WO2017142383A1 - Composition and method for preventing or treating skin disease - Google Patents

Composition and method for preventing or treating skin disease Download PDF

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Publication number
WO2017142383A1
WO2017142383A1 PCT/KR2017/001853 KR2017001853W WO2017142383A1 WO 2017142383 A1 WO2017142383 A1 WO 2017142383A1 KR 2017001853 W KR2017001853 W KR 2017001853W WO 2017142383 A1 WO2017142383 A1 WO 2017142383A1
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Prior art keywords
acetyl
lte
composition
allergic
dermatitis
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PCT/KR2017/001853
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French (fr)
Korean (ko)
Inventor
한명관
김승국
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전북대학교 산학협력단
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Priority claimed from KR1020170022185A external-priority patent/KR101819670B1/en
Publication of WO2017142383A1 publication Critical patent/WO2017142383A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids

Definitions

  • the present invention relates to a composition for the prevention or treatment of skin diseases, more specifically N-acetyl-LTE 4 or a pharmaceutically acceptable salt thereof as an active ingredient, for the prevention or treatment of allergic or inflammatory skin diseases To a composition or method.
  • Human skin is composed of the dermis and epidermis.
  • the dermis is primarily composed of fibroblasts, which synthesize collagen and other proteins, and produce small amounts of lipids.
  • the epidermis is composed mainly of keratinocytes that produce lipids and do not substantially synthesize collagen.
  • the epidermis located at the outermost surface of the skin, protects against various stimuli from the outside, such as chemicals, air pollutants, dry environments, ultraviolet and other physicochemical stimuli such as ultraviolet rays, and excessive release of moisture from the body through the skin. Prevents protection. This protective function is possible by the normal formation and maintenance of the stratum corneum consisting of keratinocytes.
  • the outermost stratum corneum (horney layer) is formed from keratinocytes and is composed of the differentiated keratinocytes and the surrounding lipid layer. Keratinocytes are cells formed through the morphological and functional changes in stages as the basal cells continuously proliferating in the stratum basale migrate to the stratum corneum. After a period of time, the old keratinocytes are eliminated from the skin and new keratinocytes from the epidermal layer take over the function. This repetitive process of epidermis differentiation or keratinization keratinization).
  • keratinocytes form a stratum corneum while producing natural moisturizing factor (NMF) and intercellular lipids (ceramides, cholesterol and fatty acids), making the stratum corneum solid and flexible, blocking it from the outside. It functions as a skin barrier that acts as a layer.
  • NMF moisturizing factor
  • ceramides, cholesterol and fatty acids intercellular lipids
  • the stratum corneum can easily lose its function due to excessive facial cleansing, lifestyle factors such as bathing, environmental factors such as dry air pollutants, and endogenous diseases such as atopic or aged skin. Indeed, in modern times, the risk factors for skin are increasing, and as the dietary patterns change, the formation and dropping rate of the stratum corneum slows down, and as the amount of moisturizing factors and lipids in the stratum corneum decreases due to the deterioration of the function of keratinocytes, There is a growing number of people with skin whose stratum corneum does not function as a normal skin barrier.
  • atopic dermatitis is a type of hypersensitivity, which has recently been highlighted with a rapid increase in prevalence, and from an immunological point of view, immunoglobulin E (Ig E) and allergens. It is defined as a group of allergic diseases with a strong genetic tendency accompanied by major symptoms caused by the immune response.
  • Ig E immunoglobulin E
  • atopic dermatitis a typical symptom of atopic dermatitis, is estimated to be related to genetic factors and immune system deficiency, although 0.5% -1% of the population and 5-10% of children complain of severe symptoms. The exact cause has not been determined yet, but it is expected to be somewhat alleviated by improving the environment and diet, and there is no fundamental treatment.
  • Symptoms of atopic dermatitis include severe itching and dry skin, rashes, rashes, scabs, scaly skin (human scales), and emotional anxiety, stress, tension, frustration, anger, and other feelings. Frequent allergies include urticaria, metal allergies, asthma and allergic rhinitis. In recent years, atopic dermatitis has also increased in adults, and as a risk factor of atopic dermatitis in adults, there have been cases of face and neck lesions, and cases of animal, pollen, and nickel allergy.
  • N-acetyl-LTE 4 has an excellent therapeutic effect and completed the present invention. It was.
  • An object of the present invention is to provide a composition or method for the prevention or treatment of allergic or inflammatory skin diseases, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient. .
  • Another object of the present invention to provide a composition for mitigating or suppressing itching comprising the active ingredient.
  • the present invention comprises N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient, for the prevention or treatment of allergic or inflammatory skin diseases To provide a composition.
  • the present invention provides a skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases comprising the active ingredient.
  • the present invention provides a health food composition for the prevention or improvement of allergic or inflammatory skin diseases comprising the active ingredient.
  • the present invention provides a cosmetic composition for itching relief or inhibition comprising the active ingredient.
  • the present invention provides a N- acetyl-LTE 4 (N-acetyl Leukotriene 4 ) or a pharmaceutically acceptable comprising administering the salts to the object, its allergenicity, or the prevention or treatment of inflammatory skin diseases.
  • N-acetyl LTE 4 (N-acetyl Leukotriene E4) of the present invention inhibits the production of water-soluble cytokines, especially IL-2 and IL-17, alleviate the symptoms of itching caused by a variety of causes, and at the same time provides an immune control effect
  • the present invention can be used in various ways, such as a composition for the relief of itching caused by histamine, chloroquine or contact dermatitis, and for preventing or treating allergic or inflammatory skin diseases including atopic dermatitis.
  • 1 is a view showing the effect of improving the itch caused by histamine following the administration of N-acetyl-LTE 4 .
  • Figure 2 is a diagram showing the itch improvement effect caused by chloroquine according to the administration of N-acetyl-LTE 4 .
  • FIG 3 is a view showing the effect of improving the itch caused by contact dermatitis according to the administration of N-acetyl-LTE 4 .
  • Figure 4 is a diagram showing the results confirmed by H & E staining to improve the atopic dermatitis according to the administration of N-acetyl-LTE 4 .
  • FIG. 5 is a diagram showing the results of confirming the change in the factors in vivo according to the administration of N-acetyl-LTE 4 through BioMAP.
  • the present invention provides a N- acetyl-LTE 4 (N-acetyl Leukotriene E4 ) or a pharmaceutically, allergic or composition for the prevention or treatment of inflammatory skin diseases or methods, including acceptable salt thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for the prophylaxis or treatment of allergic or inflammatory skin diseases, comprising N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient. do.
  • the present invention is N- acetyl-LTE 4 (N-acetyl Leukotriene 4 ) or a pharmaceutically acceptable comprising administering the salts to the object, the prevention of allergic or inflammatory skin diseases or treatment to provide.
  • N-acetyl LTE 4 as an active ingredient is also referred to as N-acetyl Leukotriene E4, and is mainly metabolized in bile, and is also found in spleen, kidney, skin, and lung, and LTE 4 is produced by metabolism.
  • N-acetyl Leukotriene E4 is also referred to as N-acetyl Leukotriene E4
  • LTE 4 is produced by metabolism.
  • As a substance it is a substance distinguished from LTE 4 .
  • the material may be specified by the following formula (1).
  • the pharmaceutically acceptable salt of N-acetyl LTE 4 represented by Formula 1 includes salts of acidic or basic groups which may be present in the compound of Formula 1, unless otherwise indicated.
  • pharmaceutically acceptable salts include sodium, calcium and potassium salts of hydroxy or carboxyl groups
  • other pharmaceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate, Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, methods of making salts known in the art However, it can be manufactured through the manufacturing process.
  • 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.
  • N-acetyl LTE 4 inhibits the production of water-soluble cytokines, especially IL-2 and IL-17, alleviates the itch caused by various causes, and at the same time has an immune control effect, allergic or It can be used in various ways as a medicine for treating inflammatory skin diseases, health functional foods, and the like.
  • the composition may further include one or more known active ingredients having an allergic or inflammatory skin disease prevention or treatment effect together with the N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
  • 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.
  • N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof 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 expected, for example, can be administered by oral, rectal or intravenous, intramuscular or subcutaneous injection, and can be administered by any route, such as the way it is plotted on 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 also provides an external preparation for preventing or treating allergic or inflammatory skin diseases, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • N-acetyl LTE 4 N-acetyl Leukotriene E4
  • a pharmaceutically acceptable salt thereof 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 the N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
  • 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, And a cooling agent, a restriction
  • the present invention provides a health functional food for preventing or improving allergic or inflammatory skin diseases, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the composition may further contain one or more known active ingredients having an effect of preventing or ameliorating allergic or inflammatory skin diseases together with N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
  • 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 N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof when the material is used as a food additive, the N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof may be added as it is or may be used together with other foods 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).
