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WO2020111621A1 - Composition for inhibiting hair loss or skin inflammation - Google Patents

Composition for inhibiting hair loss or skin inflammation Download PDF

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Publication number
WO2020111621A1
WO2020111621A1 PCT/KR2019/015797 KR2019015797W WO2020111621A1 WO 2020111621 A1 WO2020111621 A1 WO 2020111621A1 KR 2019015797 W KR2019015797 W KR 2019015797W WO 2020111621 A1 WO2020111621 A1 WO 2020111621A1
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Prior art keywords
composition
hair loss
skin inflammation
inhibiting hair
skin
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PCT/KR2019/015797
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French (fr)
Korean (ko)
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김세현
김수나
나용주
Original Assignee
(주)아모레퍼시픽
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Priority to CN201980078316.3A priority Critical patent/CN113164365A/en
Priority to JP2021521802A priority patent/JP7441217B2/en
Publication of WO2020111621A1 publication Critical patent/WO2020111621A1/en

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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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K36/13—Coniferophyta (gymnosperms)
    • A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
    • 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
    • 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
    • A61K8/60—Sugars; 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • 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
    • A61K8/9755—Gymnosperms [Coniferophyta]
    • A61K8/9761—Cupressaceae [Cypress family], e.g. juniper or cypress
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection

Definitions

  • the present invention relates to a composition for inhibiting hair loss or skin inflammation having an effect of inhibiting PTGDS (prostaglandin D2 synthase) activity, more specifically, amentoflavone (Amentoflavone) and; It relates to a composition containing at least one component selected from the group consisting of white porcelain extract, Genistein and Biochanin A, and inhibiting hair loss or skin inflammation through an excellent inhibitory effect on PTGDS.
  • PTGDS prostaglandin D2 synthase
  • amentoflavone Amentoflavone
  • the causes of hair loss include genetic factors, drug use, progression of aging, radiation therapy, and post-severe stress.
  • hair loss is known to be caused by hyperactivity, scalp blood circulation problems, and lack of nutrients essential for hair metabolism.
  • factors alone or in combination, accelerate alopecia and cause severe symptoms.
  • male hormone production, change, recognition, and signaling processes work excessively, which increases the likelihood of severe alopecia if hair follicle tissue ages prematurely.
  • Minoxidil has a capillary expansion function to prevent hair loss by applying to the scalp, but side effects such as itching, irritation, and active targets in hair loss treatment have not yet been clearly identified. I have a problem.
  • finasteride has an inhibitory effect on the production of male hormone DHT (5 ⁇ -dihydrotestosterone), which causes hair loss, and is known to have hair growth or hair loss suppression effects when taken for 6 months to 1 year. There is a problem of returning to the original state within 2 months, and it is known that side effects such as impaired fertility may occur.
  • Prostagladin D2 Synthase is an enzyme that produces Prostaglandin D2 (PGD2), which has been shown to be present at higher levels in the scalp in men with alopecia than in the scalp in men without alopecia. It is known to be an important factor causing (Garza et al . (2012) Sci . Transl . Med . 4, 126ra34).
  • PTGDS was found to modulate the inflammatory response through PGD2 ( R. Rajakariar et al., PNAS , 2007, 104 , 20979-20984) and inhibited the inflammatory response by inhibiting the activity of PTGDS as a mediator of the inflammatory response. can do.
  • the present inventors confirmed that the inflammatory reaction in the skin can be suppressed and the hair loss reaction can be suppressed by inhibiting the activity of PTGDS, and the present invention has been completed.
  • Patent Document 1 Korean Patent Registration No. 10-1766752 (Pharmaceutical composition containing minoxidil)
  • Patent Document 2 Republic of Korea Patent Publication No. 10-2015-0046332 (polymerized finasteride nanoparticles, aqueous composition including the same, composition for the treatment of hair loss and its manufacturing process and use of the composition)
  • the present inventors aim to provide a composition that effectively suppresses hair loss and skin inflammation while having fewer side effects due to continuous use.
  • the composition for inhibiting hair loss or skin inflammation is in the group consisting of amentoflavone (Amentoflavone) and white porcelain extract, Genistein and Bioanin A One or more ingredients selected.
  • the amentoflavone may be contained in an amount of 0.1 to 1,000 ppm based on the total weight of the composition.
  • the amentoflavone may be extracted from one or more selected from the group consisting of Buddha Hand, Rock Hand, Kwonbaek, Cypress and Bank.
  • the white porcelain extract may be contained in 10 to 10,000 ppm based on the total weight of the composition.
  • Genistein may be contained in an amount of 1 to 1,000 ppm based on the total weight of the composition.
  • Genistein (Genistein) may be extracted from one or more selected from the group consisting of soybean and isoflavone (Isoflavone).
  • the biochanin A may be contained in an amount of 10 to 1,000 ppm based on the total weight of the composition.
  • Biocyanin A may be extracted from one or more selected from the group consisting of Gangjinhyang, soybean, red shamrock, and isoflavone.
  • the composition can inhibit the activity of PTGDS (Prostagladin D2 Synthase) in vivo.
  • the composition for inhibiting hair loss or skin inflammation includes a cosmetic, and the formulation of the cosmetic can be selected from solutions, creams, lotions, shampoos, hair tonics, sprays, and gels.
  • composition for inhibiting hair loss or skin inflammation may be administered to the human body through transdermal injection or subcutaneous injection, and may be selected from external preparations for skin or oral administration.
  • the skin may include hair follicles and scalp.
  • the composition provided by the present invention contains at least one component selected from the group consisting of white porcelain extract, Genistein and Biochanin A in Amentoflavone, thereby inhibiting hair loss or skin inflammation. Synergy can be obtained.
  • the composition for inhibiting hair loss or skin inflammation of the present invention can be used for a long time using natural materials, but has no side effects.
  • 1 is a graph showing the results of PGD2 production inhibitory effect of PTDGS enzyme according to an embodiment of the present invention through an ELISA method.
  • Amentoflavone used as an active ingredient in the present invention has antioxidant activity (Mora A. et al., Biochem. Pharmacol., 40(4), pp793-7, 1990), lymphocyte proliferation inhibitory effect (Lee SJ. et al., Life Sci., 57(6), pp551-558, 1995), phospholipase C- ⁇ 1 enzyme activity inhibitory action (Lee HS. et al., Planta.Med., 1996, 62(4), pp293-296), anti-HIV action, anti-inflammatory action through inhibition of cyclooxygenase and lipoxygenase (Kim HP.
  • the amentoflavones can be extracted from one or more selected from the group consisting of Buddha hands, rock hands, rolls, cypresses, and banks.
  • the Buddha Hand is a perennial plant belonging to the Buddha Hand Family. It grows to about 5-20 cm, and the root derived from it is very hard and short, and has many beard roots.
  • the rock hand is a vascular plant belonging to the Buddha family, and it is characterized by growing on a rock and the end grows straight as the underground stem extends between the ground or the native plant.
  • Kwonbaek belongs to the family of the Buddha, and is a name given to it as a fist-shaped plant that dries when it dries into a flower plant attached to a rock.
  • Cypress is an evergreen tree of the Cypress family.
  • the leaves are obovate or ovate, and both sides are green or light yellow-green.
  • Ginkgo is a deciduous tree of the ginkgo family, the leaves are fan-shaped, and split into two at the center, but are not split and two or more.
  • Amentoflavone is represented by Formula 1 below.
  • the white porcelain ( Thujae semen ) used as an active ingredient in the present invention is a seed of the Thuja orientalis (occidentalis) ( Cypressaceae ) and is oval to long oval or long columnar.
