WO2020085826A1 - Composition for alleviation of skin irritation induced by environmental pollution factors or for skin protection, containing nutmeg extract or macelignan as active ingredient - Google Patents

Composition for alleviation of skin irritation induced by environmental pollution factors or for skin protection, containing nutmeg extract or macelignan as active ingredient Download PDF

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Publication number
WO2020085826A1
WO2020085826A1 PCT/KR2019/014101 KR2019014101W WO2020085826A1 WO 2020085826 A1 WO2020085826 A1 WO 2020085826A1 KR 2019014101 W KR2019014101 W KR 2019014101W WO 2020085826 A1 WO2020085826 A1 WO 2020085826A1
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Prior art keywords
skin
nutmeg extract
nutmeg
formula
derived
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PCT/KR2019/014101
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French (fr)
Korean (ko)
Inventor
황재관
박지혜
강하늘
김창희
정희철
김도언
Original Assignee
연세대학교 산학협력단
(주)뉴트리
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Priority to CN201980086457.XA priority Critical patent/CN113613666A/en
Priority to JP2021523078A priority patent/JP2022505979A/en
Publication of WO2020085826A1 publication Critical patent/WO2020085826A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/005Preparations for sensitive skin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat

Definitions

  • the present invention relates to a composition for alleviating skin irritation and protecting skin derived from environmental pollutants containing nutmeg extract or mace lignan as an active ingredient, and more specifically, mace lignan represented by Formula 1 of the present invention or nutmeg containing the same It relates to a composition for skin irritation relief and skin protection derived from environmental pollution factors containing the extract as an active ingredient.
  • the skin protects the organs in the body from stimulation of the external environment and plays an important role in maintaining bio homeostasis such as body temperature control.
  • exposure to excessive ultraviolet rays or pollutants causes skin irritation and eventually leads to skin aging.
  • fine dust and yellow sand mixed with harmful substances such as heavy metals are known to be major causes of skin aging and skin damage (J. Prev. Med. Public Health, 39: 205-212, 2006 ).
  • PM 10 Particulate matter (PM) 10 is collectively referred to a particle size of 10 ⁇ m or less fine dust and fine particles less than 2.5 ⁇ m in seconds is divided into a PM 2.5.
  • Fine dust is mainly generated when burning fossil fuels, and fine dust from China, which has a 70% dependency on coal, accounts for a large portion.
  • yellow sand is a phenomenon in which small sand or loess is floating in the inland deserts of China and Mongolia, and is transported away by upper winds and falls near the ground. About 25 to 33% of diseases in industrialized countries are caused by environmental hazards.
  • Myristica fragrans belongs to the Myristicaceae family, and the seeds of Myristica fragrans are called nutmeg. So far, activities related to nutmeg have been reported such as detoxification, anti-diabetes, and anti-inflammatory effects.
  • the representative ingredient contained in the nutmeg extract, macelignan is a PPAR ⁇ / ⁇ dual agonist, and has been reported to have anti-diabetes, liver protection, neuroprotection, antibacterial, and antioxidant activities.
  • the present inventors searched for substances having a skin irritation relief and skin protection function derived from environmental pollutants derived from natural products, and found that nutmeg extract or mace lignan has a skin irritation relief and skin protection function derived from environmental pollution factors.
  • the present invention was completed by clarification.
  • an object of the present invention is to provide a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants containing nutmeg extract or mayslignan as an active ingredient.
  • an object of the present invention is to provide a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting of nutmeg extract or mays lignan as an active ingredient.
  • an object of the present invention is to provide a pharmaceutical composition for alleviating skin irritation and skin protection derived from environmental pollution factors consisting essentially of nutmeg extract or mays lignan as an active ingredient.
  • Another object of the present invention is to provide a food composition for alleviating skin irritation and skin protection derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
  • Another object of the present invention is to provide a food composition for skin irritation relief and skin protection derived from environmental pollutants consisting of nutmeg extract or macy lignan as an active ingredient.
  • Another object of the present invention is to provide a food composition for alleviating skin irritation and skin protection derived from environmental pollution factors consisting essentially of nutmeg extract or mays lignan as an active ingredient.
  • Another object of the present invention is to provide a cosmetic composition for skin irritation relief and skin protection derived from environmental pollutants containing nutmeg extract or macy lignan as an active ingredient.
  • Another object of the present invention is to provide a cosmetic composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting of nutmeg extract or mays lignan as an active ingredient.
  • Another object of the present invention is to provide a cosmetic composition for skin irritation relief and skin protection derived from environmental pollutants consisting essentially of nutmeg extract or mace lignan as an active ingredient.
  • Another object of the present invention is to provide a composition for preventing skin contamination derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
  • Another object of the present invention is to provide a composition for preventing skin contamination derived from environmental pollution factors consisting of nutmeg extract or mays lignan as an active ingredient.
  • Another object of the present invention is to provide a composition for preventing skin contamination derived from environmental pollutants consisting essentially of nutmeg extract or mace lignan as an active ingredient.
  • Another object of the present invention is to provide a use of mace lignan or a nutmeg extract containing the same for preparing a preparation for skin irritation relief and skin protection derived from environmental pollution factors.
  • Another object of the present invention is a method for alleviating skin irritation and protecting skin induced from environmental pollutants, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. Is to provide.
  • Another object of the present invention is to provide a use of mace lignan or nutmeg extract containing the same for preparing a formulation for preventing skin contamination derived from environmental pollution factors.
  • Another object of the present invention is to provide a method for preventing skin contamination derived from environmental pollution factors, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. .
  • the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mays lignan as an active ingredient.
  • the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants consisting of nutmeg extract or mace lignan as an active ingredient.
  • the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants consisting essentially of nutmeg extract or macylignan as an active ingredient.
  • the present invention provides a food composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mace lignan.
  • the present invention provides a food composition for skin irritation relief and skin protection derived from environmental pollutants consisting of nutmeg extract or mace lignan.
  • the present invention provides a food composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting essentially of nutmeg extract or mace lignan.
  • the present invention provides a cosmetic composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mace lignan.
  • the present invention provides a cosmetic composition for skin irritation relief and skin protection derived from environmental pollutants consisting of nutmeg extract or mace lignan.
  • the present invention provides a cosmetic composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting essentially of nutmeg extract or mace lignan.
  • the present invention provides a composition for preventing skin contamination derived from environmental pollution factors containing nutmeg extract or mace lignan as an active ingredient.
  • the present invention provides a composition for preventing skin contamination derived from environmental pollutants consisting of nutmeg extract or mace lignan as an active ingredient.
  • the present invention provides a composition for preventing skin contamination derived from environmental pollutants consisting essentially of nutmeg extract or mace lignan as an active ingredient.
  • the present invention provides the use of mace lignan or a nutmeg extract containing the same to prepare a formulation for skin irritation relief and skin protection derived from environmental pollution factors.
  • the present invention derives from an environmental contaminant characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof.
  • a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof.
  • the present invention provides the use of mace lignan or nutmeg extract containing the same for preparing a formulation for preventing skin contamination derived from environmental pollution factors.
  • the present invention derives from an environmental contaminant characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. Provide a method for preventing contamination.
  • the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
  • the nutmeg extract is a Myristica plant of the Myristicaceae , and the seed of the myristica fragrant may be an extract target.
  • the nutmeg extract may be extracted using water, an organic solvent having 1 to 6 carbon atoms, or a mixture thereof as a solvent.
  • the organic solvent is C1 to C6 lower alcohol (alcohol), acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), ethyl acetate (ethyl acetate), methylene chloride (methylene chloride),
  • One or more selected from the group consisting of hexane, cyclohexane and petroleum ether is preferred, but is not limited thereto.
  • the lower alcohol used in the extraction of the nutmeg is also more preferably ethanol or methanol, most preferably ethanol.
  • the extraction temperature is preferably 20 ° C to 100 ° C, and more preferably 60 ° C to 100 ° C, but is not limited thereto.
  • the extraction time is preferably 1 hour to 10 hours, more preferably 2 hours to 5 hours, but is not limited thereto.
  • Cold extraction, ultrasonic extraction, or reflux cooling extraction may be used as the extraction method, and it is preferable to use a reflux cooling extraction method, but is not limited thereto.
  • the number of extractions is preferably 1 to 5 times, and it is more preferable to repeatedly extract 2 to 3 times, but is not limited thereto.
  • the nutmeg extract may be performed by an ultra-high pressure, subcritical fluid or supercritical fluid extraction method.
  • Nutmeg used for extraction can be used after washing after harvesting or dried.
  • a drying method a dry method, a dry method, a hot air drying method, and a natural drying method may be used.
  • nutmeg or its dry matter may be crushed and used.
  • the macelignan preferably has the structure of Formula 1 below.
  • Macelignan (macelignan) of the present invention has a structure of formula 1, can be purified from nature, commercially available for use, or prepared by chemical synthesis methods known in the art.
  • the machlignan of the present invention may be purified from nature. More preferably, it can be isolated and purified from Myristica fragrans , and most preferably, it can be isolated and purified from nutmeg or aril of Myristica fragrans .
  • Another nutmeg, Myristica Myristica argentea Warb) (Nat. Prod. Lett., 16: 1-7, 2002), and Machilus thunbergii ) (Bio. Pharm. Bull., 27: 1305-1307, 2004), Leucas aspera , etc. (Chem. Pharm. Bull., 51: 595-598, 2003) .
  • the may lignan of the present invention may be separated and purified from a nutmeg by a solvent extraction method known in the art and a separation method using chromatography.
  • the composition according to the present invention can be used for alleviating skin irritation and protecting skin and preventing skin contamination derived from environmental pollutants by reducing the expression level of a gene mediated by XRE.
  • composition of the present invention has a skin irritation alleviation and skin protection effect, and such skin irritation is a skin disease caused by deterioration of skin function due to environmental pollution factors, promotion of skin aging, etc., and is preferably a disease reported in the art. And protection.
  • Skin irritation of the present invention is more preferably any one or more selected from the group consisting of dermatitis, atopy, psoriasis, acne, skin cancer, eczema, It is not limited to this.
  • the skin irritation relief of the present invention may be "anti-pollution of the skin".
  • Prevention of skin contamination improves skin condition by protecting the skin from natural factors (endogenous aging) or environmental pollutants (poly aromatic hydrocarbons, particulate matter, tobacco smoke, yellow sand or heavy metals, etc.) It means to induce, preferably to protect the skin from environmental pollution factors.
  • the term “mayslignan represented by Formula 1 or nutmeg extract containing the same” is considered to include their pharmaceutically acceptable salts or prodrugs thereof.
  • 'prodrug' in the present invention is a biotransformation in order to secrete or convert a prodrug into an active drug (eg, enzymatically, physiologically, mechanically, electromagnetically) in a targeted physiological system.
  • an active drug eg, enzymatically, physiologically, mechanically, electromagnetically
  • a pharmaceutically inert derivative of the source 'drug' molecule eg, primary or enzymatic
  • Prodrugs are designed to overcome problems associated with stability, toxicity, lack of specificity or limited bioavailability.
  • Typical prodrugs include the active drug molecule itself and a chemical blocking group (e.g., a group that reversely inhibits the drug's activity).
  • Some preferred drugs are variants or derivatives of components with separable groups depending on metabolic conditions.
  • Typical drugs are pharmacologically activated both in vitro and in vitro when solvolysis under physiological conditions, enzymatic degradation, or other biochemical modifications (e.g. phosphorylation, hydrogenation, dehydrogenation, glycosylation reactions) are performed.
  • Prodrugs often offer advantages such as solubility, histocompatibility, or sustained release in the mammalian body.
  • Common prodrugs include acid derivatives such as esters obtained by reacting a suitable alcohol (e.g., lower alkanols) with source acids, acylated base derivatives formed by reaction of amides or basic groups with amines and source acid components ( For example, lower alkylamide).
  • the nutmeg extract or mayslignan of the present invention may be included in the composition in the form of a pharmaceutically acceptable salt.
  • “Pharmaceutically acceptable salt” refers to a physiologically acceptable salt that does not cause a common allergic reaction or similar reaction when administered to humans, and the salt is formed by a pharmaceutically acceptable free acid. Acid addition salts are preferred. As the free acid, an organic acid and an inorganic acid can be used.
  • the organic acid is not limited thereto, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Glutanoic acid and aspartic acid.
  • the inorganic acids include, but are not limited to, hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid.
  • composition of the present invention may be variously formulated according to the route of administration by a method known in the art together with a pharmaceutically acceptable carrier.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the mace lignan, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc. It is prepared by mixing. In addition, lubricants such as magnesium styrene talc are used in addition to simple excipients.
  • Liquid preparations for oral administration include suspensions, intravenous solutions, emulsions, syrups, etc.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, ointments and creams.
  • non-aqueous solvents and suspension solvents propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used.
  • composition of the present invention can be administered parenterally, parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method and transdermal administration method.
  • parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method and transdermal administration method.
  • mayslignan is mixed in water with a stabilizer or a buffer to prepare a solution or suspension, which is formulated into unit dosage forms of ampoules or vials.
  • the dosage unit can contain, for example, 1, 2, 3 or 4 times the individual dosage, or 1/2, 1/3 or 1/4 times.
  • the individual dosage preferably contains the amount of effective drug administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dosage.
  • transdermal administration means that the pharmaceutical composition is topically administered to the skin to deliver an effective amount of the active ingredient contained in the pharmaceutical composition into the skin.
  • the term 'pharmaceutically effective amount' in the present invention means an amount sufficient to alleviate skin irritation or protect the skin at a reasonable benefit / risk ratio applicable to medical uses, and the effective dose level is the individual type and severity, age, It can be determined by gender, drug activity, sensitivity to the drug, time of administration, route of administration and rate of excretion, duration of treatment, factors including co-drugs, and other factors well known in the medical field.
  • the composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be administered single or multiple. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects, and can be easily determined by those skilled in the art.
  • composition of the present invention may be administered in parallel with a known compound having an effect of preventing and treating skin irritation such as asthma and atopic dermatitis.
  • compositions of the present invention in another aspect, there is provided a method of alleviating or inhibiting skin irritation by administering the composition of the present invention to cells, tissues, organs, or individuals exhibiting skin irritation by heavy metal or the like.
  • the causative disease and pathology of skin irritation can be prevented or treated using the compositions and methods.
  • the term 'individual' in the present invention means all animals, including humans, who need to alleviate skin irritation or protect the skin, and includes diseased or sensitive skin carriers of diseases accompanied by skin irritation.
  • skin irritation can be alleviated or suppressed, and the skin can be protected.
  • composition for alleviating skin irritation and protecting the skin of the present invention is a food composition, it can be used for skin irritation alleviation and skin protection derived from environmental pollution factors.
  • the food composition of the present invention includes all forms of functional foods, nutritional supplements, health foods, food additives, and feeds, and includes animals including humans or livestock. Subject to eating. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
  • the mace lignan or nutmeg extract of the present invention or a salt thereof may be prepared in the form of tea, juice, and drink for drinking or granulated, encapsulated, and powdered.
  • it may be prepared in the form of a composition by mixing together with the mays lignan or nutmeg extract of the present invention and a known substance or active ingredient known to have an improvement effect on skin irritation.
  • Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
  • Drinks including alcoholic beverages
  • fruits and processed foods e.g. canned fruits, canned foods, jams, marmalades, etc.
  • fish e.g. ham, sausages
  • breads and noodles e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.
  • juice various drinks, cookies, syrup, dairy products (e.g.
  • a nutritional supplement in addition, but not limited to, it can be prepared by adding nutmeg extract or mace lignan to capsules, tablets, pills, and the like.
  • the health functional food is not limited to this, for example, nutmeg extract or mace lignan itself is prepared in the form of tea, juice and drink to be liquefied, granulated, encapsulated and powdered for drinking (health drink). Can be consumed.
  • nutmeg extract or mace lignan in the form of food additives, it can be prepared and used in powder or concentrate form.
  • it can be prepared in the form of a composition by mixing with nutmeg extract or known active ingredients known to have a skin irritation and skin protection effect with mace lignan.
  • the health drink composition may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients, as in a conventional beverage.
  • the natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; Sugar alcohols such as xylitol, sorbitol, and erythritol.
  • Sweeteners include natural sweeteners such as taumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame.
  • the proportion of the natural carbohydrate is generally about 0.01 to 0.04 g per 100 mL of the composition of the present invention, preferably about 0.02 to 0.03 g.
  • Nutmeg extract or mace lignan may be contained as an active ingredient in a food composition for skin irritation relief and skin protection, the amount of which is not particularly limited to an amount effective to achieve skin irritation relief and skin protection, but is not limited to the total weight of the total composition. It may be 0.01 to 100% by weight, preferably 0.01 to 50% by weight.
  • the food composition of the present invention can be prepared by mixing with nutmeg extract or macy lignan together with other active ingredients known to be effective in skin irritation and skin protection.
  • the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acids, salts of pectic acids, alginic acids, salts of alginic acids, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, Glycerin, alcohol or carbonic acid.
  • the health food of the present invention may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients may be used independently or in combination. The proportion of these additives is not critical, but is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
  • composition for alleviating skin irritation and protecting the skin of the present invention may be a cosmetic composition.
  • the cosmetic composition of the present invention can be easily prepared according to methods known in the art, including one or more excipients and additives commonly used in the field of manufacturing cosmetic compositions with the mace lignan or nutmeg extract of the present invention or salts thereof. You can.
  • the cosmetic composition of the present invention contains a nutmeg extract or mace lignan as an active ingredient and a basic cosmetic composition (face wash, cream, essence, cleansing foam and cleansing water-like cleansers, packs, and vodioyl), along with dermatologically acceptable excipients, It can be prepared in the form of color cosmetic composition (foundation, lipstick, mascara, makeup base), hair product composition (shampoo, conditioner, hair conditioner, hair gel) and soap.
