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WO2018038425A1 - Skin-whitening composition containing cytochalasin d - Google Patents

Skin-whitening composition containing cytochalasin d Download PDF

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Publication number
WO2018038425A1
WO2018038425A1 PCT/KR2017/008544 KR2017008544W WO2018038425A1 WO 2018038425 A1 WO2018038425 A1 WO 2018038425A1 KR 2017008544 W KR2017008544 W KR 2017008544W WO 2018038425 A1 WO2018038425 A1 WO 2018038425A1
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Prior art keywords
composition
skin
acid
cytocalin
day
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PCT/KR2017/008544
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French (fr)
Korean (ko)
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최현정
배일홍
김형준
이영진
이태룡
조동형
신지현
신동운
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(주)아모레퍼시픽
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Priority to JP2019506498A priority Critical patent/JP7038700B2/en
Priority to CN201780065397.4A priority patent/CN109862891A/en
Publication of WO2018038425A1 publication Critical patent/WO2018038425A1/en

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    • 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
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035Isoindoles, e.g. phthalimide
    • 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
    • A61K36/06Fungi, e.g. yeasts
    • 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
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
    • 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
    • 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
    • A61K8/9728Fungi, e.g. yeasts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present specification relates to a composition for skin whitening comprising cytocalacin D.
  • Melanin is a biopolymer of phenols, a complex of black pigments and proteins, that is produced by browning when the cut surface of apples, potatoes, and bananas is exposed to the air, or in the skin feathers, skin, hair, and eyes of animals. Is observed. When melanin is excessively produced, it is deposited on the skin and thus forms blemishes, freckles, and the like, which are directly linked to skin whitening, and the like, and melanin promotes skin aging and skin cancer.
  • Melanocyte stimulating hormone is secreted by UV rays, inflammation, and hormones, and MSH reacts with receptors to enhance cAMP in melanocytes, thereby synthesizing melanin. It is secreted to the outside to protect the skin from ultraviolet rays. Synthesis of melanin is mainly regulated by ⁇ -MSH, and MITF, TYR, TRP1, TRP2 and the like are known as proteins involved in the synthesis of melanin.
  • cytocalin D is known as a type of mycotoxin known as cytocalin, and there is no known relationship between skin whitening and cytocalin D.
  • the present invention provides a composition for skin whitening comprising Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient. It aims to promote the development of related fields.
  • the present invention relates to a composition for skin whitening comprising Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
  • the present invention provides a method of skin whitening comprising administering Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof to an individual.
  • the present invention provides Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient for use in skin whitening. Also provided are non-therapeutic cosmetic uses of Cytochalasin D, its optical or stereoisomers, acceptable salts thereof, hydrates thereof, or solvates thereof as active ingredients for skin whitening.
  • the present invention provides the use of Cytochalasin D, optical or stereoisomers thereof, acceptable salts thereof, hydrates thereof, or solvates thereof for use in the preparation of skin whitening compositions. .
  • composition that inhibits melanin production or deposition.
  • the composition may be a pharmaceutical composition or a cosmetic composition.
  • the present invention in one aspect, by discovering and providing a new skin whitening composition comprising Cytochalasin D, optical or stereoisomers thereof, acceptable salts thereof, hydrates thereof, or solvates thereof as an active ingredient. This will contribute to the development of new fields and market expansion for skin whitening.
  • Figure 1a confirms the effect of ⁇ -MSH and cytocalin D treatment on melanin production.
  • FIG. 1B shows the effect of ⁇ -MSH and cytocalin D treatment on the expression of tyrosinase and Tyrosinase-related protein 1 (TRP1) protein in Western blot.
  • Figure 2a confirms the effect of ⁇ -MSH and cytocalin D treatment on melanin production in B16F1 melanoma cell line.
  • Figure 2b confirms the effect of ⁇ -MSH and cytocalin D treatment on the expression of tyrosinase and TRP1 protein in B16F1 melanoma cell line.
  • Figure 3a shows that melanin synthesis is reduced by cytokalcin D treatment in NEHMs.
  • Figure 3b shows the brightness change after the treatment of cytocalin D in the skin model.
  • FIG. 3C shows the change in brightness with a colorimeter after treatment with cytocalin D in the skin model.
  • skin refers to a tissue covering the body surface of an animal, and is a broad concept including not only tissues covering the body surface such as the face or body, but also the scalp and hair.
  • cytokalacin D may be represented by Cytochalasin D or Cyto D.
  • isomers specifically refer to optical isomers (e.g., essentially pure enantiomers, original pure stereoisomers or mixtures thereof, as well as essentially pure diastereomers).
  • Conformation isomers ie, isomers that differ only in their angles of one or more chemical bonds
  • structural isomers ie, isomers that differ only in their angles of one or more chemical bonds
  • structural isomers ie, isomers that differ only in their angles of one or more chemical bonds
  • position isomers in particular, tautomers
  • geometric isomers eg, Cis-trans isomers
  • “essentially pure”, when used in the context of, for example, an enantiomer, stereoisomer, or diastereomer, includes about 90 specific compounds that may include enantiomers, stereoisomers, or diastereomers. At least%, preferably at least about 95%, more preferably at least about 97% or at least about 98%, even more preferably at least about 99%, even more preferably at least about 99.5% (w / w) It means to exist.
  • “acceptable” means that it can be approved or approved by the government or equivalent regulatory body for use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional or pharmaceutical dosages. Recognized or enumerated as listed in the Food Code, Health Functional Food Code, or General Pharmacopoeia or as described in other general literature.
  • acceptable salt means a salt according to one aspect of the invention, either conventional or pharmaceutically acceptable and having the desired activity of the parent compound.
  • the salt is formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid,
  • hydrate refers to a compound to which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.
  • solvate means a higher order compound produced between molecules or ions of a solute and molecules or ions of a solvent.
  • the present invention provides a composition for skin whitening comprising Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
  • the cytocalin D may be an actin polymerization inhibitor, may be an alkaloid of C 30 H 37 NO 6 , and may be represented by the following formula.
  • the cytocalin D may be derived from a fungus.
  • the cytocalacin D may be obtained through synthesis.
  • the fungus may be Zygosporium mansonii .
  • the cytocalin D may be to inhibit melanin production or deposition.
  • the cytocalin D may be to reduce the expression of tyrosinase (tyrosinase) or TRP1 (Tyrosinase-Related Protein 1). Since the expression of tyrosinase or TRP1 is less than that of cytoscalin D after the treatment with cytoscalin D, it can be seen that the cytoscalin D can be used as an active ingredient of the composition for skin whitening. In addition, the treatment of cytocalin D may reduce the number of cells expressing tyrosinase or TRP1, and it can also be seen that cytocalin D can be used as an active ingredient for skin whitening compositions.
  • tyrosinase tyrosinase
  • TRP1 Tyrosinase-Related Protein 1
  • Melanin is observed in the animal's outer skin feathers, skin, hair, eyes, etc., when the excessive production of melanin is deposited on the skin to form blemishes, freckles and the like, promote skin aging, skin cancer may also be induced.
  • the diseases or symptoms caused by the excessive production of melanin include blemishes, freckles, blotch, blemishes, epidermal melanocytic lesions, milky coffee spots (Cafe's au lait macules), birthmarks, Becker's Nevus, and stingles Nevus Spilus, Lentigines, Melanoma, Dermal melanocytic lesions, Mongolian spot, Nevus of Ota, Acquired bilateral nevus of Ota-like macules, Nevus of Ito, Blue nevus, Melanocytic nevus, Junction nevus, Compound nevus, Intradermal nevus Intradermal nevus, Halo nevus, Congenital nevocytic nevus, Spitz nevus, Dysplastic nevus, Melanoma, Malignant black melanoma (Lentigo maligna melanoma) ), Superficially expand
  • the cytocalin D is a pigmentation that occurs in blemishes, freckles, melanoma, birthmarks, melanoma, pigmentation by ultraviolet light, pigmentation by drugs, pigmentation after inflammation, and dermatitis It may be to prevent, ameliorate or treat one or more selected from the group consisting of.
  • cytocalin D can inhibit melanin formation and deposition in cell and skin models, thereby finding that it can be used as a material for skin whitening.
  • the above-mentioned effects of cytocalin D can also be used to prevent, ameliorate, and treat the above diseases and symptoms related to melanin.
  • the content of cytocalacin D, an isomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof in the composition may be from 0.0001% to 20% by weight relative to the total weight of the composition.
  • the content is at least 0.0001 wt%, at least 0.0005 wt%, at least 0.001 wt%, at least 0.005 wt%, at least 0.01 wt%, at least 0.05 wt%, at least 0.1 wt%, 0.3 wt%, based on the total weight of the composition.
  • the content is 20 wt% or less, 18 wt% or less, 15 wt% or less, 12 wt% or less, 10 wt% or less, 8 wt% or less, 5 wt% or less, 3 wt% or less, based on the total weight of the composition, 1 wt% or less, 0.8 wt% or less, 0.5 wt% or less, 0.3 wt% or less, 0.1 wt% or less, 0.05 wt% or less, 0.01 wt% or less, 0.005 wt% or less, 0.001 wt% or less, or 0.0005 wt% or less Can be.
  • the dosage of the cytocalasin D, isomer thereof, acceptable salt thereof, hydrate thereof, or solvate thereof may be from 0.0001 mg / kg / day to 20 mg / kg / day.
  • the dosage is at least 0.0001 mg / kg / day, at least 0.0005 mg / kg / day, at least 0.001 mg / kg / day, at least 0.005 mg / kg / day, at least 0.01 mg / kg / day, 0.05 mg / kg / day or more, 0.1 mg / kg / day or more, 0.5 mg / kg / day or more, 0.8 mg / kg / day or more, 1 mg / kg / day or more, 2 mg / kg / day or more, 3 mg / kg / day or more, 5 mg / kg / day or more, 8 mg / kg / day or more, 10 mg / kg / day or more, 12 mg / kg / day or day or
  • the dosage is 20 mg / kg / day or less, 18 mg / kg / day or less, 15 mg / kg / day or less, 12 mg / kg / day or less, 10 mg / kg / day or less, 8 mg / kg / Day or less, 5 mg / kg / day or less, 3 mg / kg / day or less, 2 mg / kg / day or less, 1 mg / kg / day or less, 0.8 mg / kg / day or less, 0.5 mg / kg / day Or less, 0.1 mg / kg / day or less, 0.05 mg / kg / day or less, 0.01 mg / kg / day or less, 0.005 mg / kg / day or less, 0.001 mg / kg / day or less, or 0.0005 mg / kg / day or less Can be.