  • Baekja-in is known to bring back a mustache or hair loss from the prescription of Samsung High in Donguibogam, and is included in prescriptions that are mainly used when the body becomes hungry or signs of aging, such as Saseongbulodan and Ban Ryong-hwan.
  • hair growth activity is high in two animal models, and it has been proven that it can be used as a useful substance for alopecia by controlling androgen conversion.
  • the white porcelain extract can be prepared by the following method. After extracting the white porcelain with 2 times the volume of 95% ethanol, filtering and concentrating, add 5 times the volume of water and 5 times the volume of ethyl acetate and shake to separate the layers. The water in the ethyl acetate layer is removed using magnesium sulfate, filtered and concentrated to obtain a white porcelain extract.
  • Genistein used as an active ingredient in the present invention is a plant-based estrogen analog, which promotes the replication of normal cells with a strong antioxidant effect, anti-inflammatory effect, and anti-cancer effect. SCI-class clinical papers have been published as ingredients that inhibit hair loss. Recently, clinical results have been reported as substances that inhibit photoaging. In one embodiment, it acts to promote the hormonal effect of genistein as an estrogen analog, cell regeneration effect, photoaging inhibition effect, hair loss suppression, and hair growth. Genistein, a type of polyphenol, may be separated and extracted from, for example, soybean isoflavone, but is not limited thereto.
  • Genistein (Genistein) is represented by the following formula (2).
  • Biochanin A used as an active ingredient in the present invention can be separated from one or more in the group consisting of, for example, Gangjinhyang, soybean, red shamrock, and isoflavone, but is not limited thereto.
  • Biochanin A is represented by Formula 3 below.
  • PTGDS activity is inhibited when it is combined by including at least one component selected from the group consisting of white porcelain extract, genistein, and biokanin A It was confirmed that the effect to be better.
  • the present invention provides a composition capable of effectively suppressing the activity of PTGDS to reduce the production of PGD2, which is a factor causing hair loss, to suppress the hair loss reaction, and to suppress the inflammatory reaction occurring in the skin.
  • the composition may be used as a pharmaceutical composition.
  • the pharmaceutical composition is a preservative, stabilizer, hydrating agent or emulsifying accelerator, salt and/or buffer for osmotic pressure control, in addition to an active ingredient comprising at least one component selected from the group consisting of amentoflavones and white porcelain extracts, genistein and biocyanin A It may further contain pharmaceutical adjuvants and other therapeutically useful substances, and may be formulated into various oral or parenteral dosage forms according to conventional methods.
  • the oral administration agent for example, tablets, pills, hard and soft capsules, liquids, suspensions, emulsifiers, syrups, powders, powders, granules, granules, pellets, etc.
  • these formulations are surfactants in addition to the active ingredient , Diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (e.g. 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, and optionally starch, agar, alginic acid or its sodium salt It may contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavoring agents and sweetening agents.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, and optionally starch, agar, alginic acid or its sodium salt It may contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavoring agents and sweetening agents.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, and optionally starch, agar, alginic acid or its sodium salt
  • agar alginic
  • parenteral dosage form may be a transdermal, subcutaneous, intravenous and intramuscular dosage form, for example, injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories ( ⁇ ), patch, etc., but is not limited thereto.
  • the dosage of the active ingredient is within the level of a person skilled in the art, and the daily dosage of the drug varies depending on various factors such as the degree of progression, onset time, age, health condition, and complications of the subject to be administered.
  • the dosage On the basis of the composition in one aspect 1 ⁇ g / kg to 200 mg / kg, in another aspect 50 ⁇ g / kg to 50 mg / kg can be administered by dividing 1 to 3 times a day, the dosage Does not limit the scope of the invention in any way.
  • the pharmaceutical composition may be an external preparation for skin, and the external preparation for skin may be a generic term that may include anything applied externally to the skin, and various types of pharmaceutical products may be included therein.
  • the composition may be used as a cosmetic composition.
  • the cosmetic composition may further include a functional additive and a component included in a general cosmetic composition in addition to the eluate of the Lactococcus lactis W-camellia strain.
  • the functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids, and seaweed extract.
  • oils and fats include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavors, blood circulation Accelerators, cooling agents, limiting agents, purified water, and the like.
  • the formulation of the cosmetic composition is not particularly limited, and may be appropriately selected according to the purpose.
  • skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing Foam, cleansing lotion, cleansing cream, body lotion and body cleanser may be prepared in any one or more formulations selected from the group consisting of, but is not limited thereto.
  • the cosmetic composition may be formulated to contain a cosmetic or dermatologically acceptable medium or base.
  • a cosmetic or dermatologically acceptable medium or base are all formulations suitable for topical application, for example solutions, gels, solids, dough anhydrous products, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) and ratios obtained by dispersing an oil phase in an aqueous phase.
  • It can be provided in the form of an ionic vesicle dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or conceal stick.
  • It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.
  • the cosmetic composition may be used as a scalp or hair composition. Therefore, the cosmetic composition is a formulation used for both scalp and hair, for example, shampoo, conditioner, scalp treatment, hair treatment, scalp hair combination treatment, hair loss prevention treatment, hair damage treatment, residual (leave- in) may be formulated as a scalp or hair such as a conditioner, a wash-off conditioner or a hair essence, a product that combines scalp and hair, and the like.
  • the formulation of the present invention is a paste, cream or gel, animal fibers, plant fibers, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
  • a carrier component such as silicone, bentonite, silica, talc or zinc oxide.
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane /Propellant such as butane or dimethyl ether.
  • a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester.
  • liquid diluents such as water, ethanol or propylene glycol as carrier components
  • suspensions such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.
  • the formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivatives, methyltaurate, sarcosinate, fatty acid amide ether as carrier components Sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linoline derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
  • composition according to an embodiment of the present invention may contain a pigment, a preservative, a metal ion blocker, a fragrance, etc. within a range maintaining stability.
  • the present invention also relates to a method for inhibiting hair loss or skin inflammation.
  • the method for inhibiting hair loss or skin inflammation includes applying the composition for inhibiting hair loss or skin inflammation as described above to a subject suffering from hair loss or skin inflammation.
  • the method for inhibiting hair loss or skin inflammation may mean a method for preventing, improving and/or treating hair loss or skin inflammation.
  • the composition for inhibiting hair loss or skin inflammation may be applied by applying to the skin, preferably, it is applied by applying to the scalp or inflammation where the hair loss phenomenon is concerned or the inflammation is concerned or the inflammation appears. Can be.
  • the composition is applied to the skin of the face, it can be more advantageous to get a good night's sleep by obtaining stability of the mind and body from the fragrance of citron oil beads.
  • the composition for inhibiting hair loss or skin inflammation may be applied to the scalp or skin once a day.
  • white porcelain extract, at least one component selected from the group consisting of Genistein and Biochanin A; inhibits the activity of PTGDS to reduce the production of PGD2, a factor that causes hair loss, thereby inhibiting the alopecia reaction
  • PGD2 a factor that causes hair loss
  • it may be advantageous to suppress hair loss or skin inflammation.
  • the composition for inhibiting hair loss or skin inflammation once a day, when applied to the skin for 3 to 8 weeks, may exhibit more improved hair loss or skin inflammation inhibitory effect.
  • the composition for inhibiting hair loss or skin inflammation exhibits excellent hair loss or skin inflammation suppression effect only by being applied to the skin once a day, and is usually used when continuously used for 3 weeks or more, preferably 3 weeks to 8 weeks. It can exhibit excellent hair loss or skin inflammation suppression effect.