  • the excipients include, but are not limited to, for example, skin emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents.
  • it may further include fragrances, pigments, fungicides, antioxidants, preservatives and moisturizers, and may include thickeners, inorganic salts, synthetic polymer materials, etc. for the purpose of improving physical properties.
  • the excipients include, but are not limited to, for example, skin emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents.
  • it may further include fragrances, pigments, fungicides, antioxidants, preservatives and moisturizers, and may include thickeners, inorganic salts, synthetic polymer materials, etc. for the purpose of improving physical properties.
  • a cleanser and soap with the cosmetic composition of the present invention it can be easily prepared by adding a nutmeg extract or mace lignan to a conventional cleanser and soap base.
  • the cream in the case of manufacturing the cream, it can be prepared by adding a nutmeg extract or mace lignan or a salt thereof to a cream base of a general oil-in-water type (O / W).
  • Synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties may be additionally added to fragrances, chelating agents, pigments, antioxidants, preservatives, and the like.
  • the face wash and soap containing the mace lignan or nutmeg extract of the present invention can be easily prepared by adding the mace lignan or nutmeg extract to the conventional face wash and soap base.
  • the cream it may be prepared by adding mace lignan or nutmeg extract to a cream base of a general oil-in-water type (O / W).
  • Synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties may be additionally added to fragrances, chelating agents, pigments, antioxidants, preservatives, and the like.
  • the content of nutmeg extract or mayslignan contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight relative to the total weight of the total composition. If the content is less than 0.001% by weight, the desired anti-aging or anti-wrinkle effect cannot be expected, and when it is more than 10% by weight, there may be difficulties in safety or preparation of the formulation.
  • the present invention provides a composition for preventing skin contamination derived from environmental pollutants containing nutmeg extract or mace lignan as an active ingredient.
  • composition may be provided in the form of a pharmaceutical composition, cosmetic composition, and food composition. Description of this is as described above.
  • the present invention provides a use of mace lignan or a nutmeg extract containing the same for preparing a preparation for skin irritation relief and skin protection derived from environmental pollution factors.
  • the present invention provides a method for alleviating skin irritation and protecting skin induced from environmental pollutants, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. do.
  • the present invention provides the use of mace lignan or nutmeg extract containing the same for preparing a formulation for preventing skin contamination derived from environmental pollution factors.
  • the present invention provides a method for preventing skin contamination derived from environmental pollutants, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof.
  • the 'effective amount' of the present invention when administered to an individual, improves, treats, prevents, detects, diagnoses skin irritation and skin damage or skin contamination, or suppresses or reduces skin irritation and skin damage or skin contamination.
  • the 'individual' may be an animal, preferably a mammal, particularly an animal including a human, or may be cells, tissues, organs, etc. derived from an animal. The subject may be a patient in need of the effect.
  • the 'treatment' of the present invention broadly refers to improving the symptoms of skin irritation and skin damage or skin contamination or skin irritation and skin damage or skin contamination, which heals, substantially prevents, or prevents these diseases May include, but is not limited to, alleviating, healing or preventing one symptom or most symptoms resulting from skin irritation and skin damage or skin contamination.
  • the term 'comprising' of the present invention is used in the same way as 'containing' or 'as a feature', and does not exclude additional component elements or method steps not mentioned in the composition or method. .
  • the term 'consisting of' means excluding additional elements, steps or ingredients, which are not described separately.
  • the term 'essentially consisting of' means that in the scope of a composition or method, it includes the described component elements or steps, as well as component elements or steps that do not materially affect its basic properties.
  • Nutmeg extract or mace lignan according to the present invention reduces the amount of expression of genes such as CYP1A1 mediated by XRE in skin cells, and thus has excellent skin irritation and skin protection functions derived from environmental pollutants, and is a food and cosmetic composition. Can be used for
  • Figure 1 shows the results of the inhibitory activity of luciferase increase mediated by XRE according to BaP treatment of nutmeg extract.
  • Figure 2 shows the results of the inhibitory activity of CYP1A1 expression increase according to BaP treatment of nutmeg extract.
  • Figure 3 shows the results of the inhibitory activity of increased luciferase mediated by XRE according to BaP treatment of mace lignan.
  • Figure 4 shows the results of the inhibitory activity of increased expression of CYP1A1 according to BaP treatment of mace lignan.
  • Figure 5 shows the results of the inhibitory activity of increased luciferase mediated by XRE by f treatment of macylignan.
  • Figure 7 shows the results of the inhibitory activity of increased expression of CYP1A1, CYP1B1, CYP1A2 mRNA by PM treatment of mays lignan.
  • Figure 8 shows the results of the effect of improving skin epidermal layer damage by PM treatment of mace lignan.
  • a nutmeg ethanol extract was obtained in the same manner as in Example 1-1, except that it was extracted at 50 ° C using 100% ethanol, 70% ethanol, 50% ethanol, and 30% ethanol.
  • a nutmeg ethyl acetate extract was obtained in the same manner as in Example 1-1, except that 100% ethyl acetate was used.
  • a nutmeg hexane extract was obtained in the same manner as in Example 1-1, except that 100% hexane was used.
  • a nutmeg hot water extract was obtained in the same manner as in Example 1-2, except that water was used and the condition was 80 ° C.
  • the dried nutmeg was ground with a mixer, and then 1 g of the ground nutmeg sample was charged into a sample cartridge and extracted using a supercritical device (SFX 3560, Isco Inc., Lincoln, NE, USA).
  • the supercritical fluid extraction conditions were an extraction pressure of 40 MPa, an extraction temperature of 50, a supercritical carbon dioxide flow rate of 60 mL / min, and an extraction time of 60 min.
  • the pressure of the extraction device was lowered to release the supercritical fluid state, thereby obtaining a nutmeg supercritical extract.
  • a subcritical water reactor of a subcritical extraction device Biovan, Gyeonggi, Korea
  • the temperature of the reactor was increased to 200 ° C and the pressure was increased to 20 MPa, and when the temperature of the reactor reached 200 ° C, the temperature was maintained for 20 minutes to extract.
  • the extract was transferred to a storage tank to which cooling water is supplied, rapidly cooled to 30 ° C, and centrifuged at 3,600 rpm for 30 minutes to separate the floating residue, and only the supernatant was taken.
  • a subcritical extract of nutmeg was prepared by removing all water using a freeze dryer (ilShin Lab Co. Ltd., Seoul, Korea).
  • Example 1-2 the concentrated nutmeg ethanol extract obtained using 100% ethanol was partitioned into ethyl acetate, butanol, and water.
  • the ethyl acetate fraction (4.2 g) was eluted with a solvent mixed with hexane and ethyl acetate at a ratio of 10: 1 (v / v) using silica gel column chromatography to obtain fraction III (1 g).
  • Fraction III was subjected to column chromatography with a solvent mixed with hexane and ethyl acetate at a ratio of 20: 1 (v / v) to obtain fraction III-B (0.52 g).
  • fraction III-B was eluted with 80% methanol using Rp-18 column chromatography (Lichroprep RP-18 25-40 um; Merck & Co.) to obtain single substance fraction III-B-2 (0.5 g).
  • 1 H-NMR spectrum and 13 C-NMR spectrum were measured at 600 MHz and 150 MHz (solvent: DMSO), respectively, in order to determine the structure of the isolated single substance III-B-2.
  • 13 C-NMR spectrum and the 1 H-NMR 1 H- 1 H COSY spectrum and 1 H- 13 to measure the correlation of the correlation of the 1 H- 1 H, based on the result of the spectrum related to the 1 H- 13 C HMBC C Spectra were measured.
  • EI / MS for mass spectrometry of the isolated single substance [M] + was observed at m / z 328 in EI / MS and the molecular weight was found to be 328, and the molecular formula was C 20 H 24 It was O 4 .
  • Example 3 XP-mediated luciferase increase inhibitory activity according to BaP treatment of nutmeg extract
  • COS-7 monkey kidney cells (ATCC, Manassas, VA, USA) were cultured in Dulbecco's modified Eagle's media (DMEM; Hyclone) containing 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA) 24- Incubated in well plates for 24 hours or more.
  • DMEM Dulbecco's modified Eagle's media
  • FBS fetal bovine serum
  • Example 4 Inhibitory activity of CYP1A1 expression increase according to BaP treatment of nutmeg extract
  • the skin keratinocytes HaCaT was placed in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone) to 2 x 10 5 cells / mL.
  • DMEM Hyclone
  • FBS Hyclone
  • the nutmeg 100% ethanol extract of Example 1-2 was treated with 0.5 and 1 ⁇ g / mL for 24 hours with 5 ⁇ M BaP (Sigma-aldrich).
  • total RNA was isolated using a TRIzol reagent (Takara, Tokyo, Japan). Total RNA isolated was quantified using a nanodrop (NanoDrop 1000; Thermo Fisher Scientific Inc., MA, USA).
  • RNA was synthesized by cDNA under conditions of 42 ° C 55 minutes and 70 ° C 15 minutes using Reverse Transcriptase Premix (Elpis) and PCR machine (Gene Amp PCR System 2700; Applied Biosystems, MA, USA).
  • Elpis Reverse Transcriptase Premix
  • PCR machine Gene Amp PCR System 2700; Applied Biosystems, MA, USA.
  • 3 ⁇ L cDNA the following specific primers (Bioneer, Daejeon, Korea) and PCR premix (Elpis) at 95 ° C for 30 seconds, 60 ° C for 1 minute, and 72 ° C for 1 minute 30 times PCR was performed repeatedly.
  • the cDNA amplified by PCR was separated by electrophoresis with a 1.5% agarose gel, and the cDNA band was confirmed using a G; BOX EF imaging system (Syngene). The results are shown in FIG. 2.
  • Reverse primer 5'-CGCCCCTTGGGGATGTAAAA-3 '(SEQ ID NO: 2)
  • Reverse primer 5'-TCGCCCCACTTGATTTTGGA-3 '(SEQ ID NO: 4)
  • Example 5 XRE-mediated luciferase increase inhibitory activity according to PM treatment of nutmeg extract
  • Example 1-5 Nutmeg extract 50% ethanol extract and 100% ethanol extract prepared in Example 1-2, nutmeg ethyl acetate prepared in Example 1-3 to examine the luciferase inhibitory activity mediated by XRE induced by PM of nutmeg extract Extract, nutmeg hexane extract prepared in Example 1-4, Nutmeg hot water extract prepared in Example 1-5 was treated with cells at 1 ⁇ g / mL, and inducers were standardized fine dust (PM; NIST, Gaithersburg instead of BaP). , MD, USA) The experiment was carried out in the same manner as in Example 3, except that 100 ⁇ g / mL was used.
  • Example 6 Inhibitory activity of CYP1A1 expression increase according to BaP treatment of maylignan
  • Example 4 In order to investigate the inhibitory activity of CYP1A1 mRNA expression level of mays lignan, the cells were treated with 1 and 5 ⁇ M of mays lignan prepared in Example 2-1 to conduct experiments in the same manner as in Example 4.
  • Example 7 Inhibitory activity of increased luciferase mediated by XRE by PM treatment of mays lignan
  • Example 2-1 To examine the luciferase inhibitory activity mediated by XRE induced by PM of mays lignan, the mace lignan prepared in Example 2-1) was treated with cells at 0.5 and 1 ⁇ M to induce the inducer PM 100 ⁇ g / mL. The experiment was conducted in the same manner as in Example 3, except that it was used.
  • Example 8 Inhibitory activity of increased expression of AhR mRNA by PM treatment of mace lignan
  • the cells were treated with 0.5 and 1 ⁇ M of mays lignan prepared in Example 2-1 to use 100 ⁇ g / mL of PM.
  • the experiment was conducted in the same manner as in Example 4, except that the point and the AhR primer were used.
  • Reverse primer 5'-AAGCAGGCGTGCATTAGACT-3 '(SEQ ID NO: 6)
  • the mays lignan of the present invention effectively reduces skin irritation caused by environmental pollutants by reducing the mRNA expression level of receptors to which environmental pollutants can bind.
  • Example 9 Inhibitory activity of increased expression of CYP1A1, CYP1B1, CYP1A2 mRNA by PM treatment of mace lignan
  • Example 2-1 To investigate the activity of CYP1A1, CYP1B1, and CYP1A2 mRNA expression induced by PM of mays lignan, the mace lignan prepared in Example 2-1 was treated with cells at 0.5 and 1 ⁇ M to induce the inducer PM 100 ⁇ g / mL Experiments were conducted in the same manner as in Example 4, except that and CYP1B1 and CYP1A2 primers were additionally used.
  • Reverse primer 5'-AAGGAACTGGGACCTTTGCC-3 '(SEQ ID NO: 8)
  • Reverse primer 5'-TGAGTGTTCTTCACGAGGCTG-3 '(SEQ ID NO: 10)
  • Example 10 Effect of improving skin epidermal layer damage by PM treatment of mace lignan
  • Neoderm-ED 3D artificial skin model
  • the experimental group was divided into normal group, PM 100 ⁇ g / mL treatment group, mace lignan 0.5 ⁇ M treatment group, and mace lignan 1 ⁇ M treatment group, and 6 artificial skin tissues were used for each group.
  • Neoderm-ED was prepared according to the method of manufacturing the tegoscience, and the experiment was conducted after stabilizing artificial skin tissue at 5% CO 2 and 37 ° C. conditions using a dedicated medium provided by tegoscience for 6 hours.
  • Skin damage caused by PM was induced by treating PM 100 ⁇ g / mL with 50 ⁇ L per well on the Neoderm-ED surface, and DPBS was treated with the same dose in the normal group. Simultaneously with PM induction, the mace lignan prepared in Example 2-1 was treated with Neoderm-ED's exclusive medium at 0.5 and 1 ⁇ M to induce improvement of skin damage due to PM. The cells were cultured for 72 hours at 5% CO 2 and 37 ° C., and PM and mace lignan were further treated every 24 hours. After the 72-hour incubation, the artificial skin tissue was fixed with 10% formalin to produce a paraffin block.
  • Hematoxylin & eosin staining was performed to measure the improvement of skin damage caused by PM of mace lignan from the histological aspect using the fixed tissue, and the stained tissue was eXcope T500 camera (DIXI Science, Daejeon) , Korea) was observed with a photochemical microscope (CK40; Olympus, Tokyo, Japan).
  • a powder was prepared by filling in an airtight bag according to a conventional powder manufacturing method.
  • tablets After mixing the nutmeg extract of Example 1 to 2, or 50 mg of maylignan, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate, tablets were prepared by tableting according to a conventional tablet manufacturing method.
  • Example 1 After mixing the nutmeg extract of Example 1 to 2, or 30 mg of maylignan, whey protein, 100 mg of crystalline cellulose, 400 mg of magnesium stearate, and filling it into a gelatin capsule according to a conventional capsule preparation method, a capsule is prepared. Did.
  • Nutmeg extract of Examples 1 to 2 or 1000 mg of maylignan, 1000 mg of citric acid, 100 g of oligosaccharides, 2 g of plum concentrate, and 1 g of taurine were added to purified water to add the above ingredients according to the general method for preparing a health drink of 900 mL. After mixing, after stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered, obtained in a sterilized 2 L container, sealed and sterilized, then refrigerated and then used in the manufacture of a health drink composition.
  • Chewing gum was prepared by a conventional method by mixing 20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of fragrance, and 2% by weight of water and 0.1% by weight of nutmeg extract or mace lignan of Examples 1 to 2 above.
  • Candy was prepared by a conventional method by mixing 60% by weight of sugar, 39.8% by weight of starch syrup and 0.1% by weight of fragrance and 0.1% by weight of nutmeg extract or maceignan of Examples 1 to 2 above.
  • Nutmeg extract or mace lignan of Examples 1 to 2 was prepared in the nutritional lotion according to a conventional method with the ingredients and contents of Table 2 below.
  • Example 1-1 (% by weight) Nutmeg extract or mace lignan 2.0 Squalane 5.0 Wax 4.0 Polysorbate 60 1.5 Sorbitan sesquioleate 1.5 Floating paraffin 0.5 Caprylic / Capric Triglyceride 5.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Triethanolamine 0.2 Preservatives, pigments, flavors Proper Purified water to 100
  • the nutmeg extract or mays lignan of Examples 1 to 2 was prepared with a flexible lotion according to a conventional method with the ingredients and contents of Table 3 below.
  • Nutmeg extract or mays lignan of Examples 1 to 2 was prepared in the nutritional cream according to a conventional method with the components and contents of Table 4 below.
  • Massage cream was prepared according to a conventional method with the ingredients and contents of the nutmeg extract or mace lignan of Examples 1 to 2 below.
  • the nutmeg extract or mace lignan of Examples 1 to 2 was prepared according to a conventional method with the ingredients and contents of Table 6 below.
  • the nutmeg extract or mace lignan of Examples 1 to 2 was prepared according to a conventional method with the ingredients and contents of Table 7 below.
  • the present invention relates to a composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or macy lignan as an active ingredient. More specifically, the nutmeg extract and mays lignan of the present invention reduced the expression of CYP1A1 gene mediated by XRE in skin cells and improved the skin damaged by fine dust, and thus skin irritation caused by fine dust, heavy metals, or yellow dust It has an excellent effect on relief and skin protection. Therefore, the nutmeg extract and mace lignan of the present invention is a natural product, and thus can be safely used without side effects, and is highly industrially applicable because it can provide a composition showing excellent effects on skin irritation and skin protection.