  • N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof 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 also provides a cosmetic composition for alleviating or suppressing itching, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a cosmetic composition for alleviating or suppressing itching including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the composition may further contain at least one known active ingredient having an itch relieving or suppressing effect with N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
  • 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 through the enhancement of skin moisturizing or preventing skin keratinization, it is characterized by having a skin condition improvement effect accordingly.
  • the composition is in addition to N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof, 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 ester, polyethylene glycol, fatty acid ester 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, Moreover, although all said components can be mix
  • N-acetyl-LTE 4 (N-acetyl Leukotriene E4) used in the examples below was supplied from Santa Cruz biotechnology (Dallas, Texas, USA).
  • the N-acetyl-LTE 4 is specified by the following formula.
  • mice All animal experiments were conducted in accordance with the guidelines of the Experimental Animal Committee of Chonbuk National University. Weights from 6 to 8 weeks old 20-24 g Balb / c mice were purchased from Orient Bio (Seongnam, Korea), and animals were given specific radishes with varying contrast and free food and water at 12-34 ° C and 12-hour intervals. -Breeding in antigen (SPF; specific pathogen free) laboratory. In in vivo experiments, mice were randomly divided to include more than 6 animals in each group, and then the experiments were performed by designating them as control or experimental groups.
  • SPF specific pathogen free
  • N-acetyl-LTE 4 In order to confirm the itch relieving effect by N-acetyl-LTE 4 , it caused contact dermatitis caused by histamine and chloroquine known to cause itching in the intradermal neck and DNBF. After the itching effect according to N-acetyl-LTE 4 was confirmed. Specifically, it is as follows.
  • DNFB 1-fluoro-2,4-dinitrobenzene
  • NC / Nga mice male, 10 weeks old were used. Experimental animals were maintained at a temperature of 20 ° C. and 50% of humidity, and were used for experiments after adapting for one week in a normal breeding room where the contrast was changed every 12 hours.
  • hair was completely removed by shaving the upper back of the NC / Nga mouse to the dorsal wheel.
  • 4% SDS solution was sprayed to remove the fat component of the skin, and after the material was completely dried, a 100 mg of atopic dermatitis reagent, Biostir AD (house dust mite), was used with a stick.
  • Biostir AD house dust mite
  • H & E staining was used to determine whether atopic dermatitis was alleviated by N-acetyl-LTE 4 .
  • N-acetyl-LTE 4 a total of 1 ⁇ M solution of N-acetyl-LTE 4 dissolved in ethanol was prepared, and then 100 ⁇ l was applied to the atopy-induced experimental animal of Example 3-1. This was repeated daily for two weeks from three weeks after atopic induction.
  • 100 ⁇ l of ethanol was applied to the negative control group instead of N-acetyl-LTE 4 . Thereafter, mice were sacrificed when a total of five weeks had elapsed after atopic dermatitis.
  • N-acetyl-LTE 4 has a significant atopic dermatitis improvement effect.
  • BioMAP analysis was performed with the help of DiscoveRx (Fremont, CA) using primary human cells. This study complied with the guidelines for the study of human subjects under the US HHS Human Subject Regulation (45 CFR Part 46).
  • PBMCs peripheral blood mononuclear cells
  • TH2 polarized CD4 + T-cells
  • All Cells LLC Emeryville, Calif.
  • the BT system consists of CD19 + B-cells (AllCells LLC.
  • Foreskin fibroblasts (HDFn; human neonatal foreskin fibroblasts) from three newborns were isolated and cultured according to a manual provided by the supplier (Lonza, Inc., Allendale, NJ) for the HDF3GF system. HDFn was cytokine and placed in low plasma for 24 hours prior to stimulation.
  • PBMCs Peripheral blood mononuclear cells
  • cytokines IL1 ⁇ , 1 ng / ml; TNF ⁇ , 5 ng / ml; IFN- ⁇ , 20 ng / ml; IL4, 5 ng / ml
  • IL2 2 ng / ml
  • activator SAg, 20 ng / ml; histamine, 10 ⁇ M; or LPS, 2 ng / ml
  • growth factor TGF- ⁇ , 5 ng / ml; EGF, bFGF, and PDGF-BB, 10 ng / ml
  • PBMC 7.5 ⁇ 10 4 cells / well.
  • DiscoveRx PathHunter technology was used to confirm whether N-acetyl LTE 4 activates or inhibits ⁇ -arrestin-2 using BioMAP constructed according to the above procedure. This includes enzymatic complementation of fusion-tagged receptors according to the Arestin Lycrute regulatory sequence and the ⁇ -Arrestin-2 protein.
  • CHO-K1 cells expressing various types of G-protein coupled receptors were plated at a concentration of 2625 cells / well in a plate consisting of 384-well black transparent bottoms.
  • (DiscoveRx) was inoculated. After 24 hours of incubation, cells were treated with N-acetyl-LTE 4 at various concentrations (1.8 ⁇ M, 600 nM, 200 nM and 67 nM) in PBS containing 1% dimethylsulfoxide (results for this). 5, red, orange, yellow, and green, respectively, in FIG. 5A), and incubated at 37 ° C. for 90 minutes.
  • DiscoveRx reagent was then added to the cells according to the manufacturer's manual and incubated for 30-60 minutes at room temperature. Fluorescence was measured on a Hamamatsu FDSS ⁇ Cell reader. Collected data are entered into the RLUs and the control group (N-acetyl-LTE 4) shows the maximum concentration of dopamine in the 0% RLUs state. Normalized to the fluorescence ratio of no addition). The results are shown in Figure 5a.
  • the activity profile (in blue) of the high concentration of 3700 ng / ml of human gamma globulin and the 600 nM of N-acetyl-LTE 4 A comparison of the cell activity profiles (in orange) derived with addition is shown in FIG. 5B.
  • the information read was written along the X-axis, where the Y-axis represents the logarithm of the value relative to the control solvent (ethanol), and the gray areas at the top and bottom of the dashed line showed 95% significance relative to the control. .
  • the N-acetyl LTE 4 (N-acetyl Leukotriene E4) of the present invention inhibits the production of water soluble cytokines, especially IL-2 and IL-17, alleviating the symptoms of itching caused by various causes, while simultaneously immunizing Has a control effect. Therefore, the present invention can be used in various ways, such as a composition for the relief of itching caused by histamine, chloroquine or contact dermatitis, and for preventing or treating allergic or inflammatory skin diseases including atopic dermatitis.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
  • the amount of the above ingredient is prepared per ampoule (2 ml).
  • 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.
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.
  • composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
  • a small amount of fragrance, a small amount of preservative, and a residual amount of purified water were mixed to prepare flexible cosmetic water in a conventional manner.
  • Carboxy vinyl polymer 1.5 wt%
  • a small amount of fragrance, a small amount of preservative, and a residual amount of purified water were mixed to prepare a milk lotion in a conventional manner.
  • a nutritious cream was prepared in a conventional manner by mixing a small amount of fragrance, a small amount of preservative and a residual amount of purified water.

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Abstract

The present invention relates to a composition or a method for preventing or treating skin disease, and more specifically, to a composition or a method for preventing or treating allergic or inflammatory skin disease, the composition comprising N-acetyl Leukotriene E4 (N-acetyl-LTE4) or a pharmaceutically acceptable salt as an effective ingredient. The N-acetyl LTE4 alleviates itching, caused by various causes, by suppressing the generation of water-soluble cytokine, in particular, IL-2 and IL-17, and at the same time has an immunomodulatory effect. Thus, the present invention can be variously used as a composition for alleviating itching induced by histamine, chloroquine, contact dermatitis, or the like, an agent for preventing or treating allergic or inflammatory skin disease including atopic dermatitis, and the like.

Description

피부질환 예방 또는 치료용 조성물 또는 방법Compositions or methods for preventing or treating skin diseases
본 발명은 피부질환 예방 또는 치료용 조성물에 관한 것으로, 보다 구체적으로는 N-아세틸-LTE4 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물 또는 방법에 관한 것이다.The present invention relates to a composition for the prevention or treatment of skin diseases, more specifically N-acetyl-LTE 4 or a pharmaceutically acceptable salt thereof as an active ingredient, for the prevention or treatment of allergic or inflammatory skin diseases To a composition or method.
