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WO2018038425A1 - Composition de blanchiment de la peau contenant de la cytochalasine d - Google Patents

Composition de blanchiment de la peau contenant de la cytochalasine 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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English (en)
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/ja
Priority to CN201780065397.4A priority patent/CN109862891A/zh
Publication of WO2018038425A1 publication Critical patent/WO2018038425A1/fr

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    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic 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
    • A61K31/403—Heterocyclic 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
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics 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
    • A61K8/492—Cosmetics 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
    • 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
    • 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
    • A61K8/9728—Fungi, e.g. yeasts
    • 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
    • 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
    • A61Q19/02—Preparations 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

Un aspect de la présente invention concerne une composition de blanchiment de la peau contenant comme principe actif de la cytochalasine D, des isomères optiques ou stéréoscopiques de cette dernière, des sels pharmaceutiquement acceptables de cette dernière, des hydrates de cette dernière, ou des solvates de cette dernière. Selon un aspect de la présente invention, un nouveau matériau de blanchiment peut être fourni à des consommateurs, et le développement d'industries liées au blanchiment de la peau peut être favorisé.
PCT/KR2017/008544 2016-08-24 2017-08-08 Composition de blanchiment de la peau contenant de la cytochalasine d WO2018038425A1 (fr)

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JP2019506498A JP7038700B2 (ja) 2016-08-24 2017-08-08 サイトカラシンｄを含む皮膚美白用組成物
CN201780065397.4A CN109862891A (zh) 2016-08-24 2017-08-08 包含细胞松弛素d的用于皮肤美白组合物

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US11007176B2 (en) 2019-02-19 2021-05-18 Tzu Chi University Use of actin depolymerizing agents for the treatment of anxiety disorders

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JP7038700B2 (ja) 2022-03-18

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