  • the application amount of the composition for inhibiting hair loss or skin inflammation varies depending on the condition of the subject suffering from hair loss or skin inflammation, the degree of sleep disorder, the application area, and the composition type, and may be typically 25 mg to 150 mg, It can be applied by appropriately adjusting within the application amount range.
  • composition of the comparative example was prepared by using the same active ingredient used in Examples 1 to 3 alone but having a component content of 10 times. Specifically, after adding one of amentoflavone, white porcelain extract, Genistein and Biochanon A to 1000 ml of purified water, the mixture is stirred.
  • the content of specific active ingredients is shown in Table 1 below.
  • Test example > PTGDS Active inhibitory effect (ELISA assay)
  • Prostaglandin D2 is produced by treating prostaglandin H2 (PGH2), a substrate of enzymatic reaction, in PTGDS, after the composition prepared in Examples 1 to 3 is added together, The production reduction was measured to confirm the inhibitory effect of PTGDS activity.
  • the production amount of the PGD2 was measured by an enzyme-linked immunosorbent assay (ELISA) method.
  • Enzyme-linked immunosorbent assay (ELISA) was conducted in the following steps.
  • step (c) reacting the product of step (b) with a secondary antibody to which an enzyme is bound;
  • the activity of the enzyme is indicated by measuring the absorbance at 410 nm with an ELISA reader.
  • Suitable solid substrates are hydrocarbon polymers (such as polystyrene and polypropylene), glass, metals or gels, most preferably microtiter plates.
  • the enzyme bound to the secondary antibody includes, but is not limited to, an enzyme that catalyzes a color reaction, a fluorescence reaction, a luminescence reaction, or an infrared reaction, for example, alkaline phosphatase, ⁇ -galactosidase, hose Radish peroxidase, luciferase and cytochrome P450.
  • alkaline phosphatase When alkaline phosphatase is used as the enzyme that binds to the secondary antibody, bromochloroindolyl phosphate (BCIP), nitro blue tetrazolium (NBT), naphthol-ASB1-phosphate (naphthol-AS-B1) is used as the substrate.
  • BCIP bromochloroindolyl phosphate
  • NBT nitro blue tetrazolium
  • naphthol-ASB1-phosphate naphthol-AS-B1
  • Color reaction substrates such as -phosphate) and ECF (enhanced chemifluorescence) are used, and when hose-radish peroxidase is used, chloronaphthol, aminoethylcarbazole, diaminobenzidine, D-luciferin, and lucigenin (bis-N -Methylacridinium nitrate), resorphine benzyl ether, luminol, Amplex red reagent (10-acetyl-3,7-dihydroxyphenoxazin), TMB (3,3,5,5-tetramethylbenzidine), ABTS Substrates such as (2,2'-Azine-di[3-ethylbenzthiazoline sulfonate]) and o-phenylenediamine (OPD) can be used.
  • hose-radish peroxidase chloronaphthol, aminoethylcarbazole, diaminobenzidine, D-luciferin
  • tablets After mixing 100 mg of the composition prepared according to Examples 1 to 3 of the present invention, 400 mg of lactose, 400 mg of corn starch, and 2 mg of magnesium stearate, tablets were prepared by tableting according to a conventional tablet manufacturing method.
  • the capsules were prepared by filling the gelatin capsules according to a conventional capsule preparation method.
  • composition prepared according to Examples 1 to 3 of the present invention 50 mg of the composition prepared according to Examples 1 to 3 of the present invention, 250 mg of anhydrous crystalline glucose, and 550 mg of starch were mixed, molded into granules using a fluidized bed granulator, and then filled into the fabric.
  • Injections were prepared by conventional methods according to the composition shown in Table 2.
  • compositions prepared according to Examples 1 to 3 10-50 mg Sterile distilled water for injection Proper pH adjuster Proper
  • a softening agent was prepared by a conventional method.
  • compositions prepared according to Examples 1 to 3 0.2 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 PG-12 nonylphenyl ether 0.2 Polysorbate 80 0.4 ethanol 10.0 Triethanolamine 0.1 Preservatives, pigments, flavors Proper Purified water Balance
  • nutrient makeup was prepared by a conventional method.
  • compositions prepared according to Examples 1 to 3 1.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Wax 4.0 Polysorbate 60 1.5 Caprylic/Capric Triglyceride 5.0 Squalane 5.0 Solvitasesquioleate 1.5 Floating paraffin 0.5 Cetearyl alcohol 1.0 Triethanolamine 0.2 Preservatives, pigments, flavors Proper Purified water Balance
  • compositions prepared according to Examples 1 to 3 2.0 glycerin 8.0 Butylene glycol 4.0 Floating paraffin 45.0 Beta glucan 7.0 Carbomer 0.1 Caprylic/Capric Triglyceride 3.0 Wax 4.0 Cetearyl Glucoside 1.5 Sesqui oleic acid sorbitan 0.9 Vaseline 3.0 paraffin 1.5 Preservatives, pigments, flavors Proper Purified water Balance
  • a hair lotion was prepared according to a conventional method with the composition shown in Table 6 below.
  • compositions prepared according to Examples 1 to 3 2.0 Purified water Balance glycerin 3.0 Butylene glycol 3.0 Floating paraffin 7.0 Beta glucan 7.0 Carbomer 0.1 Edelweiss extract 2.0 Caprylic capric triglyceride 3.0 Squalene 5.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Polysorbate 1.2 antiseptic Proper incense Proper Coloring Proper Triethanol amine 0.1
  • a shampoo composition was prepared according to a conventional method with the composition shown in Table 7 below.
  • a hair treatment was prepared according to a conventional method with the composition shown in Table 8 below.
  • compositions prepared according to Examples 1 to 3 0.5 Stearamidopropyldimethylamine 2 glycerin 0.5 Spices 0.5 antiseptic 0.03 Cetostearyl alcohol 5 Lactic acid One Distilled water to 100

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Abstract

The present invention relates to a composition for inhibiting hair loss or skin inflammation, comprising: amentoflavone; and one or more ingredients selected from the group consisting of an extract of Thuja seeds, genistein, and biochanin A.

Description

탈모 또는 피부 염증 억제용 조성물Composition for inhibiting hair loss or skin inflammation
본 출원은 2018년 11월 29일자 한국 특허 출원 제10-2018-0150304호에 기초한 우선권의 이익을 주장하며, 해당 한국 특허 출원의 문헌에 개시된 모든 내용은 본 명세서의 일부로서 포함한다.This application claims the benefit of priority based on Korean Patent Application No. 10-2018-0150304 dated November 29, 2018, and all contents disclosed in the literature of the Korean patent application are included as part of this specification.
본 발명은 PTGDS(prostaglandin D2 synthase) 활성억제 효과를 갖는 탈모 또는 피부 염증 억제용 조성물에 관한 것으로, 보다 상세하게는 아멘토플라본(Amentoflavone) 및; 백자인 추출물, 제니스테인(Genistein) 및 비오카닌 A(Biochanin A)로 구성된 군에서 선택된 하나 이상의 성분을 포함하고, 우수한 PTGDS 활성억제 효과를 통해 탈모 또는 피부 염증을 억제하는 조성물에 관한 것이다.The present invention relates to a composition for inhibiting hair loss or skin inflammation having an effect of inhibiting PTGDS (prostaglandin D2 synthase) activity, more specifically, amentoflavone (Amentoflavone) and; It relates to a composition containing at least one component selected from the group consisting of white porcelain extract, Genistein and Biochanin A, and inhibiting hair loss or skin inflammation through an excellent inhibitory effect on PTGDS.