사람의 피부는 진피(dermis)와 표피(epidermis)로 구성되어 있다. 진피는 콜라겐과 기타 단백질을 주로 합성하며, 소량의 지질을 생산하는 섬유아세포(fibroblast)로 주로 구성되어 있다. 이와는 대조적으로, 표피는 지질을 주로 생성하고, 콜라겐을 실질적으로 합성하지 않는 각질형성세포(keratinocyte)로 주로 구성되어 있다. 특히, 피부의 최외각에 위치하고 있는 표피는 외부로부터의 다양한 자극, 예를 들면 화학 물질, 대기 오염 물질, 건조한 환경, 자외선 등의 물리화학적 자극인자에 대한 방어와 피부를 통한 체내 수분의 과도한 발산을 막는 보호 기능을 수행하고 있다. 이러한 보호 기능은 각질형성세포로 구성된 각질층이 정상적으로 형성되고 유지됨으로써 가능하다.Human skin is composed of the dermis and epidermis. The dermis is primarily composed of fibroblasts, which synthesize collagen and other proteins, and produce small amounts of lipids. In contrast, the epidermis is composed mainly of keratinocytes that produce lipids and do not substantially synthesize collagen. In particular, the epidermis, located at the outermost surface of the skin, protects against various stimuli from the outside, such as chemicals, air pollutants, dry environments, ultraviolet and other physicochemical stimuli such as ultraviolet rays, and excessive release of moisture from the body through the skin. Prevents protection. This protective function is possible by the normal formation and maintenance of the stratum corneum consisting of keratinocytes.
표피 중에서도 가장 바깥에 존재하는 각질층(Stratum corneum, horney layer)은 각질 형성세포로부터 형성되며, 분화가 완결된 각질세포와 그를 둘러싼 지질층으로 구성되어 있다. 각질세포는 표피 최하층(stratum basale)에서 지속적으로 증식하는 기저 세포(basal cell)가 각질층(stratum corneum)으로 이동하면서 단계적으로 형태 및 기능상의 변화를 거치며 형성된 세포이다. 일정 기간이 경과하면 오래된 각질세포는 피부에서 탈락되고, 표피 최하층으로부터 올라온 새로운 각질형성세포(keratinocyte)가 그 기능을 대신하게 되는데, 이러한 반복적인 일련의 변화 과정을 표피 분화(epidermis differentiation) 또는 각화(keratinization)라 한다. 이러한 각화 과정에서 각질형성세포는 천연보습인자(Natural Moisturizing Factor; NMF)와 세포 간 지질 (세라마이드, 콜레스테롤 및 지방산)을 생성하면서 각질층을 형성하여, 각질층이 견고함과 유연성을 갖도록 하여 외부와의 차단층 역할을 하는 피부장벽(skin barrier)으로서의 기능을 보유하게 된다.The outermost stratum corneum (horney layer) is formed from keratinocytes and is composed of the differentiated keratinocytes and the surrounding lipid layer. Keratinocytes are cells formed through the morphological and functional changes in stages as the basal cells continuously proliferating in the stratum basale migrate to the stratum corneum. After a period of time, the old keratinocytes are eliminated from the skin and new keratinocytes from the epidermal layer take over the function. This repetitive process of epidermis differentiation or keratinization keratinization). In this keratinization process, keratinocytes form a stratum corneum while producing natural moisturizing factor (NMF) and intercellular lipids (ceramides, cholesterol and fatty acids), making the stratum corneum solid and flexible, blocking it from the outside. It functions as a skin barrier that acts as a layer.
이러한 각질층은 과도한 세안이나, 목욕 등의 생활 습관적 요소나, 건조한 대기 오염 물질 등의 환경적인 요인, 및 아토피성 피부나 노인성 피부 같은 내인성 질환 등으로 인해 쉽게 그 기능이 손실될 수 있다. 실제로 현대에 들어서 피부에 대한 위해 요인이 점점 증가되고 있으며, 식생활 양상의 변화로 각질층의 생성 및 탈락 속도가 늦어지고, 각질형성세포의 기능 저하로 각질층의 보습인자와 지질의 양이 감소됨에 따라, 각질층이 정상적인 피부 장벽 기능을 발휘하지 못하는 피부를 가진 사람들이 증가하고 있는 추세이다.The stratum corneum can easily lose its function due to excessive facial cleansing, lifestyle factors such as bathing, environmental factors such as dry air pollutants, and endogenous diseases such as atopic or aged skin. Indeed, in modern times, the risk factors for skin are increasing, and as the dietary patterns change, the formation and dropping rate of the stratum corneum slows down, and as the amount of moisturizing factors and lipids in the stratum corneum decreases due to the deterioration of the function of keratinocytes, There is a growing number of people with skin whose stratum corneum does not function as a normal skin barrier.
특히 아토피(atopy) 피부염은 최근 들어, 유병률이 급격히 증가함에 따라 그 위험성이 크게 부각되고 있는 과민증(hypersensitivity)의 일종으로, 면역학적 관점에서는 면역글로불린E(immunoglobulin E, Ig E)와 알레르겐(allergen)의 면역반응에 의한 주요증상을 동반하는 유전경향이 강한 알레르기성 질환군으로 정의된다. 특히, 아토피의 대표적 증상인 아토피 피부염(atopic dermatitis)은 전 인구의 0.5%-1%, 어린이의 5-10%가 심각한 증상을 호소하고 있지만, 유전적인 요인과 면역계 결핍에 관련 있는 것으로 추정될 뿐 아직 정확한 원인은 밝혀진 바 없고, 환경 및 식생활 개선을 통해 다소 완화되는 것으로 기대될 뿐 근본적인 치료방법이 전무한 실정이다.In particular, atopic dermatitis is a type of hypersensitivity, which has recently been highlighted with a rapid increase in prevalence, and from an immunological point of view, immunoglobulin E (Ig E) and allergens. It is defined as a group of allergic diseases with a strong genetic tendency accompanied by major symptoms caused by the immune response. In particular, atopic dermatitis, a typical symptom of atopic dermatitis, is estimated to be related to genetic factors and immune system deficiency, although 0.5% -1% of the population and 5-10% of children complain of severe symptoms. The exact cause has not been determined yet, but it is expected to be somewhat alleviated by improving the environment and diet, and there is no fundamental treatment.
아토피 피부염의 증상으로는 극심한 가려움증을 비롯한 피부건조증, 발진, 진물, 부스럼딱지, 비늘 같은 껍질이 있는 피부(인비늘) 등이 있으며, 이로 인한 정서적 불안, 스트레스, 긴장, 좌절, 분노의 감정과 함께 기타 알레르기 질환인 두드러기, 금속 알레르기, 천식이나 알레르기성 비염 등을 동반하는 경우가 빈번하다. 또한 최근에는 성인에서도 아토피 피부염이 증가하고 있으며, 성인에서 아토피 피부염의 위험 인자로 얼굴과 목에 병변이 있는 경우나 동물, 꽃가루, 니켈 알레르기가 있는 경우 등이 제시되고 있다.Symptoms of atopic dermatitis include severe itching and dry skin, rashes, rashes, scabs, scaly skin (human scales), and emotional anxiety, stress, tension, frustration, anger, and other feelings. Frequent allergies include urticaria, metal allergies, asthma and allergic rhinitis. In recent years, atopic dermatitis has also increased in adults, and as a risk factor of atopic dermatitis in adults, there have been cases of face and neck lesions, and cases of animal, pollen, and nickel allergy.
따라서 본 발명자들은 가려움증 및 아토피를 포함하는 알레르기성 또는 염증성 피부질환을 현저하게 개선시킬 수 있는 방법에 대하여 연구하던 중, N-아세틸-LTE4이 우수한 치료 효과를 가짐을 확인하고, 본 발명을 완성하였다.Therefore, the inventors of the present invention, while studying a method for remarkably improving allergic or inflammatory skin diseases including itching and atopy, confirmed that N-acetyl-LTE 4 has an excellent therapeutic effect and completed the present invention. It was.
본 발명의 목적은 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물 또는 방법을 제공하는 것이다.An object of the present invention is to provide a composition or method for the prevention or treatment of allergic or inflammatory skin diseases, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient. .
본 발명의 또다른 목적은 상기 유효성분을 포함하는 가려움증 완화 또는 억제용 조성물을 제공하는 것이다.Another object of the present invention to provide a composition for mitigating or suppressing itching comprising the active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention comprises N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient, for the prevention or treatment of allergic or inflammatory skin diseases To provide a composition.
또한 본 발명은 상기 유효성분을 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 comprising the active ingredient.
또한 본 발명은 상기 유효성분을 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 the active ingredient.