  • the composition may be a composition for skin whitening which is a pharmaceutical composition.
  • the pharmaceutical composition may further contain pharmaceutical supplements such as preservatives, preservatives, stabilizers, hydrating or emulsifying accelerators, salts for regulating osmotic pressure and / or buffers, and other therapeutically useful substances, And can be formulated in various oral or parenteral dosage forms.
  • pharmaceutical supplements such as preservatives, preservatives, stabilizers, hydrating or emulsifying accelerators, salts for regulating osmotic pressure and / or buffers, and other therapeutically useful substances.
  • the oral dosage forms include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, powders, powders, fine granules, granules, pellets, and the like, and these formulations include surfactants in addition to active ingredients. , Diluents (eg lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), glidants (eg silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols). .
  • Diluents eg lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine
  • glidants eg silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols.
  • Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt
  • Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners.
  • the tablets can be prepared by conventional mixing, granulating or coating methods.
  • parenteral dosage form may be a transdermal dosage form, for example, an injection, drop, ointment, lotion, gel, cream, spray, suspension, emulsion, suppository, patch, or the like. It may be, but is not limited thereto.
  • the pharmaceutical composition may be administered parenterally, rectally, topically, transdermally, subcutaneously, and the like.
  • the daily dosage of the drug may vary depending on various factors such as the progress of the subject to be administered, the onset, age, health condition, complications.
  • the pharmaceutical composition may be an external preparation for skin, and the external preparation for skin may be included herein as a generic term that may include anything applied outside the skin.
  • the composition may be a composition for skin whitening which is a cosmetic composition.
  • the cosmetic composition may further include a functional additive and components included in the general cosmetic composition.
  • the functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract.
  • oils and fats moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, blood circulation And accelerators, cooling agents, limiting agents, purified water, and the like.
  • the cosmetic composition is not particularly limited in formulation, and may be appropriately selected as desired.
  • skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing It may be prepared in any one or more formulations selected from the group consisting of foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto.
  • the carrier component is animal fiber, vegetable fiber, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. And the like can be used.
  • lactose talc
  • silica aluminum hydroxide
  • calcium silicate or polyamide powder may be used as the carrier component, in particular, in the case of a spray, additionally chlorofluoro Propellants such as hydrocarbon, propane / butane or dimethyl ether.
  • a solvent, solvating agent or emulsifying agent is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Fatty acid esters of propylene glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycols or sorbitan.
  • the carrier component is water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester.
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester.
  • Microcrystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • the dosage form according to one aspect of the present invention is a surfactant-containing cleansing agent, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, and sarcosy Nates, fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
  • the composition may be a composition for skin whitening which is a food or health food composition.
  • the food or health food composition may be in a liquid or solid dosage form, for example, various foods, beverages, gums, teas, vitamin complexes, health functional foods, health supplements, and the like, powders, granules, tablets, It can be used in the form of a capsule or a beverage.
  • the food composition of each formulation may be appropriately selected and blended by those skilled in the art according to the formulation or purpose of use, in addition to the active ingredient, and synergistic effects may occur when applied simultaneously with other raw materials.
  • liquid component that can be contained in addition to the active ingredient disclosed herein, and may include various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include conventional sugars such as disaccharides such as monosaccharides, glucose and fructose, polysaccharides such as maltose and sucrose, dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. Etc.
  • natural flavoring agents such as, tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (for example, saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of natural carbohydrates may generally be about 1-20 g, in one aspect about 5-12 g, per 100 ml of the composition disclosed herein.
  • the food composition may contain various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, flavoring agents such as coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and salts thereof.
  • it may include a pulp for the production of natural fruit juices and vegetable drinks.
  • the components can be used independently or in combination.
  • the ratio of the additive may vary, but is generally selected from 0.001 to about 20 parts by weight per 100 parts by weight of the composition disclosed herein.
  • Melan-A a melanogenesis cell derived from C57BL / 6 J (black, a / a) mice, obtained from normal human epidermal melanocytes (NHEMs, Cascade Biologics, Portland, OR, USA) -A) Cell lines were obtained from Dr. Dorothy C. Bennett (St. George's Hospital Medical School, London, UK). B16F1 mouse melanoma cell line was obtained from ATCC (Manassas, VA, USA).
  • Human epidermal melanocyte forming cells were maintained under Human Melanocyte Growth Supplements (HMGS) (Cascade Biologics, Inc., Mansfield, UK) in M-254 medium.
  • Melan-A cells were maintained under 10% (v / v) fetal bovine serum, 1% (v / v) penicillin-streptomycin, and 0.2 ⁇ M phorbol 12-myristate 13-acetate in RPMI 1640 medium.
  • B16F1 mouse melanoma cell lines were cultured in DMEM with 10% (v / v) fetal bovine serum and 1% (v / v) penicillin-streptomycin.
  • Three-dimensional human skin substitutes (MelanoDerm TM, MEL-312-B, MatTek, Seoul, Korea) were obtained, followed by keratinocyte growth factor (KGF), fibroblast growth factor (b-FGF), and It was maintained according to the manufacturer's instructions in EPI-100-NMM-113 medium optimized with alpha-melanocyte stimulating hormones ( ⁇ -MSH).
  • KGF keratinocyte growth factor
  • b-FGF fibroblast growth factor
  • Cytokalacin D, ⁇ -MSH, arbutin, and kojic acid were obtained from Sigma-Aldrich (St. Louis, MO, USA).
  • Anti-actin antibody (MAB1501, 1: 10,000) was obtained from Millipore (Temecula, Calif., USA), and anti- ⁇ PEP7 (tyrosinase) antibody, 1 : 1000) and anti- ⁇ PEP1 (TRP1) antibody (anti- ⁇ PEP1 (TRP1) antibody, 1: 1000) were obtained from VJ Hearing (NIH, Bethesda, MD).
  • TRP1 anti- ⁇ PEP1 antibody, 1: 1000
  • the membrane was incubated with an HRP- conjugated secondary antibody gated signal was measured using a SuperSignal ® West Dura HRP Detection Kit ( Pierce Inc., Rockford, IL, USA).
  • Cytochalasin D is an alkaloid produced by the fungus or filamentous fungus Zygosporium mansonii , represented by the following Chemical Formula 1 (C 30 H 37 NO 6 ).
  • B16F1 mouse melanoma cell line This phenomenon was confirmed in the B16F1 mouse melanoma cell line. Specifically, B16F1 cells were pretreated with ⁇ -MSH (1 ⁇ M), and then treated with cytocalin D (0.25 ⁇ M, 0.5 ⁇ M) to measure cellular melanin after 48 hours (FIG. 2A). In addition, tyrosinase, and TRP1 were analyzed by Western blot (FIG. 2B).
  • cytocalin D was found to reduce the levels of tyrosinase and TRP1 protein, thus inhibiting melanin formation and deposition. That is, it has been found that it can be used as a composition for whitening, especially for skin whitening, using cytocalin D.
  • the regulation of melanin production was tested using NHEMs and three-dimensional human skin substitutes (reconstituted epidermal models including normal human epidermal keratinocytes and NHEMs).
  • cytomelacin D (0.5 ⁇ M and 1 ⁇ M) was treated with NHEMs and the cell melanin content was checked after 48 hours.
  • cytocalin D inhibited melanin formation and inhibited pigmentation.
  • Cytokalacin D 20mg, L-carnitine 80 ⁇ 140mg, soybean oil 180mg, palm oil 2mg, vegetable hardened oil 8mg, lead 4mg and lecithin 6mg were mixed and filled in one capsule according to a conventional method to prepare a soft capsule.
  • Cyclocalin D 20mg, galactooligosaccharide 200mg, lactose 60mg and malt sugar 140mg were mixed and granulated using a fluidized bed dryer, and the sugar ester (sugar ester) was added by tableting with a tablet press to prepare a tablet.
  • Injectables were prepared in a conventional manner using cytokalcin D 50 mg, sterile distilled water titrant for injection, and a pH adjuster titrant.
  • cytoscalin D 3.00% by weight of cytoscalin D, 2.00% by weight of polyethylene glycol monostearate, 5.00% by weight of self-emulsifying monostearate, 4.00% by weight of propylene glycol, 6.00% by weight of squalene, 6.00% by weight of tri2-ethylhexaneglyceryl,
  • a cream formulation was prepared using 1.00% by weight of sphingoglycolipids, 7.00% by weight of 1,3-butylene glycol, 5.00% by weight of beeswax and the balance of purified water.
  • cytoscalin D 3.00% by weight of cytoscalin D, 13.00% by weight of polyvinyl alcohol, 1.00% by weight of L-ascorbic acid-2-phosphate, 1.00% by weight of lauroylhydroxyproline, 2.00% by weight of water-soluble collagen (1% aqueous solution) , 1,3-butylene glycol 3.00% by weight, 5.00% by weight of ethanol, using the remaining amount of purified water to prepare a pack.
  • Health food was prepared by conventional methods according to the compositions described in the table below.
  • Vitamin A Acetate 70 ⁇ g Vitamin E 1.0 mg Vitamin B1 0.13 mg Vitamin B2 0.15 mg Vitamin B6 0.5 mg Vitamin B12 0.2 ⁇ g Vitamin c 10 mg Biotin 10 ⁇ g Nicotinic acid amide 1.7 mg Folic acid 50 ⁇ g Calcium Pantothenate 0.5 mg Mineral mixture Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium phosphate monobasic 15 mg Dicalcium Phosphate 55 mg Potassium citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8 mg
  • composition ratio of the vitamin and inorganic mixture is a composition that is relatively suitable for health foods, for example, the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method, and then the conventional method. According to the health food composition can be used.
  • the remaining amount of purified water was added to a total volume of 900 ml, and the above ingredients were mixed according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ° C. for about 1 hour. Obtained in a sterilized 2 liter container, sterilized sealed, and then refrigerated to prepare a healthy beverage.