일반적으로 탈모의 원인으로는 유전적 요인, 약물 복용, 노화의 진행, 방사선 치료 및 중병 후 스트레스 등을 들 수 있다. 또한 생화학적 관점이나 생리학적 관점에서 탈모 현상은 과다 활동, 두피 혈액순환의 문제 및 모발대사에 필수적인 영양소의 결핍에 의한 것으로 알려져 있다. 이와 같은 요인들이 단독 또는 복합되어 탈모증을 가속화하고 증상이 심해지게 된다. 특히, 유전적 요인 또는 후천적 요인으로 인하여 남성호르몬의 생성, 변화, 인식 및 신호전달 과정이 과도하게 작동하므로 모낭 조직이 조기 노화될 경우 탈모증이 심해질 확률이 높아진다. In general, the causes of hair loss include genetic factors, drug use, progression of aging, radiation therapy, and post-severe stress. In addition, from a biochemical point of view or a physiological point of view, hair loss is known to be caused by hyperactivity, scalp blood circulation problems, and lack of nutrients essential for hair metabolism. These factors, alone or in combination, accelerate alopecia and cause severe symptoms. In particular, due to genetic or acquired factors, male hormone production, change, recognition, and signaling processes work excessively, which increases the likelihood of severe alopecia if hair follicle tissue ages prematurely.
탈모치료를 위해 현재까지 다양한 시도가 이루어져 왔는데, 외과적인 방법으로는 두피피판술, 탈모부위축소술 및 조직확장술에 의한 두피성형술과 자가모발 이식술 등이 있다. 상기 외과적 치료 방법은 효과면에서 우수한 점이 있으나, 환자의 경제적, 정신적 부담이 매우 커서 널리 이용되지 어렵다는 단점을 가지고 있다.Various attempts have been made to treat hair loss, and surgical methods include scalp flap surgery, alopecia reduction and scalp surgery by tissue expansion and autologous hair transplantation. The surgical treatment method has an advantage in terms of effectiveness, but has a disadvantage that it is difficult to be widely used because the patient's economic and mental burden is very large.
이 외 다양한 치료제가 사용되고 있는데, 대표적인 외용제인 미녹시딜(Minoxidil)은 모세혈관 확장 기능이 있어 두피에 바름으로써 탈모를 방지하지만, 가려움증, 자극 등의 부작용과 탈모치료에서 능동표적이 아직 확실하게 밝혀지지 않았다는 문제를 가지고 있다. 내복약인 피나스테라이드(finasteride)는 탈모를 유발하는 남성 호르몬인 DHT(5α-dihydrotestosterone) 생성 억제 작용을 갖고 있으며, 6개월에서 1년 정도 복용 시 발모 또는 탈모억제 효과가 나타나는 것으로 알려져 있으나, 복용을 중단하면 2개월 내에 원래 상태로 돌아가는 문제점이 있으며, 생식 능력 장애 등의 부작용이 발생할 수 있다고 알려져 있다.Various other treatments are used, and the representative external agent, Minoxidil, has a capillary expansion function to prevent hair loss by applying to the scalp, but side effects such as itching, irritation, and active targets in hair loss treatment have not yet been clearly identified. I have a problem. As an internal medicine, finasteride has an inhibitory effect on the production of male hormone DHT (5α-dihydrotestosterone), which causes hair loss, and is known to have hair growth or hair loss suppression effects when taken for 6 months to 1 year. There is a problem of returning to the original state within 2 months, and it is known that side effects such as impaired fertility may occur.
따라서 부작용이 없고 인체에 무해하며 탈모 억제효과가 있는 탈모억제제의 개발이 지속적으로 요구되고 있는 실정이다.Therefore, there is a continuous need to develop a hair loss inhibitor that has no side effects, is harmless to the human body, and has an effect of suppressing hair loss.
PTGDS(Prostagladin D2 Synthase)는 프로스타글라딘(Prostaglandin) D2(PGD2)를 생성하는 효소로서, PGD2는 탈모증이 없는 남성의 두피에서 보다 탈모증을 갖는 남성의 두피에서 더 높은 수준으로 존재한다는 것이 밝혀져 탈모를 일으키는 중요한 요소로 알려져 있다(Garza et al.(2012) Sci . Transl . Med . 4, 126ra34). 또한, PTGDS는 PGD2를 통해서 염증반응을 조절하는 것으로 밝혀졌고(R. Rajakariar et al., PNAS , 2007, 104, 20979-20984), 염증반응의 매개물질로서 PTGDS의 활성을 억제하여 염증반응을 저해할 수 있다. Prostagladin D2 Synthase (PTGDS) is an enzyme that produces Prostaglandin D2 (PGD2), which has been shown to be present at higher levels in the scalp in men with alopecia than in the scalp in men without alopecia. It is known to be an important factor causing (Garza et al . (2012) Sci . Transl . Med . 4, 126ra34). In addition, PTGDS was found to modulate the inflammatory response through PGD2 ( R. Rajakariar et al., PNAS , 2007, 104 , 20979-20984) and inhibited the inflammatory response by inhibiting the activity of PTGDS as a mediator of the inflammatory response. can do.
이에, 본 발명자들은 PTGDS의 활성을 억제함으로써 피부에서의 염증 반응을 억제함과 동시에 탈모 반응도 억제할 수 있음을 확인하고 본 발명을 완성하게 되었다.Accordingly, the present inventors confirmed that the inflammatory reaction in the skin can be suppressed and the hair loss reaction can be suppressed by inhibiting the activity of PTGDS, and the present invention has been completed.
[선행기술문헌][Advanced technical literature]
[특허문헌][Patent Document]
(특허문헌 1) 대한민국 등록특허 제10-1766752호 (미녹시딜을 함유하는 약제학적 조성물)(Patent Document 1) Korean Patent Registration No. 10-1766752 (Pharmaceutical composition containing minoxidil)
(특허문헌 2) 대한민국 공개특허 제10-2015-0046332호 (중합 피나스테리드 나노입자, 이를 포함한 수성 조성물, 탈모 치료를 위한 조성물 및 이의 제조 공정 및 이 조성물의 용도)(Patent Document 2) Republic of Korea Patent Publication No. 10-2015-0046332 (polymerized finasteride nanoparticles, aqueous composition including the same, composition for the treatment of hair loss and its manufacturing process and use of the composition)
본 발명자들은 상기와 같은 문제점을 해결하기 위하여, 지속적인 사용에 따른 부작용이 적으면서 탈모 및 피부 염증을 효과적으로 억제하는 조성물을 제공하는 것을 목적으로 한다.In order to solve the above problems, the present inventors aim to provide a composition that effectively suppresses hair loss and skin inflammation while having fewer side effects due to continuous use.
상기 목적을 달성하기 위하여, 본 발명의 일 실시예에 따른 탈모 또는 피부 염증 억제용 조성물은 아멘토플라본(Amentoflavone) 및 백자인 추출물, 제니스테인(Genistein) 및 비오카닌 A(Biochanin A)로 구성된 군에서 선택된 하나 이상의 성분을 포함한다.In order to achieve the above object, the composition for inhibiting hair loss or skin inflammation according to an embodiment of the present invention is in the group consisting of amentoflavone (Amentoflavone) and white porcelain extract, Genistein and Bioanin A One or more ingredients selected.
상기 아멘토플라본(Amentoflavone)은 상기 조성물 총 중량에 대하여 0.1 내지 1,000 ppm 함유될 수 있다. 아멘토플라본은 부처손, 바위손, 권백, 편백 및 은행으로 구성된 군에서 선택된 하나 이상으로부터 추출된 것 일 수 있다.The amentoflavone (Amentoflavone) may be contained in an amount of 0.1 to 1,000 ppm based on the total weight of the composition. The amentoflavone may be extracted from one or more selected from the group consisting of Buddha Hand, Rock Hand, Kwonbaek, Cypress and Bank.