또한 본 발명은 상기 유효성분을 포함하는 가려움증 완화 또는 억제용 화장료 조성물을 제공한다.In another aspect, the present invention provides a cosmetic composition for itching relief or inhibition comprising the active ingredient.
또한 본 발명은 N-아세틸 LTE4(N-acetyl Leukotriene 4) 또는 이의 약학적으로 허용가능한 염을 개체에 투여하는 단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 방법을 제공한다.In another aspect, the present invention provides a N- acetyl-LTE 4 (N-acetyl Leukotriene 4 ) or a pharmaceutically acceptable comprising administering the salts to the object, its allergenicity, or the prevention or treatment of inflammatory skin diseases.
본 발명의 N-아세틸 LTE4(N-acetyl Leukotriene E4)는 수용성 사이토카인, 특히 IL-2 및 IL-17의 생성을 억제하여 다양한 원인에 의해 발생하는 가려움 증상을 완화시키며, 동시에 면역 제어 효과를 가진다. 따라서 본 발명은 히스타민, 클로로퀸 또는 접촉성 피부염 등에 의해 유발된 가려움증의 완화를 위한 조성물, 및 아토피 피부염을 비롯한 알레르기성 또는 염증성 피부질환의 예방 또는 치료제 등으로 다양하게 활용될 수 있다.N-acetyl LTE 4 (N-acetyl Leukotriene E4) of the present invention inhibits the production of water-soluble cytokines, especially IL-2 and IL-17, alleviate the symptoms of itching caused by a variety of causes, and at the same time provides an immune control effect Have Therefore, the present invention can be used in various ways, such as a composition for the relief of itching caused by histamine, chloroquine or contact dermatitis, and for preventing or treating allergic or inflammatory skin diseases including atopic dermatitis.
도 1은 N-아세틸-LTE4의 투여에 따른 히스타민에 의해 야기된 가려움증 개선 효과를 나타내는 도이다.1 is a view showing the effect of improving the itch caused by histamine following the administration of N-acetyl-LTE 4 .
도 2는 N-아세틸-LTE4의 투여에 따른 클로로퀸에 의해 야기된 가려움증 개선 효과를 나타내는 도이다.Figure 2 is a diagram showing the itch improvement effect caused by chloroquine according to the administration of N-acetyl-LTE 4 .
도 3은 N-아세틸-LTE4의 투여에 따른 접촉성 피부염에 의해 야기된 가려움증 개선 효과를 나타내는 도이다.3 is a view showing the effect of improving the itch caused by contact dermatitis according to the administration of N-acetyl-LTE 4 .
도 4는 N-아세틸-LTE4의 투여에 따른 아토피 피부염의 개선 효과를 H&E 염색을 통하여 확인한 결과를 나타내는 도이다.Figure 4 is a diagram showing the results confirmed by H & E staining to improve the atopic dermatitis according to the administration of N-acetyl-LTE 4 .
도 5는 N-아세틸-LTE4의 투여에 따른 생체 내 인자들의 변화를 BioMAP를 통하여 확인한 결과를 나타내는 도이다.5 is a diagram showing the results of confirming the change in the factors in vivo according to the administration of N-acetyl-LTE 4 through BioMAP.
본 발명은 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 조성물 또는 방법을 제공한다.The present invention provides a N- acetyl-LTE 4 (N-acetyl Leukotriene E4 ) or a pharmaceutically, allergic or composition for the prevention or treatment of inflammatory skin diseases or methods, including acceptable salt thereof as an active ingredient.
이하 본 발명을 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
일 태양으로서, 본 발명은 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 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, comprising N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient. do.
또 다른 태양으로서, 본 발명은 N-아세틸 LTE4(N-acetyl Leukotriene 4) 또는 이의 약학적으로 허용가능한 염을 개체에 투여하는 단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 방법을 제공한다.As another aspect, the present invention is N- acetyl-LTE 4 (N-acetyl Leukotriene 4 ) or a pharmaceutically acceptable comprising administering the salts to the object, the prevention of allergic or inflammatory skin diseases or treatment to provide.
본 발명에 있어서, 유효성분인 N-아세틸 LTE4는 N-acetyl Leukotriene E4로도 지칭하며, 담즙에서 주로 대사되는 물질로, 지라, 콩팥, 피부 및 폐에서도 발견되며, LTE4이 물질대사하여 생성되는 물질로서 LTE4와는 구분되는 물질이다. 본 물질은 하기의 화학식 1로 특정될 수 있다. In the present invention, N-acetyl LTE 4 as an active ingredient is also referred to as N-acetyl Leukotriene E4, and is mainly metabolized in bile, and is also found in spleen, kidney, skin, and lung, and LTE 4 is produced by metabolism. As a substance, it is a substance distinguished from LTE 4 . The material may be specified by the following formula (1).
[화학식 1][Formula 1]
Figure PCTKR2017001853-appb-I000001
Figure PCTKR2017001853-appb-I000001
본 발명에 있어서, 상기 화학식 1로 표시되는 N-아세틸 LTE4의 약학적으로 허용가능한 염은, 달리 지시되지 않는 한, 화학식 1의 화합물에 존재할 수 있는 산성 또는 염기성 기의 염을 포함한다. 예를 들면, 약학적으로 허용가능한 염으로는 히드록시기 또는 카르복시기의 나트륨, 칼슘 및 칼륨염이 포함되며, 아미노기의 기타 약학적으로 허용가능한 염으로는 히드로브로마이드, 황산염, 수소 황산염, 인산염, 수소 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만델레이트, 메탄설포네이트(메실레이트) 및 p-톨루엔설포네이트(토실레이트) 염이 있으며, 당해 기술분야에서 알려진 염의 제조방법이나 제조과정을 통하여 제조될 수 있다.In the present invention, the pharmaceutically acceptable salt of N-acetyl LTE 4 represented by Formula 1 includes salts of acidic or basic groups which may be present in the compound of Formula 1, unless otherwise indicated. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of hydroxy or carboxyl groups, and other pharmaceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate, Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, methods of making salts known in the art However, it can be manufactured through the manufacturing process.
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 발명에 따르면 N-아세틸 LTE4는 수용성 사이토카인, 특히 IL-2 및 IL-17의 생성을 억제하여 다양한 원인에 의해 발생하는 가려움 증상을 완화시키며, 동시에 면역 제어 효과를 가지는 바, 알레르기성 또는 염증성 피부 질환을 치료하는 약제, 건강기능식품 등으로 다양하게 활용 가능하다.According to the present invention, N-acetyl LTE 4 inhibits the production of water-soluble cytokines, especially IL-2 and IL-17, alleviates the itch caused by various causes, and at the same time has an immune control effect, allergic or It can be used in various ways as a medicine for treating inflammatory skin diseases, health functional foods, and the like.
본 발명에 있어서, 상기 조성물은 상기 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염과 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 the N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
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 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염은 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, N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof 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 도표되는 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 expected, for example, can be administered by oral, rectal or intravenous, intramuscular or subcutaneous injection, and can be administered by any route, such as the way it is plotted on 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 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 피부외용제를 제공한다.The present invention also provides an external preparation for preventing or treating allergic or inflammatory skin diseases, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, 상기 조성물은 상기 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염과 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 the N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof. .
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, 제한(制汗)제, 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, And a cooling agent, a restriction | limiting agent, purified water, etc. can be included.
또한, 본 발명은 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 개선용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for preventing or improving allergic or inflammatory skin diseases, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, 상기 조성물은 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염과 함께 알레르기성 또는 염증성 피부질환의 예방 또는 개선 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 an effect of preventing or ameliorating allergic or inflammatory skin diseases together with N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
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 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염을 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 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염은 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 material is used as a food additive, the N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof may be added as it is or may be used together with other foods 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, N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof 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 N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 가려움증 완화 또는 억제용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for alleviating or suppressing itching, including N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, 상기 조성물은 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염과 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 with N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof.
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 피부 보습 증진 또는 피부 과각질화 방지를 통해 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 through the enhancement of skin moisturizing or preventing skin keratinization, it is characterized by having a skin condition improvement effect accordingly.
본 발명에 있어서, 상기 조성물은 N-아세틸 LTE4 또는 이의 약학적으로 허용가능한 염 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 N-acetyl LTE 4 or a pharmaceutically acceptable salt thereof, 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 클린싱, 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 에스테 르 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 ester, polyethylene glycol, fatty acid ester 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, 또, 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.In addition, the compounding component which may be added other than this is not limited to this, Moreover, Although all said components 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 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 발명의 이해를 돕기 위하여 실시예 및 제조예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예 및 제조예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예 및 제조예에 한정되는 것은 아니다. 본 발명의 실시예 및 제조예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, the present invention will be described in detail with reference to Examples and Preparation Examples in order to help understanding of the present invention. However, the following Examples and Preparation Examples are merely to illustrate the content of the present invention is not limited to the following Examples and Preparation Examples. Examples and preparations of the present invention are provided to more fully explain the present invention to those skilled in the art.