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Abstract

The present invention relates to a composition for the alleviation of skin irritation induced by environmental pollution factors or for skin protection, containing a nutmeg extract or macelignan as an active ingredient. A nutmeg extract and macelignan of the present invention have reduced the expression of gene CYP1A1 mediated by XRE, and have alleviated skin damaged by fine dust, thereby having excellent effects in the alleviation of skin irritation induced by environmental pollution factors and in skin protection. In addition, the composition of the present invention is a natural material, and thus can be safely used without side effects, thereby being usable as food and a cosmetic composition.

Description

육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 조성물Composition for alleviating skin irritation and protecting skin derived from environmental pollutants containing nutmeg extract or mace lignan as an active ingredient
본 출원은 2018년 10월 26일에 출원된 대한민국 특허출원 제10-2018-0129382호를 우선권으로 주장하고, 상기 명세서 전체는 본 출원의 참고문헌이다.This application claims priority to Korean Patent Application No. 10-2018-0129382 filed on October 26, 2018, and the entire specification is a reference of the present application.
본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 조성물에 관한 것으로, 보다 상세하게는 본 발명의 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 조성물에 관한 것이다.The present invention relates to a composition for alleviating skin irritation and protecting skin derived from environmental pollutants containing nutmeg extract or mace lignan as an active ingredient, and more specifically, mace lignan represented by Formula 1 of the present invention or nutmeg containing the same It relates to a composition for skin irritation relief and skin protection derived from environmental pollution factors containing the extract as an active ingredient.
피부는 외부환경의 자극으로부터 체내의 기관들을 보호해주며, 체온조절 등의 생체 항상성 유지에 중요한 역할을 한다. 하지만 과도한 자외선이나 오염물질에 노출되면 피부 자극을 유발하게 되고 결국 피부 노화로 이어지게 된다. 이러한 외부 자극 중에서도 특히, 중금속 등의 유해물질이 섞인 미세먼지와 황사(yellow sand)는 피부 노화 및 피부 손상의 주요 원인으로 알려져 있다(J. Prev. Med. Public Health, 39: 205-212, 2006).The skin protects the organs in the body from stimulation of the external environment and plays an important role in maintaining bio homeostasis such as body temperature control. However, exposure to excessive ultraviolet rays or pollutants causes skin irritation and eventually leads to skin aging. Among these external stimuli, fine dust and yellow sand mixed with harmful substances such as heavy metals are known to be major causes of skin aging and skin damage (J. Prev. Med. Public Health, 39: 205-212, 2006 ).
Particulate matter (PM) 10는 입자크기 10 μm 이하 미세먼지를 통칭하며 2.5 μm 이하 초 미세먼지는 PM 2.5로 구분된다. 미세먼지는 주로 화석연료를 연소할 때 발생하며, 석탄의존도가 70%인 중국발 미세먼지가 상당부분을 차지한다. 한편, 황사는 중국 및 몽고 등의 내륙에 위치한 사막에서 작은 모래나 황토가 부유하여 상층 바람을 타고 멀리 수송되어, 지면 가까이 낙하는 현상이다. 산업국가의 질병 약 25 ~33%가 환경적 위해 요인에 의해 발생한다. 유럽에서는 오염된 공기로 연간 약 31만 명이 조기에 사망하는 것으로 추정되고 있으며, 초미세먼지가 m 3당 10 μg가 증가할 경우 전체 사망률은 7% 증가한다. 국내에서 PM 10을 대기오염물질로 규제하고 있으며 이런 미세먼지 등 대기오염물질은 호흡기질환과 심장질환을 유발한다고 알려져 있다(J. Exp. Biol. Med., 232: 1109-1118, 2007; J. Biosci., 28: 77-81, 2003). Particulate matter (PM) 10 is collectively referred to a particle size of 10 μm or less fine dust and fine particles less than 2.5 μm in seconds is divided into a PM 2.5. Fine dust is mainly generated when burning fossil fuels, and fine dust from China, which has a 70% dependency on coal, accounts for a large portion. On the other hand, yellow sand is a phenomenon in which small sand or loess is floating in the inland deserts of China and Mongolia, and is transported away by upper winds and falls near the ground. About 25 to 33% of diseases in industrialized countries are caused by environmental hazards. In Europe, it is estimated that approximately 310,000 people die prematurely each year from polluted air, and if the ultrafine dust increases by 10 μg per m 3 , the overall mortality rate increases by 7%. PM 10 is regulated as an air pollutant in Korea, and air pollutants such as fine dust are known to cause respiratory and heart diseases (J. Exp. Biol. Med., 232: 1109-1118, 2007; J. Biosci., 28: 77-81, 2003).
민감성 피부의 경우에는 대기오염물질과 같은 환경의 변화에 대하여 일반적인 피부보다 3배 이상 피부 자극이 발생한다는 연구가 있다. 특히 PM 2.5는 일반 먼지보다 입자가 작아 피부 모공 속에 깊숙이 들어가 피부 트러블을 일으키며, 자극성 피부염, 여드름, 알레르기 피부염 등 각종 증상을 더욱 악화시킨다. 또한 역학적 연구에 의하면 미세먼지에 노출된 피부가 주름을 증가시켜 노화에 직접적인 영향을 미치는 것으로 알려져 있다. 미세먼지 표면에 흡착된 polycyclic aromatic hydrocarbon (다환 방향족 탄화수소, PAH)가 aryl hydrocarbon receptor (AhR)의 활성을 증가시키고 xenobiotic response receptor (XRE)에 부착하여 XRE에 의해 매개되는 cytochrome P450 (CYP) 1A1 유전자의 발현이 증가함에 따라 피부 노화가 발생한다. 따라서 미세먼지와 황사에 의해 유발된 피부 자극 반응을 완화시킬 수 있는 안전하고도 효능이 높은 천연 소재의 개발이 필요하다. In the case of sensitive skin, studies have shown that skin irritation occurs three times more than normal skin against environmental changes such as air pollutants. Particularly, PM 2.5 has smaller particles than ordinary dust, deep into the skin pores, causing skin trouble, and exacerbates various symptoms such as irritating dermatitis, acne, and allergic dermatitis. In addition, epidemiological studies show that skin exposed to fine dust increases wrinkles and directly affects aging. Polycyclic aromatic hydrocarbon (PAH) adsorbed on the surface of fine dust increases the activity of the aryl hydrocarbon receptor (AhR) and attaches to the xenobiotic response receptor (XRE), a cytochrome P450 (CYP) 1A1 gene mediated by XRE. Skin aging occurs as expression increases. Therefore, it is necessary to develop a safe and highly effective natural material capable of alleviating the skin irritation reaction caused by fine dust and yellow dust.
이에 따라 환경오염인자에 의해 유도되는 피부노화를 막을 수 있는 소재를 "피부 오염 방지물(antipollutant)"로 정의하며, 이에 대한 연구가 이루어지고 있으나(Tsai MJ et al., J Mol Med (Berl). 2014 Jun;92(6):615-28.; Ono Y et al., Exp Dermatol. 2013 May;22(5):349-53), 아직까지 뚜렷한 연구 성과가 있는 것은 아니다.Accordingly, a material capable of preventing skin aging induced by environmental pollution factors is defined as an "antipollutant", and research has been conducted (Tsai MJ et al., J Mol Med (Berl)) 2014 Jun; 92 (6): 615-28 .; Ono Y et al., Exp Dermatol. 2013 May; 22 (5): 349-53), so far, there has been no significant research achievement.
미리스티카 프라그란스( Myristica fragrans)는 육두구과(Myristicaceae)에 속하며 미리스티카 프라그란스의 씨앗을 육두구(nutmeg)라고 지칭한다. 지금까지 육두구와 관련하여 해독작용, 항당뇨, 항염 효과 등의 활성이 보고된 바 있다. 또한 육두구 추출물에 함유되어 있는 대표 성분인 메이스리그난(macelignan)은 PPARα/γ dual agonist로써, 항당뇨, 간 보호, 신경보호, 항균, 항산화 활성 등이 보고된 바 있다. Myristica fragrans belongs to the Myristicaceae family, and the seeds of Myristica fragrans are called nutmeg. So far, activities related to nutmeg have been reported such as detoxification, anti-diabetes, and anti-inflammatory effects. In addition, the representative ingredient contained in the nutmeg extract, macelignan, is a PPARα / γ dual agonist, and has been reported to have anti-diabetes, liver protection, neuroprotection, antibacterial, and antioxidant activities.
그러나, 본 발명의 이전에는 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 효과에 관해서는 알려진 바 없다.However, prior to the present invention, there is no known skin irritation mitigation and skin protection effect derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
이에 본 발명자들은 천연물 유래의 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 기능이 있는 물질을 탐색한 결과, 육두구 추출물 또는 메이스리그난이 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 기능이 있음을 규명함으로써 본 발명을 완성하였다.Accordingly, the present inventors searched for substances having a skin irritation relief and skin protection function derived from environmental pollutants derived from natural products, and found that nutmeg extract or mace lignan has a skin irritation relief and skin protection function derived from environmental pollution factors. The present invention was completed by clarification.
따라서, 본 발명의 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants containing nutmeg extract or mayslignan as an active ingredient.
또한, 본 발명의 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공하는 것이다.In addition, an object of the present invention is to provide a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting of nutmeg extract or mays lignan as an active ingredient.
또한, 본 발명의 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공하는 것이다.In addition, an object of the present invention is to provide a pharmaceutical composition for alleviating skin irritation and skin protection derived from environmental pollution factors consisting essentially of nutmeg extract or mays lignan as an active ingredient.
본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for alleviating skin irritation and skin protection derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
또한, 본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 식품 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a food composition for skin irritation relief and skin protection derived from environmental pollutants consisting of nutmeg extract or macy lignan as an active ingredient.
또한, 본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 식품 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a food composition for alleviating skin irritation and skin protection derived from environmental pollution factors consisting essentially of nutmeg extract or mays lignan as an active ingredient.
본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 화장품 조성물을 제공하는 것이다.Another object of the present invention is to provide a cosmetic composition for skin irritation relief and skin protection derived from environmental pollutants containing nutmeg extract or macy lignan as an active ingredient.
또한, 본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 화장품 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a cosmetic composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting of nutmeg extract or mays lignan as an active ingredient.
또한, 본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 화장품 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a cosmetic composition for skin irritation relief and skin protection derived from environmental pollutants consisting essentially of nutmeg extract or mace lignan as an active ingredient.
본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공하는 것이다.Another object of the present invention is to provide a composition for preventing skin contamination derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
또한, 본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 구성되는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a composition for preventing skin contamination derived from environmental pollution factors consisting of nutmeg extract or mays lignan as an active ingredient.
또한, 본 발명의 다른 목적은 육두구 추출물 또는 메이스리그난을 유효성분으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a composition for preventing skin contamination derived from environmental pollutants consisting essentially of nutmeg extract or mace lignan as an active ingredient.
본 발명의 다른 목적은 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 제제를 제조하기 위한 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도를 제공하는 것이다.Another object of the present invention is to provide a use of mace lignan or a nutmeg extract containing the same for preparing a preparation for skin irritation relief and skin protection derived from environmental pollution factors.
본 발명의 다른 목적은 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 방법을 제공하는 것이다.Another object of the present invention is a method for alleviating skin irritation and protecting skin induced from environmental pollutants, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. Is to provide.
본 발명의 다른 목적은 환경오염인자로부터 유도되는 피부오염 방지용 제제를 제조하기 위한 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도를 제공하는 것이다.Another object of the present invention is to provide a use of mace lignan or nutmeg extract containing the same for preparing a formulation for preventing skin contamination derived from environmental pollution factors.
본 발명의 다른 목적은 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부오염 방지 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing skin contamination derived from environmental pollution factors, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. .
상기 과제를 해결하기 위한 수단으로서, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공한다.As a means for solving the above problems, the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mays lignan as an active ingredient.
또한, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants consisting of nutmeg extract or mace lignan as an active ingredient.
또한, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants consisting essentially of nutmeg extract or macylignan as an active ingredient.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 육두구 추출물 또는 메이스리그난을 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부 보호용 식품 조성물을 제공한다.In order to achieve another object of the present invention, the present invention provides a food composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mace lignan.
또한, 본 발명은 육두구 추출물 또는 메이스리그난으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부 보호용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for skin irritation relief and skin protection derived from environmental pollutants consisting of nutmeg extract or mace lignan.
또한, 본 발명은 육두구 추출물 또는 메이스리그난으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부 보호용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting essentially of nutmeg extract or mace lignan.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 육두구 추출물 또는 메이스리그난을 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부 보호용 화장품 조성물을 제공한다.In order to achieve another object of the present invention, the present invention provides a cosmetic composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mace lignan.
또한, 본 발명은 육두구 추출물 또는 메이스리그난으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부 보호용 화장품 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for skin irritation relief and skin protection derived from environmental pollutants consisting of nutmeg extract or mace lignan.
또한, 본 발명은 육두구 추출물 또는 메이스리그난으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부자극 완화 및 피부 보호용 화장품 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for alleviating skin irritation and protecting skin derived from environmental pollution factors consisting essentially of nutmeg extract or mace lignan.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공한다.In order to achieve another object of the present invention, the present invention provides a composition for preventing skin contamination derived from environmental pollution factors containing nutmeg extract or mace lignan as an active ingredient.
또한, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 구성되는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공한다.In addition, the present invention provides a composition for preventing skin contamination derived from environmental pollutants consisting of nutmeg extract or mace lignan as an active ingredient.
또한, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 필수적으로 구성되는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공한다.In addition, the present invention provides a composition for preventing skin contamination derived from environmental pollutants consisting essentially of nutmeg extract or mace lignan as an active ingredient.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 제제를 제조하기 위한 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도를 제공한다.In order to achieve another object of the present invention, the present invention provides the use of mace lignan or a nutmeg extract containing the same to prepare a formulation for skin irritation relief and skin protection derived from environmental pollution factors.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 방법을 제공한다.In order to achieve another object of the present invention, the present invention derives from an environmental contaminant characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. Provides a method for alleviating irritation and protecting skin.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 환경오염인자로부터 유도되는 피부오염 방지용 제제를 제조하기 위한 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도를 제공한다.In order to achieve another object of the present invention, the present invention provides the use of mace lignan or nutmeg extract containing the same for preparing a formulation for preventing skin contamination derived from environmental pollution factors.
본 발명의 다른 목적을 달성하기 위하여, 본 발명은 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부오염 방지 방법을 제공한다.In order to achieve another object of the present invention, the present invention derives from an environmental contaminant characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. Provide a method for preventing contamination.
이하, 본 발명의 구성을 구체적으로 설명한다.Hereinafter, the configuration of the present invention will be described in detail.
본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or mace lignan as an active ingredient.
상기 육두구 추출물은 육두구과(Myristicaceae)의 미리스티카속( Myristica) 식물인 것으로, 상기 미리스티카 프라그란스의 씨앗(seed)이 추출 대상이 될 수 있다. The nutmeg extract is a Myristica plant of the Myristicaceae , and the seed of the myristica fragrant may be an extract target.
구체적으로, 상기 육두구 추출물은 물, 탄소수 1 내지 6의 유기용매 또는 이들의 혼합물을 용매로 하여 추출할 수 있다. 이때, 상기 유기용매는 C1 내지 C6의 저급 알코올(alcohol), 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌 클로라이드(methylene chloride), 헥산(hexane), 시클로헥산(cyclohexane) 및 석유에테르(petroleum ether)로 이루어진 군으로부터 선택된 하나 이상인 것이 바람직하나, 이에 한정되지 않는다. Specifically, the nutmeg extract may be extracted using water, an organic solvent having 1 to 6 carbon atoms, or a mixture thereof as a solvent. At this time, the organic solvent is C1 to C6 lower alcohol (alcohol), acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), ethyl acetate (ethyl acetate), methylene chloride (methylene chloride), One or more selected from the group consisting of hexane, cyclohexane and petroleum ether is preferred, but is not limited thereto.
또한, 상기 육두구의 추출에 사용되는 저급 알코올 역시 에탄올 또는 메탄올인 것이 더욱 바람직하며, 에탄올인 것이 가장 바람직하다. In addition, the lower alcohol used in the extraction of the nutmeg is also more preferably ethanol or methanol, most preferably ethanol.
추출 시 건조된 육두구를 분쇄한 후, 물, 알코올 또는 이의 혼합물을 분쇄된 육두구 무게의 2배 내지 20배를 첨가하여 추출하는 것이 바람직하고, 3배 내지 10배를 첨가하여 추출하는 것이 더욱 바람직하나, 이에 한정되지 않는다. 추출온도는 20℃ 내지 100℃인 것이 바람직하며, 60℃ 내지 100℃인 것이 더욱 바람직하나, 이에 한정되지 않는다. After pulverizing the dried nutmeg at the time of extraction, it is preferable to extract water, alcohol or a mixture thereof by adding 2 to 20 times the weight of the crushed nutmeg, and it is more preferable to extract by adding 3 to 10 times. , But is not limited to this. The extraction temperature is preferably 20 ° C to 100 ° C, and more preferably 60 ° C to 100 ° C, but is not limited thereto.
추출시간은 1시간 내지 10시간인 것이 바람직하며, 2시간 내지 5시간인 것이 더욱 바람직하나, 이에 한정되지 않는다. The extraction time is preferably 1 hour to 10 hours, more preferably 2 hours to 5 hours, but is not limited thereto.
추출방법은 냉침, 초음파 추출 또는 환류냉각 추출방법이 모두 이용가능하며, 환류 냉각 추출방법을 이용하는 것이 바람직하나, 이에 한정되지 않는다. 추출 회수는 1회 내지 5회인 것이 바람직하며, 2회 내지 3회 반복 추출하는 것이 더욱 바람직하나 이에 한정되지 않는다.Cold extraction, ultrasonic extraction, or reflux cooling extraction may be used as the extraction method, and it is preferable to use a reflux cooling extraction method, but is not limited thereto. The number of extractions is preferably 1 to 5 times, and it is more preferable to repeatedly extract 2 to 3 times, but is not limited thereto.