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Abstract

One aspect of the present invention relates to a skin-whitening composition containing, as an active ingredient, cytochalasin D, optical or stereoscopic isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof. Through the one aspect of the present invention, a novel whitening material can be provided to consumers and development of skin whitening-related industries can be promoted.

Description

사이토칼라신 D를 포함하는 피부 미백용 조성물Skin whitening composition comprising cytokalcin D
본 명세서는 사이토칼라신 D를 포함하는 피부 미백용 조성물에 관한 것이다.The present specification relates to a composition for skin whitening comprising cytocalacin D.
멜라닌(melanin)은 검은 색소와 단백질의 복합체 형태를 지니는 페놀류의 생체 고분자 물질로서, 사과, 감자, 바나나의 잘린 표면이 공기 중에 노출될 때 발생하는 갈변 또는 동물의 외피 깃털, 피부, 머리, 눈 등에서 관찰된다. 멜라닌이 과잉 생산되는 경우 피부에 침착되어 기미, 주근깨 등이 형성되므로 피부 미백 등과 직결되고, 멜라닌으로 인해 피부 노화도 촉진되며 피부암도 유발될 수 있다.Melanin is a biopolymer of phenols, a complex of black pigments and proteins, that is produced by browning when the cut surface of apples, potatoes, and bananas is exposed to the air, or in the skin feathers, skin, hair, and eyes of animals. Is observed. When melanin is excessively produced, it is deposited on the skin and thus forms blemishes, freckles, and the like, which are directly linked to skin whitening, and the like, and melanin promotes skin aging and skin cancer.
자외선, 염증, 호르몬 등에 의해서 멜라닌 형성 세포 자극 호르몬(melanocyte stimulating hormone, MSH)이 분비되고, MSH는 수용체와 반응하여 멜라닌 형성 세포 내에 cAMP를 향상시켜 멜라닌을 합성하며, 합성된 멜라닌은 멜라닌 형성 세포의 외부로 분비되어 자외선 등으로부터 피부를 보호하는 역할을 하게 된다. 멜라닌의 합성은 주로 α-MSH에 의해 조절되고, 멜라닌의 합성에 관여하는 단백질로는 MITF, TYR, TRP1, TRP2 등이 알려져 있다.Melanocyte stimulating hormone (MSH) is secreted by UV rays, inflammation, and hormones, and MSH reacts with receptors to enhance cAMP in melanocytes, thereby synthesizing melanin. It is secreted to the outside to protect the skin from ultraviolet rays. Synthesis of melanin is mainly regulated by α-MSH, and MITF, TYR, TRP1, TRP2 and the like are known as proteins involved in the synthesis of melanin.
한편, 사이토칼라신 D는 사이토칼라신으로 알려진 마이코톡신의 한 종류로 알려져 있고, 피부 미백과 사이토칼라신 D와의 관련성에 대해서는 아직 알려진 바가 없다.On the other hand, cytocalin D is known as a type of mycotoxin known as cytocalin, and there is no known relationship between skin whitening and cytocalin D.
본 발명은 일측면에서, 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 유효성분으로 포함하는 피부 미백용 조성물을 제공하여, 피부 미백 관련 분야의 발전을 도모하기 위한 목적을 가진다.In one aspect, the present invention provides a composition for skin whitening comprising Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient. It aims to promote the development of related fields.
본 발명은 일측면에서, 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 유효성분으로 포함하는 피부 미백용 조성물에 관한 것이다.In one aspect, the present invention relates to a composition for skin whitening comprising Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
본 발명은 다른 측면에서, 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 개체에 투여하는 것을 포함하는 피부 미백 방법을 제공한다.In another aspect, the present invention provides a method of skin whitening comprising administering Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof to an individual.
본 발명은 다른 측면에서, 피부 미백 용도로 사용하기 위한 유효성분으로서 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 제공한다. 또한, 피부 미백을 위한 유효성분으로서 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물의 비치료적 화장 용도를 제공한다. In another aspect, the present invention provides Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient for use in skin whitening. Also provided are non-therapeutic cosmetic uses of Cytochalasin D, its optical or stereoisomers, acceptable salts thereof, hydrates thereof, or solvates thereof as active ingredients for skin whitening.
본 발명은 또 다른 측면에서, 피부 미백용 조성물의 제조에 사용하기 위한 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물의 용도를 제공한다. In another aspect, the present invention provides the use of Cytochalasin D, optical or stereoisomers thereof, acceptable salts thereof, hydrates thereof, or solvates thereof for use in the preparation of skin whitening compositions. .
본 발명의 다른 측면에서, 멜라닌 생성 또는 침착을 억제하는 조성물에 관한 것이기도 하다.In another aspect of the invention, it is also directed to a composition that inhibits melanin production or deposition.
또한, 본 발명의 다른 측면에서, 상기 조성물은 약학 조성물 또는 화장료 조성물일 수 있다.In another aspect of the invention, the composition may be a pharmaceutical composition or a cosmetic composition.
본 발명은 일측면에서, 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 유효성분으로 포함하는 새로운 피부 미백용 조성물을 발굴 및 제공함으로써, 피부 미백에 관한 새로운 분야의 개척 및 시장 확장에 기여할 수 있을 것이다.The present invention in one aspect, by discovering and providing a new skin whitening composition comprising Cytochalasin D, optical or stereoisomers thereof, acceptable salts thereof, hydrates thereof, or solvates thereof as an active ingredient. This will contribute to the development of new fields and market expansion for skin whitening.
도 1a는 α-MSH 및 사이토칼라신 D 처리가 멜라닌 생성량에 미치는 영향을 확인한 것이다.Figure 1a confirms the effect of α-MSH and cytocalin D treatment on melanin production.
도 1b는 α-MSH 및 사이토칼라신 D 처리가 타이로시나제(tyrosinase), 및 TRP1(Tyrosinase-related protein 1) 단백질의 발현에 미치는 영향을 웨스턴 블럿으로 나타낸 것이다.FIG. 1B shows the effect of α-MSH and cytocalin D treatment on the expression of tyrosinase and Tyrosinase-related protein 1 (TRP1) protein in Western blot.
도 2a는 B16F1 흑색종 세포주에서 α-MSH 및 사이토칼라신 D 처리가 멜라닌 생성량에 미치는 영향을 확인한 것이다.Figure 2a confirms the effect of α-MSH and cytocalin D treatment on melanin production in B16F1 melanoma cell line.
도 2b는 B16F1 흑색종 세포주에서 α-MSH 및 사이토칼라신 D 처리가 타이로시나제(tyrosinase), 및 TRP1 단백질의 발현에 미치는 영향을 확인한 것이다.Figure 2b confirms the effect of α-MSH and cytocalin D treatment on the expression of tyrosinase and TRP1 protein in B16F1 melanoma cell line.
도 3a는 NEHMs에서 사이토칼라신 D 처리에 의해 멜라닌 합성이 감소함을 나타낸 것이다.Figure 3a shows that melanin synthesis is reduced by cytokalcin D treatment in NEHMs.
도 3b는 피부 모델에 사이토칼라신 D 를 처리한 뒤 밝기 변화를 확인한 것이다.Figure 3b shows the brightness change after the treatment of cytocalin D in the skin model.
도 3c는 피부 모델에 사이토칼라신 D 를 처리한 뒤 색도계로 밝기 변화를 평가한 것이다.FIG. 3C shows the change in brightness with a colorimeter after treatment with cytocalin D in the skin model.
이하, 본 명세서에 대하여 상세히 설명한다. Hereinafter, this specification is demonstrated in detail.
본 명세서에서 "피부"라 함은, 동물의 체표를 덮는 조직을 의미하는 것으로서, 얼굴 또는 바디 등의 체표를 덮는 조직뿐만 아니라, 두피와 모발을 포함하는 최광의의 개념이다.As used herein, the term "skin" refers to a tissue covering the body surface of an animal, and is a broad concept including not only tissues covering the body surface such as the face or body, but also the scalp and hair.
본 명세서에서 “사이토칼라신 D”는 Cytochalasin D 또는 Cyto D로 표현될 수 있다.In the present specification, "cytokalacin D" may be represented by Cytochalasin D or Cyto D.
본 명세서에서 "이성질체"는 특히 광학 이성질체(optical isomers)(예를 들면, 본래 순수한 거울상 이성질체(essentially pure enantiomers), 본래 순수한 입체 이성질체 또는 이들의 혼합물, 본래 순수한 부분 입체 이성질체(essentially pure diastereomers) 뿐만 아니라, 형태 이성질체(conformation isomers)(즉, 하나 이상의 화학 결합의 그 각도만 다른 이성질체), 구조 이성질체, 위치 이성질체(position isomers)(특히, 호변이성체(tautomers)) 또는 기하 이성질체(geometric isomers)(예컨대, 시스-트랜스 이성질체)를 포함한다.As used herein, "isomers" specifically refer to optical isomers (e.g., essentially pure enantiomers, original pure stereoisomers or mixtures thereof, as well as essentially pure diastereomers). , Conformation isomers (ie, isomers that differ only in their angles of one or more chemical bonds), structural isomers, position isomers (in particular, tautomers) or geometric isomers (eg, Cis-trans isomers).
본 명세서에서 "본래 순수(essentially pure)"란, 예컨대 거울상 이성질체, 입체 이성질체, 또는 부분 입체 이성질체와 관련하여 사용한 경우, 거울상 이성질체, 입체 이성질체, 또는 부분 입체 이성질체를 예로 들 수 있는 구체적인 화합물이 약 90% 이상, 바람직하게는 약 95% 이상, 보다 바람직하게는 약 97% 이상 또는 약 98% 이상, 보다 더 바람직하게는 약 99% 이상, 보다 더욱 더 바람직하게는 약 99.5% 이상(w/w) 존재하는 것을 의미한다.As used herein, “essentially pure”, when used in the context of, for example, an enantiomer, stereoisomer, or diastereomer, includes about 90 specific compounds that may include enantiomers, stereoisomers, or diastereomers. At least%, preferably at least about 95%, more preferably at least about 97% or at least about 98%, even more preferably at least about 99%, even more preferably at least about 99.5% (w / w) It means to exist.