실시예 1. N-아세틸-LTE4(N-acetyl Leukotriene E4)의 준비Example 1. Preparation of N-acetyl-LTE 4 (N-acetyl Leukotriene E4)
이하 실시예에서 사용한 N-아세틸-LTE4(N-acetyl Leukotriene E4)는 Santa Cruz biotechnology(Dallas, Texas, USA)로부터 공급받아 사용하였다. 상기 N-아세틸-LTE4는 하기 화학식으로 특정된다.N-acetyl-LTE 4 (N-acetyl Leukotriene E4) used in the examples below was supplied from Santa Cruz biotechnology (Dallas, Texas, USA). The N-acetyl-LTE 4 is specified by the following formula.
Figure PCTKR2017001853-appb-C000001
Figure PCTKR2017001853-appb-C000001
실시예 2. N-아세틸-LTE4에 의한 가려움증 완화 효과 확인Example 2. Confirmation of itching relief by N-acetyl-LTE 4
2-1. 실험 동물2-1. Experimental animals
모든 동물 관련 실험은 국립 전북대학교의 실험동물위원회의 가이드라인에 따라 수행하였다. 6~8 주령의 무게 20~24 g Balb/c 마우스는 Orient 바이오(한국 성남)로부터 구입하였고, 동물들은 21~34 ℃의 온도, 12시간 간격으로 명암이 바뀌고 자유로운 음식 및 물이 제공되는 특정 무-항원(SPF; specific pathogen free) 실험실에서 사육하였다. 생체 내(in vivo) 실험에서, 마우스는 무작위적으로 각 그룹 당 6 마리 이상을 포함하도록 나누었으며, 이 후 대조군 또는 실험군으로 지정하여 실험을 수행하였다. All animal experiments were conducted in accordance with the guidelines of the Experimental Animal Committee of Chonbuk National University. Weights from 6 to 8 weeks old 20-24 g Balb / c mice were purchased from Orient Bio (Seongnam, Korea), and animals were given specific radishes with varying contrast and free food and water at 12-34 ° C and 12-hour intervals. -Breeding in antigen (SPF; specific pathogen free) laboratory. In in vivo experiments, mice were randomly divided to include more than 6 animals in each group, and then the experiments were performed by designating them as control or experimental groups.
2-2. 가려움증 완화 효과 확인2-2. Identify the effects of itching
N-아세틸-LTE4에 의한 가려움증 완화 효과를 확인하기 위하여, 피내(intradermal) 목(neck)에서 가려움증을 야기하는 것으로 알려진 히스타민 및 클로로퀸과, DNBF를 이용하여 유발된 접촉성 피부염을 야기하였고, 이 후 N-아세틸-LTE4에 따른 가려움 완화 효과를 확인하였다. 구체적으로는 다음과 같다.In order to confirm the itch relieving effect by N-acetyl-LTE 4 , it caused contact dermatitis caused by histamine and chloroquine known to cause itching in the intradermal neck and DNBF. After the itching effect according to N-acetyl-LTE 4 was confirmed. Specifically, it is as follows.
2-2-1. 히스타민에 의해 야기된 가려움증 완화 효과 확인2-2-1. Identifying the effects of itching caused by histamine
0 내지 1 μM(1 nM, 10 nM, 100 nM 또는 1 μM)의 농도로 N-아세틸 LTE4 투여와 함께 100 μl의 PBS(phosphate bufferd saline)에 포함된 200 μg의 히스타민을 마우스의 오른쪽 귀 뒷부분으로 피내 주입하였다. 주입 후, 관찰 챔버(11 cm x 11 cm, 18 cm 높이) 하나 당 한 마리의 마우스를 위치시켰다. 비디오 카메라로 마우스의 행동을 녹화하였고, 1 시간 동안 마우스의 스크래치(긁음) 횟수를 세었다. 그 결과는 도 1에 나타내었다. 200 μg of histamine contained in 100 μl of phosphate buffered saline (PBS) with N-acetyl LTE 4 at a concentration of 0 to 1 μM (1 nM, 10 nM, 100 nM or 1 μM) in the back of the right ear of the mouse Intradermal injection. After infusion, one mouse was placed per observation chamber (11 cm x 11 cm, 18 cm high). The behavior of the mouse was recorded with a video camera and the number of scratches of the mouse was counted for 1 hour. The results are shown in FIG.
도 1에 나타낸 바와 같이, 마우스에 N-아세틸-LTE4 없이 히스타민만을 주입한 경우 86±8.1(n=5) 보트의 가려움증이 유발되었고, 주입되는 N-아세틸 LTE4의 주입량에 따라 가려움증이 현저하게 억제되는 것을 확인하였다. 특히 1 μM의 N-아세틸 LTE4을 투여할 경우 가려움증에 대한 최대 억제 활성(62%)을 나타내었다.1, the case where only the N- acetyl -LTE 4 without histamine in mice injected 86 ± 8.1 (n = 5) were itching of the boat caused, injection itching according to the injection amount of the N- acetyl-LTE 4 which is considerably It was confirmed that it is suppressed. In particular, administration of 1 μM N-acetyl LTE 4 showed a maximum inhibitory activity (62%) against itching.
2-2-2. 클로로퀸에 의해 야기된 가려움 완화 효과 확인2-2-2. Identifying the itch relieving effect caused by chloroquine
0 내지 1 μM(1 nM, 10 nM, 100 nM 또는 1 μM)의 농도로 N-아세틸 LTE4 투여와 함께 100 μl의 PBS(phosphate bufferd saline)에 포함된 400 μg의 클로로퀸을 마우스의 오른쪽 귀 뒷부분으로 피내 주입하였다. 주입 후, 관찰 챔버(11 cm x 11 cm, 18 cm 높이) 하나 당 한 마리의 마우스를 위치시켰다. 비디오 카메라로 마우스의 행동을 녹화하였고, 1 시간 동안 마우스의 스크래치(긁음) 횟수를 세었다. 그 결과는 도 2에 나타내었다.400 μg of chloroquine contained in 100 μl of phosphate buffered saline (PBS) with N-acetyl LTE 4 at a concentration of 0 to 1 μM (1 nM, 10 nM, 100 nM or 1 μM) at the back of the right ear of the mouse Intradermal injection. After infusion, one mouse was placed per observation chamber (11 cm x 11 cm, 18 cm high). The behavior of the mouse was recorded with a video camera and the number of scratches of the mouse was counted for 1 hour. The results are shown in FIG.
도 2에 나타낸 바와 같이, 마우스에 N-아세틸-LTE4 없이 클로로퀸만을 주입한 경우 244±56(n=5) 보트의 가려움증이 유발되었고, 주입되는 N-아세틸 LTE4의 주입량에 따라 가려움증이 현저하게 억제되는 것을 확인하였다. 특히 1 μM의 N-아세틸 LTE4을 투여할 경우 가려움증에 대한 최대 억제 활성(84%)을 나타내었다.2, the case where the mouse N- acetyl -LTE only chloroquine injection without 4 to 244 ± 56 (n = 5) were itching of the boat caused, injection itching according to the injection amount of the N- acetyl-LTE 4 which is considerably It was confirmed that it is suppressed. In particular, administration of 1 μM of N-acetyl LTE 4 showed a maximum inhibitory activity (84%) against itching.
2-2-3. 접촉성 피부염에 의해 야기된 가려움 완화 효과 확인2-2-3. Identify the itch relieving effect caused by contact dermatitis
1-플로로-2,4-디니트로벤젠(DNFB) 투여에 따라 발생하는 접촉성 피부염에 의해 유도된 가려움증 치료 효과를 측정하기 위하여, 마우스 귀의 뒷부분을 Dorco 레이저로 제모하고, 아세톤에 녹인 0.3% 1-플로로-2,4-디니트로벤젠으로 처리하였다. 5일이 경과한 후에, 0.15%로 희석된 DNFB를 동일한 부위에 처리하였고, 3일에 한 번씩, 총 3번 반복하였다. 마지막 DNFB 처리 30분 후 국소적으로 N-아세틸-LTE4를 처리하였다. 그 결과는 도 3에 나타내었다.To measure the itch treatment effect induced by contact dermatitis caused by 1-fluoro-2,4-dinitrobenzene (DNFB) administration, the back of the mouse ear was removed with Dorco laser and 0.3% dissolved in acetone. Treated with 1-fluoro-2,4-dinitrobenzene. After 5 days, DNFB diluted to 0.15% was treated at the same site, once every 3 days, in total 3 times. N-acetyl-LTE 4 was topically treated 30 minutes after the last DNFB treatment. The results are shown in FIG.