또한, 상기 육두구 추출물은 초고압, 아임계 유체 또는 초임계 유체 추출법에 의해 수행될 수 있다. In addition, the nutmeg extract may be performed by an ultra-high pressure, subcritical fluid or supercritical fluid extraction method.
추출에 사용되는 육두구는 수확한 후 세척하여 그대로 사용하거나 건조하여 사용할 수 있다. 건조방법으로는 양건, 음건, 열풍건조 및 자연 건조하는 방법을 모두 사용할 수 있다. 또한, 추출효율을 증대시키기 위해 육두구 또는 그 건체를 분쇄기로 분쇄하여 사용할 수 있다.Nutmeg used for extraction can be used after washing after harvesting or dried. As a drying method, a dry method, a dry method, a hot air drying method, and a natural drying method may be used. In addition, in order to increase the extraction efficiency, nutmeg or its dry matter may be crushed and used.
상기 메이스리그난(macelignan)은 바람직하게 하기 화학식 1의 구조를 갖는다.The macelignan preferably has the structure of Formula 1 below.
[화학식 1][Formula 1]
Figure PCTKR2019014101-appb-img-000001
Figure PCTKR2019014101-appb-img-000001
본 발명의 메이스리그난(macelignan)은 화학식 1의 구조를 가지며, 천연으로부터 분리 정제하거나, 상업적으로 구입하여 사용하거나 또는 당 업계에 공지된 화학적 합성법으로 제조할 수 있다.Macelignan (macelignan) of the present invention has a structure of formula 1, can be purified from nature, commercially available for use, or prepared by chemical synthesis methods known in the art.
바람직하게 본 발명의 메이스리그난은 천연으로부터 분리 정제될 수 있다. 더 바람직하게는, 미리스티카 프라그란스( Myristica fragrans)로부터 분리 정제될 수 있으며, 가장 바람직하게는 미리스티카 프라그란스의 육두구(nutmeg)나 가종피(aril)로부터 분리 정제될 수 있다. 또한 다른 육두구과 식물인 미리스티카 아르겐티아 워르브( Myristica argentea Warb)에서도 분리정제될 수 있으며(Nat. Prod. Lett., 16: 1-7, 2002), 후박나무( Machilus thunbergii)(Bio. Pharm. Bull., 27: 1305-1307, 2004), 레우카스 아스페라( Leucas aspera) 등에서도 분리정제될 수 있다(Chem. Pharm. Bull., 51: 595-598, 2003).Preferably, the machlignan of the present invention may be purified from nature. More preferably, it can be isolated and purified from Myristica fragrans , and most preferably, it can be isolated and purified from nutmeg or aril of Myristica fragrans . Another nutmeg, Myristica Myristica argentea Warb) (Nat. Prod. Lett., 16: 1-7, 2002), and Machilus thunbergii ) (Bio. Pharm. Bull., 27: 1305-1307, 2004), Leucas aspera , etc. (Chem. Pharm. Bull., 51: 595-598, 2003) .
바람직하게는 본 발명의 메이스리그난은 육두구에서 당업계에 공지된 용매 추출법 및 크로마토그래피를 이용한 분리방법에 의해 분리, 정제될 수 있다.Preferably, the may lignan of the present invention may be separated and purified from a nutmeg by a solvent extraction method known in the art and a separation method using chromatography.
본 발명의 일실시예에 따르면, 본 발명에 따른 조성물은 XRE에 의해 매개되는 유전자의 발현량을 감소시킴으로써 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 및 피부 오염 방지에 이용될 수 있다.According to one embodiment of the present invention, the composition according to the present invention can be used for alleviating skin irritation and protecting skin and preventing skin contamination derived from environmental pollutants by reducing the expression level of a gene mediated by XRE.
본 발명의 조성물은 피부자극 완화 및 피부보호 효과를 가지며, 이러한 피부 자극은 환경오염인자에 의한 피부기능 저하, 피부 노화 촉진 등으로의 피부 질환으로서 당업계에 보고된 질병인 것이 바람직하며, 이를 예방 및 보호하는 것을 말한다. The composition of the present invention has a skin irritation alleviation and skin protection effect, and such skin irritation is a skin disease caused by deterioration of skin function due to environmental pollution factors, promotion of skin aging, etc., and is preferably a disease reported in the art. And protection.
본 발명의 피부자극은 피부염(dermatitis), 아토피(atopy), 건선(psoriasis), 여드름(acne), 피부암(skin cancer), 습진(eczema)으로 이루어진 군으로부터 선택되는 어느 하나 이상인 것이 보다 바람직하나, 이에 한정되지 않는다.Skin irritation of the present invention is more preferably any one or more selected from the group consisting of dermatitis, atopy, psoriasis, acne, skin cancer, eczema, It is not limited to this.
또한, 본 발명의 피부자극 완화는 “피부의 오염 방지(anti-pollution)”하는 것 일 수 있다. 피부의 오염 방지는 자연적 요인(내인성 노화) 또는 환경오염인자(다환방향족탄화수소(poly aromatic hydrocarbons), 미세먼지(particulate matter), 담배연기, 황사 또는 중금속 등)로부터 피부를 보호하여 피부상태의 개선을 유도하는 것을 의미하며, 바람직하게는 환경오염인자로부터 피부를 보호하는 것을 의미한다.In addition, the skin irritation relief of the present invention may be "anti-pollution of the skin". Prevention of skin contamination improves skin condition by protecting the skin from natural factors (endogenous aging) or environmental pollutants (poly aromatic hydrocarbons, particulate matter, tobacco smoke, yellow sand or heavy metals, etc.) It means to induce, preferably to protect the skin from environmental pollution factors.
본 발명에서의 용어 “하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물”에는 이들의 약학적으로 허용 가능한 이들의 염 또는 이들의 전구 약물을 포함하는 것으로 본다.In the present invention, the term “mayslignan represented by Formula 1 or nutmeg extract containing the same” is considered to include their pharmaceutically acceptable salts or prodrugs thereof.
본 발명에서의 용어 '전구 약물'은 표적이 되는 생리학적 시스템 내에서 전구 약물이 활성 약물로 분비 또는 전환(예컨대, 효소 적으로, 생리학적으로, 기기적으로, 전자기적으로) 되기 위해서는 생변이(예컨대, 원발적인 또는 효소 적인)가 요구되는 근원 '약물' 분자의 약학적으로 불활성인 유도체를 말한다. 전구 약물은 안정성, 독성, 특이성의 결여 또는 제한된 생체이용률과 연관된 문제점들을 극복하기 위해 디자인된다. 전형적인 전구 약물들은 활성 약물 분자 그 자체와 화학적 차단그룹(예컨대, 역으로 그 약물의 활성을 저지하는 그룹)을 포함한다. 몇몇 선호되는 약물들은 대사조건에 따라 분리가능한 그룹을 가진 성분들의 변형체 또는 유도체이다. 전형적인 약물들은 생리학적 조건하에서 가용매 분해를 수행하거나 효소적 분해를 수행하거나 기타 다른 생화학적 변형(예컨대, 인산화, 수소화, 탈수소화, 글리코실화 반응)이 이뤄질 때 약학적으로 체내 및 체외에서 활성화된다. 전구 약물은 종종 용해도, 조직 적합성, 또는 포유류 체내에서의 서방성 등의 장점을 제공한다. 일반적인 전구 약물은 적절한 알코올(예컨대, 저급 알칸올)을 근원 산들과 반응시킴으로써 얻어지는 에스테르와 같은 산유도체, 아민과 근원산 성분이 반응하여 이루어진 아미드 또는 염기성 그룹이 반응하여 형성하는 아실화된 염기유도체 (예컨대, 저급 알킬아미드) 등을 포함한다.The term 'prodrug' in the present invention is a biotransformation in order to secrete or convert a prodrug into an active drug (eg, enzymatically, physiologically, mechanically, electromagnetically) in a targeted physiological system. Refers to a pharmaceutically inert derivative of the source 'drug' molecule (eg, primary or enzymatic) required. Prodrugs are designed to overcome problems associated with stability, toxicity, lack of specificity or limited bioavailability. Typical prodrugs include the active drug molecule itself and a chemical blocking group (e.g., a group that reversely inhibits the drug's activity). Some preferred drugs are variants or derivatives of components with separable groups depending on metabolic conditions. Typical drugs are pharmacologically activated both in vitro and in vitro when solvolysis under physiological conditions, enzymatic degradation, or other biochemical modifications (e.g. phosphorylation, hydrogenation, dehydrogenation, glycosylation reactions) are performed. . Prodrugs often offer advantages such as solubility, histocompatibility, or sustained release in the mammalian body. Common prodrugs include acid derivatives such as esters obtained by reacting a suitable alcohol (e.g., lower alkanols) with source acids, acylated base derivatives formed by reaction of amides or basic groups with amines and source acid components ( For example, lower alkylamide).
본 발명의 육두구 추출물 또는 메이스리그난은 약학적으로 허용가능한 염의 형태로 조성물 내에 포함될 수 있다. “약학적으로 허용가능한 염”은 생리학적으로 허용되고 인간에게 투여시 통상적인 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 것을 말하며, 상기 염으로는 약학적으로 허용 가능한 유리산(free acid)에 의하여 형성된 산 부가염이 바람직하다. 상기 유리산은 유기산과 무기산을 사용할 수 있다. 상기 유기산은 이에 제한되는 것은 아니나, 구연산, 초산, 젖산, 주석산, 말레인산, 푸마르산, 포름산, 프로피온산, 옥살산, 트리플로오로아세트산, 벤조산, 글루콘산, 메타술폰산, 글리콜산, 숙신산, 4-톨루엔술폰산, 글루탄산 및 아스파르트산을 포함한다. 또한, 상기 무기산은 이에 제한되는 것은 아니나 염산, 브롬산, 황산 및 인산을 포함한다.The nutmeg extract or mayslignan of the present invention may be included in the composition in the form of a pharmaceutically acceptable salt. “Pharmaceutically acceptable salt” refers to a physiologically acceptable salt that does not cause a common allergic reaction or similar reaction when administered to humans, and the salt is formed by a pharmaceutically acceptable free acid. Acid addition salts are preferred. As the free acid, an organic acid and an inorganic acid can be used. The organic acid is not limited thereto, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Glutanoic acid and aspartic acid. In addition, the inorganic acids include, but are not limited to, hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid.
본 발명의 약학적 조성물은 약학적으로 허용되는 담체와 함께 당업계에 공지된 방법으로 투여경로에 따라 다양하게 제형화될 수 있다.The pharmaceutical composition of the present invention may be variously formulated according to the route of administration by a method known in the art together with a pharmaceutically acceptable carrier.
일반적인 의약품의 형태로 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 메이스리그난에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제,시럽제 등이When formulated in the form of general pharmaceuticals, it is usually prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the mace lignan, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc. It is prepared by mixing. In addition, lubricants such as magnesium styrene talc are used in addition to simple excipients. Liquid preparations for oral administration include suspensions, intravenous solutions, emulsions, syrups, etc.
해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 연고제, 크림제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.In addition to the simple diluents commonly used, water and liquid paraffin, various excipients may be included, such as wetting agents, sweeteners, fragrances, and preservatives. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, ointments and creams. As non-aqueous solvents and suspension solvents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used.
또한, 본 발명의 조성물은 비경구로 투여할 수 있으며, 비경구 투여는 피하주사, 정맥주사, 근육 내 주사 또는 흉부 내 주사 주입방식 및 경피 투여 방식에 의한다. 주사 주입 방식의 비경구 투여용 제형으로 제제화하기 위해서는 메이스리그난을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고 이를 앰플 또는 바이알의 단위 투여형으로 제제화한다. 투약 단위는, 예를 들면 개별 투약량의 1, 2, 3 또는 4배로, 또는 1/2, 1/3 또는 1/4배를 함유할 수 있다. 개별 투약량은 바람직하기로는 유효 약물이 1회에 투여되는 양을 함유하며, 이는 통상 1일 투여량의 전부, 1/2, 1/3 또는 1/4배에 해당한다. 경피 투여제의 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태가 포함된다. 상기에서 "경피 투여"는 약학적 조성물을 국소적으로 피부에 투여하여 약학적 조성물에 함유된 유효한 양의 활성성분이 피부 내로 전달되는 것을 의미한다.In addition, the composition of the present invention can be administered parenterally, parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method and transdermal administration method. To formulate a formulation for parenteral administration in an injection-injected manner, mayslignan is mixed in water with a stabilizer or a buffer to prepare a solution or suspension, which is formulated into unit dosage forms of ampoules or vials. The dosage unit can contain, for example, 1, 2, 3 or 4 times the individual dosage, or 1/2, 1/3 or 1/4 times. The individual dosage preferably contains the amount of effective drug administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dosage. In the case of transdermal dosage forms, ointments, creams, lotions, gels, external solutions, pasta agents, linen agents, aerosols, and the like are included. In the above, "dermal administration" means that the pharmaceutical composition is topically administered to the skin to deliver an effective amount of the active ingredient contained in the pharmaceutical composition into the skin.
본 발명에서의 용어 '약학적으로 유효한 양'은 의학적 용도에 적용 가능한 합리적인 수혜/위험 비율로 피부자극 완화 또는 피부를 보호하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.The term 'pharmaceutically effective amount' in the present invention means an amount sufficient to alleviate skin irritation or protect the skin at a reasonable benefit / risk ratio applicable to medical uses, and the effective dose level is the individual type and severity, age, It can be determined by gender, drug activity, sensitivity to the drug, time of administration, route of administration and rate of excretion, duration of treatment, factors including co-drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be administered single or multiple. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects, and can be easily determined by those skilled in the art.
이들 제형은 제약 화학에 일반적으로 공지된 처방서에 기술되어 있다.These formulations are described in recipes generally known in pharmaceutical chemistry.
그 밖의 약학적으로 허용되는 담체로는 당업계에 공지되어 있는 것을 참고로 할 수 있다.As other pharmaceutically acceptable carriers, reference may be made to those known in the art.
나아가, 본 발명의 약학적 조성물은 천식, 아토피 피부염과 같은 피부 자극을 예방 및 치료하는 효과를 가지는 공지의 화합물과 병행하여 투여할 수 있다.Furthermore, the pharmaceutical composition of the present invention may be administered in parallel with a known compound having an effect of preventing and treating skin irritation such as asthma and atopic dermatitis.
다른 양상으로, 본 발명의 조성물을, 중금속 등에 의하여 피부 자극을 나타내는 세포, 조직, 기관 또는 개체에 투여하여 피부 자극을 완화 또는 억제시키는 방법을 제공한다. 이와 관련하여, 피부자극의 원인 질환 및 병리상태는 본 조성물 및 방법을 사용하여 예방 또는 치료될 수 있다.In another aspect, there is provided a method of alleviating or inhibiting skin irritation by administering the composition of the present invention to cells, tissues, organs, or individuals exhibiting skin irritation by heavy metal or the like. In this regard, the causative disease and pathology of skin irritation can be prevented or treated using the compositions and methods.
본 발명에서 용어, '개체'란 피부자극을 완화하거나 피부를 보호할 필요성이 있는 인간을 포함한 모든 동물을 의미하고 피부 자극을 동반하는 질환의 질환자 또는 민감성 피부 보유자를 포함한다. 본 발명의 조성물을 개체에 투여함으로써, 피부자극을 완화 또는 억제, 피부를 보호할 수 있다.The term 'individual' in the present invention means all animals, including humans, who need to alleviate skin irritation or protect the skin, and includes diseased or sensitive skin carriers of diseases accompanied by skin irritation. By administering the composition of the present invention to an individual, skin irritation can be alleviated or suppressed, and the skin can be protected.
본 발명의 피부자극 완화 및 피부보호용 조성물이 식품 조성물인 경우, 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호에 사용될 수 있다. When the composition for alleviating skin irritation and protecting the skin of the present invention is a food composition, it can be used for skin irritation alleviation and skin protection derived from environmental pollution factors.
본 발명의 식품 조성물은 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health food), 식품 첨가제(food additives) 및 사료 등의 모든 형태를 포함하며, 인간 또는 가축을 비롯한 동물을 취식대상으로 한다. 상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.The food composition of the present invention includes all forms of functional foods, nutritional supplements, health foods, food additives, and feeds, and includes animals including humans or livestock. Subject to eating. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
예를 들면, 건강식품으로는 본 발명의 메이스리그난 또는 육두구 추출물 또는 이의 염 자체를 차, 주스 및 드링크의 형태로 제조하여 음용하도록 하거나, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 본 발명의 메이스리그난 또는 육두구 추출물과 피부 자극에 개선효과가 있다고 알려진 공지의 물질 또는 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.For example, as a health food, the mace lignan or nutmeg extract of the present invention or a salt thereof may be prepared in the form of tea, juice, and drink for drinking or granulated, encapsulated, and powdered. In addition, it may be prepared in the form of a composition by mixing together with the mays lignan or nutmeg extract of the present invention and a known substance or active ingredient known to have an improvement effect on skin irritation.
상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 일반 식품으로는 이에 한정되지 않지만 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마아말레이드 등), 어류, 육류 및 그 가공식품(예: 햄, 소시지 콘비이프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게이트, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치이즈 등), 식용식물 유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 육두구 추출물 또는 메이스리그난을 첨가하여 제조할 수 있다. Food compositions of this type can be prepared in various forms according to conventional methods known in the art. Drinks (including alcoholic beverages), fruits and processed foods (e.g. canned fruits, canned foods, jams, marmalades, etc.), fish, meat and processed foods (e.g. ham, sausages) Corn beef, etc.), breads and noodles (e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.), juice, various drinks, cookies, syrup, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , Plant protein, retort food, frozen food, various seasonings (eg miso, soy sauce, sauce, etc.) can be prepared by adding nutmeg extract or mace lignan.