상기 백자인 추출물은 상기 조성물 총 중량에 대하여 10 내지 10,000 ppm 함유될 수 있다. The white porcelain extract may be contained in 10 to 10,000 ppm based on the total weight of the composition.
제니스테인(Genistein)은 상기 조성물 총 중량에 대하여 1 내지 1,000 ppm 함유될 수 있다. 제니스테인(Genistein)은 콩 및 이소플라본(Isoflavone) 으로 구성된 군에서 선택된 하나 이상으로부터 추출된 것 일 수 있다.Genistein may be contained in an amount of 1 to 1,000 ppm based on the total weight of the composition. Genistein (Genistein) may be extracted from one or more selected from the group consisting of soybean and isoflavone (Isoflavone).
상기 비오카닌 A(Biochanin A)는 상기 조성물 총 중량에 대하여 10 내지 1,000 ppm 함유될 수 있다. 비오카닌 A는 강진향, 콩, 붉은토끼풀 및 이소플라본(Isoflavone)으로 구성된 군에서 선택된 하나 이상으로부터 추출된 것일 수 있다.The biochanin A may be contained in an amount of 10 to 1,000 ppm based on the total weight of the composition. Biocyanin A may be extracted from one or more selected from the group consisting of Gangjinhyang, soybean, red shamrock, and isoflavone.
상기 조성물은 생체 내 PTGDS(Prostagladin D2 Synthase)의 활성을 억제할 수 있다. 상기 탈모 또는 피부 염증 억제용 조성물은 화장료를 포함하고, 화장료의 제형은 용액, 크림, 로션, 샴푸, 헤어토닉, 스프레이 및 겔 중 선택될 수 있다.The composition can inhibit the activity of PTGDS (Prostagladin D2 Synthase) in vivo. The composition for inhibiting hair loss or skin inflammation includes a cosmetic, and the formulation of the cosmetic can be selected from solutions, creams, lotions, shampoos, hair tonics, sprays, and gels.
상기 탈모 또는 피부 염증 억제용 조성물은 경피주사 또는 피하주사를 통해 인체에 투여될 수 있으며, 피부 외용제 또는 경구 투여제 중 선택될 수 있다.The composition for inhibiting hair loss or skin inflammation may be administered to the human body through transdermal injection or subcutaneous injection, and may be selected from external preparations for skin or oral administration.
상기 피부는 모낭 및 두피를 포함할 수 있다.The skin may include hair follicles and scalp.
본 발명의 의해 제공되는 조성물은 아멘토플라본(Amentoflavone)에 백자인 추출물, 제니스테인(Genistein) 및 비오카닌 A(Biochanin A)로 구성된 군에서 선택된 하나 이상의 성분을 함유함으로써, 탈모 또는 피부 염증을 억제하는 시너지 효과를 획득할 수 있다. 또한, 본 발명의 탈모 또는 피부 염증 억제용 조성물은 천연물질을 사용하여 장기간 사용이 가능하면서도 부작용이 없다.The composition provided by the present invention contains at least one component selected from the group consisting of white porcelain extract, Genistein and Biochanin A in Amentoflavone, thereby inhibiting hair loss or skin inflammation. Synergy can be obtained. In addition, the composition for inhibiting hair loss or skin inflammation of the present invention can be used for a long time using natural materials, but has no side effects.
도 1은 본 발명의 일 실시예에 따른 PTDGS 효소의 PGD2 생성 억제효과를 ELISA 방법을 통해 나타낸 결과 그래프이다.1 is a graph showing the results of PGD2 production inhibitory effect of PTDGS enzyme according to an embodiment of the present invention through an ELISA method.
이하, 본 발명에 대한 이해를 돕기 위하여 본 발명을 더욱 상세하게 설명한다.Hereinafter, the present invention will be described in more detail to aid understanding of the present invention.
본 발명에서 유효성분으로 사용하는 아멘토플라본(Amentoflavone)은 항산화 작용(Mora A. et al., Biochem. Pharmacol., 40(4), pp793-7, 1990), 림프구 증식(lymphocyte proliferation) 억제 작용(Lee SJ. et al., Life Sci., 57(6), pp551-558, 1995), 포스포리파아제(phospholipase) C-γ1 효소 활성 억제 작용(Lee HS. et al., Planta. Med., 1996, 62(4), pp293-296), 항-HIV 작용, 시클로옥시게나제(cyclooxygenase) 및 리폭시게나아제 (lipoxygenase)의 억제를 통한 항염증 작용(Kim HP. et al., Prostaglandins Leukot Essent Fatty Acids, 58(1), pp17-24, 1998), cAMP-인디에스테라제(cAMP-phosphodiesterase) 억제 작용, 바이러스에 대한 항생 작용, 항균 작용 등에 대해 연구되었다(Kim HK. et al., Arch. Pharm. Res., 21(4), pp406-410, 1998; Lin YM. et al., Planta. Med., 65(2), pp120-125, 1999; Krauze-Baranowska M. et al., Planta. Med., 65(6), pp572-573, 1999).Amentoflavone used as an active ingredient in the present invention has antioxidant activity (Mora A. et al., Biochem. Pharmacol., 40(4), pp793-7, 1990), lymphocyte proliferation inhibitory effect (Lee SJ. et al., Life Sci., 57(6), pp551-558, 1995), phospholipase C-γ1 enzyme activity inhibitory action (Lee HS. et al., Planta.Med., 1996, 62(4), pp293-296), anti-HIV action, anti-inflammatory action through inhibition of cyclooxygenase and lipoxygenase (Kim HP. et al., Prostaglandins Leukot Essent Fatty Acids, 58(1), pp17-24, 1998), cAMP-phosphodiesterase (cAMP-phosphodiesterase) inhibitory action, antiviral action against viruses, antibacterial action, etc. were studied (Kim HK. et al., Arch. Pharm. Res., 21(4), pp406-410, 1998; Lin YM. et al., Planta.Med., 65(2), pp120-125, 1999; Krauze-Baranowska M. et al., Planta. Med., 65(6), pp572-573, 1999).
아멘토플라본은 부처손, 바위손, 권백, 편백 및 은행으로 구성된 군에서 선택된 하나 이상으로부터 추출될 수 있다. 부처손은 부처손과에 속하는 여러해살이풀로 5∼20cm 내외로 자라고 밑에서 파생된 근경은 매우 단단하고 짧으며, 많은 수염뿌리가 나는 특징이 있다. 바위손은 부처손과에 속하는 관다발식물이며, 바위 위에서 자라 땅속줄기가 땅속이나 선태식물 사이로 뻗으면서 끝이 곧게 자라는 것이 특징이다. 권백은 부처손과에 속하며, 바위에 붙어사는 민꽃식물로 말리면 주먹모양으로 생겨서 붙여진 이름이다. 편백은 측백나무과의 상록교목으로 잎은 도란형 또는 난형이고 양면이 모두 녹색이거나 연한 황록색이다. 은행은 은행나무과의 낙엽교목으로 잎은 부채꼴이며 중앙에서 2개로 갈라지지만 갈라지지 않는 것과 2개 이상 갈라지는 것 등이 있다.The amentoflavones can be extracted from one or more selected from the group consisting of Buddha hands, rock hands, rolls, cypresses, and banks. The Buddha Hand is a perennial plant belonging to the Buddha Hand Family. It grows to about 5-20 cm, and the root derived from it is very hard and short, and has many beard roots. The rock hand is a vascular plant belonging to the Buddha family, and it is characterized by growing on a rock and the end grows straight as the underground stem extends between the ground or the native plant. Kwonbaek belongs to the family of the Buddha, and is a name given to it as a fist-shaped plant that dries when it dries into a flower plant attached to a rock. Cypress is an evergreen tree of the Cypress family. The leaves are obovate or ovate, and both sides are green or light yellow-green. Ginkgo is a deciduous tree of the ginkgo family, the leaves are fan-shaped, and split into two at the center, but are not split and two or more.