본 명세서에서 “허용 가능"이란 통상적 또는 의약학적 사용량(dosage)으로 이용할 때 상당한 독성 효과를 피함으로써, 동물, 더 구체적으로는 인간에게 사용할 수 있다는 정부 또는 이에 준하는 규제 기관의 승인을 받을 수 있거나 승인 받거나, 식품공전(Food code), 건강기능식품공전, 또는 일반적인 약전에 열거되거나 기타 일반적인 문헌에 기재된 것으로 인지되는 것을 의미한다.As used herein, “acceptable” means that it can be approved or approved by the government or equivalent regulatory body for use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional or pharmaceutical dosages. Recognized or enumerated as listed in the Food Code, Health Functional Food Code, or General Pharmacopoeia or as described in other general literature.
본 명세서에서 “허용 가능한 염”은 통상적 또는 의약학적으로 허용 가능하고 모 화합물(parent compound)의 바람직한 활성을 갖는 본 발명의 일측면에 따른 염을 의미한다. 상기 염은 (1) 염산, 브롬화수소산, 황산, 질산, 인산 등과 같은 무기산으로 형성되거나; 또는 아세트산, 프로파이온산, 헥사노산, 시클로펜테인프로피온산, 글라이콜산, 피루브산, 락트산, 말론산, 숙신산, 말산, 말레산, 푸마르산, 타르타르산, 시트르산, 벤조산, 3-(4-히드록시벤조일) 벤조산, 신남산, 만델산, 메테인설폰산, 에테인설폰산, 1,2-에테인-디설폰산, 2-히드록시에테인설폰산, 벤젠설폰산, 4-클로로벤젠설폰산, 2-나프탈렌설폰산, 4-톨루엔설폰산, 캄퍼설폰산, 4-메틸바이시클로 [2,2,2]-oct-2-엔-1-카르복실산, 글루코헵톤산, 3-페닐프로파이온산, 트리메틸아세트산, tert-부틸아세트산, 라우릴 황산, 글루콘산, 글루탐산, 히드록시나프토산, 살리실산, 스테아르산, 뮤콘산과 같은 유기산으로 형성되는 산 부가염(acid addition salt); 또는 (2) 모 화합물에 존재하는 산성 프로톤이 치환될 때 형성되는 염을 포함할 수 있다.As used herein, “acceptable salt” means a salt according to one aspect of the invention, either conventional or pharmaceutically acceptable and having the desired activity of the parent compound. The salt is formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo [2,2,2] -oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert Acid addition salts formed with organic acids such as butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) salts formed when the acidic protons present in the parent compound are substituted.
본 명세서에서 “수화물(hydrate)”은 물이 결합되어 있는 화합물을 의미하며, 물과 화합물 사이에 화학적인 결합력이 없는 내포 화합물을 포함하는 광범위한 개념이다.As used herein, “hydrate” refers to a compound to which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.
본 명세서에서 “용매화물”은 용질의 분자나 이온과 용매의 분자나 이온 사이에 생긴 고차의 화합물을 의미한다.As used herein, "solvate" means a higher order compound produced between molecules or ions of a solute and molecules or ions of a solvent.
본 발명은 일측면에서, 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 유효성분으로 포함하는 피부 미백용 조성물을 제공한다. In one aspect, the present invention provides a composition for skin whitening comprising Cytochalasin D, an optical or stereoisomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
일 구현 예로서, 상기 사이토칼라신 D는 액틴 중합 억제제(actin polymerization inhibitor)일 수 있고, C30H37NO6의 알칼로이드일 수도 있으며, 하기 화학식으로 나타나는 것일 수 있다.In one embodiment, the cytocalin D may be an actin polymerization inhibitor, may be an alkaloid of C 30 H 37 NO 6 , and may be represented by the following formula.
[화학식 1][Formula 1]
Figure PCTKR2017008544-appb-I000001
Figure PCTKR2017008544-appb-I000001
다른 구현 예로서, 상기 사이토칼라신 D는 곰팡이로부터 유래된 것일 수 있다. 또는, 상기 사이토칼라신 D는 합성을 통해 얻은 것일 수도 있다. In another embodiment, the cytocalin D may be derived from a fungus. Alternatively, the cytocalacin D may be obtained through synthesis.
다른 구현 예로서, 상기 곰팡이는 자이고스포리움 만소니(Zygosporium mansonii)일 수 있다.In another embodiment, the fungus may be Zygosporium mansonii .
다른 구현 예로서, 상기 사이토칼라신 D는 멜라닌 생성 또는 침착을 억제하는 것일 수 있다.In another embodiment, the cytocalin D may be to inhibit melanin production or deposition.
본 발명의 다른 측면에 따르면, 상기 사이토칼라신 D는 티로시나제(tyrosinase) 또는 TRP1(Tyrosinase-Related Protein 1)의 발현을 감소시키는 것일 수 있다. 상기 사이토칼라신 D 처리 후 티로시나제 또는 TRP1의 발현이 사이토칼라신 D 처리 전보다 적어지므로, 이를 통해 상기 사이토칼라신 D을 피부 미백용 조성물의 유효성분으로 사용할 수 있음을 알 수 있다. 또한, 사이토칼라신 D를 처리할 경우 티로시나제 또는 TRP1이 발현된 세포수를 감소시키기도 하는데, 이를 통해서도 사이토칼라신 D를 피부 미백용 조성물의 유효성분으로 사용할 수 있음을 알 수 있다.According to another aspect of the invention, the cytocalin D may be to reduce the expression of tyrosinase (tyrosinase) or TRP1 (Tyrosinase-Related Protein 1). Since the expression of tyrosinase or TRP1 is less than that of cytoscalin D after the treatment with cytoscalin D, it can be seen that the cytoscalin D can be used as an active ingredient of the composition for skin whitening. In addition, the treatment of cytocalin D may reduce the number of cells expressing tyrosinase or TRP1, and it can also be seen that cytocalin D can be used as an active ingredient for skin whitening compositions.
멜라닌(melanin)은 동물의 외피 깃털, 피부, 머리, 눈 등에서 관찰되는데, 멜라닌이 과잉 생산되는 경우 피부에 침착되어 기미, 주근깨 등이 형성되고 피부 노화도 촉진되며, 피부암도 유발될 수 있다. 상기 멜라닌 과다 생성으로 인한 질환 또는 증상은 기미, 주근깨, 검버섯, 잡티, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑생종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 색소 침착, 및 색소성 각질극세포종(keratoacanthomas)으로 구성된 군에서 선택되는 1 이상일 수 있다.Melanin (melanin) is observed in the animal's outer skin feathers, skin, hair, eyes, etc., when the excessive production of melanin is deposited on the skin to form blemishes, freckles and the like, promote skin aging, skin cancer may also be induced. The diseases or symptoms caused by the excessive production of melanin include blemishes, freckles, blotch, blemishes, epidermal melanocytic lesions, milky coffee spots (Cafe's au lait macules), birthmarks, Becker's Nevus, and stingles Nevus Spilus, Lentigines, Melanoma, Dermal melanocytic lesions, Mongolian spot, Nevus of Ota, Acquired bilateral nevus of Ota-like macules, Nevus of Ito, Blue nevus, Melanocytic nevus, Junction nevus, Compound nevus, Intradermal nevus Intradermal nevus, Halo nevus, Congenital nevocytic nevus, Spitz nevus, Dysplastic nevus, Melanoma, Malignant black melanoma (Lentigo maligna melanoma) ), Superficially expandable melanoma (Superficial spreading melanoma, Acral lentiginous melanoma, Nodular melanoma, Pigment basal cell carcinoma, Pigmentary dermofibromas, Pigmentary dermal cyst At least one day selected from the group consisting of pigmented keloids, pigmentation by ultraviolet light, pigmentation by drugs, pigmentation after inflammation, and pigmentation resulting from dermatitis, and keratoacanthomas. Can be.
본 발명의 일 측면에서, 상기 사이토칼라신 D는 기미, 주근깨, 흑색점, 모반, 흑색종, 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 색소 침착으로 이루어진 군에서 선택되는 하나 이상을 예방, 개선 또는 치료하는 것일 수 있다.In one aspect of the invention, the cytocalin D is a pigmentation that occurs in blemishes, freckles, melanoma, birthmarks, melanoma, pigmentation by ultraviolet light, pigmentation by drugs, pigmentation after inflammation, and dermatitis It may be to prevent, ameliorate or treat one or more selected from the group consisting of.
본 발명자들은 사이토칼라신 D를 이용하여 세포 및 피부모델에서 멜라닌 형성 및 침착을 억제시킬 수 있음을 확인하였고 이를 통해 사이토칼라신 D를 피부 미백용 물질로 사용할 수 있음을 알아낸 것이다. 이러한 사이토칼라신 D의 효능을 이용하여 멜라닌과 관계되는 상기 질환이나 증상에 대하여 예방, 개선, 및 치료 등을 도모할 수도 있다. The present inventors confirmed that the use of cytocalin D can inhibit melanin formation and deposition in cell and skin models, thereby finding that it can be used as a material for skin whitening. The above-mentioned effects of cytocalin D can also be used to prevent, ameliorate, and treat the above diseases and symptoms related to melanin.