또한, 영양보조제로는 이에 한정되지 않지만 캡슐, 타블렛, 환 등에 육두구 추출물 또는 메이스리그난을 첨가하여 제조할 수 있다. 또한, 건강기능식품으로는 이에 한정되지 않지만 예를 들면, 육두구 추출물 또는 메이스리그난 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용(건강음료)할 수 있도록 액상화, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 육두구 추출물 또는 메이스리그난을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다. 또한, 육두구 추출물 또는 메이스리그난과 피부자극 완화 및 피부보호용 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.In addition, as a nutritional supplement, but not limited to, it can be prepared by adding nutmeg extract or mace lignan to capsules, tablets, pills, and the like. In addition, the health functional food is not limited to this, for example, nutmeg extract or mace lignan itself is prepared in the form of tea, juice and drink to be liquefied, granulated, encapsulated and powdered for drinking (health drink). Can be consumed. In addition, in order to use nutmeg extract or mace lignan in the form of food additives, it can be prepared and used in powder or concentrate form. In addition, it can be prepared in the form of a composition by mixing with nutmeg extract or known active ingredients known to have a skin irritation and skin protection effect with mace lignan.
본 발명의 피부자극 완화 및 피부보호용 조성물이 건강음료 조성물로 이용되는 경우, 상기 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL 당 일반적으로 약 0.01 ∼ 0.04 g, 바람직하게는 약 0.02 ∼ 0.03 g 이다.When the composition for relieving skin irritation and protecting the skin of the present invention is used as a health drink composition, the health drink composition may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients, as in a conventional beverage. The natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; Sugar alcohols such as xylitol, sorbitol, and erythritol. Sweeteners include natural sweeteners such as taumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g per 100 mL of the composition of the present invention, preferably about 0.02 to 0.03 g.
육두구 추출물 또는 메이스리그난은 피부자극 완화 및 피부보호용 식품 조성물의 유효성분으로 함유될 수 있는데, 그 양은 피부자극 완화 및 피부보호 작용을 달성하기에 유효한 양으로 특별히 한정되는 것은 아니나, 전체 조성물 총 중량에 대하여 0.01 내지 100 중량%일 수 있으며, 0.01 내지 50 중량% 인것이 바람직하다. 본 발명의 식품 조성물은 육두구 추출물 또는 메이스리그난과 함께 피부자극 완화 및 피부보호에 효과가 있는 것으로 알려진 다른 활성 성분과 함께 혼합하여 제조될 수 있다.Nutmeg extract or mace lignan may be contained as an active ingredient in a food composition for skin irritation relief and skin protection, the amount of which is not particularly limited to an amount effective to achieve skin irritation relief and skin protection, but is not limited to the total weight of the total composition. It may be 0.01 to 100% by weight, preferably 0.01 to 50% by weight. The food composition of the present invention can be prepared by mixing with nutmeg extract or macy lignan together with other active ingredients known to be effective in skin irritation and skin protection.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acids, salts of pectic acids, alginic acids, salts of alginic acids, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, Glycerin, alcohol or carbonic acid. In addition, the health food of the present invention may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients may be used independently or in combination. The proportion of these additives is not critical, but is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
또한, 본 발명의 피부자극 완화 및 피부보호용 조성물은 화장품 조성물일 수 있다. 본 발명의 화장료 조성물은 본 발명의 메이스리그난 또는 육두구 추출물 또는 이들의 염과 함께 화장료 조성물의 제조 분야에서 일반적으로 사용되는 하나 이상의 부형제 및 첨가제를 포함하여 당 분야의 공지의 방법에 따라 용이하게 제조될 수 있다. In addition, the composition for alleviating skin irritation and protecting the skin of the present invention may be a cosmetic composition. The cosmetic composition of the present invention can be easily prepared according to methods known in the art, including one or more excipients and additives commonly used in the field of manufacturing cosmetic compositions with the mace lignan or nutmeg extract of the present invention or salts thereof. You can.
본 발명의 화장품 조성물은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하며 피부학적으로 허용 가능한 부형제와 함께 기초 화장품 조성물(화장수, 크림, 에센스, 클렌징 폼 및 클렌징 워터와 같은 세안제, 팩, 보디오일), 색조 화장품 조성물(화운데이션, 립스틱, 마스카라, 메이크업 베이스), 두발 제품 조성물(샴푸, 린스, 헤어컨디셔너, 헤어젤) 및 비누 등의 형태로 제조될 수 있다. 상기 부형제로는 이에 한정되지는 않으나 예를 들어, 피부연화제, 피부 침투 증강제, 착색제, 방향제, 유화제, 농화제 및 용매를 포함할 수 있다. 또한, 향료, 색소, 살균제, 산화방지제, 방부제 및 보습제 등을 추가로 포함할 수 있으며, 물성개선을 목적으로 점증제, 무기염류, 합성 고분자 물질 등을 포함할 수 있다.The cosmetic composition of the present invention contains a nutmeg extract or mace lignan as an active ingredient and a basic cosmetic composition (face wash, cream, essence, cleansing foam and cleansing water-like cleansers, packs, and vodioyl), along with dermatologically acceptable excipients, It can be prepared in the form of color cosmetic composition (foundation, lipstick, mascara, makeup base), hair product composition (shampoo, conditioner, hair conditioner, hair gel) and soap. The excipients include, but are not limited to, for example, skin emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents. In addition, it may further include fragrances, pigments, fungicides, antioxidants, preservatives and moisturizers, and may include thickeners, inorganic salts, synthetic polymer materials, etc. for the purpose of improving physical properties.
상기 부형제로는 이에 한정되지는 않으나 예를 들어, 피부연화제, 피부 침투 증강제, 착색제, 방향제, 유화제, 농화제 및 용매를 포함할 수 있다. 또한, 향료, 색소, 살균제, 산화방지제, 방부제 및 보습제 등을 추가로 포함할 수 있으며, 물성개선을 목적으로 점증제, 무기염류, 합성 고분자 물질 등을 포함할 수 있다. 예를 들면, 본 발명의 화장품 조성물로 세안제 및 비누를 제조하는 경우에는 통상의 세안제 및 비누 베이스에 육두구 추출물 또는 메이스리그난을 첨가하여 용이하게 제조할 수 있다. 크림을 제조하는 경우에는 일반적인 수중유적형(O/W)의 크림베이스에 육두구 추출물 또는 메이스리그난 또는 이의 염을 첨가하여 제조할 수 있다. 여기에 향료, 킬레이트제, 색소, 산화방지제, 방부제 등과 물성개선을 목적으로 한 단백질, 미네랄, 비타민 등 합성 또는 천연소재를 추가로 첨가할 수 있다.The excipients include, but are not limited to, for example, skin emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents. In addition, it may further include fragrances, pigments, fungicides, antioxidants, preservatives and moisturizers, and may include thickeners, inorganic salts, synthetic polymer materials, etc. for the purpose of improving physical properties. For example, in the case of preparing a cleanser and soap with the cosmetic composition of the present invention, it can be easily prepared by adding a nutmeg extract or mace lignan to a conventional cleanser and soap base. In the case of manufacturing the cream, it can be prepared by adding a nutmeg extract or mace lignan or a salt thereof to a cream base of a general oil-in-water type (O / W). Synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties may be additionally added to fragrances, chelating agents, pigments, antioxidants, preservatives, and the like.
예를 들면, 본 발명의 메이스리그난 또는 육두구 추출물을 포함하는 세안제 및 비누를 제조하는 경우에는 통상의 세안제 및 비누 베이스에 메이스리그난 또는 육두구 추출물을 첨가하여 용이하게 제조할 수 있다. 크림을 제조하는 경우에는 일반적인 수중유적형(O/W)의 크림베이스에 메이스리그난 또는 육두구 추출물을 첨가하여 제조할 수 있다. 여기에 향료, 킬레이트제, 색소, 산화방지제, 방부제 등과 물성개선을 목적으로 한 단백질, 미네랄, 비타민 등 합성 또는 천연소재를 추가로 첨가할 수 있다.For example, in the case of preparing the face wash and soap containing the mace lignan or nutmeg extract of the present invention, it can be easily prepared by adding the mace lignan or nutmeg extract to the conventional face wash and soap base. In the case of manufacturing the cream, it may be prepared by adding mace lignan or nutmeg extract to a cream base of a general oil-in-water type (O / W). Synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties may be additionally added to fragrances, chelating agents, pigments, antioxidants, preservatives, and the like.
본 발명의 화장품 조성물에 함유되는 육두구 추출물 또는 메이스리그난의 함량은 이에 한정되지 않지만 전체 조성물 총중량에 대하여 0.001 내지 10 중량%인 것이 바람직하고, 0.01 내지 5중량%인 것이 더욱 바람직하다. 상기 함량이 0.001중량% 미만에서는 목적하는 항노화 또는 주름개선 효과를 기대할 수 없고, 10중량% 초과에서는 안전성 또는 제형상의 제조에 어려움이 있을 수 있다.The content of nutmeg extract or mayslignan contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight relative to the total weight of the total composition. If the content is less than 0.001% by weight, the desired anti-aging or anti-wrinkle effect cannot be expected, and when it is more than 10% by weight, there may be difficulties in safety or preparation of the formulation.
또한, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부오염 방지용 조성물을 제공한다.In addition, the present invention provides a composition for preventing skin contamination derived from environmental pollutants containing nutmeg extract or mace lignan as an active ingredient.
상기 조성물은 약학적 조성물, 화장료 조성물, 및 식품 조성물의 형태로 제공될 수 있다. 이에 대한 설명은 상기 전술한 바와 같다.The composition may be provided in the form of a pharmaceutical composition, cosmetic composition, and food composition. Description of this is as described above.
본 발명은 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 제제를 제조하기 위한 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도를 제공한다.The present invention provides a use of mace lignan or a nutmeg extract containing the same for preparing a preparation for skin irritation relief and skin protection derived from environmental pollution factors.
또한, 본 발명은 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 방법을 제공한다.In addition, the present invention provides a method for alleviating skin irritation and protecting skin induced from environmental pollutants, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof. do.
본 발명은 환경오염인자로부터 유도되는 피부오염 방지용 제제를 제조하기 위한 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도를 제공한다.The present invention provides the use of mace lignan or nutmeg extract containing the same for preparing a formulation for preventing skin contamination derived from environmental pollution factors.
본 발명은 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부오염 방지 방법을 제공한다.The present invention provides a method for preventing skin contamination derived from environmental pollutants, characterized by administering an effective amount of a composition containing mace lignan or nutmeg extract containing it as an active ingredient to an individual in need thereof.
본 발명의 상기 ‘유효량’이란 개체에게 투여하였을 때, 피부자극 및 피부손상 또는 피부 오염의 개선, 치료, 예방, 검출, 진단 또는 피부자극 및 피부손상 또는 피부 오염의 억제 또는 감소 효과를 나타내는 양을 말하며, 상기‘개체’란 동물, 바람직하게는 포유동물, 특히 인간을 포함하는 동물일 수 있으며, 동물에서 유래한 세포, 조직, 기관 등일 수도 있다. 상기 개체는 상기 효과가 필요한 환자(patient) 일 수 있다.The 'effective amount' of the present invention, when administered to an individual, improves, treats, prevents, detects, diagnoses skin irritation and skin damage or skin contamination, or suppresses or reduces skin irritation and skin damage or skin contamination. In other words, the 'individual' may be an animal, preferably a mammal, particularly an animal including a human, or may be cells, tissues, organs, etc. derived from an animal. The subject may be a patient in need of the effect.
본 발명의 상기 ‘치료’는 피부자극 및 피부손상 또는 피부 오염 또는 피부자극 및 피부손상 또는 피부 오염의 증상을 개선시키는 것을 포괄적으로 지칭하고, 이는 이러한 질환을 치유하거나, 실질적으로 예방하거나, 또는 상태를 개선시키는 것을 포함할 수 있으며, 피부자극 및 피부손상 또는 피부 오염으로부터 비롯된 한 가지 증상 또는 대부분의 증상을 완화시키거나, 치유하거나 예방하는 것을 포함하나, 이에 제한되는 것은 아니다.The 'treatment' of the present invention broadly refers to improving the symptoms of skin irritation and skin damage or skin contamination or skin irritation and skin damage or skin contamination, which heals, substantially prevents, or prevents these diseases May include, but is not limited to, alleviating, healing or preventing one symptom or most symptoms resulting from skin irritation and skin damage or skin contamination.
본 발명의 용어 ‘~을 포함하는(comprising)’이란 ‘함유하는’ 또는 ‘특징으로 하는’과 동일하게 사용되며, 조성물 또는 방법에 있어서, 언급되지 않은 추가적인 성분 요소 또는 방법 단계 등을 배제하지 않는다. 용어 ‘~로 구성되는(consisting of)’이란 별도로 기재되지 않은 추가적인 요소, 단계 또는 성분 등을 제외하는 것을 의미한다. 용어 ‘필수적으로 구성되는(essentially consisting of)’이란 조성물 또는 방법의 범위에 있어서, 기재된 성분 요소 또는 단계와 더불어 이의 기본적인 특성에 실질적으로 영향을 미치지 않는 성분 요소 또는 단계 등을 포함하는 것을 의미한다.The term 'comprising' of the present invention is used in the same way as 'containing' or 'as a feature', and does not exclude additional component elements or method steps not mentioned in the composition or method. . The term 'consisting of' means excluding additional elements, steps or ingredients, which are not described separately. The term 'essentially consisting of' means that in the scope of a composition or method, it includes the described component elements or steps, as well as component elements or steps that do not materially affect its basic properties.
본 발명에 따른 육두구 추출물 또는 메이스리그난은 피부 세포 내에서 XRE에 의해 매개되는 CYP1A1 등과 같은 유전자의 발현량을 감소시킴으로써, 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 기능이 탁월하여 식품, 화장품 조성물에 사용될 수 있다.Nutmeg extract or mace lignan according to the present invention reduces the amount of expression of genes such as CYP1A1 mediated by XRE in skin cells, and thus has excellent skin irritation and skin protection functions derived from environmental pollutants, and is a food and cosmetic composition. Can be used for
도 1은 육두구 추출물의 BaP 처리에 따른 XRE에 의해 매개되는 luciferase 증가 억제 활성 결과를 나타낸 것이다. Figure 1 shows the results of the inhibitory activity of luciferase increase mediated by XRE according to BaP treatment of nutmeg extract.
도 2는 육두구 추출물의 BaP 처리에 따른 CYP1A1 발현량 증가 저해 활성결과를 나타낸 것이다. Figure 2 shows the results of the inhibitory activity of CYP1A1 expression increase according to BaP treatment of nutmeg extract.
도 3은 메이스리그난의 BaP 처리에 따른 XRE에 의해 매개되는 luciferase 증가 억제 활성 결과를 나타낸 것이다.Figure 3 shows the results of the inhibitory activity of increased luciferase mediated by XRE according to BaP treatment of mace lignan.
도 4는 메이스리그난의 BaP 처리에 따른 CYP1A1 발현량 증가 저해 활성 결과를 나타낸 것이다.Figure 4 shows the results of the inhibitory activity of increased expression of CYP1A1 according to BaP treatment of mace lignan.
도 5는 메이스리그난의 f처리에 의한 XRE에 의해 매개되는 luciferase 증가 억제 활성 결과를 나타낸 것이다.Figure 5 shows the results of the inhibitory activity of increased luciferase mediated by XRE by f treatment of macylignan.
도 6은 메이스리그난의 PM처리에 의한 AhR mRNA 발현량 증가 저해 활성 결과를 나타낸 것이다.6 shows the results of the inhibitory activity of increased expression of AhR mRNA by PM treatment of mays lignan.
도 7은 메이스리그난의 PM처리에 의한 CYP1A1, CYP1B1, CYP1A2 mRNA 발현량 증가 저해 활성 결과를 나타낸 것이다.Figure 7 shows the results of the inhibitory activity of increased expression of CYP1A1, CYP1B1, CYP1A2 mRNA by PM treatment of mays lignan.
도 8은 메이스리그난의 PM처리에 의한 피부 표피층 손상 개선 효과 결과를 나타낸 것이다.Figure 8 shows the results of the effect of improving skin epidermal layer damage by PM treatment of mace lignan.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.However, the following examples are only to illustrate the present invention, the content of the present invention is not limited to the following examples.
실시예 1: 육두구 추출물의 제조Example 1: Preparation of nutmeg extract
1-1. 메탄올 추출물1-1. Methanol extract
건조된 육두구를 믹서로 분쇄한 다음, 분쇄한 육두구 100 g을 100% 메탄올 1 L에 넣고 3시간 상온에서 추출하였다. 추출된 시료는 와트만(Whatman) 2번 여과지로 감압여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거한 후 육두구 메탄올 추출물을 얻었다.After pulverizing the dried nutmeg with a mixer, 100 g of the ground nutmeg was added to 1 L of 100% methanol and extracted at room temperature for 3 hours. The extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component to obtain a nutmeg methanol extract.
1-2. 에탄올 추출물1-2. Ethanol extract
100% 에탄올, 70% 에탄올, 50% 에탄올, 30% 에탄올을 사용하여 50℃에서 추출하였다는 점을 제외하고는 상기 실시예 1-1과 동일한 방법으로 수행하여 육두구 에탄올 추출물을 얻었다. A nutmeg ethanol extract was obtained in the same manner as in Example 1-1, except that it was extracted at 50 ° C using 100% ethanol, 70% ethanol, 50% ethanol, and 30% ethanol.
