WO2020085826A1 - Composition pour soulager une irritation de la peau induite par des facteurs de pollution environnementaux ou pour la protection de la peau, contenant comme principe actif un extrait de noix de muscade ou du macelignane - Google Patents

Composition pour soulager une irritation de la peau induite par des facteurs de pollution environnementaux ou pour la protection de la peau, contenant comme principe actif un extrait de noix de muscade ou du macelignane Download PDF

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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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English (en)
Korean (ko)
Inventor
황재관
박지혜
강하늘
김창희
정희철
김도언
Original Assignee
연세대학교 산학협력단
(주)뉴트리
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Priority to JP2021523078A priority Critical patent/JP2022505979A/ja
Priority to CN201980086457.XA priority patent/CN113613666A/zh
Publication of WO2020085826A1 publication Critical patent/WO2020085826A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic 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
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics 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
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, 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

La présente invention concerne une composition pour soulager une irritation de la peau induite par des facteurs de pollution environnementaux ou pour la protection de la peau, contenant comme principe actif un extrait de noix de muscade ou du macelignane. L'extrait de noix de muscade et le macelignane de la présente invention ont permis de diminuer l'expression du gène CYP1A1 dépendante d'éléments XRE, et ont soulagé la peau endommagée par de la poussière fine, présentant ainsi d'excellents effets de soulagement de l'irritation de la peau induite par des facteurs de pollution environnementaux et de protection de la peau. De plus, la composition de la présente invention est une substance naturelle, et peut ainsi être utilisée en toute sécurité sans effets indésirables, ce qui lui permet d'être utilisée comme aliment et comme composition cosmétique.
PCT/KR2019/014101 2018-10-26 2019-10-24 Composition pour soulager une irritation de la peau induite par des facteurs de pollution environnementaux ou pour la protection de la peau, contenant comme principe actif un extrait de noix de muscade ou du macelignane WO2020085826A1 (fr)

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JP2021523078A JP2022505979A (ja) 2018-10-26 2019-10-24 ナツメグエキス又はメイスリグナンを有効成分として含有する、環境汚染因子から誘導される皮膚刺激緩和及び皮膚保護用組成物
CN201980086457.XA CN113613666A (zh) 2018-10-26 2019-10-24 包含肉豆蔻提取物或肉豆蔻木酚素作为有效成分的用于缓解由环境污染因素引起的皮肤刺激及保护皮肤的组合物

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