본 발명의 또 다른 측면에 의하면, 상기 조성물 내 사이토칼라신 D, 이의 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물의 함량은 상기 조성물 총중량 대비 0.0001 중량% 내지 20 중량%일 수 있다. 일 구현 예에서, 상기 함량은 상기 조성물 총중량 대비 0.0001 중량% 이상, 0.0005 중량% 이상, 0.001 중량% 이상, 0.005 중량% 이상, 0.01 중량% 이상, 0.05 중량% 이상, 0.1 중량% 이상, 0.3 중량% 이상, 0.5 중량% 이상, 0.8 중량% 이상, 1 중량% 이상, 3 중량% 이상, 5 중량% 이상, 8 중량% 이상, 10 중량% 이상, 12 중량% 이상, 15 중량% 이상, 또는 18 중량% 이상일 수 있다. 또한, 상기 함량은 상기 조성물 총 중량 대비 20 중량% 이하, 18 중량% 이하, 15 중량% 이하, 12 중량% 이하, 10 중량% 이하, 8 중량% 이하, 5 중량% 이하, 3 중량% 이하, 1 중량% 이하, 0.8 중량% 이하, 0.5 중량% 이하, 0.3 중량% 이하, 0.1 중량% 이하, 0.05 중량% 이하, 0.01 중량% 이하, 0.005 중량% 이하, 0.001 중량% 이하, 또는 0.0005 중량% 이하일 수 있다.According to another aspect of the present invention, the content of cytocalacin D, an isomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof in the composition may be from 0.0001% to 20% by weight relative to the total weight of the composition. In one embodiment, the content is at least 0.0001 wt%, at least 0.0005 wt%, at least 0.001 wt%, at least 0.005 wt%, at least 0.01 wt%, at least 0.05 wt%, at least 0.1 wt%, 0.3 wt%, based on the total weight of the composition. At least 0.5 wt%, at least 0.8 wt%, at least 1 wt%, at least 3 wt%, at least 5 wt%, at least 8 wt%, at least 10 wt%, at least 12 wt%, at least 15 wt%, or 18 wt% It may be more than%. In addition, the content is 20 wt% or less, 18 wt% or less, 15 wt% or less, 12 wt% or less, 10 wt% or less, 8 wt% or less, 5 wt% or less, 3 wt% or less, based on the total weight of the composition, 1 wt% or less, 0.8 wt% or less, 0.5 wt% or less, 0.3 wt% or less, 0.1 wt% or less, 0.05 wt% or less, 0.01 wt% or less, 0.005 wt% or less, 0.001 wt% or less, or 0.0005 wt% or less Can be.
본 발명의 또 다른 측면에 의하면, 상기 사이토칼라신 D, 이의 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물의 투여량은 0.0001mg/kg/일 내지 20mg/kg/일 일 수 있다. 일 구현 예에서, 상기 투여량은 0.0001 mg/kg/일 이상, 0.0005 mg/kg/일 이상, 0.001 mg/kg/일 이상, 0.005 mg/kg/일 이상, 0.01 mg/kg/일 이상, 0.05 mg/kg/일 이상, 0.1 mg/kg/일 이상, 0.5 mg/kg/일 이상, 0.8 mg/kg/일 이상, 1 mg/kg/일 이상, 2 mg/kg/일 이상, 3 mg/kg/일 이상, 5 mg/kg/일 이상, 8 mg/kg/일 이상, 10 mg/kg/일 이상, 12 mg/kg/일 이상, 15 mg/kg/일 이상, 또는 18 mg/kg/일 이상일 수 있다. 또한, 상기 투여량은 20 mg/kg/일 이하, 18 mg/kg/일 이하, 15 mg/kg/일 이하, 12 mg/kg/일 이하, 10 mg/kg/일 이하, 8 mg/kg/일 이하, 5 mg/kg/일 이하, 3 mg/kg/일 이하, 2 mg/kg/일 이하, 1 mg/kg/일 이하, 0.8 mg/kg/일 이하, 0.5 mg/kg/일 이하, 0.1 mg/kg/일 이하, 0.05 mg/kg/일 이하, 0.01 mg/kg/일 이하, 0.005 mg/kg/일 이하, 0.001 mg/kg/일 이하, 또는 0.0005 mg/kg/일 이하일 수 있다.According to another aspect of the invention, the dosage of the cytocalasin D, isomer thereof, acceptable salt thereof, hydrate thereof, or solvate thereof may be from 0.0001 mg / kg / day to 20 mg / kg / day. In one embodiment, the dosage is at least 0.0001 mg / kg / day, at least 0.0005 mg / kg / day, at least 0.001 mg / kg / day, at least 0.005 mg / kg / day, at least 0.01 mg / kg / day, 0.05 mg / kg / day or more, 0.1 mg / kg / day or more, 0.5 mg / kg / day or more, 0.8 mg / kg / day or more, 1 mg / kg / day or more, 2 mg / kg / day or more, 3 mg / kg / day or more, 5 mg / kg / day or more, 8 mg / kg / day or more, 10 mg / kg / day or more, 12 mg / kg / day or more, 15 mg / kg / day or more, or 18 mg / kg Can be more than / day. In addition, the dosage is 20 mg / kg / day or less, 18 mg / kg / day or less, 15 mg / kg / day or less, 12 mg / kg / day or less, 10 mg / kg / day or less, 8 mg / kg / Day or less, 5 mg / kg / day or less, 3 mg / kg / day or less, 2 mg / kg / day or less, 1 mg / kg / day or less, 0.8 mg / kg / day or less, 0.5 mg / kg / day Or less, 0.1 mg / kg / day or less, 0.05 mg / kg / day or less, 0.01 mg / kg / day or less, 0.005 mg / kg / day or less, 0.001 mg / kg / day or less, or 0.0005 mg / kg / day or less Can be.
본 발명의 일 측면에 의하면, 상기 조성물은 약학 조성물인 피부 미백용 조성물일 수 있다.According to one aspect of the invention, the composition may be a composition for skin whitening which is a pharmaceutical composition.
상기 약학 조성물은 보존제, 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 약제학적 보조제, 및 기타 치료적으로 유용한 물질을 추가로 함유할 수 있으며, 통상적인 방법에 따라 다양한 경구 투여제 또는 비경구 투여제 형태로 제형화할 수 있다.The pharmaceutical composition may further contain pharmaceutical supplements such as preservatives, preservatives, stabilizers, hydrating or emulsifying accelerators, salts for regulating osmotic pressure and / or buffers, and other therapeutically useful substances, And can be formulated in various oral or parenteral dosage forms.
상기 경구 투여제는 예를 들면, 정제, 환제, 경질 및 연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 분제, 산제, 세립제, 과립제, 펠렛제 등이 있으며, 이들 제형은 유효성분 이외에 계면 활성제, 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로오스 및 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및 폴리에틸렌 글리콜)를 함유할 수 있다. 정제는 또한 마그네슘 알루미늄 실리케이트, 전분페이스트, 젤라틴, 트라가칸스, 메틸셀룰로오스, 나트륨 카복시메틸셀룰로오스 및 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제, 흡수제, 착색제, 향미제, 및 감미제 등의 약제학적 첨가제를 함유할 수 있다. 상기 정제는 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.The oral dosage forms include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, powders, powders, fine granules, granules, pellets, and the like, and these formulations include surfactants in addition to active ingredients. , Diluents (eg lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), glidants (eg silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols). . Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners. The tablets can be prepared by conventional mixing, granulating or coating methods.
또한, 상기 비경구 투여 형태로는 경피 투여형 제형일 수 있으며, 예를 들어 주사제, 점적제, 연고, 로션, 겔, 크림, 스프레이, 현탁제, 유제, 좌제(坐劑), 패취 등의 제형일 수 있으나, 이에 제한되는 것은 아니다.In addition, the parenteral dosage form may be a transdermal dosage form, for example, an injection, drop, ointment, lotion, gel, cream, spray, suspension, emulsion, suppository, patch, or the like. It may be, but is not limited thereto.
상기 약학 조성물은 비경구, 직장, 국소, 경피, 피하 등으로 투여될 수 있다. The pharmaceutical composition may be administered parenterally, rectally, topically, transdermally, subcutaneously, and the like.
상기 유효성분의 투여량 결정은 통상의 기술자의 수준 내에 있으며, 약물의 1일 투여 용량은 투여하고자 하는 대상의 진행 정도, 발병 시기, 연령, 건강상태, 합병증 등의 다양한 요인에 따라 달라질 수 있다. Determination of the dosage of the active ingredient is within the level of those skilled in the art, the daily dosage of the drug may vary depending on various factors such as the progress of the subject to be administered, the onset, age, health condition, complications.
상기 약학 조성물은 피부 외용제일 수 있으며, 상기 피부 외용제는 피부 외부에서 도포되는 어떠한 것이라도 포함될 수 있는 총칭으로서 다양한 제형의 의약품 또는 의약외품이 여기에 포함될 수 있다.The pharmaceutical composition may be an external preparation for skin, and the external preparation for skin may be included herein as a generic term that may include anything applied outside the skin.
본 발명의 또 다른 측면에 의하면, 상기 조성물은 화장료 조성물인 피부 미백용 조성물일 수 있다. According to another aspect of the invention, the composition may be a composition for skin whitening which is a cosmetic composition.
상기 화장료 조성물에는 기능성 첨가물 및 일반적인 화장료 조성물에 포함되는 성분이 추가로 포함될 수 있다. 상기 기능성 첨가물로는 수용성 비타민, 유용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 성분을 포함할 수 있다. 이외에 포함되는 배합 성분으로서는 유지 성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한(制汗)제, 정제수 등을 들 수 있다.The cosmetic composition may further include a functional additive and components included in the general cosmetic composition. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract. In addition to the other components included, oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, blood circulation And accelerators, cooling agents, limiting agents, purified water, and the like.
상기 화장료 조성물은 제형이 특별히 한정되지 않으며, 목적하는 바에 따라 적절히 선택할 수 있다. 예를 들어, 스킨로션, 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양로션, 맛사지크림, 영양크림, 모이스처크림, 핸드크림, 파운데이션, 에센스, 영양에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션 및 바디클린저로 이루어진 군으로부터 선택된 어느 하나 이상의 제형으로 제조될 수 있으나, 이에 제한되는 것은 아니다.The cosmetic composition is not particularly limited in formulation, and may be appropriately selected as desired. For example, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing It may be prepared in any one or more formulations selected from the group consisting of foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto.
본 발명의 일 측면에 의한 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물섬유, 식물섬유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation according to one aspect of the present invention is a paste, cream or gel, the carrier component is animal fiber, vegetable fiber, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. And the like can be used.
본 발명의 일 측면에 의한 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation according to one aspect of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as the carrier component, in particular, in the case of a spray, additionally chlorofluoro Propellants such as hydrocarbon, propane / butane or dimethyl ether.
본 발명의 일 측면에 의한 제형이 용액 또는 유탁액의 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation according to one aspect of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Fatty acid esters of propylene glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycols or sorbitan.
본 발명의 일 측면에 의한 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation according to one aspect of the invention is a suspension, the carrier component is water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester. , Microcrystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
본 발명의 일 측면에 의한 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the dosage form according to one aspect of the present invention is a surfactant-containing cleansing agent, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, and sarcosy Nates, fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
본 발명의 다른 측면에 의하면, 상기 조성물은 식품 또는 건강식품 조성물인 피부 미백용 조성물일 수 있다. According to another aspect of the invention, the composition may be a composition for skin whitening which is a food or health food composition.