1-3. 에틸아세테이트 추출물1-3. Ethyl acetate extract
100% 에틸아세테이트를 사용하였다는 점을 제외하고는 상기 실시예 1-1과 동일한 방법으로 수행하여 육두구 에틸아세테이트 추출물을 얻었다. A nutmeg ethyl acetate extract was obtained in the same manner as in Example 1-1, except that 100% ethyl acetate was used.
1-4. 헥산 추출물1-4. Hexane extract
100% 헥산을 사용하였다는 점을 제외하고는 상기 실시예 1-1과 동일한 방법으로 수행하여 육두구 헥산 추출물을 얻었다. A nutmeg hexane extract was obtained in the same manner as in Example 1-1, except that 100% hexane was used.
1-5. 열수 추출물1-5. Hot water extract
물을 사용하였다는 점과 80℃ 조건을 제외하고는 상기 실시예 1-2와 동일한 방법으로 수행하여 육두구 열수 추출물을 얻었다. A nutmeg hot water extract was obtained in the same manner as in Example 1-2, except that water was used and the condition was 80 ° C.
1-6. 초고압 추출물1-6. Ultra high pressure extract
건조된 육두구를 믹서로 분쇄한 다음, 18% 에탄올 76 mL을 폴리에틸렌(polyethylene) 팩에 넣고 밀봉한 후 초고압 추출장치(Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan)를 이용하여 추출하였다. 초고압 추출 조건은 추출압력이 320 MPa, 추출시간은 5 min 이였다. 이후, 상기 실시예 1-1)과 동일한 방법을 수행하여 육두구 초고압 추출물을 얻었다. After grinding the dried nutmeg with a mixer, 76 mL of 18% ethanol was placed in a polyethylene pack, sealed, and then extracted using an ultra high pressure extraction device (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan). The extraction conditions of the ultra-high pressure were 320 MPa and the extraction time was 5 min. Thereafter, the same method as in Example 1-1) was performed to obtain a nutmeg ultra-high pressure extract.
1-7. 초임계 추출물1-7. Supercritical extract
건조된 육두구를 믹서로 분쇄 한 다음, 분쇄한 육두구 시료 1 g을 시료 카트리지에 충전하고 초임계 장치(SFX 3560, Isco Inc., Lincoln, NE, USA)를 이용하여 추출하였다. 초임계 유체 추출 조건은 추출 압력이 40 MPa, 추출 온도는 50, 초임계 이산화탄소의 유속은 60 mL/min, 추출 시간은 60 min이었다. 초임계 추출이 완료되면, 추출 장치의 압력을 낮춰 초임계 유체 상태를 해제하여 육두구 초임계 추출물을 얻었다.The dried nutmeg was ground with a mixer, and then 1 g of the ground nutmeg sample was charged into a sample cartridge and extracted using a supercritical device (SFX 3560, Isco Inc., Lincoln, NE, USA). The supercritical fluid extraction conditions were an extraction pressure of 40 MPa, an extraction temperature of 50, a supercritical carbon dioxide flow rate of 60 mL / min, and an extraction time of 60 min. When the supercritical extraction was completed, the pressure of the extraction device was lowered to release the supercritical fluid state, thereby obtaining a nutmeg supercritical extract.
1-8. 아임계 추출물1-8. Subcritical extract
분쇄한 육두구 50 g을 1 L 물과 함께 아임계 추출장치(Biovan, Gyeonggi, Korea)의 아임계수 반응기에 넣고 밀폐하였다. 밀폐 후, 반응기의 온도를 200℃로 압력은 20 MPa로 상승시켰으며, 반응기의 온도가 200℃에 도달하면 상기 온도를 20분간 유지하여 추출을 하였다. 20분 후 추출물의 냉각수가 공급되는 저장탱크로 이송하여 30℃까지 급속 냉각시킨 후, 부유 잔사를 분리하기 위해 3,600 rpm으로 30분 동안 원심분리하여 상등액만 취하였다. 동결건조기(ilShin Lab Co. Ltd., Seoul, Korea)를 이용하여 물을 전부 제거함으로써 육두구 아임계 추출물을 제조하였다.50 g of crushed nutmeg was placed in a subcritical water reactor of a subcritical extraction device (Biovan, Gyeonggi, Korea) together with 1 L water and sealed. After sealing, the temperature of the reactor was increased to 200 ° C and the pressure was increased to 20 MPa, and when the temperature of the reactor reached 200 ° C, the temperature was maintained for 20 minutes to extract. After 20 minutes, the extract was transferred to a storage tank to which cooling water is supplied, rapidly cooled to 30 ° C, and centrifuged at 3,600 rpm for 30 minutes to separate the floating residue, and only the supernatant was taken. A subcritical extract of nutmeg was prepared by removing all water using a freeze dryer (ilShin Lab Co. Ltd., Seoul, Korea).
실시예Example 2:  2: 메이스리그난의Mace League 분리 및 구조결정 Separation and structure determination
상기 실시예 1-2에서 100% 에탄올을 사용하여 얻은 농축된 육두구 에탄올 추출물을 에틸아세테이트, 부탄올, 물로 분획하였다. 에틸아세테이트 분획물(4.2 g)을 실리카겔 컬럼 크로마토그래피를 이용하여 헥산과 에틸아세테이트를 10:1(v/v)의 비율로 혼합한 용매로 용출시켜 분획물 Ⅲ(1 g)를 얻었다. 분획물 Ⅲ를 헥산과 에틸아세테이트 20:1(v/v)의 비율로 혼합한 용매로 컬럼 크로마토그래피하여 분획물 Ⅲ-B(0.52 g)을 얻었다. 이후, 분획물 Ⅲ-B를 Rp-18 컬럼 크로마토그래피(Lichroprep RP-18 25~40 um; Merck & Co.)를 이용하여 80% 메탄올로 용출시켜 단일물질 분획 Ⅲ-B-2(0.5 g)을 얻었다.In Example 1-2, the concentrated nutmeg ethanol extract obtained using 100% ethanol was partitioned into ethyl acetate, butanol, and water. The ethyl acetate fraction (4.2 g) was eluted with a solvent mixed with hexane and ethyl acetate at a ratio of 10: 1 (v / v) using silica gel column chromatography to obtain fraction III (1 g). Fraction III was subjected to column chromatography with a solvent mixed with hexane and ethyl acetate at a ratio of 20: 1 (v / v) to obtain fraction III-B (0.52 g). Then, fraction III-B was eluted with 80% methanol using Rp-18 column chromatography (Lichroprep RP-18 25-40 um; Merck & Co.) to obtain single substance fraction III-B-2 (0.5 g). Got.
상기에서 분리된 단일물질 Ⅲ-B-2의 구조를 결정하기 위하여 1H-NMR 스펙트럼과 13C-NMR 스펙트럼을 각각 600 MHz와 150 MHz(용매: DMSO)에서 측정하였다. 13C-NMR 스펙트럼과 1H-NMR 스펙트럼의 결과를 토대로 1H- 1H의 상관관계와 1H- 13C의 상관관계를 측정하기 위하여 1H- 1H COSY 스펙트럼과 1H- 13C HMBC 스펙트럼을 측정하였다. 상기 분리된 단일물질의 질량 분석을 위해 EI/MS로 측정한 결과, 본 화합물은 EI/MS에서 [M]+가 m/z 328에서 관측되어 분자량이 328로 판명되었고, 분자식은 C 20H 24O 4이었다. 아울러, 상기 분리된 단일물질 Ⅲ-B-2 20mg을 클로로포름(CHCl 3) 2ml에 녹인 후 Polarimeter(Automatic Polarimeter, APⅢ-589, Rodulph, NJ, USA)로 비선광도([α]D) 값을 측정한 결과 [α]D = +4.0 (CHCl 3 , c=1.0)으로 나타났다. 이상의 1H-NMR, 13C-NMR, 1H- 1H COSY, 1H- 13C HMBC, EI/MS 및 [α]D 에 대한 결과와 기존에 발표된 연구보고(Woo, W.S. et al., Phytochemistry, 26: 1542-1543, 1987)를 비교 분석하여 동정한 결과, 분리된 단일 물질은 화학식 1로 표시되는 메이스리그난(macelignan)인 것으로 확인되었다. 1 H-NMR spectrum and 13 C-NMR spectrum were measured at 600 MHz and 150 MHz (solvent: DMSO), respectively, in order to determine the structure of the isolated single substance III-B-2. 13 C-NMR spectrum and the 1 H-NMR 1 H- 1 H COSY spectrum and 1 H- 13 to measure the correlation of the correlation of the 1 H- 1 H, based on the result of the spectrum related to the 1 H- 13 C HMBC C Spectra were measured. As a result of measurement by EI / MS for mass spectrometry of the isolated single substance, [M] + was observed at m / z 328 in EI / MS and the molecular weight was found to be 328, and the molecular formula was C 20 H 24 It was O 4 . In addition, after dissolving 20 mg of the separated single substance Ⅲ-B-2 in 2 ml of chloroform (CHCl 3 ), the non-linearity ([α] D) value was measured with a Polarimeter (Automatic Polarimeter, APIII-589, Rodulph, NJ, USA). As a result, [α] D = +4.0 (CHCl 3 , c = 1.0). Results for the above 1 H-NMR, 13 C-NMR, 1 H- 1 H COSY, 1 H- 13 C HMBC, EI / MS and [α] D and previously published research reports (Woo, WS et al. , Phytochemistry, 26: 1542-1543, 1987). As a result, it was confirmed that the isolated single substance was macelignan represented by Chemical Formula 1.
[화학식 1] [Formula 1]
Figure PCTKR2019014101-appb-img-000002
Figure PCTKR2019014101-appb-img-000002
실시예 3: 육두구 추출물의 BaP 처리에 따른 XRE에 의해 매개되는 luciferase 증가 억제 활성Example 3: XP-mediated luciferase increase inhibitory activity according to BaP treatment of nutmeg extract
COS-7 원숭이 신장세포 (ATCC, Manassas, VA, USA) 세포를 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA)가 포함된 Dulbecco's modified Eagle's media (DMEM; Hyclone)에서 배양하여 24-웰 플레이트에 24시간 이상 배양하였다. Transfection을 위해 혈청이 없는 DMEM (Hyclone)에 plus reagent (Aptabio, Gyeonggi, Korea)와 XRE plasmid를 함께 섞고 15분간 incubation 시켰다. 그 후, lipofecter reagent (Aptabio)를 혼합하여 상온에 다시 15분간 incubation시킨 다음 세포에 처리하였다. 4 시간 후, 10% FBS (Hyclone)이 포함된 DMEM (Hyclone)에서 세포를 24 시간 안정화시켰다. 안정화 후, 다환 방향족 탄화수소에 속하는 물질 benzo(a)pyrene (BaP; Sigma-aldrich, St. Louis, MO, USA) 5 μM와 함께 실시예 1-2)에서 제조한 육두구 100% 에탄올 추출물을 0.5과 1 μg/mL으로 처리하였다. 24 시간이 지난 후, proteinase inhibitor cocktail (Sigma-aldrich)이 포함된 NP-40 lysis buffer (Elpis, Daejeon, Korea)로 세포를 용해시켰다. Luciferase 활성 정도를 luciferase substrate (Promega, Madison, WI, USA)를 넣어준 다음 Microlumateplus LB 96V luminometer (Berthlod, Wildbab, Germany)로 사용하여 측정하였다.COS-7 monkey kidney cells (ATCC, Manassas, VA, USA) were cultured in Dulbecco's modified Eagle's media (DMEM; Hyclone) containing 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA) 24- Incubated in well plates for 24 hours or more. For transfection, serum-free DMEM (Hyclone) was mixed with plus reagent (Aptabio, Gyeonggi, Korea) and XRE plasmid and incubated for 15 minutes. Then, the lipofecter reagent (Aptabio) was mixed and incubated for 15 minutes at room temperature, and then treated with cells. After 4 hours, cells were stabilized in DMEM (Hyclone) containing 10% FBS (Hyclone) for 24 hours. After stabilization, the nutmeg 100% ethanol extract prepared in Example 1-2) with 5 μM of benzo (a) pyrene (BaP; Sigma-aldrich, St. Louis, MO, USA) belonging to a polycyclic aromatic hydrocarbon was added to 0.5 and Treatment was at 1 μg / mL. After 24 hours, cells were lysed with NP-40 lysis buffer (Elpis, Daejeon, Korea) containing proteinase inhibitor cocktail (Sigma-aldrich). Luciferase activity was measured using a luciferase substrate (Promega, Madison, WI, USA) and then using a Microlumateplus LB 96V luminometer (Berthlod, Wildbab, Germany).
그 결과, 도 1에 나타난 바와 같이, BaP는 XRE 통제하에 있는 luciferase의 활성을 유의적( ## p < 0.01)으로 증가시켰으며, 육두구 추출물을 처리함에 따라 증가한 luciferase 활성이 유의적( ** p < 0.01)으로 감소하였다. 이는 본 발명의 육두구 추출물이 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다. As a result, as shown in Figure 1, BaP significantly increased the activity of luciferase under XRE control ( ## p <0.01), and increased luciferase activity was significantly ( ** p <0.01). This means that the nutmeg extract of the present invention effectively reduces skin irritation caused by environmental pollution factors.
실시예 4: 육두구 추출물의 BaP 처리에 따른 CYP1A1 발현량 증가 저해 활성Example 4: Inhibitory activity of CYP1A1 expression increase according to BaP treatment of nutmeg extract
피부 각질세포인 HaCaT (ATCC)을 10% FBS (Hyclone)가 함유된 DMEM (Hyclone)와 함께 6-웰 플레이트에 2 × 10 5 cell/mL이 되도록 넣었다. 세포밀도가 약 80~85%가 되었을 때, 5 μM BaP(Sigma-aldrich)와 함께 실시예 1-2의 육두구 100% 에탄올 추출물을 0.5와 1 μg/mL로 24시간 처리하였다. 배양이 끝난 뒤, TRIzol시약(Takara, Tokyo, Japan)을 사용하여 총 RNA를 분리하였다. 분리한 총 RNA는 나노드랍(NanoDrop 1000; Thermo Fisher Scientific Inc., MA, USA)을 이용하여 정량하였다. 정량된 16 μL RNA를 Reverse Transcriptase Premix (Elpis)와 PCR 기계(Gene Amp PCR System 2700; Applied Biosystems, MA, USA)를 이용하여 42℃ 55분, 70℃ 15분의 조건에서 cDNA로 합성하였다. 16 μL의 생성된 cDNA 중 3 μL의 cDNA, 하기의 특정 프라이머(Bioneer, Daejeon, Korea) 그리고 PCR premix (Elpis)로 95℃에서 30초, 60℃에서 1분, 72℃에서 1분을 30번 반복하여 PCR을 수행하였다. PCR로 인해 증폭된 cDNA를 1.5% agarose gel로 전기영동하여 분리하였으며, G;BOX EF imaging system (Syngene)을 이용하여 cDNA band를 확인하였다. 그 결과를 도 2에 나타내었다.The skin keratinocytes HaCaT (ATCC) was placed in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone) to 2 x 10 5 cells / mL. When the cell density was about 80-85%, the nutmeg 100% ethanol extract of Example 1-2 was treated with 0.5 and 1 μg / mL for 24 hours with 5 μM BaP (Sigma-aldrich). After incubation, total RNA was isolated using a TRIzol reagent (Takara, Tokyo, Japan). Total RNA isolated was quantified using a nanodrop (NanoDrop 1000; Thermo Fisher Scientific Inc., MA, USA). Quantitative 16 μL RNA was synthesized by cDNA under conditions of 42 ° C 55 minutes and 70 ° C 15 minutes using Reverse Transcriptase Premix (Elpis) and PCR machine (Gene Amp PCR System 2700; Applied Biosystems, MA, USA). Of 16 cLNA generated cDNA, 3 μL cDNA, the following specific primers (Bioneer, Daejeon, Korea) and PCR premix (Elpis) at 95 ° C for 30 seconds, 60 ° C for 1 minute, and 72 ° C for 1 minute 30 times PCR was performed repeatedly. The cDNA amplified by PCR was separated by electrophoresis with a 1.5% agarose gel, and the cDNA band was confirmed using a G; BOX EF imaging system (Syngene). The results are shown in FIG. 2.
CYP1A1CYP1A1
Forward primer: 5’-CTACCCAACCCTTCCCTGAAT-3’(서열번호 1)Forward primer: 5'-CTACCCAACCCTTCCCTGAAT-3 '(SEQ ID NO: 1)
Reverse primer: 5’-CGCCCCTTGGGGATGTAAAA-3’(서열번호 2)Reverse primer: 5'-CGCCCCTTGGGGATGTAAAA-3 '(SEQ ID NO: 2)
GAPDHGAPDH
Forward primer: 5’-ATTGTTGCCATCAATGACCC-3’(서열번호 3)Forward primer: 5'-ATTGTTGCCATCAATGACCC-3 '(SEQ ID NO: 3)
Reverse primer: 5’-TCGCCCCACTTGATTTTGGA-3’(서열번호 4)Reverse primer: 5'-TCGCCCCACTTGATTTTGGA-3 '(SEQ ID NO: 4)
그 결과, 도 2에 나타낸 바와 같이 BaP를 처리하였을 때 XRE에 의해 매개되는 CYP1A1 mRNA 발현량이 증가하였으나, 육두구 추출물을 처리함에 따라 농도 의존적으로 감소하였다. 이는 본 발명의 육두구 추출물이 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다. As a result, as shown in FIG. 2, when the BaP treatment was performed, the expression level of CYP1A1 mRNA mediated by XRE increased, but it decreased in a concentration-dependent manner as the nutmeg extract was treated. This means that the nutmeg extract of the present invention effectively reduces skin irritation caused by environmental pollution factors.