도 3에 나타낸 바와 같이, N-아세틸 LTE4의 주입량에 따라 접촉성 피부염에 의한 가려움증이 현저하게 억제되는 것을 확인하였다.As shown in FIG. 3, itching was confirmed that itching due to contact dermatitis was significantly suppressed according to the injection amount of N-acetyl LTE 4 .
실시예 3. N-아세틸-LTE4에 의한 아토피 피부염 완화 효과 확인Example 3. Confirmation of atopic dermatitis alleviation effect by N-acetyl-LTE 4
3-1. 실험 동물 - 아토피 동물 모델3-1. Experimental Animals-Atopy Animal Models
모든 동물 관련 실험은 국립 전북대학교의 실험동물위원회의 가이드라인에 따라 수행하였다. NC/Nga 마우스(수컷, 10주령)를 사용하였다. 실험동물들은 20℃의 온도, 50%의 습도가 유지되며, 12시간 간격으로 명암이 바뀌는 통상적 사육실에서 1주간 적응시킨 후 실험에 사용하였다. 먼저, NC/Nga 마우스의 등쪽, 귓 바퀴 윗부분까지 제모하여 털을 완벽하게 제거하였다. 추후 N-아세틸-LTE4를 도포할 부위에 4％ SDS 수용액을 분무하여 피부의 지방 성분을 제거하였고, 상기 물질이 완전히 마른 후 스틱을 이용하여 100 mg의 아토피 피부염 유발 시약인 Biostir　 AD(집먼지진드기)를 등쪽, 귓바퀴 부분에 균일하게 도포하였다. 상기 시약의 도포는 주 2회로 5주간 총 10회 반복 실시하여 아토피가 유발된 실험동물을 제조하였다.All animal experiments were conducted in accordance with the guidelines of the Experimental Animal Committee of Chonbuk National University. NC / Nga mice (male, 10 weeks old) were used. Experimental animals were maintained at a temperature of 20 ° C. and 50% of humidity, and were used for experiments after adapting for one week in a normal breeding room where the contrast was changed every 12 hours. First, hair was completely removed by shaving the upper back of the NC / Nga mouse to the dorsal wheel. After the application of N-acetyl-LTE 4 , 4% SDS solution was sprayed to remove the fat component of the skin, and after the material was completely dried, a 100 mg of atopic dermatitis reagent, Biostir AD (house dust mite), was used with a stick. ) Was uniformly applied to the dorsal and auricle parts. The application of the reagent was performed twice a week for 5 weeks in total 10 times to prepare atopy-induced experimental animals.
3-2. H&E 염색을 통한 아토피 피부염 완화 효과 확인3-2. Confirmation of atopic dermatitis relief effect through H & E staining
H&E 염색법을 이용하여 N-아세틸-LTE4에 의하여 아토피 피부염이 완화되는 지 여부를 확인하였다. 이를 위하여 N-아세틸-LTE4를 에탄올에 녹인 총 1 μM의 용액을 만든 후 상기 실시예 3-1의 아토피가 유발된 실험 동물에 100 μl씩 발라주었다. 이는 아토피가 유발 3주 후부터 2주간 매일 반복하여 수행하였다. 한편, 음성대조군에는 N-아세틸-LTE4 대신 100 μl씩 에탄올을 발라주었다. 이 후 아토피 피부염을 유발한 후 총 5주가 경과되었을 때 마우스를 희생시켰다. 희생시킨 마우스로부터 등(back) 피부를 적출하였으며, 이를 아쿠스타인 무-포르말린 정착액으로 조직을 고정하여 파라핀 블록(block)을 제작하였다. 상기 파라핀 블록를 5 μm의 두께로 얇게 잘랐고, 이에 헤마톡시린/에오신 염색을 수행한 후 현미경을 이용하여 표피 및 진피층의 두께 변화를 관찰하였다. 그 결과는 도 4a에 나타내었다. 상기 도 4a를 통해 관찰한 내용을 그래프화한 것을 도 4b에 나타내었다. H & E staining was used to determine whether atopic dermatitis was alleviated by N-acetyl-LTE 4 . To this end, a total of 1 μM solution of N-acetyl-LTE 4 dissolved in ethanol was prepared, and then 100 μl was applied to the atopy-induced experimental animal of Example 3-1. This was repeated daily for two weeks from three weeks after atopic induction. On the other hand, 100 μl of ethanol was applied to the negative control group instead of N-acetyl-LTE 4 . Thereafter, mice were sacrificed when a total of five weeks had elapsed after atopic dermatitis. Back skin was extracted from the sacrificed mice, and paraffin blocks were prepared by fixing tissues with acusstein-free formalin fixative. The paraffin block was thinly cut to a thickness of 5 μm, after which hematoxylin / eosin staining was performed, and the thickness change of the epidermal and dermal layers was observed using a microscope. The results are shown in Figure 4a. A graph of the contents observed through FIG. 4A is shown in FIG. 4B.
도 4에 나타낸 바와 같이, N-아세틸-LTE4에 의하여 아토피가 유발된 동물의 표피에서 발생한 피부염이 완화됨을 확인하였다. 즉 N-아세틸-LTE4는 현저한 아토피 피부염 개선 효과를 가짐을 알 수 있다.As shown in FIG. 4, it was confirmed that dermatitis in the epidermis of an atopic dermatitis induced by N-acetyl-LTE 4 was alleviated. That is, it can be seen that N-acetyl-LTE 4 has a significant atopic dermatitis improvement effect.
실시예 4. BioMAP 분석을 통한 N-아세틸-LTE4에 의한 생체 인자 변화 확인Example 4. Confirmation of biofactor change by N-acetyl-LTE 4 through BioMAP analysis
BioMAP 분석은 1차 인간 세포를 이용하여 DiscoveRx 사(Fremont, CA)의 도움으로 수행하였다. 본 연구는 미국의 HHS 인간 피실험체 규율(45 CFR Part 46) 하에 인간 피실험체 연구를 위한 가이드라인을 준수하였다. BioMAP analysis was performed with the help of DiscoveRx (Fremont, CA) using primary human cells. This study complied with the guidelines for the study of human subjects under the US HHS Human Subject Regulation (45 CFR Part 46).
먼저 BioMAP 분석을 위하여 내피 세포의 준비 및 배양을 수행하였다. 보다 구체적으로는 다양한 공여체로부터 인간 탯줄정맥 내피 세포(HUVEC; umbilical vein endothelial cells)를 얻었고, 표준방법에 따라 배양하였으며, 4번째 계대배양 단계에서 미세정량판(microtiter plate)으로 옮겼다. 말초혈액 단핵세포(PBMC; Peripheral blood mononuclear cells)는 표준방법에 따라 정상적인 공여인의 버피코트(buffy coats)로부터 수득하였다. 아울러 lTH2 또는 lMphg 시스템을 위하여 14일 동안 분극화된 CD4+ T-세포(TH2) 또는 인간 혈액 유래 CD14+ 대식세포(All Cells LLC. Emeryville, CA)를 각각 HUVEC에 첨가하여 공배양(co-culture)하였다. BT 시스템은 84시간 동안 공-배양된 낮은 수준의 TCR 자극을 고려하여 PBMC와 공배양된 항-IgM으로 자극된 CD19+ B-세포(AllCells LLC. Emeryville, CA)로 구성되어 있다. HDF3GF 시스템을 위하여 3명의 신생아로부터 포피(foreskin) 섬유아세포(HDFn; human neonatal foreskin fibroblasts)를 공급자(Lonza, Inc., Allendale, NJ)가 제공하는 매뉴얼에 따라 분리하고 배양하였다. HDFn은 사이토카인으로 자극 전 24시간 동안 낮은 농도의 혈장에 두었다. BE3C, BF4T, CASM3C 및 KF3CT 시스템을 위하여, 1차 인간 기관지 표피 세포(bronchial epithelial cells; Cell Applications, Inc., San Diego, CA), 관상동맥 SMC, 케라틴세포 및 HDFn(Lonza, Inc., Allendale, NJ)은 제작자가 제공하는 방법에 따라 배양하였다. 말초혈액 단핵세포(PBMC)는 이 기술 분야의 일반적인 방법에 따라 정상적인 사람 공여체의 버피코트(buffy coat)로부터 수득하였다. First, preparation and culture of endothelial cells were performed for BioMAP analysis. More specifically, human umbilical vein endothelial cells (HUVECs) were obtained from various donors, cultured according to standard methods, and transferred to microtiter plates at the fourth passaging stage. Peripheral blood mononuclear cells (PBMCs) were obtained from buffy coats of normal donors according to standard methods. Co-cultures were also added to HUVECs for 14 days of polarized CD4 + T-cells (TH2) or human blood-derived CD14 + macrophages (All Cells LLC. Emeryville, Calif.) For l TH2 or l Mphg systems. It was. The BT system consists of CD19 + B-cells (AllCells LLC. Emeryville, Calif.) Stimulated with anti-IgM co-cultured with PBMC taking into account low levels of TCR stimulation co-cultured for 84 hours. Foreskin fibroblasts (HDFn; human neonatal foreskin fibroblasts) from three newborns were isolated and cultured according to a manual provided by the supplier (Lonza, Inc., Allendale, NJ) for the HDF3GF system. HDFn was cytokine and placed in low plasma for 24 hours prior to stimulation. For BE3C, BF4T, CASM3C and KF3CT systems, primary human bronchial epithelial cells (Cell Applications, Inc., San Diego, Calif.), Coronary artery SMC, keratinocytes and HDFn (Lonza, Inc., Allendale, NJ) was incubated according to the method provided by the manufacturer. Peripheral blood mononuclear cells (PBMCs) were obtained from the buffy coat of normal human donors according to the general methods in the art.