상기 식품 또는 건강식품 조성물은 액상 또는 고체 상태의 제형일 수 있고, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능식품류, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용될 수 있다. 각 제형의 식품 조성물은 유효성분 이외에 해당 분야에서 통상적으로 사용되는 성분들을 제형 또는 사용 목적에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있으며, 다른 원료와 동시에 적용할 경우 상승 효과가 일어날 수 있다.The food or health food composition may be in a liquid or solid dosage form, for example, various foods, beverages, gums, teas, vitamin complexes, health functional foods, health supplements, and the like, powders, granules, tablets, It can be used in the form of a capsule or a beverage. In addition to the active ingredient, the food composition of each formulation may be appropriately selected and blended by those skilled in the art according to the formulation or purpose of use, in addition to the active ingredient, and synergistic effects may occur when applied simultaneously with other raw materials.
본 명세서에 개시된 유효성분 외에 함유할 수 있는 액체 성분에는 특별한 제한점이 없으며, 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가성분으로 포함할 수 있다. 상기 천연 탄수화물의 예로는 모노사카라이드, 포도당, 과당 등의 디사카라이드, 말토스, 슈크로스 등의 폴리사카라이드, 덱스트린, 시클로덱스트린 등의 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당 알코올 등이 있다. 상기의 향미제로는 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(예를 들어 사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 명세서에 개시된 조성물 100ml 당 일반적으로 약 1 내지 20g, 일측면에서 약 5 내지 12g일 수 있다.There is no particular limitation on the liquid component that can be contained in addition to the active ingredient disclosed herein, and may include various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the natural carbohydrates include conventional sugars such as disaccharides such as monosaccharides, glucose and fructose, polysaccharides such as maltose and sucrose, dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. Etc. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (for example, saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates may generally be about 1-20 g, in one aspect about 5-12 g, per 100 ml of the composition disclosed herein.
상기 식품 조성물은 일 측면에서 여러가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그 염, 알긴산 및 그 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 포함할 수 있다. 다른 측면에서 천연 과일 주스 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 상기 성분들은 독립적으로 또는 조합하여 사용될 수 있다. 상기 첨가제의 비율은 다양할 수 있으나, 본 명세서에 개시된 조성물 100 중량부 당 0.001 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In one aspect, the food composition may contain various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, flavoring agents such as coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In another aspect it may include a pulp for the production of natural fruit juices and vegetable drinks. The components can be used independently or in combination. The ratio of the additive may vary, but is generally selected from 0.001 to about 20 parts by weight per 100 parts by weight of the composition disclosed herein.
이하, 실시예, 실험예를 통하여, 본 발명 일측면의 구성 및 효과를 보다 구체적으로 설명한다. 그러나 아래 예는 본 발명에 대한 이해를 돕기 위해 예시의 목적으로만 제공된 것일 뿐 본 발명의 범주 및 범위가 그에 의해 제한되는 것은 아니다.Hereinafter, the configuration and effects of one aspect of the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the examples below are provided for the purpose of illustration only to help the understanding of the present invention, and the scope and scope of the present invention are not limited thereto.
[실시예 1]Example 1
세포 및 피부 모델 준비Cell and skin model preparation
인간 표피 멜라닌 형성 세포(Normal human epidermal melanocytes, NHEMs, Cascade Biologics, Portland, OR, USA)를 입수하고, C57BL/6 J (black, a/a) 마우스에서 유래한 멜라닌 형성 세포인 멜란-A(Melan-A) 세포주를 Dorothy C. Bennett 박사(St. George's Hospital Medical School, London, UK)로부터 입수하였다. B16F1 마우스 흑색종(melanoma) 세포주는 ATCC (Manassas, VA, USA)에서 입수하였다. Melan-A, a melanogenesis cell derived from C57BL / 6 J (black, a / a) mice, obtained from normal human epidermal melanocytes (NHEMs, Cascade Biologics, Portland, OR, USA) -A) Cell lines were obtained from Dr. Dorothy C. Bennett (St. George's Hospital Medical School, London, UK). B16F1 mouse melanoma cell line was obtained from ATCC (Manassas, VA, USA).
인간 표피 멜라닌 형성 세포는 M-254 배지에서 인간 멜라닌 형성 세포 성장 보충제(Human Melanocyte Growth Supplements, HMGS) (Cascade Biologics, Inc., Mansfield, UK)하에서 유지시켰다. Melan-A세포는 RPMI 1640배지에서 10%(v/v) 우태아혈정, 1%(v/v) 페니실린-스트렙토마이신, 및 0.2 μM phorbol 12-myristate 13-acetate 하에서 유지시켰다. B16F1 마우스 흑색종 세포주는 10% (v/v) 우태아혈청 및 1% (v/v) 페니실린-스트렙토마이신을 첨가한 DMEM에서 배양하였다. Human epidermal melanocyte forming cells were maintained under Human Melanocyte Growth Supplements (HMGS) (Cascade Biologics, Inc., Mansfield, UK) in M-254 medium. Melan-A cells were maintained under 10% (v / v) fetal bovine serum, 1% (v / v) penicillin-streptomycin, and 0.2 μM phorbol 12-myristate 13-acetate in RPMI 1640 medium. B16F1 mouse melanoma cell lines were cultured in DMEM with 10% (v / v) fetal bovine serum and 1% (v / v) penicillin-streptomycin.
3차원 인간 피부 대체재(Three-dimensional human skin substitute, MelanoDerm™, MEL-312-B, MatTek사, Seoul, Korea)는 입수한 뒤 KGF(Keratinocyte Growth Factor), b-FGF(Fibroblast Growth Factor), 및 α-MSH(alpha-melanocyte stimulating hormones)로 최적화한 EPI-100-NMM-113 배지에서 제조자의 지시에 따라 유지하였다. Three-dimensional human skin substitutes (MelanoDerm ™, MEL-312-B, MatTek, Seoul, Korea) were obtained, followed by keratinocyte growth factor (KGF), fibroblast growth factor (b-FGF), and It was maintained according to the manufacturer's instructions in EPI-100-NMM-113 medium optimized with alpha-melanocyte stimulating hormones (α-MSH).
상기 피부모델의 밝기 변화(ΔL) 지수는 색도계(colorimeter, CR-300, Konica Minolta사, Tokyo, Japan)에 의해 측정된 L 지수(L value, lightness index)로 계산하였고, ΔL = 13일차 또는 20일차의 L (처치 피부) - L (대조군 피부) 로 계산하였다. ΔL 지수의 증가는 피부에서 화합물 유도에 의한 색소의 과소침착을 나타낸다(Lee et al., 2013). The brightness change (ΔL) index of the skin model was calculated using an L index (L value, lightness index) measured by a colorimeter (CRimeter, CR-300, Konica Minolta, Tokyo, Japan), and ΔL = day 13 or 20 It was calculated as primary L (treatment skin)-L (control skin). Increasing the ΔL index indicates underdeposition of the pigment by compound induction in the skin (Lee et al., 2013).
시약 reagent
사이토칼라신 D, α-MSH, 알부틴(arbutin), 및 코지산(kojic acid)은 Sigma-Aldrich사 (St. Louis, MO, USA)에서 입수하였다. Cytokalacin D, α-MSH, arbutin, and kojic acid were obtained from Sigma-Aldrich (St. Louis, MO, USA).
멜라닌 에세이Melanin Essay
세포를 트립신/EDTA로 처리 후 1000 x g에서 5분간 원심분리하고, PBS로 2회 세척하였다. 튜브 내의 최종 세포 펠렛을 사진으로 찍고, 세포 펠렛은 1 N NaOH에 용해시켰다. 균질화시킨 세포 추출물을 96-웰(well) 플레이트에 옮기고, ELISA 플레이트 리더를 이용하여 흡광도 405 nm에서 상대적 멜라닌 양을 측정하였다.Cells were centrifuged at 1000 x g for 5 minutes after trypsin / EDTA and washed twice with PBS. The final cell pellet in the tube was photographed and the cell pellet was dissolved in 1 N NaOH. Homogenized cell extracts were transferred to 96-well plates and the relative melanin amount was measured at absorbance 405 nm using an ELISA plate reader.
웨스턴Weston 블럿Blot 분석 analysis
모든 용해물은 2 × 램라이 시료 완충액(2 × Laemmli sample buffer, 62.5 mM Tris-HCl, pH 6.8, 25% [v/v] glycerol, 2% [w/v] SDS, 5% [v/v] β-mercaptoethanol, 및 0.01% [w/v] bromophenol blue) (Bio-Rad, Hercules사, CA, USA)을 이용하여 준비하였다. 모든 세포 단백질은 Bradford solution (Bio-Rad)을 이용하여 측정하였다. 그 후, 상기 시료는 SDS-PAGE로 분리하고, PVDF 멤브레인(Bio-Rad)으로 이전하였다. TBST(25 mM Tris, 140 mM NaCl, 및 0.05% [v/v] Tween® 20) 내의 4% (w/v) 스킴 밀크(skim milk)로 블로킹한 뒤, 멤브레인을 특정 1차 항체들과 함께 오버나이트(overnight) 배양시켰다. All lysates were 2 × Laemmli sample buffer, 62.5 mM Tris-HCl, pH 6.8, 25% [v / v] glycerol, 2% [w / v] SDS, 5% [v / v β-mercaptoethanol, and 0.01% [w / v] bromophenol blue) (Bio-Rad, Hercules, CA, USA). All cellular proteins were measured using Bradford solution (Bio-Rad). The sample was then separated by SDS-PAGE and transferred to PVDF membrane (Bio-Rad). TBST 4% (w / v) skim milk (skim milk) for one rear, the membrane blocking in conjunction with the specific primary antibody in (25 mM Tris, 140 mM NaCl, and 0.05% [v / v] Tween ® 20) Overnight incubation.