실시예 5: 육두구 추출물의 PM 처리에 따른 XRE에 의해 매개되는 luciferase 증가 억제 활성Example 5: XRE-mediated luciferase increase inhibitory activity according to PM treatment of nutmeg extract
육두구 추출물의 PM으로 유도된 XRE에 의해 매개되는 luciferase 억제 활성을 알아보기 위하여 상기 실시예 1-2에서 제조한 육두구 50% 에탄올 추출물과 100% 에탄올 추출물, 실시예 1-3에서 제조한 육두구 에틸아세테이트 추출물, 실시예 1-4에서 제조한 육두구 헥산 추출물, 실시예 1-5에서 제조한 육두구 열수 추출물을 1 μg/mL로 세포에 처리하고 유도물질을 BaP 대신 표준화된 미세먼지(PM; NIST, Gaithersburg, MD, USA) 100 μg/mL을 사용하였다는 점을 제외하고는 상기 실시예 3과 동일한 방법으로 수행하여 실험을 진행하였다. Nutmeg extract 50% ethanol extract and 100% ethanol extract prepared in Example 1-2, nutmeg ethyl acetate prepared in Example 1-3 to examine the luciferase inhibitory activity mediated by XRE induced by PM of nutmeg extract Extract, nutmeg hexane extract prepared in Example 1-4, Nutmeg hot water extract prepared in Example 1-5 was treated with cells at 1 μg / mL, and inducers were standardized fine dust (PM; NIST, Gaithersburg instead of BaP). , MD, USA) The experiment was carried out in the same manner as in Example 3, except that 100 μg / mL was used.
그 결과, 하기 표 1에 나타난 바와 같이, PM은 XRE 통제 하에 있는 luciferase의 활성을 유의적( ## p < 0.01)으로 증가시켰으며, 육두구 추출물을 처리함에 따라 증가한 luciferase 활성이 유의적( ** p < 0.01)으로 감소하였다. 이는 본 발명의 육두구 추출물이 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다.As a result, as shown in Table 1 below, PM significantly increased the activity of luciferase under XRE control ( ## p <0.01), and the increased luciferase activity was significantly ( ** p <0.01). This means that the nutmeg extract of the present invention effectively reduces skin irritation caused by environmental pollution factors.
group 상대적 luciferase 활성(%)Relative luciferase activity (%)
대조군Control 100.0 ± 4.84100.0 ± 4.84
PM 처리군PM treatment group 271.38 ± 5.99 ## 271.38 ± 5.99 ##
PM + 육두구 50% 에탄올 추출물 처리군PM + Nutmeg 50% ethanol extract treatment group 207.24 ± 2.62 ** 207.24 ± 2.62 **
PM + 육두구 100% 에탄올 추출물 처리군PM + Nutmeg 100% ethanol extract treatment group 186.94 ± 3.21 ** 186.94 ± 3.21 **
PM + 육두구 에틸아세테이트 추출물 처리군PM + Nutmeg ethyl acetate extract treatment group 190.73 ± 9.92 ** 190.73 ± 9.92 **
PM + 육두구 헥산 추출물 처리군PM + Nutmeg hexane extract treatment group 201.79 ± 4.71 ** 201.79 ± 4.71 **
PM + 육두구 열수 추출물 처리군PM + Nutmeg hot water extract treatment group 182.89 ± 3.52 ** 182.89 ± 3.52 **
실시예 6: 메이스리그난의 BaP 처리에 따른 CYP1A1 발현량 증가 저해 활성Example 6: Inhibitory activity of CYP1A1 expression increase according to BaP treatment of maylignan
메이스리그난의 CYP1A1 mRNA 발현량 저해 활성을 알아보기 위하여 상기 실시예 2-1에서 제조한 메이스리그난을 1과 5 μM로 세포에 처리하여 실시예 4와 동일한 방법으로 실험을 진행하였다. In order to investigate the inhibitory activity of CYP1A1 mRNA expression level of mays lignan, the cells were treated with 1 and 5 μM of mays lignan prepared in Example 2-1 to conduct experiments in the same manner as in Example 4.
그 결과, 도 4에 나타낸 바와 같이 BaP를 처리하였을 때 XRE에 의해 매개되는 CYP1A1 mRNA 발현량이 증가하였으나, 메이스리그난을 처리함에 따라 농도 의존적으로 감소하였다. 이는 본 발명의 메이스리그난이 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다. As a result, as shown in FIG. 4, when the BaP treatment was performed, the expression level of CYP1A1 mRNA mediated by XRE increased, but it was decreased in a concentration-dependent manner with the treatment of macylignan. This means that the mac lignan of the present invention effectively reduces skin irritation caused by environmental pollution factors.
실시예 7: 메이스리그난의 PM처리에 의한 XRE에 의해 매개되는 luciferase 증가 억제 활성Example 7: Inhibitory activity of increased luciferase mediated by XRE by PM treatment of mays lignan
메이스리그난의 PM으로 유도된 XRE에 의해 매개되는 luciferase 억제 활성을 알아보기 위하여 상기 실시예 2-1)에서 제조한 메이스리그난을 0.5와 1 μM로 세포에 처리하여 유도물질을 PM 100 μg/mL을 사용하였다는 점을 제외하고는 상기 실시예 3과 동일한 방법으로 수행하여 실험을 진행하였다. To examine the luciferase inhibitory activity mediated by XRE induced by PM of mays lignan, the mace lignan prepared in Example 2-1) was treated with cells at 0.5 and 1 μM to induce the inducer PM 100 μg / mL. The experiment was conducted in the same manner as in Example 3, except that it was used.
그 결과, 도 5에 나타난 바와 같이, PM은 XRE 통제 하에 있는 luciferase의 활성을 유의적( ## p < 0.01)으로 증가시켰으며, 메이스리그난을 처리함에 따라 증가한 luciferase 활성이 유의적( ** p < 0.01)으로 감소하였다. 이는 본 발명의 메이스리그난이 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다.As a result, as shown in FIG. 5, PM increased the activity of luciferase under XRE control significantly ( ## p <0.01), and the increased luciferase activity was significantly ( ** p <0.01). This means that the mac lignan of the present invention effectively reduces skin irritation caused by environmental pollution factors.
실시예 8: 메이스리그난의 PM처리에 의한 AhR mRNA 발현량 증가 저해 활성Example 8: Inhibitory activity of increased expression of AhR mRNA by PM treatment of mace lignan
메이스리그난의 PM으로 유도되는 AhR의 mRNA 발현량 저해 활성을 알아보기 위하여 상기 실시예 2-1에서 제조한 메이스리그난을 0.5와 1 μM로 세포에 처리하여 유도물질을 PM 100 μg/mL을 사용하였다는 점과 AhR primer를 사용한 점을 제외하고는 상기 실시예 4와 동일한 방법으로 실험을 진행하였다. In order to investigate the inhibitory activity of the mRNA expression level of AhR induced by PM of mays lignan, the cells were treated with 0.5 and 1 μM of mays lignan prepared in Example 2-1 to use 100 μg / mL of PM. The experiment was conducted in the same manner as in Example 4, except that the point and the AhR primer were used.
AhRAhR
Forward primer: 5’-CCACTTCAGCCACCATCCAT-3’(서열번호 5)Forward primer: 5'-CCACTTCAGCCACCATCCAT-3 '(SEQ ID NO: 5)
Reverse primer: 5’-AAGCAGGCGTGCATTAGACT-3’(서열번호 6)Reverse primer: 5'-AAGCAGGCGTGCATTAGACT-3 '(SEQ ID NO: 6)
그 결과, 도 6에 나타낸 바와 같이 PM을 처리하였을 때 AhR의 mRNA 발현량이 증가하였으나, 메이스리그난을 처리함에 따라 농도 의존적으로 감소하였다. 이는 본 발명의 메이스리그난이 환경오염인자가 결합할 수 있는 수용체의 mRNA 발현량을 감소시켜 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다.As a result, as shown in FIG. 6, when the PM was treated, the mRNA expression level of AhR was increased, but it was decreased in a concentration-dependent manner with the treatment of macylignan. This means that the mays lignan of the present invention effectively reduces skin irritation caused by environmental pollutants by reducing the mRNA expression level of receptors to which environmental pollutants can bind.
실시예 9: 메이스리그난의 PM처리에 의한 CYP1A1, CYP1B1, CYP1A2 mRNA 발현량 증가 저해 활성Example 9: Inhibitory activity of increased expression of CYP1A1, CYP1B1, CYP1A2 mRNA by PM treatment of mace lignan
메이스리그난의 PM으로 유도되는 CYP1A1, CYP1B1, CYP1A2 mRNA 발현량 저해 활성을 알아보기 위하여 상기 실시예 2-1에서 제조한 메이스리그난을 0.5와 1 μM로 세포에 처리하여 유도물질을 PM 100 μg/mL을 사용하였다는 점과 하기 CYP1B1, CYP1A2 primer를 추가로 사용한 점을 제외하고는 상기 실시예 4와 동일한 방법으로 실험을 진행하였다. To investigate the activity of CYP1A1, CYP1B1, and CYP1A2 mRNA expression induced by PM of mays lignan, the mace lignan prepared in Example 2-1 was treated with cells at 0.5 and 1 μM to induce the inducer PM 100 μg / mL Experiments were conducted in the same manner as in Example 4, except that and CYP1B1 and CYP1A2 primers were additionally used.
CYP1B1CYP1B1
Forward primer: 5’-CTGCGACTCCAGTTGTGAGA-3’(서열번호 7)Forward primer: 5'-CTGCGACTCCAGTTGTGAGA-3 '(SEQ ID NO: 7)
Reverse primer: 5’-AAGGAACTGGGACCTTTGCC-3’(서열번호 8)Reverse primer: 5'-AAGGAACTGGGACCTTTGCC-3 '(SEQ ID NO: 8)
CYP1A2CYP1A2
Forward primer: 5’-GCACTGTCAAGGATGAGCCA-3’(서열번호 9)Forward primer: 5'-GCACTGTCAAGGATGAGCCA-3 '(SEQ ID NO: 9)
Reverse primer: 5’-TGAGTGTTCTTCACGAGGCTG-3’(서열번호 10)Reverse primer: 5'-TGAGTGTTCTTCACGAGGCTG-3 '(SEQ ID NO: 10)
그 결과, 도 7에 나타낸 바와 같이 PM을 처리하였을 때 AhR에 의해 활성화되어 XRE에 의해 매개되는 CYP1A1, CYP1B1, CYP1A2의 mRNA 발현량이 증가하였으나, 메이스리그난을 처리함에 따라 농도 의존적으로 감소하였다. 이는 본 발명의 메이스리그난이 환경오염인자에 의한 피부 자극을 효율적으로 감소시킨다는 것을 의미한다.As a result, as shown in FIG. 7, when the PM was treated, the mRNA expression levels of CYP1A1, CYP1B1, and CYP1A2 activated by AhR and mediated by XRE were increased, but the concentration was decreased depending on the treatment of macylignan. This means that the mac lignan of the present invention effectively reduces skin irritation caused by environmental pollution factors.
실시예 10: 메이스리그난의 PM처리에 의한 피부 표피층 손상 개선 효과Example 10: Effect of improving skin epidermal layer damage by PM treatment of mace lignan
메이스리그난의 PM으로 유도되는 피부 표피층 손상 억제 활성을 알아보기 위하여 3D 인공피부 모델 (Neoderm-ED, 테고사이언스)을 구입하여 실험을 진행하였다. 실험군은 정상군, PM 100 μg/mL 처리군, 메이스리그난 0.5 μM 처리군, 메이스리그난 1 μM 처리군으로 나누었으며 각 군당 6개의 인공피부조직을 사용하였다. Neoderm-ED는 테고사이언스의 제조방법에 따라 제조하였으며, 6시간 동안 테고사이언스에서 제공하는 전용 배지를 이용하여 5% CO 2, 37℃ 조건에서 인공피부조직을 안정화시킨 후 실험을 진행하였다. PM으로 인한 피부 손상은 PM 100 μg/mL을 Neoderm-ED 표면에 well 당 50 μL씩 처리하여 유도하였으며, 정상군에는 DPBS를 같은 용량으로 처리하였다. PM 유도와 동시에 상기 실시예 2-1에서 제조한 메이스리그난을 0.5와 1 μM로 Neoderm-ED의 전용 배지에 처리하여 PM으로 인한 피부손상 개선을 유도하였다. 5% CO 2, 37℃ 조건에서 총 72시간 배양하였으며, 24시간마다 PM과 메이스리그난을 추가로 처리해주었다. 72시간 배양이 끝난 인공피부 조직은 10% 포르말린으로 고정시킨 후 파라핀 블록을 제작했다. 고정시킨 조직을 이용하여 조직학적인 측면에서 메이스리그난의 PM에 의한 피부 손상 개선을 측정하기 위해 헤마톡실린 & 에오신(hematoxylin & eosin) 염색을 실시하였으며, 염색된 조직은 eXcope T500 카메라(DIXI Science, Daejeon, Korea)가 장착된 광화학현미경(CK40; Olympus, Tokyo, Japan)으로 관찰하였다.In order to investigate the activity of inhibiting skin epidermal layer damage induced by PM of Maylignan, a 3D artificial skin model (Neoderm-ED, Tego Science) was purchased and tested. The experimental group was divided into normal group, PM 100 μg / mL treatment group, mace lignan 0.5 μM treatment group, and mace lignan 1 μM treatment group, and 6 artificial skin tissues were used for each group. Neoderm-ED was prepared according to the method of manufacturing the tegoscience, and the experiment was conducted after stabilizing artificial skin tissue at 5% CO 2 and 37 ° C. conditions using a dedicated medium provided by tegoscience for 6 hours. Skin damage caused by PM was induced by treating PM 100 μg / mL with 50 μL per well on the Neoderm-ED surface, and DPBS was treated with the same dose in the normal group. Simultaneously with PM induction, the mace lignan prepared in Example 2-1 was treated with Neoderm-ED's exclusive medium at 0.5 and 1 μM to induce improvement of skin damage due to PM. The cells were cultured for 72 hours at 5% CO 2 and 37 ° C., and PM and mace lignan were further treated every 24 hours. After the 72-hour incubation, the artificial skin tissue was fixed with 10% formalin to produce a paraffin block. Hematoxylin & eosin staining was performed to measure the improvement of skin damage caused by PM of mace lignan from the histological aspect using the fixed tissue, and the stained tissue was eXcope T500 camera (DIXI Science, Daejeon) , Korea) was observed with a photochemical microscope (CK40; Olympus, Tokyo, Japan).
그 결과, 도 8에 나타난 바와 같이, 정상군과 비교하여 PM 처리군에서 피부의 표피층 중 각질층의 구조적 형태학적 변화가 관찰되었으며, 표피층에 속하는 과립층, 유극층, 기저층의 총 두께가 정상군에 비해 매우 감소한 것을 확인하였다. 반대로, 메이스리그난을 처리하였을 때, 각질층의 형태와 각질층을 제외한 표피층의 총 두께가 농도 의존적으로 정상군과 유사하게 회복된 것을 확인하였다. 이는 본 발명의 메이스리그난이 PM으로 인한 피부 표피층의 손상을 억제하고 개선시키는 효과가 있음을 의미한다. As a result, as shown in FIG. 8, structural morphological changes of the stratum corneum of the epidermal layer of the skin were observed in the PM-treated group compared to the normal group, and the total thickness of the granular layer, the polar layer, and the base layer belonging to the epidermal layer compared to the normal group. It was confirmed that it was very reduced. On the contrary, it was confirmed that when the macylignan was treated, the morphology of the stratum corneum and the total thickness of the epidermal layer excluding the stratum corneum were recovered in a concentration-dependent manner similar to the normal group. This means that the machlignan of the present invention has an effect of inhibiting and improving damage to the skin epidermal layer due to PM.
이하, 본 발명에 따른 육두구 추출물 또는 메이스리그난을 유효성분으로 포함하는 피부자극 완화 및 피부보호용 또는 의약품, 식품, 화장품의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다. 피부자극 완화 및 피부보호 활성이 우수한 육두구 추출물 또는 메이스리그난을 가지고 하기와 같은 조성 성분 및 조성비에 따라 제조예 1 내지 3의 의약품, 식품, 화장품을 통상적인 방법에 따라서 제조하였다.Hereinafter, an example of preparing skin stimulation and skin protection or a pharmaceutical, food, or cosmetic product containing nutmeg extract or mace lignan as an active ingredient according to the present invention will be described, but the present invention is not intended to be limited thereto, but only specifically It is. Medicines, foods and cosmetics of Preparation Examples 1 to 3 were prepared according to the following compositional components and composition ratios with nutmeg extract or mace lignan having excellent skin irritation alleviation and skin protection activity.
제조예 1: 의약품Preparation Example 1: Pharmaceutical
1) 산제1) Powder
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 50 mg, 결정셀룰로오즈 2 g을 혼합한 후 통상의 산제 제조방법에 따라서 기밀포에 충진하여 산제를 제조하였다.After mixing the nutmeg extract of Example 1 to 2 or 50 mg of mace lignan and 2 g of crystalline cellulose, a powder was prepared by filling in an airtight bag according to a conventional powder manufacturing method.
2) 정제2) Tablet
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 50 mg, 결정셀룰로오즈 400 mg, 스테아린산 마그네슘 5 mg을 혼합한 후 통상의 정제 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the nutmeg extract of Example 1 to 2, or 50 mg of maylignan, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate, tablets were prepared by tableting according to a conventional tablet manufacturing method.
3) 캡슐제3) Capsule
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 30 mg, 유청단백질 100 mg, 결정셀룰로오즈 400 mg, 스테아린산 마그네슘 6 mg을 혼합한 후 통상의 캡슐제 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the nutmeg extract of Example 1 to 2, or 30 mg of maylignan, whey protein, 100 mg of crystalline cellulose, 400 mg of magnesium stearate, and filling it into a gelatin capsule according to a conventional capsule preparation method, a capsule is prepared. Did.