아멘토플라본(Amentoflavone)은 하기 화학식 1로 표시된다.Amentoflavone is represented by Formula 1 below.
<화학식 1><Formula 1>
Figure PCTKR2019015797-appb-I000001
Figure PCTKR2019015797-appb-I000001
본 발명에서 유효성분으로 사용하는 백자인(Thujae semen)은 측백나무(Thuja orientalis(occidentalis) (측백나무과)Curpressaceae)의 종자로서 난원형에서 긴 타원형이거나 또는 긴 원주형이다. 백자인은 동의보감 삼성고(三聖膏) 처방에 콧수염이나 머리털이 빠진 것을 다시 나오게 한다고 알려져 있으며 사성불로단 및 반룡환 등 주로 몸이 허해졌거나 노화 증상이 나타났을 때 사용하는 처방에 포함되어 있다. 또한 현대과학적 측면에서는 2가지 동물모델에서 육모활성이 높게 나타나 안드로젠 변환을 조절하여 탈모증에 유용한 물질로써 사용될 수 있음이 입증된 바 있다.The white porcelain ( Thujae semen ) used as an active ingredient in the present invention is a seed of the Thuja orientalis (occidentalis) ( Cypressaceae ) and is oval to long oval or long columnar. Baekja-in is known to bring back a mustache or hair loss from the prescription of Samsung High in Donguibogam, and is included in prescriptions that are mainly used when the body becomes hungry or signs of aging, such as Saseongbulodan and Ban Ryong-hwan. In addition, in the modern scientific aspect, hair growth activity is high in two animal models, and it has been proven that it can be used as a useful substance for alopecia by controlling androgen conversion.
본 발명에서는 예를 들어 하기와 같은 방법으로 백자인 추출물을 제조할 수 있다. 백자인을 2배 용량의 95% 에탄올로 추출하여 여과, 농축한 후 5배 용량의 물과 5배 용량의 에틸아세테이트를 넣어 진탕하여 층을 분리한다. 에틸아세테이트층의 수분을 황산마그네슘을 이용하여 제거하고 여과, 농축하여 백자인 추출물을 얻는다.In the present invention, for example, the white porcelain extract can be prepared by the following method. After extracting the white porcelain with 2 times the volume of 95% ethanol, filtering and concentrating, add 5 times the volume of water and 5 times the volume of ethyl acetate and shake to separate the layers. The water in the ethyl acetate layer is removed using magnesium sulfate, filtered and concentrated to obtain a white porcelain extract.
본 발명에서 유효성분으로 사용하는 제니스테인(Genistein)은 식물계의 에스트로겐 유사체로서 강력한 항산화 효과, 항염증 효과, 항암 효과와 함께 정상세포의 복제를 촉진한다. 탈모를 억제하는 성분으로 SCI급 임상논문이 게재되었으며, 최근에는 광노화를 억제하는 물질로도 임상결과가 보고되었다. 일 구현예에서는 제니스테인의 에스트로겐 유사체로서의 호르몬 효과, 세포재생효과, 광노화 억제 효과, 탈모 억제 및 육모를 촉진하는 작용을 한다. 폴리페놀의 일종인 제니스테인은 예를 들어 대두 이소플라본(isoflavone)에서 분리 추출할 수 있으나, 이에 제한되는 것은 아니다.Genistein (Genistein) used as an active ingredient in the present invention is a plant-based estrogen analog, which promotes the replication of normal cells with a strong antioxidant effect, anti-inflammatory effect, and anti-cancer effect. SCI-class clinical papers have been published as ingredients that inhibit hair loss. Recently, clinical results have been reported as substances that inhibit photoaging. In one embodiment, it acts to promote the hormonal effect of genistein as an estrogen analog, cell regeneration effect, photoaging inhibition effect, hair loss suppression, and hair growth. Genistein, a type of polyphenol, may be separated and extracted from, for example, soybean isoflavone, but is not limited thereto.
제니스테인(Genistein)은 하기 화학식 2로 표시된다.Genistein (Genistein) is represented by the following formula (2).
<화학식 2><Formula 2>
Figure PCTKR2019015797-appb-I000002
Figure PCTKR2019015797-appb-I000002
본 발명에서 유효성분으로 사용하는 비오카닌 A(Biochanin A)는 예를 들어 강진향, 콩, 붉은토끼풀 및 이소플라본으로 구성된 군에서 하나 이상으로부터 분리할 수 있으나 이에 제한되는 것은 아니다.Biochanin A (Biochanin A) used as an active ingredient in the present invention can be separated from one or more in the group consisting of, for example, Gangjinhyang, soybean, red shamrock, and isoflavone, but is not limited thereto.
비오카닌 A(Biochanin A)은 하기 화학식 3으로 표시된다.Biochanin A is represented by Formula 3 below.
<화학식 3><Formula 3>
Figure PCTKR2019015797-appb-I000003
Figure PCTKR2019015797-appb-I000003
본 발명의 일 실시예에서, 아멘토플라본을 단독 유효성분으로 포함하는 조성물에 비해, 추가적으로 백자인 추출물, 제니스테인 및 비오카닌 A로 구성된 군에서 선택된 하나 이상의 성분을 포함하여 조합할 경우 PTGDS 활성을 억제하는 효과가 더 우수한 것으로 확인되었다.In one embodiment of the present invention, compared to a composition containing amentoflavone as the sole active ingredient, PTGDS activity is inhibited when it is combined by including at least one component selected from the group consisting of white porcelain extract, genistein, and biokanin A It was confirmed that the effect to be better.
즉, 본 발명은 효과적으로 PTGDS의 활성을 억제하여 탈모를 일으키는 요소인 PGD2의 생성을 감소시켜 탈모반응을 억제하고, 피부에서 발생되는 염증반응을 억제할 수 있는 조성물을 제공한다.That is, the present invention provides a composition capable of effectively suppressing the activity of PTGDS to reduce the production of PGD2, which is a factor causing hair loss, to suppress the hair loss reaction, and to suppress the inflammatory reaction occurring in the skin.
본 발명의 일 실시예에서, 상기 조성물은 약학 조성물로 사용될 수 있다.In one embodiment of the present invention, the composition may be used as a pharmaceutical composition.
상기 약학 조성물은 아멘토플라본과 백자인 추출물, 제니스테인 및 비오카닌 A로 구성된 군에서 선택된 하나 이상의 성분을 포함하는 유효성분 이외에 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 제형화 할 수 있다.The pharmaceutical composition is a preservative, stabilizer, hydrating agent or emulsifying accelerator, salt and/or buffer for osmotic pressure control, in addition to an active ingredient comprising at least one component selected from the group consisting of amentoflavones and white porcelain extracts, genistein and biocyanin A It may further contain pharmaceutical adjuvants and other therapeutically useful substances, and may be formulated into various oral or parenteral dosage forms according to conventional methods.
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 administration agent, for example, tablets, pills, hard and soft capsules, liquids, suspensions, emulsifiers, syrups, powders, powders, granules, granules, pellets, etc., these formulations are surfactants in addition to the active ingredient , Diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (e.g. 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, and optionally starch, agar, alginic acid or its sodium salt It may contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavoring agents and sweetening agents. The tablets can be prepared by conventional mixing, granulating or coating methods.