항-액틴 항체(anti-actin antibody, MAB1501, 1:10,000)는 Millipore사 (Temecula, CA, USA)에서 입수하였고, 항-αPEP7(타이로시나제) 항체(anti-αPEP7(tyrosinase) antibody, 1:1000)와 항-αPEP1(TRP1) 항체(anti-αPEP1(TRP1) antibody, 1:1000)는 V. J. Hearing (NIH, Bethesda, MD)로부터 입수하였다. 단백질 검출을 위하여, 상기 멤브레인은 HRP-컨쥬게이티드 이차 항체를 이용하여 배양하였고, 신호는 SuperSignal® West Dura HRP Detection Kit (Pierce사, Rockford, IL, USA)를 이용하여 측정하였다. Anti-actin antibody (MAB1501, 1: 10,000) was obtained from Millipore (Temecula, Calif., USA), and anti-αPEP7 (tyrosinase) antibody, 1 : 1000) and anti-αPEP1 (TRP1) antibody (anti-αPEP1 (TRP1) antibody, 1: 1000) were obtained from VJ Hearing (NIH, Bethesda, MD). For protein detection, the membrane was incubated with an HRP- conjugated secondary antibody gated signal was measured using a SuperSignal ® West Dura HRP Detection Kit ( Pierce Inc., Rockford, IL, USA).
통계 분석Statistical analysis
각 데이터는 적어도 3회의 독립적인 실험을 거쳐서 얻었고, 평균±SE(표준오차)로 나타내었다. 결과의 통계적 평가는 일원분산분석(1-way ANOVA)를 이용하여 수행하였다(* p < 0.05, ** p < 0.01). Each data was obtained through at least three independent experiments and expressed as mean ± SE (standard error). Statistical evaluation of the results was performed using one-way ANOVA (* p <0.05, ** p <0.01).
[실험예 1] 사이토칼라신 D에 의한 멜라닌 생성 조절Experimental Example 1 Control of Melanin Production by Cytokalacin D
사이토칼라신 D(Cytochalasin D, Cyto D)는 곰팡이 또는 사상균인 자이고스코리움 만소니(Zygosporium mansonii)에서 생산하는 알칼로이드(alkaloid)로서 아래 화학식 1로 나타난다(C30H37NO6).Cytochalasin D (Cytochalasin D) is an alkaloid produced by the fungus or filamentous fungus Zygosporium mansonii , represented by the following Chemical Formula 1 (C 30 H 37 NO 6 ).
[화학식 1][Formula 1]
Figure PCTKR2017008544-appb-I000002
Figure PCTKR2017008544-appb-I000002
α-MSH (1 μM)로 24시간 동안 사전 처리한 멜란-a 세포에 사이토칼라신 D(0.25 및 0.5μM)로 처리 뒤 세포의 멜라닌 함량을 측정하였고, 멜라닌 생성 효소인 타이로시나제(tyrosinase) 및 TRP1 단백질 발현 수준을 웨스턴 블럿으로 확인하였다. 그 결과, α-MSH를 처리할 경우 멜라닌 합성이 증가하고 타이로시나제 및 TRP1의 발현 수준이 증가하였는데, 사이토칼라신 D를 처리한 경우에는 그러한 α-MSH에 의한 멜라닌 합성이 현저하게 감소하였고(도 1a), 타이로시나제 및 TRP1 발현 또한 현저히 감소되었다(도 1b).Melan-a cells pretreated with α-MSH (1 μM) for 24 hours were treated with cytocalin D (0.25 and 0.5 μM), and then the melanin content of the cells was measured, and tyrosinase, a melanogenesis enzyme, tyrosinase. ) And TRP1 protein expression levels were confirmed by Western blot. As a result, treatment with α-MSH increased melanin synthesis and expression levels of tyrosinase and TRP1, whereas treatment with cytocalin D significantly reduced melanin synthesis by α-MSH. (FIG. 1A), tyrosinase and TRP1 expression were also significantly reduced (FIG. 1B).
이러한 현상이 B16F1 마우스 흑색종(melanoma) 세포주에서도 나타나는지 확인하였다. 구체적으로, B16F1 세포에 α-MSH(1μM)로 선 처리한 뒤, 사이토칼라신 D(0.25μM, 0.5μM)를 처리하여 48시간 후 세포 멜라닌 양을 측정하였다(도 2a). 또한, 타이로시나제, 및 TRP1를 웨스턴 블롯으로 분석하였다(도 2b).This phenomenon was confirmed in the B16F1 mouse melanoma cell line. Specifically, B16F1 cells were pretreated with α-MSH (1 μM), and then treated with cytocalin D (0.25 μM, 0.5 μM) to measure cellular melanin after 48 hours (FIG. 2A). In addition, tyrosinase, and TRP1 were analyzed by Western blot (FIG. 2B).
그 결과, B16F1 세포주에서도 사이토칼라신 D 처리에 의해 멜라닌 함량이 감소하였으며, 타이로시나제와 TRP1의 발현을 억제시킴을 알 수 있었다(도 2a 내지 도 2b).As a result, in the B16F1 cell line, melanin content was decreased by the treatment with cytocarcin D, and it was found that the expression of tyrosinase and TRP1 was suppressed (FIGS. 2A to 2B).
종합하면, 사이토칼라신 D는 타이로시나제(tyrosinase) 및 TRP1 단백질의 수준을 감소시키고, 그에 따라 멜라닌 형성 및 침착이 억제됨을 확인하였다. 즉, 사이토칼라신 D를 이용하여 미백용 특히 피부 미백용 조성물로 사용할 수 있음을 규명한 것이다.Taken together, cytocalin D was found to reduce the levels of tyrosinase and TRP1 protein, thus inhibiting melanin formation and deposition. That is, it has been found that it can be used as a composition for whitening, especially for skin whitening, using cytocalin D.
[실험예 2] 정상 인간 표피 멜라닌 형성 세포(normal human epidermal melanocytes, NHEMs) 및 인공 피부 실험Experimental Example 2 Normal human epidermal melanocytes (NHEMs) and artificial skin experiments
NHEMs와 3차원 인간 피부 대체재(정상 인간 표피 각질세포 및 NHEMs를 포함하는 재구성 표피 모델)를 이용하여 멜라닌 생성의 조절을 실험하였다. The regulation of melanin production was tested using NHEMs and three-dimensional human skin substitutes (reconstituted epidermal models including normal human epidermal keratinocytes and NHEMs).
구체적으로, NHEMs에 사이토칼라신 D(0.5 μM 및 1 μM)를 처리하고 48시간 후 세포 멜라닌 함량을 확인하였다.Specifically, cytomelacin D (0.5 μM and 1 μM) was treated with NHEMs and the cell melanin content was checked after 48 hours.
그 결과, NHEMs에서도 사이토칼라신 D 처리에 의해 멜라닌 합성 감소가 유도됨을 확인하였다(도 3a).  As a result, it was confirmed that melanin synthesis was induced by cytocalin D treatment even in NHEMs (FIG. 3A).
또한, 사이토칼라신 D(0.5μM), 코지산(kojic acid, KA, 5mM)를 3일에 한번씩 3차원 인간 피부 대체재에 3일에 한번씩 13일 간 및 20일 간 투여하고 색소침착에 미치는 영향을 평가하였다. 색소침착은 색도계(colorimeter)로 평가하였고 도 3c에서 ΔL는 대조군과 물질 처리군 간의 밝기 차이를 계산한 값이다. In addition, the effects of cytocalin D (0.5μM) and kojic acid (KA, 5mM) to the three-dimensional human skin substitutes once every three days for 13 days and 20 days and the effect on pigmentation Was evaluated. Pigmentation was evaluated using a colorimeter, and ΔL in FIG. 3C was calculated by calculating the difference in brightness between the control group and the substance treatment group.
그 결과, 사이토칼라신 D에 의해 피부 색소침착이 감소하였다(도 3b 및 도 3c). 이를 통해, 사이토칼라신 D가 멜라닌 형성을 억제하고 색소침착을 억제함을 확인하였다. As a result, skin pigmentation was reduced by cytocalin D (FIGS. 3B and 3C). Through this, it was confirmed that cytocalin D inhibited melanin formation and inhibited pigmentation.
본 발명의 일 측면에 따른 조성물의 제형예를 아래에서 설명하나, 다른 여러 가지 제형으로도 응용 가능하며, 이는 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Examples of the formulation of the composition according to one aspect of the present invention will be described below, but it is also applicable to various other formulations, which are intended to explain in detail only and not intended to limit the present invention.
[제형예 1] 연질캅셀제Formulation Example 1 Soft Capsule
사이토칼라신 D 20mg, L-카르니틴 80~140mg, 대두유 180mg, 팜유 2mg, 식물성 경화유 8mg, 황납 4mg 및 레시틴 6mg을 혼합하고, 통상의 방법에 따라 1캡슐에 충진하여 연질캅셀제를 제조하였다.Cytokalacin D 20mg, L-carnitine 80 ~ 140mg, soybean oil 180mg, palm oil 2mg, vegetable hardened oil 8mg, lead 4mg and lecithin 6mg were mixed and filled in one capsule according to a conventional method to prepare a soft capsule.
[제형예 2] 정제Formulation Example 2 Tablet
사이토칼라신 D 20mg, 갈락토올리고당 200mg, 유당 60mg 및 맥아당 140mg을 혼합하고 유동층 건조기를 이용하여 과립한 후 당 에스테르(sugar ester)를 6mg을 첨가하여 타정기로 타정하여 정제를 제조하였다.Cyclocalin D 20mg, galactooligosaccharide 200mg, lactose 60mg and malt sugar 140mg were mixed and granulated using a fluidized bed dryer, and the sugar ester (sugar ester) was added by tableting with a tablet press to prepare a tablet.
[제형예 3] 과립제Formulation Example 3 Granules
사이토칼라신 D 20mg, 무수결정 포도당 250mg 및 전분 550mg을 혼합하고, 유동층 과립기를 사용하여 과립으로 성형한 후 포에 충진하여 과립제를 제조하였다.20 mg of cytocalin D, 250 mg of anhydrous glucose, and 550 mg of starch were mixed, molded into granules using a fluidized bed granulator, and filled into fabrics to prepare granules.
[제형예 4] 드링크제[Formulation Example 4] Drinks
사이토칼라신 D 20mg, 포도당 10g, 구연산 0.6g, 및 액상 올리고당 25g을 혼합한 후 정제수 300ml를 가하여 각 병에 200ml씩 충진한다. 병에 충진한 후 130℃ 에서 4~5 초간 살균하여 드링크제를 제조하였다.20 mg of cytocalin D, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharides are mixed, and then 300 ml of purified water is added to each bottle for 200 ml. After filling the bottle sterilized for 4-5 seconds at 130 ℃ to prepare a drink.