제조예 2: 식품Preparation Example 2: Food
1) 건강식품의 제조1) Manufacture of health food
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 1000 mg, 비타민 A 아세테이트 70 μL, 비타민 E 1.0 mg, 비타민 B1 0.13 mg, 비타민 B2 0.15 mg, 비타민 B6 0.5 mg, 비타민 B12 0.2 μg, 비타민 C 10 mg, 비오틴 10 μg, 니코틴산아미드 1.7 mg, 엽산 50 μg, 판토텐산 칼슘 0.5 mg, 황산 제1철 1.75 mg, 산화아연 0.82 mg, 탄산마그네슘 25.3 mg, 제1인산칼륨 15 mg, 제2인산칼슘 55 mg, 구연산칼륨 90 mg, 탄산칼슘 100 mg, 염화마그네슘 24.8 mg를 혼합하여 제조할 수 있으며, 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.Nutmeg extract or mays lignan 1000 mg, vitamin A acetate 70 μL, vitamin E 1.0 mg, vitamin B1 0.13 mg, vitamin B2 0.15 mg, vitamin B6 0.5 mg, vitamin B12 0.2 μg, vitamin C 10 mg of Examples 1 to 2 , 10 μg biotin, 1.7 mg nicotinamide, 50 μg folic acid, 0.5 mg calcium pantothenate, 1.75 mg ferrous sulfate, 0.82 mg zinc oxide, 25.3 mg magnesium carbonate, 15 mg potassium phosphate, 55 mg calcium diphosphate, Potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg can be prepared by mixing, and the mixing ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method, and then granulated It can be prepared and used in the preparation of a health food composition according to a conventional method.
2) 건강음료의 제조2) Production of health drinks
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 1000 mg, 구연산 1000 mg, 올리고당 100 g, 매실농축액 2 g, 타우린 1 g에 정제수를 가하여 전체 900 mL 통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2L용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 건강음료 조성물 제조에 사용할 수 있다.Nutmeg extract of Examples 1 to 2 or 1000 mg of maylignan, 1000 mg of citric acid, 100 g of oligosaccharides, 2 g of plum concentrate, and 1 g of taurine were added to purified water to add the above ingredients according to the general method for preparing a health drink of 900 mL. After mixing, after stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered, obtained in a sterilized 2 L container, sealed and sterilized, then refrigerated and then used in the manufacture of a health drink composition.
3) 츄잉껌3) Chewing gum
껌 베이스 20 중량%, 설탕 76.9 중량%, 향료 1 중량% 및 물 2 중량%와 상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 0.1 중량%를 배합하여 통상의 방법으로 츄잉껌을 제조하였다.Chewing gum was prepared by a conventional method by mixing 20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of fragrance, and 2% by weight of water and 0.1% by weight of nutmeg extract or mace lignan of Examples 1 to 2 above.
4) 캔디4) Candy
설탕 60 중량%, 물엿 39.8 중량% 및 향료 0.1 중량%와 상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 0.1 중량%를 배합하여 통상의 방법으로 캔디를 제조하였다.Candy was prepared by a conventional method by mixing 60% by weight of sugar, 39.8% by weight of starch syrup and 0.1% by weight of fragrance and 0.1% by weight of nutmeg extract or maceignan of Examples 1 to 2 above.
5) 비스켓5) Biscuit
박력 1급 25.59 중량%, 중력 1급 22.22 중량%, 정백당 4.80 중량%, 식염 0.73 중량%, 포도당 0.78 중량%, 팜쇼트닝 11.78 중량%, 암모늄 1.54 중량%, 중조 0.17 중량%, 중아황산나트륨 0.16 중량%, 쌀가루 1.45 중량%, 비타민 B 0.0001 중량%, 밀크향 0.04 중량%, 물 20.6998 중량%, 전지분유 1.16 중량%, 대용분유 0.29 중량%, 제1인산칼슘 0.03 중량%, 살포염 0.29 중량% 및 분무유 7.27 중량%와 상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난 1 중량%를 배합하여 통상의 방법으로 비스켓을 제조하였다.Power 1st class 25.59% by weight, Gravity 1st class 22.22% by weight, 4.80% by weight per white sugar, 0.73% by weight salt, 0.78% by weight of glucose, 11.78% by weight of palm shortening, 1.54% by weight of ammonium, 0.17% by weight of sodium bicarbonate, 0.16% by weight of sodium bisulfite , Rice flour 1.45% by weight, vitamin B 0.0001% by weight, milk flavor 0.04% by weight, water 20.6998% by weight, whole milk powder 1.16% by weight, substitute milk powder 0.29% by weight, calcium phosphate 0.03% by weight, spray salt 0.29% by weight and spray Biscuits were prepared by a conventional method by mixing 7.27% by weight with 1% by weight of the nutmeg extract or mace lignan of Examples 1 to 2 above.
제조예Manufacturing example 3: 화장품 3: Cosmetics
1) 영양 화장수(밀크 로션)1) Nutrition lotion (milk lotion)
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난을 하기 표 2의 성분 및 함량으로 통상적인 방법에 따라 영양 화장수를 제조하였다.Nutmeg extract or mace lignan of Examples 1 to 2 was prepared in the nutritional lotion according to a conventional method with the ingredients and contents of Table 2 below.
배합성분 Ingredients 제조예1-1(중량%)Preparation Example 1-1 (% by weight)
육두구 추출물 또는 메이스리그난Nutmeg extract or mace lignan 2.02.0
스쿠알란Squalane 5.05.0
밀납Wax 4.04.0
폴리솔베이트 60Polysorbate 60 1.51.5
솔비탄세스퀴올레이트Sorbitan sesquioleate 1.51.5
유동파라핀Floating paraffin 0.50.5
카프릴릭/카프릭트리글리세라이드Caprylic / Capric Triglyceride 5.05.0
글리세린glycerin 3.03.0
부틸렌글리콜Butylene glycol 3.03.0
프로필렌글리콜Propylene glycol 3.03.0
카르복시비닐폴리머Carboxyvinyl polymer 0.10.1
트리에탄올아민Triethanolamine 0.20.2
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water to 100to 100
2) 유연 화장수(스킨 로션)2) Flexible lotion (skin lotion)
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난을 하기 표 3의 성분 및 함량으로 통상적인 방법에 따라 유연 화장수를 제조하였다.The nutmeg extract or mays lignan of Examples 1 to 2 was prepared with a flexible lotion according to a conventional method with the ingredients and contents of Table 3 below.
배합성분 Ingredients 제조예1-2(중량%)Preparation Example 1-2 (% by weight)
육두구 추출물 또는 메이스리그난Nutmeg extract or mace lignan 2.02.0
글리세린glycerin 3.03.0
부틸렌글리콜Butylene glycol 2.02.0
프로필렌글리콜Propylene glycol 2.02.0
카르복시비닐폴리머Carboxyvinyl polymer 0.10.1
PEG 12 노닐페닐에테르PEG 12 nonylphenyl ether 0.20.2
폴리솔베이트 80Polysorbate 80 0.40.4
에탄올ethanol 10.010.0
트리에탄올아민Triethanolamine 0.10.1
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water to 100to 100
3) 영양크림3) Nutrition cream
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난을 하기 표 4의 성분 및 함량으로 통상적인 방법에 따라 영양크림을 제조하였다.Nutmeg extract or mays lignan of Examples 1 to 2 was prepared in the nutritional cream according to a conventional method with the components and contents of Table 4 below.
배합성분 Ingredients 제조예1-3(중량%)Preparation Example 1-3 (% by weight)
육두구 추출물 또는 메이스리그난Nutmeg extract or mace lignan 2.02.0
폴리솔베이트 60Polysorbate 60 1.51.5
솔비탄세스퀴올레이트Sorbitan sesquioleate 0.50.5
PEG60 경화피마자유PEG60 hard castor oil 2.02.0
유동파라핀Floating paraffin 1010
스쿠알란Squalane 5.05.0
카프릴릭/카프릭트리글리세라이드Caprylic / Capric Triglyceride 5.05.0
글리세린glycerin 5.05.0
부틸렌글리콜Butylene glycol 3.03.0
프로필렌글리콜Propylene glycol 3.03.0
트리에탄올아민Triethanolamine 0.20.2
방부제antiseptic 적량Proper
색소Coloring 적량Proper
향료Spices 적량Proper
정제수Purified water to 100to 100
4) 마사지 크림4) Massage cream
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난을 하기 표 5의 성분 및 함량으로 통상적인 방법에 따라 마사지 크림을 제조하였다.Massage cream was prepared according to a conventional method with the ingredients and contents of the nutmeg extract or mace lignan of Examples 1 to 2 below.
배합성분 Ingredients 제조예1-4(중량%)Preparation Example 1-4 (% by weight)
육두구 추출물 또는 메이스리그난Nutmeg extract or mace lignan 1.01.0
밀납Wax 10.010.0
폴리솔베이트 60Polysorbate 60 1.51.5
PEG 60 경화피마자유 PEG 60 hardened castor oil 2.02.0
솔비탄세스퀴올레이트Sorbitan sesquioleate 0.80.8
유동파라핀Floating paraffin 40.040.0
스쿠알란Squalane 5.05.0
카프릴릭/카프릭트리글리세라이드Caprylic / Capric Triglyceride 4.04.0
글리세린glycerin 5.05.0
부틸렌글리콜Butylene glycol 3.03.0
프로필렌글리콜Propylene glycol 3.03.0
트리에탄올아민Triethanolamine 0.20.2
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water to 100to 100
5) 팩5) Pack
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난을 하기 표 6의 성분 및 함량으로 통상적인 방법에 따라 팩을 제조하였다.The nutmeg extract or mace lignan of Examples 1 to 2 was prepared according to a conventional method with the ingredients and contents of Table 6 below.
배합성분 Ingredients 제조예1-5(중량%)Preparation Example 1-5 (% by weight)
육두구 추출물 또는 메이스리그난Nutmeg extract or mace lignan 1.01.0
폴리비닐알콜Polyvinyl alcohol 13.013.0
소듐카르복시메틸셀룰로오스Sodium carboxymethylcellulose 0.20.2
글리세린glycerin 5.05.0
알란토인Allantoin 0.10.1
에탄올ethanol 6.06.0
PEG 12 노닐페닐에테르PEG 12 nonylphenyl ether 0.30.3
폴리솔베이트 60Polysorbate 60 0.30.3
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water to 100to 100
6) 젤6) Gel
상기 실시예 1 내지 2의 육두구 추출물 또는 메이스리그난을 하기 표 7의 성분 및 함량으로 통상적인 방법에 따라 젤을 제조하였다.The nutmeg extract or mace lignan of Examples 1 to 2 was prepared according to a conventional method with the ingredients and contents of Table 7 below.
배합성분Ingredients 제조예1-6(중량%)Preparation Example 1-6 (wt%)
육두구 추출물 또는 메이스리그난Nutmeg extract or mace lignan 0.50.5
에틸렌디아민초산나트륨Sodium ethylenediamine acetate 0.050.05
글리세린glycerin 5.05.0
카르복시비닐폴리머Carboxyvinyl polymer 0.30.3
에탄올ethanol 5.05.0
PEG 60 경화피마자유 PEG 60 hardened castor oil 0.50.5
트리에탄올아민Triethanolamine 0.30.3
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water to 100to 100
이상 살펴본 바와 같이, 본 발명은 육두구 추출물 또는 메이스리그난을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 조성물에 관한 것이다. 보다 상세하게는 본 발명의 육두구 추출물 및 메이스리그난은 피부 세포에서 XRE에 의해 매개되는 CYP1A1 유전자 발현을 감소시켰으며 미세먼지에 의해 손상된 피부를 개선시켰으므로, 미세먼지, 중금속, 또는 황사에 의한 피부자극 완화 및 피부보호에 우수한 효과가 있다. 따라서 본 발명의 육두구 추출물 및 메이스리그난은 천연물이므로 부작용 없이 안전하게 사용될 수 있으며, 피부자극 완화 및 피부보호에 탁월한 효과를 보이는 조성물을 제공할 수 있으므로 산업상 이용가능성이 높다.As described above, the present invention relates to a composition for alleviating skin irritation and protecting skin derived from environmental contaminants containing nutmeg extract or macy lignan as an active ingredient. More specifically, the nutmeg extract and mays lignan of the present invention reduced the expression of CYP1A1 gene mediated by XRE in skin cells and improved the skin damaged by fine dust, and thus skin irritation caused by fine dust, heavy metals, or yellow dust It has an excellent effect on relief and skin protection. Therefore, the nutmeg extract and mace lignan of the present invention is a natural product, and thus can be safely used without side effects, and is highly industrially applicable because it can provide a composition showing excellent effects on skin irritation and skin protection.

Claims (14)

  1. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물.A pharmaceutical composition for alleviating skin irritation and protecting skin derived from environmental pollutants containing Mayslignan represented by the following Chemical Formula 1 or nutmeg extract containing the same as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000003
    Figure PCTKR2019014101-appb-img-000003
  2. 제1항에 있어서, 상기 화학식 1로 표시되는 메이스리그난은 육두구 추출물로부터 분리된 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물.[5] The pharmaceutical composition for relieving skin irritation and protecting skin derived from environmental pollutants according to claim 1, wherein the mace lignan represented by Chemical Formula 1 is isolated from nutmeg extract.
  3. 제1항에 있어서, 상기 육두구 추출물은 육두구의 씨앗을 추출물인 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물.The method of claim 1, wherein the nutmeg extract is a pharmaceutical composition for skin irritation relief and skin protection derived from environmental pollutants, characterized in that the seeds of the nutmeg extract.
  4. 제1항에 있어서, 상기 육두구 추출물은 육두구를 물, 탄소수 1 내지 6의 유기용매, 아임계 유체 및 초임계 유체로 이루어진 군에서 선택되는 1 이상의 용매 또는 초고압으로 추출한 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물. The method of claim 1, wherein the nutmeg extract is from an environmental pollution factor characterized in that the nutmeg is extracted with one or more solvents or ultra-high pressure selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, subcritical fluid and supercritical fluid. Pharmaceutical composition for alleviating induced skin irritation and protecting skin.
  5. 제1항에 있어서, 상기 피부자극은 피부염(dermatitis), 아토피(atopy), 건선(psoriasis), 여드름(acne), 습진(eczema), 피부암(skin cancer)으로 이루어진 군에서 선택되는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 약학적 조성물.The method of claim 1, wherein the skin irritation is characterized in that it is selected from the group consisting of dermatitis, atopy, psoriasis, acne, eczema, and skin cancer. A pharmaceutical composition for skin irritation relief and skin protection derived from environmental pollution factors.
  6. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 식품 조성물.A food composition for relieving skin irritation and protecting skin derived from environmental contaminants containing mace lignan represented by Formula 1 or a nutmeg extract containing the same as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000004
    Figure PCTKR2019014101-appb-img-000004
  7. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 화장품 조성물.Cosmetic composition for relieving skin irritation and protecting skin derived from environmental contaminants containing as an active ingredient mace lignan represented by Formula 1 or nutmeg extract containing the same.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000005
    Figure PCTKR2019014101-appb-img-000005
  8. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부오염 방지용 약학적 조성물.A pharmaceutical composition for preventing skin contamination derived from an environmental pollution factor containing mayslignan represented by the following Chemical Formula 1 or nutmeg extract containing the same as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000006
    Figure PCTKR2019014101-appb-img-000006
  9. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부오염 방지용 식품 조성물.A food composition for preventing skin contamination derived from an environmental pollution factor containing mace lignan represented by the following Chemical Formula 1 or a nutmeg extract containing the same as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000007
    Figure PCTKR2019014101-appb-img-000007
  10. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 환경오염인자로부터 유도되는 피부오염 방지용 화장품 조성물.A cosmetic composition for preventing skin contamination derived from environmental pollution factors containing mayslignan represented by the following Chemical Formula 1 or nutmeg extract containing the same as an active ingredient.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000008
    Figure PCTKR2019014101-appb-img-000008
  11. 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호용 제제를 제조하기 위한 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도.Use of mace lignan represented by the following formula (1) or nutmeg extract containing the same to prepare an agent for alleviating skin irritation and protecting skin derived from environmental pollution factors.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000009
    Figure PCTKR2019014101-appb-img-000009
  12. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부자극 완화 및 피부보호 방법.A method for alleviating skin irritation and protecting skin derived from environmental pollutants, comprising administering an effective amount of a composition containing mayslignan represented by Formula 1 or nutmeg extract containing the same as an active ingredient to an individual in need thereof.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000010
    Figure PCTKR2019014101-appb-img-000010
  13. 환경오염인자로부터 유도되는 피부오염 방지용 제제를 제조하기 위한 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물의 용도.Use of mace lignan represented by the following Chemical Formula 1 or nutmeg extract containing the same for preparing a preparation for preventing skin contamination derived from environmental pollution factors.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000011
    Figure PCTKR2019014101-appb-img-000011
  14. 하기 화학식 1로 표시되는 메이스리그난 또는 이를 함유하는 육두구 추출물을 유효성분으로 함유하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 특징으로 하는 환경오염인자로부터 유도되는 피부오염 방지 방법.A method for preventing skin contamination derived from environmental pollutants, comprising administering an effective amount of a composition containing mayslignan represented by the following Chemical Formula 1 or nutmeg extract containing it as an active ingredient to an individual in need thereof.
    [화학식 1][Formula 1]
    Figure PCTKR2019014101-appb-img-000012
    Figure PCTKR2019014101-appb-img-000012
PCT/KR2019/014101 2018-10-26 2019-10-24 Composition for alleviation of skin irritation induced by environmental pollution factors or for skin protection, containing nutmeg extract or macelignan as active ingredient WO2020085826A1 (en)

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