또한, 상기 비경구 투여 형태로는 경피, 피하, 정맥 및 근육 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, subcutaneous, intravenous and intramuscular dosage form, for example, injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories (坐劑), patch, etc., but is not limited thereto.
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 달라지지만, 성인을 기준으로 할 때 일 측면에서 상기 조성물 1 ㎍/㎏ 내지 200 ㎎/㎏, 다른 일 측면에서 50 ㎍/㎏ 내지 50 ㎎/㎏을 1일 1 내지 3회 분할하여 투여할 수 있으며, 상기 투여량은 어떠한 방법으로도 본 발명의 범위를 한정하는 것이 아니다.Determination of the dosage of the active ingredient is within the level of a person skilled in the art, and the daily dosage of the drug varies depending on various factors such as the degree of progression, onset time, age, health condition, and complications of the subject to be administered. On the basis of the composition in one aspect 1 ㎍ / ㎏ to 200 ㎎ / ㎏, in another aspect 50 ㎍ / ㎏ to 50 ㎎ / ㎏ can be administered by dividing 1 to 3 times a day, the dosage Does not limit the scope of the invention in any way.
상기 약학 조성물은 피부 외용제일 수 있으며, 상기 피부 외용제는 피부 외부에서 도포되는 어떠한 것이라도 포함될 수 있는 총칭으로서 다양한 제형의 의약품이 여기에 포함될 수 있다.The pharmaceutical composition may be an external preparation for skin, and the external preparation for skin may be a generic term that may include anything applied externally to the skin, and various types of pharmaceutical products may be included therein.
본 발명의 일 실시예에서, 상기 조성물은 화장료 조성물로 사용될 수 있다. 상기 화장료 조성물에는 락토코커스 락티스 W-camellia 균주의 용출물 이외에 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, 알코올, 색소, 향료, 혈행 촉진제, 냉감제, 제한(制汗)제, 정제수 등을 들 수 있다.In one embodiment of the present invention, the composition may be used as a cosmetic composition. The cosmetic composition may further include a functional additive and a component included in a general cosmetic composition in addition to the eluate of the Lactococcus lactis W-camellia strain. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids, and seaweed extract. Other ingredients included include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavors, blood circulation 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 formulation of the cosmetic composition is not particularly limited, and may be appropriately selected according to the purpose. For example, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing Foam, cleansing lotion, cleansing cream, body lotion and body cleanser may be prepared in any one or more formulations selected from the group consisting of, but is not limited thereto.
또한, 상기 화장료 조성물은 화장품학 또는 피부과학적으로 허용가능한 매질 또는 기제를 함유하여 제형화 될 수 있다. 이는 국소적용에 적합한 모든 제형으로서, 예를 들면, 용액, 겔, 고체, 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는 이온형(리포좀) 및 비이온형의 소낭 분산제의 형태로, 또는 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱의 형태로 제공될 수 있다. 또한 포말(foam)의 형태로 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 사용될 수 있다. 이들 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다.In addition, the cosmetic composition may be formulated to contain a cosmetic or dermatologically acceptable medium or base. These are all formulations suitable for topical application, for example solutions, gels, solids, dough anhydrous products, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) and ratios obtained by dispersing an oil phase in an aqueous phase. It can be provided in the form of an ionic vesicle dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or conceal stick. It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant. These compositions can be prepared according to conventional methods in the art.
이뿐만 아니라, 상기 화장료 조성물은 두피용 또는 모발용 조성물 등으로 사용될 수 있다. 따라서 상기 화장료 조성물은 두피 및 모발에 함께 사용하는 제형, 예를 들어 샴푸, 린스, 스칼프트리트먼트, 헤어트리트먼트, 두피 모발 겸용 트리트먼트, 탈모 방지 모발용 트리트먼트, 손상모발용 트리트먼트, 잔류(leave-in) 컨디셔너, 워시오프(wash-off) 컨디셔너 또는 헤어 에센스 등 두피 또는 모발, 두피 및 모발 겸용 제품 등으로 제형화될 수 있다.In addition to this, the cosmetic composition may be used as a scalp or hair composition. Therefore, the cosmetic composition is a formulation used for both scalp and hair, for example, shampoo, conditioner, scalp treatment, hair treatment, scalp hair combination treatment, hair loss prevention treatment, hair damage treatment, residual (leave- in) may be formulated as a scalp or hair such as a conditioner, a wash-off conditioner or a hair essence, a product that combines scalp and hair, and the like.
본 발명의 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 of the present invention is a paste, cream or gel, animal fibers, plant fibers, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. Can be.
본 발명의 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 of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane /Propellant such as butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액의 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester.
본 발명의 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 of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, suspensions such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.
본 발명의 제형이 계면활성제 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 formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivatives, methyltaurate, sarcosinate, fatty acid amide ether as carrier components Sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linoline derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
한편, 본 발명의 일실시예에 따른 조성물은 안정도를 유지하는 범위 내에서 색소, 방부제, 금속이온 봉쇄제, 향 등을 함유할 수 있다. On the other hand, the composition according to an embodiment of the present invention may contain a pigment, a preservative, a metal ion blocker, a fragrance, etc. within a range maintaining stability.
탈모 또는 피부 염증 억제 방법How to suppress hair loss or skin inflammation
본 발명은 또한, 탈모 또는 피부 염증 억제 방법에 관한 것이다. 상기 탈모 또는 피부 염증 억제 방법은, 상술한 바와 같은 탈모 또는 피부 염증 억제용 조성물을, 탈모 또는 피부 염증을 겪는 대상에게 적용하는 단계를 포함한다. 상기 탈모 또는 피부 염증 억제 방법은 탈모 또는 피부 염증을 예방, 개선 및/또는 치료 방법을 의미하는 것일 수 있다. The present invention also relates to a method for inhibiting hair loss or skin inflammation. The method for inhibiting hair loss or skin inflammation includes applying the composition for inhibiting hair loss or skin inflammation as described above to a subject suffering from hair loss or skin inflammation. The method for inhibiting hair loss or skin inflammation may mean a method for preventing, improving and/or treating hair loss or skin inflammation.
이때, 상기 탈모 또는 피부 염증 억제용 조성물은 피부에 도포하여 적용하는 것일 수 있으며, 바람직하게는, 탈모 현상이 염려되거나 탈모 현상이 나타난 두피 또는 염증이 염려되거나 염증이 나타난 피부에 도포하여 적용하는 것일 수 있다. 상기 조성물을 얼굴 피부에 도포할 경우, 유자 오일 비드의 향으로부터 심신의 안정을 얻어 숙면을 취하는데 더욱 유리할 수 있다.At this time, the composition for inhibiting hair loss or skin inflammation may be applied by applying to the skin, preferably, it is applied by applying to the scalp or inflammation where the hair loss phenomenon is concerned or the inflammation is concerned or the inflammation appears. Can be. When the composition is applied to the skin of the face, it can be more advantageous to get a good night's sleep by obtaining stability of the mind and body from the fragrance of citron oil beads.