상기의 각 시스템의 계대배양 미량정량판으로 다음의 물질을 첨가하였다: 사이토카인(IL1β, 1 ng/ml; TNFα, 5 ng/ml; IFN-γ, 20 ng/ml; IL4, 5 ng/ml 또는 IL2, 2 ng/ml), 활성화제(SAg, 20 ng/ml; 히스타민, 10 μM; 또는 LPS, 2 ng/ml), 성장인자(TGF-β, 5 ng/ml; EGF, bFGF, 및 PDGF-BB, 10 ng/ml), 또는 PBMC (7.5x104 세포/웰). Substituting microtiter plates for each system above added the following materials: cytokines (IL1β, 1 ng / ml; TNFα, 5 ng / ml; IFN-γ, 20 ng / ml; IL4, 5 ng / ml) Or IL2, 2 ng / ml), activator (SAg, 20 ng / ml; histamine, 10 μM; or LPS, 2 ng / ml), growth factor (TGF-β, 5 ng / ml; EGF, bFGF, and PDGF-BB, 10 ng / ml), or PBMC (7.5 × 10 4 cells / well).
상기의 과정에 따라 구축된 BioMAP을 이용하여 N-아세틸 LTE4가 β-아레스틴-2을 활성화 또는 억제시키는 지 여부를 확인하기 위하여 DiscoveRx PathHunter technology(DiscoveRx)를 이용하였다. 이는 아레스틴 리크루트 조절 서열 및 β-아레스틴-2 단백질에 따라 융합-태그된 수용체의 효소 컨플리멘테이션(complementation)을 포함한다. DiscoveRx PathHunter technology (DiscoveRx) was used to confirm whether N-acetyl LTE 4 activates or inhibits β-arrestin-2 using BioMAP constructed according to the above procedure. This includes enzymatic complementation of fusion-tagged receptors according to the Arestin Lycrute regulatory sequence and the β-Arrestin-2 protein.
구체적으로, 다양한 종류의 G-단백질이 커플된 수용체를 발현하는 CHO-K1 세포(DiscoveRx)를 384-웰의 검은색의 투명한 밑바닥으로 구성된 플레이트 내에서 2625 세포/웰의 농도로 세포 플레이팅 미디어 2(DiscoveRx)에 접종하였다. 배양 후 24시간이 경과한 후, 세포는 1% 디메틸설폭사이드를 포함하는 PBS에서 다양한 농도(1.8 μM, 600 nM, 200 nM 및 67 nM)의 N-아세틸-LTE4를 처리(이에 대한 결과값은 도 5a에서 각각 붉은색, 오렌지색, 노란색, 녹색으로 표시)하고, 90분 동안 37°C에서 배양하였다. 이 후 DiscoveRx 시약을 제조자가 제공하는 매뉴얼에 따라 상기 세포를 첨가하고, 상온에서 30-60 분 동안 배양하였다. 형광은 하마마츄(Hamamatsu) FDSS μCell 리더에서 측정하였다. 수집된 자료는 RLUs에 입력하고 0% RLUs 상태의 도파민의 최대 농도로 보이는 대조군(N-아세틸-LTE4 무첨가)의 형광 비율로 표준화하였다. 그 결과는 도 5a에 나타내었다. 이에 추가적으로 고농도인 3700 ng/ml의 인간 감마 글로불린의 세포 활성 프로파일(파란색으로 표시)과 상기 600 nM의 N-아세틸-LTE4 첨가에 따라 도출된 세포 활성 프로파일(오렌지색으로 표시)을 비교한 것을 도 5b에 나타내었다.Specifically, CHO-K1 cells expressing various types of G-protein coupled receptors (DiscoveRx) were plated at a concentration of 2625 cells / well in a plate consisting of 384-well black transparent bottoms. (DiscoveRx) was inoculated. After 24 hours of incubation, cells were treated with N-acetyl-LTE 4 at various concentrations (1.8 μM, 600 nM, 200 nM and 67 nM) in PBS containing 1% dimethylsulfoxide (results for this). 5, red, orange, yellow, and green, respectively, in FIG. 5A), and incubated at 37 ° C. for 90 minutes. DiscoveRx reagent was then added to the cells according to the manufacturer's manual and incubated for 30-60 minutes at room temperature. Fluorescence was measured on a Hamamatsu FDSS μ Cell reader. Collected data are entered into the RLUs and the control group (N-acetyl-LTE 4) shows the maximum concentration of dopamine in the 0% RLUs state. Normalized to the fluorescence ratio of no addition). The results are shown in Figure 5a. In addition, the activity profile (in blue) of the high concentration of 3700 ng / ml of human gamma globulin and the 600 nM of N-acetyl-LTE 4 A comparison of the cell activity profiles (in orange) derived with addition is shown in FIG. 5B.
판독된 정보는 X-축에 따라 기재하였고, Y-축은 대조군 용매(에탄올)에 상대적으로 나타나는 값을 log10으로 표현한 것이며, 점선의 위 아래 부분의 회색 영역은 대조군 기준으로 95%의 유의성을 나타내었다. The information read was written along the X-axis, where the Y-axis represents the logarithm of the value relative to the control solvent (ethanol), and the gray areas at the top and bottom of the dashed line showed 95% significance relative to the control. .
도 5a에 나타낸 바와 같이, N-아세틸 LTE4의 67 nM 내지 1.8 μM 농도의 처리에서도 현저한 세포독성이 발생하지 않으며, 동시에 넓은 항염증 활성을 가짐을 확인하였다. 보다 구체적으로는 BT에서 IL-17 및 IL-2가 낮게 조절되고 lMphg에서 IL-10이 낮게 조절됨을 확인하였다. 이는 N-아세틸 LTE4가 면역 조절 효과를 가짐을 나타낸다. 아울러 전반적으로 콜라겐 Ⅲ의 수준이 크게 변화하지 않음을 확인하였고, 이는 제형된 기질/조직이 재형(remodeling)됨을 나타낸다.As shown in Figure 5a, it was confirmed that even in the treatment of the concentration of 67 nM to 1.8 μM of N-acetyl LTE 4 there is no significant cytotoxicity, and at the same time has a broad anti-inflammatory activity. More specifically, it was confirmed that IL-17 and IL-2 are lowered in BT and IL-10 is lowered in lMphg. This indicates that N-acetyl LTE 4 has an immunomodulatory effect. In addition, it was confirmed that the level of collagen III did not change significantly overall, indicating that the formulated substrate / tissue was remodeled.
