808-appb-I000020
    Figure PCTKR2017001808-appb-I000020
    [화학식 3][Formula 3]
    Figure PCTKR2017001808-appb-I000021
    Figure PCTKR2017001808-appb-I000021
PCT/KR2017/001808 2016-02-19 2017-02-17 Composition for preventing and treating allergic or inflammatory skin disease WO2017142368A2 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018070774A1 (en) * 2016-10-11 2018-04-19 전북대학교 산학협력단 Use of cadpr or naadp antagonists
CN116747213A (en) * 2023-06-30 2023-09-15 大连医科大学附属第一医院 Application of emodin in inhibiting sebaceous gland synthesis and secretion

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9828071D0 (en) * 1998-12-18 1999-02-17 Univ Bath Therapeutics
KR100812596B1 (en) * 2006-12-15 2008-03-13 바이오스펙트럼 주식회사 Compositions comprising compounds of natural origin for damaged skin
KR100832332B1 (en) * 2007-02-12 2008-05-26 바이오스펙트럼 주식회사 Compositions for ameliorating symptom of atopic dermatitis
GB0811587D0 (en) * 2008-06-25 2008-07-30 Isis Innovation Novel Compounds

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018070774A1 (en) * 2016-10-11 2018-04-19 전북대학교 산학협력단 Use of cadpr or naadp antagonists
US11071748B2 (en) * 2016-10-11 2021-07-27 Industrial Cooperation Foundation Chonbuk National University Use of cADPR or NAADP antagonists
CN116747213A (en) * 2023-06-30 2023-09-15 大连医科大学附属第一医院 Application of emodin in inhibiting sebaceous gland synthesis and secretion

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