[제형예 5] 주사제Formulation Example 5 Injection
사이토칼라신 D 50mg, 주사용 멸균증류수 적량, pH조절제 적량을 이용하여 통상적인 방법으로 주사제를 제조하였다.Injectables were prepared in a conventional manner using cytokalcin D 50 mg, sterile distilled water titrant for injection, and a pH adjuster titrant.
[제형예 6] 유연화장수(스킨로션)Formulation Example 6 Softener (Skin Lotion)
사이토칼라신 D 3.0 중량%, L-아스코르빈산-2-인산마그네슘염 1.00 중량%, 수용성 콜라겐 (1% 수용액) 1.00 중량%, 시트르산나트륨 0.10 중량%, 시트르산 0.05중량%, 감초 엑기스 0.20 중량%, 1,3-부틸렌글리콜 3.00 중량%, 정제수 잔량을 이용하여 유연화장수(스킨로션)을 제조하였다. Cytocarcinin D 3.0 wt%, L-ascorbic acid-2-magnesium phosphate salt 1.00 wt%, water-soluble collagen (1% aqueous solution) 1.00 wt%, sodium citrate 0.10 wt%, citric acid 0.05 wt%, licorice extract 0.20 wt% , 1,3-butylene glycol 3.00% by weight, purified water (skin lotion) was prepared using the remaining amount of purified water.
[제형예 7] 크림Formulation Example 7 Cream
사이토칼라신 D 3.00중량%, 폴리에틸렌글리콜모노스테아레이트 2.00 중량%, 자기유화형 모노스테아르산글리세린 5.00 중량%, 프로필렌글리콜 4.00 중량%, 스쿠알렌 6.00 중량%, 트리2-에틸헥산글리세릴 6.00 중량%, 스핑고당지질 1.00 중량%, 1,3-부틸렌글리콜 7.00 중량%, 밀랍 5.00 중량%, 정제수 잔량을 사용하여 크림형 제제를 제조하였다. 3.00% by weight of cytoscalin D, 2.00% by weight of polyethylene glycol monostearate, 5.00% by weight of self-emulsifying monostearate, 4.00% by weight of propylene glycol, 6.00% by weight of squalene, 6.00% by weight of tri2-ethylhexaneglyceryl, A cream formulation was prepared using 1.00% by weight of sphingoglycolipids, 7.00% by weight of 1,3-butylene glycol, 5.00% by weight of beeswax and the balance of purified water.
[제형예 8] 팩[Formulation Example 8] Pack
사이토칼라신 D 3.00 중량%, 폴리비닐알코올 13.00 중량%, L-아스코르빈산-2-인산마그네슘염 1.00 중량%, 라우로일히드록시프롤린 1.00 중량%, 수용성 콜라겐 (1% 수용액) 2.00 중량%, 1,3-부틸렌글리콜 3.00 중량%, 에탄올 5.00 중량%, 정제수 잔량을 사용하여 팩을 제조하였다.3.00% by weight of cytoscalin D, 13.00% by weight of polyvinyl alcohol, 1.00% by weight of L-ascorbic acid-2-phosphate, 1.00% by weight of lauroylhydroxyproline, 2.00% by weight of water-soluble collagen (1% aqueous solution) , 1,3-butylene glycol 3.00% by weight, 5.00% by weight of ethanol, using the remaining amount of purified water to prepare a pack.
[제형예 9] 건강식품Formulation Example 9 Health Food
하기 표에 기재된 조성에 따라 통상적인 방법으로 건강 식품을 제조하였다.Health food was prepared by conventional methods according to the compositions described in the table below.
성분ingredient 함량content
사이토칼라신 DCytokalcin D 10㎎ 10mg
비타민 혼합물 Vitamin mixtures
비타민 A 아세테이트 Vitamin A Acetate 70 ㎍ 70 μg
비타민 E Vitamin E 1.0 ㎎1.0 mg
비타민 B1 Vitamin B1 0.13 ㎎0.13 mg
비타민 B2 Vitamin B2 0.15 ㎎0.15 mg
비타민 B6Vitamin B6 0.5 ㎎ 0.5 mg
비타민 B12Vitamin B12 0.2 ㎍ 0.2 μg
비타민 CVitamin c 10 ㎎ 10 mg
비오틴 Biotin 10 ㎍10 μg
니코틴산아미드 Nicotinic acid amide 1.7 ㎎1.7 mg
엽산 Folic acid 50 ㎍ 50 μg
판토텐산 칼슘Calcium Pantothenate 0.5 ㎎ 0.5 mg
무기질 혼합물 Mineral mixture
황산제1철 Ferrous sulfate 1.75 ㎎1.75 mg
산화아연 Zinc oxide 0.82 ㎎0.82 mg
탄산마그네슘Magnesium carbonate 25.3 ㎎ 25.3 mg
제1인산칼륨Potassium phosphate monobasic 15 ㎎ 15 mg
제2인산칼슘Dicalcium Phosphate 55 ㎎ 55 mg
구연산칼륨Potassium citrate 90 ㎎ 90 mg
탄산칼슘 Calcium carbonate 100 ㎎100 mg
염화마그네슘Magnesium chloride 24.8 ㎎ 24.8 mg
상기 비타민 및 무기질 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 예로 혼합 조성하였으나, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the vitamin and inorganic mixture is a composition that is relatively suitable for health foods, for example, the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method, and then the conventional method. According to the health food composition can be used.
[제형예 10] 건강음료Formulation Example 10 Health Drink
성분ingredient 함량content
사이토칼라신 DCytokalcin D 15㎎ 15mg
구연산 Citric acid 1000 ㎎1000 mg
올리고당 oligosaccharide 100 g100 g
매실농축액 Plum concentrate 2 g2 g
타우린Taurine 1 g 1 g
정제수Purified water 잔량Remaining amount
총 부피Total volume 900 ㎖900 ml
상기 표 2와 같이 총 부피 900㎖가 되도록 잔량의 정제수를 첨가하여 통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2리터 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관하여 건강음료를 제조하였다.As shown in Table 2, the remaining amount of purified water was added to a total volume of 900 ml, and the above ingredients were mixed according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ° C. for about 1 hour. Obtained in a sterilized 2 liter container, sterilized sealed, and then refrigerated to prepare a healthy beverage.
이상, 본 발명내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적인 기술은 단지 바람직한 실시태양일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의해 정의된다고 할 것이다.As described above, specific portions of the present disclosure have been described in detail, and for those skilled in the art, these specific techniques are merely preferred embodiments, and the scope of the present disclosure is not limited thereto. Will be obvious. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

  1. 사이토칼라신 D(Cytochalasin D), 이의 광학 또는 입체 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물을 유효성분으로 포함하는 피부 미백용 조성물.Cytochalasin D (Cytochalasin D), optical or stereoisomers thereof, acceptable salts thereof, hydrates thereof, or solvates thereof as an active ingredient.
  2. 제1항에 있어서, 상기 사이토칼라신 D는 곰팡이로부터 유래된 것인, 피부 미백용 조성물.The composition for skin whitening according to claim 1, wherein the cytocalin D is derived from a fungus.
  3. 제2항에 있어서, 상기 곰팡이는 자이고스포리움 만소니(Zygosporium mansonii)인, 피부 미백용 조성물.According to claim 2, The mold is Zygosporium mansonii , Zygosporium mansonii , the composition for skin whitening.
  4. 제1항에 있어서, 상기 사이토칼라신 D는 멜라닌 생성 또는 침착을 억제하는 것인, 피부 미백용 조성물.The composition for skin whitening according to claim 1, wherein the cytocalin D inhibits melanin production or deposition.
  5. 제1항에 있어서, 상기 사이토칼라신 D는 티로시나제(tyrosinase) 또는 TRP1(Tyrosinase-Related Protein 1)의 발현을 감소시키는 것인, 피부 미백용 조성물.According to claim 1, wherein the cytocalin D is to reduce the expression of tyrosinase (tyrosinase) or Tyrosinase-Related Protein 1 (TRP1), the composition for skin whitening.
  6. 제1항에 있어서, 상기 사이토칼라신 D는 기미, 주근깨, 흑색점, 모반, 흑색종, 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 색소 침착으로 이루어진 군에서 선택되는 하나 이상을 예방, 개선 또는 치료하는, 피부 미백용 조성물.The method according to claim 1, wherein the cytocalin D is composed of blemishes, freckles, melanoma, birthmarks, melanoma, pigmentation by ultraviolet light, pigmentation by drugs, pigmentation after inflammation, and pigmentation occurring in dermatitis A composition for whitening skin, which prevents, ameliorates or treats one or more selected from the group.
  7. 제1항에 있어서, 상기 조성물 내 사이토칼라신 D, 이의 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물의 함량은 상기 조성물 총중량 대비 0.0001 중량% 내지 20 중량%인, 피부 미백용 조성물.The composition for skin whitening according to claim 1, wherein the content of cytocalin D, an isomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof in the composition is 0.0001% to 20% by weight based on the total weight of the composition.
  8. 제1항에 있어서, 상기 사이토칼라신 D, 이의 이성질체, 이의 허용가능한 염, 이의 수화물, 또는 이의 용매화물의 투여량은 0.0001mg/kg/일 내지 20mg/kg/일인, 피부 미백용 조성물.The composition for skin whitening according to claim 1, wherein the dose of cytocarcin D, an isomer thereof, an acceptable salt thereof, a hydrate thereof, or a solvate thereof is 0.0001 mg / kg / day to 20 mg / kg / day.
  9. 제1항 내지 제8항 중 어느 한 항에 있어서, 상기 조성물은 약학 조성물인 피부 미백용 조성물.The composition for skin whitening according to any one of claims 1 to 8, wherein the composition is a pharmaceutical composition.
  10. 제1항 내지 제8항 중 어느 한 항에 있어서, 상기 조성물은 화장료 조성물인 피부 미백용 조성물.The composition for skin whitening according to any one of claims 1 to 8, wherein the composition is a cosmetic composition.
PCT/KR2017/008544 2016-08-24 2017-08-08 Skin-whitening composition containing cytochalasin d WO2018038425A1 (en)

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