아울러, 추가적으로 도 5b에 나타낸 바와 같이, 인간 감마 글로불린의 세포활성 프로파일과 N-아세틸-LTE4 첨가에 따라 도출된 세포 활성 프로파일을 비교한 결과, N-아세틸-LTE4에 대한 세포 활성 프로파일이 면역 억제제로 사용되는 인간 감마 글로불린의 세포 활성 프로파일과 유사하게 나타남을 확인하였다. 이는 생체 내에서 N-아세틸-LTE4가 면역 질환에 대한 면역 제어 기능을 가짐을 나타낸다.In addition, as shown in Figure 5b, the activity profile and N-acetyl-LTE 4 of human gamma globulin Comparing the cell activity profile derived from the addition, it was confirmed that the cell activity profile for N-acetyl-LTE 4 appeared similar to the cell activity profile of human gamma globulin used as an immunosuppressant. This indicates that N-acetyl-LTE 4 has immune control function against immune disease in vivo.
상기의 결과 값은 모두 평균±SEM(n=5)으로 나타내었다(*P<0.05, **P<0.01).The above results were all expressed as mean ± SEM (n = 5) (* P <0.05, ** P <0.01).
종합적으로, 본 발명의 N-아세틸 LTE4(N-acetyl Leukotriene E4)는 수용성 사이토카인, 특히 IL-2 및 IL-17의 생성을 억제하여 다양한 원인에 의해 발생하는 가려움 증상을 완화시키며, 동시에 면역 제어 효과를 가진다. 따라서 본 발명은 히스타민, 클로로퀸 또는 접촉성 피부염 등에 의해 유발된 가려움증의 완화를 위한 조성물, 및 아토피 피부염을 비롯한 알레르기성 또는 염증성 피부질환의 예방 또는 치료제 등으로 다양하게 활용될 수 있다.Overall, the N-acetyl LTE 4 (N-acetyl Leukotriene E4) of the present invention inhibits the production of water soluble cytokines, especially IL-2 and IL-17, alleviating the symptoms of itching caused by various causes, while simultaneously immunizing Has a control effect. Therefore, the present invention can be used in various ways, such as a composition for the relief of itching caused by histamine, chloroquine or contact dermatitis, and for preventing or treating allergic or inflammatory skin diseases including atopic dermatitis.
제제예 1. 약학적 제제의 제조Formulation Example 1 Preparation of a Pharmaceutical Formulation
1. 산제의 제조 1. Preparation of powder
N-아세틸 LTE4 20 mgN-acetyl LTE 4 20 mg
유당 100 mg Lactose 100 mg
탈크 10 mg Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
2. 정제의 제조2. Preparation of Tablets
N-아세틸 LTE4 10 mgN-acetyl LTE 4 10 mg
옥수수전분 100 mg Corn starch 100 mg
유당 100 mg Lactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components and tableting according to the manufacturing method of the conventional tablet to prepare a tablet.
3. 캡슐제의 제조3. Preparation of Capsule
N-아세틸 LTE4 10 mgN-acetyl LTE 4 10 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
4. 주사제의 제조4. Preparation of Injectables
N-아세틸 LTE4 10 mgN-acetyl LTE 4 10 mg
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO42H2O26mgNa 2 HPO 4 2H 2 O26mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ml) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
5. 액제의 제조5. Preparation of Liquid
N-아세틸 LTE4 20 mg N-acetyl LTE 4 20 mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding a proper amount of lemon aroma, and then mixing the above components, adding purified water and adjusting the whole to 100 ml by adding purified water and filling into a brown bottle. The solution is prepared by sterilization.
제제예 2. 식품 제제의 제조Formulation Example 2 Preparation of Food Formulation
1. 건강식품의 제조1. Preparation of health food
N-아세틸 LTE4 100 mgN-acetyl LTE 4 100 mg
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 g 70 g 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 g 0.2 g of vitamin B12
비타민 C 10 mg Vitamin C 10 mg
비오틴 10 g 10 g of biotin
니코틴산아미드 1.7 mgNicotinamide 1.7 mg
엽산 50 g Folic acid 50 g
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.
2. 건강음료의 제조2. Manufacture of health drinks
N-아세틸 LTE4 100 mgN-acetyl LTE 4 100 mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3 g0.3 g of vitamin B2
물 정량Water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components in accordance with the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
제제예 3. 화장료 제제의 제조Formulation Example 3 Preparation of Cosmetic Formulation
1. 유연화장수 제조1. Manufacturing Flexible Cosmetics
N-아세틸 LTE4 0.1중량%N-acetyl LTE 4 0.1 wt%
1,3-부틸렌글리콜 5.2중량%, 올레일알코올 1.5중량%5.2 wt% of 1,3-butylene glycol, 1.5 wt% of oleyl alcohol
에탄올 3.2중량%Ethanol 3.2% by weight
폴리솔베이트 20 3.2중량% Polysorbate 20 3.2% by weight
벤조페논-9 2.0중량%Benzophenone-9 2.0 wt%
카르복실비닐폴리머 1.0중량%, 글리세린 3.5중량%1.0 wt% carboxyvinyl polymer, 3.5 wt% glycerin
미량의 향, 미량의 방부제 및 잔량의 정제수를 혼합하여 통상의 방법으로 유연화장수를 제조하였다.A small amount of fragrance, a small amount of preservative, and a residual amount of purified water were mixed to prepare flexible cosmetic water in a conventional manner.
2. 밀크로션 제조2. Wheat Crop Manufacture
N-아세틸 LTE4 0.1중량%N-acetyl LTE 4 0.1 wt%
글리세린 5.1중량%Glycerin 5.1 wt%
프로필렌글리콜 4.2중량%Propylene glycol 4.2 wt%
토코페릴아세테이트 3.0중량%Tocopheryl Acetate 3.0 wt%
유동파라핀 4.6중량%4.6 wt% of liquid paraffin
트리에탄올아민 1.0중량%Triethanolamine 1.0% by weight
스쿠알란 3.1중량%Squalane 3.1 wt%
마카다미아너트오일 2.5중량%Macadamia Nut Oil 2.5% by weight
폴리솔베이트 60 1.6중량% Polysorbate 60 1.6% by weight
솔비탄세스퀴롤레이트 1.6중량%Sorbitan sesquirrolate 1.6% by weight
프로필파라벤 0.6중량%Propylparaben 0.6 wt%
카르복실비닐폴리머 1.5중량%Carboxy vinyl polymer 1.5 wt%
미량의 향, 미량의 방부제, 잔량의 정제수를 혼합하여 통상의 방법으로 밀크로션을 제조하였다.A small amount of fragrance, a small amount of preservative, and a residual amount of purified water were mixed to prepare a milk lotion in a conventional manner.
3. 영양크림 제조3. Nutrition Cream
N-아세틸 LTE4 0.5중량%N-acetyl LTE 4 0.5 wt%
글리세린 4.0중량%Glycerin 4.0% by weight
바셀린 3.5중량%3.5% by weight of petroleum jelly
트리에탄올아민 2.1중량%Triethanolamine 2.1 wt%
유동파라핀 5.3중량%5.3% by weight of liquid paraffin
스쿠알란 3.0중량%Squalane 3.0 wt%
밀납 2.6중량%Beeswax 2.6% by weight
토코페릴아세테이트 5.4중량%Tocopheryl Acetate 5.4 wt%
폴리솔베이트 60 3.2중량% Polysorbate 60 3.2% by weight
카르복실비닐폴리머 1.0중량%1.0% by weight of carboxyvinyl polymer
솔비탄세스퀴올레이트 3.1중량%Sorbitan sesquioleate 3.1 wt%
미량의 향, 미량의 방부제 및 잔량의 정제수를 혼합하여 통상의 방법으로 영양크림을 제조하였다.A nutritious cream was prepared in a conventional manner by mixing a small amount of fragrance, a small amount of preservative and a residual amount of purified water.

Claims (9)

  1. N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 약학적 조성물.N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient, a pharmaceutical composition for the prevention or treatment of allergic or inflammatory skin diseases.
  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. N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료용 피부외용제.N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient, skin external preparation for the prevention or treatment of allergic or inflammatory skin diseases.
  4. N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 개선용 건강식품 조성물.N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient, a health food composition for the prevention or improvement of allergic or inflammatory skin diseases.
  5. N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, 가려움증 완화 또는 억제용 화장료 조성물.N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof as an active ingredient, itching relief or inhibition cosmetic composition.
  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. N-아세틸 LTE4(N-acetyl Leukotriene E4) 또는 이의 약학적으로 허용가능한 염을 개체에 투여하는 단계를 포함하는, 알레르기성 또는 염증성 피부질환의 예방 또는 치료 방법.A method of preventing or treating allergic or inflammatory skin disease, comprising administering to a subject N-acetyl LTE 4 (N-acetyl Leukotriene E4) or a pharmaceutically acceptable salt thereof.
PCT/KR2017/001853 2016-02-19 2017-02-20 Composition and method for preventing or treating skin disease WO2017142383A1 (en)

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