또한, 상기 탈모 또는 피부 염증 억제용 조성물은 하루에 1회, 두피 또는 피부에 도포하는 것일 수 있다. 상기 조성물에 포함된 아멘토플라본(Amentoflavone); 및 백자인 추출물, 제니스테인(Genistein) 및 비오카닌 A(Biochanin A)로 구성된 군에서 선택된 하나 이상의 성분;의 조합이 PTGDS의 활성을 억제하여 탈모를 일으키는 요소인 PGD2의 생성을 감소시켜 탈모반응을 억제하고, 피부에서 발생되는 염증반응을 억제시켜, 탈모 또는 피부 염증 억제에 유리할 수 있다. In addition, the composition for inhibiting hair loss or skin inflammation may be applied to the scalp or skin once a day. Amentoflavone contained in the composition (Amentoflavone); And white porcelain extract, at least one component selected from the group consisting of Genistein and Biochanin A; inhibits the activity of PTGDS to reduce the production of PGD2, a factor that causes hair loss, thereby inhibiting the alopecia reaction And, by suppressing the inflammatory reaction occurring in the skin, it may be advantageous to suppress hair loss or skin inflammation.
또한, 상기 탈모 또는 피부 염증 억제용 조성물은 하루에 1회, 3주 내지 8주 동안 피부에 도포시, 더욱 개선된 탈모 또는 피부 염증 억제 효과를 나타낼 수 있다. 상기 탈모 또는 피부 염증 억제용 조성물은 하루 1회 피부에 적용하는 것만으로도 우수한 탈모 또는 피부 염증 억제 효과를 나타내며, 통상, 3주 이상, 바람직하게는 3주 내지 8주 동안 지속적으로 사용했을 때 매우 우수한 탈모 또는 피부 염증 억제 효과를 나타낼 수 있다.In addition, the composition for inhibiting hair loss or skin inflammation once a day, when applied to the skin for 3 to 8 weeks, may exhibit more improved hair loss or skin inflammation inhibitory effect. The composition for inhibiting hair loss or skin inflammation exhibits excellent hair loss or skin inflammation suppression effect only by being applied to the skin once a day, and is usually used when continuously used for 3 weeks or more, preferably 3 weeks to 8 weeks. It can exhibit excellent hair loss or skin inflammation suppression effect.
또한, 상기 탈모 또는 피부 염증 억제용 조성물의 1회 적용량은 탈모 또는 피부 염증을 겪는 대상의 상태, 수면 장애 정도, 도포 면적 및 조성물 형태에 따라 다르지만, 통상적으로 25 mg ~ 150 mg 일 수 있으며, 상기 1회 적용량 범위 내에서 적절히 조절하여 도포할 수 있다.In addition, the application amount of the composition for inhibiting hair loss or skin inflammation varies depending on the condition of the subject suffering from hair loss or skin inflammation, the degree of sleep disorder, the application area, and the composition type, and may be typically 25 mg to 150 mg, It can be applied by appropriately adjusting within the application amount range.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명하다 할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are intended to illustrate the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.
<< 실시예Example > 탈모 또는 피부 염증 억제용 조성물 제조> Preparation of composition for inhibiting hair loss or skin inflammation
<< 실시예Example 1 내지 3> 1 to 3>
정제수 1000ml에 아멘토플라본(Amentoflavone)에 더하여; 백자인 추출물, 제니스틴(Genistein) 및 비오카닌 A(Biochanon A)로 구성된 군에서 선택된 하나 이상의 성분을 첨가 후 교반 하였다. 구체적인 유효성분의 함량은 아래 표 1에 나타냈다.1000 ml of purified water was added to Amentoflavone; One or more components selected from the group consisting of white porcelain extract, Genistein and Biochanon A were added and stirred. The contents of specific active ingredients are shown in Table 1 below.
<< 비교예Comparative example 1 내지 4> 1 to 4>
비교예의 조성물은 실시예 1 내지 3에서 이용한 동일한 유효성분을 단독으로 사용하되 성분함량이 10배가 되게 제조하였다. 구체적으로는 정제수 1000 ml에 아멘토플라본(Amentoflavone), 백자인 추출물, 제니스틴(Genistein) 및 비오카닌 A(Biochanon A) 중 1종을 첨가 후 교반한다. 구체적인 유효성분의 함량은 아래 표 1과 같다.The composition of the comparative example was prepared by using the same active ingredient used in Examples 1 to 3 alone but having a component content of 10 times. Specifically, after adding one of amentoflavone, white porcelain extract, Genistein and Biochanon A to 1000 ml of purified water, the mixture is stirred. The content of specific active ingredients is shown in Table 1 below.
분류Classification 정제수 1000ml 당 투여 용량 (ppm)Dose per 1000 ml of purified water (ppm)
아멘토플라본Amentoflavone 백자인 추출물Baekjain extract 제니스틴Genistin 비오카닌 ABiocyanin A
실시예 1Example 1 1One 100100 -- --
실시예 2Example 2 1One -- 1010 --
실시예 3Example 3 1One -- -- 1010
비교예 1Comparative Example 1 1010 -- -- --
비교예 2Comparative Example 2 -- 10001000 -- --
비교예 3Comparative Example 3 -- -- 100100 --
비교예 4Comparative Example 4 -- -- -- 100100
<< 시험예Test example > > PTGDSPTGDS 활성억제 효과(ELISA assay) Active inhibitory effect (ELISA assay)
PTGDS에 효소 반응의 기질인 프로스타글라딘 H2(PGH2)를 처리하여 프로스타글라딘 D2(PGD2)를 생성되는데, 상기 실시예 1 내지 실시예 3에서 제조된 조성물을 함께 투입한 후, PGD2의 생성 감소량을 측정하여 PTGDS 활성 억제 효과를 확인하였다.Prostaglandin D2 (PGD2) is produced by treating prostaglandin H2 (PGH2), a substrate of enzymatic reaction, in PTGDS, after the composition prepared in Examples 1 to 3 is added together, The production reduction was measured to confirm the inhibitory effect of PTGDS activity.
상기 PGD2의 생성량 측정은 효소-결합된 면역흡착시험(Enzyme Linked Immuno Sorbent Assay; ELISA) 방법에 의해서 측정하였다. 효소-결합된 면역흡착시험(ELISA)의 실시는 아래의 단계로 이루어졌다.The production amount of the PGD2 was measured by an enzyme-linked immunosorbent assay (ELISA) method. Enzyme-linked immunosorbent assay (ELISA) was conducted in the following steps.
(a) 실시예 1 내지 3을 고체 기질의 표면에 코팅하는 단계; (a) coating Examples 1 to 3 on the surface of the solid substrate;
(b) PTGDS와 상기 PGH2를 반응시키는 단계; (b) reacting PTGDS with the PGH2;
(c) 상기 단계 (b)의 결과물을 효소가 결합된 이차항체와 반응시키는 단계; 및 (c) reacting the product of step (b) with a secondary antibody to which an enzyme is bound; And
(d) 상기 효소의 활성을 ELISA reader로 410nm에서 흡광도 측정을 통해 나타내는 단계를 포함한다. (d) the activity of the enzyme is indicated by measuring the absorbance at 410 nm with an ELISA reader.
상기 고체 기질로 적합한 것은 탄화수소 폴리머(예컨대, 폴리스틸렌 및 폴리프로필렌), 유리, 금속 또는 젤이며, 가장 바람직하게는 마이크로타이터 플레이트이다. 상기 이차항체에 결합된 효소는 발색반응, 형광반응, 발광반응 또는 적외선 반응을 촉매하는 효소를 포함하나, 이에 한정되지 않으며, 예를 들어, 알칼린 포스파타아제, β-갈락토시다아제, 호스 래디쉬 퍼옥시다아제, 루시퍼라아제 및 사이토크롬 P450을 포함한다. 상기 이차항체에 결합하는 효소로서 알칼린 포스파타아제가 이용되는 경우에는, 기질로서 브로모클로로인돌일 포스페이트(BCIP), 니트로 블루 테트라졸리움(NBT), 나프톨-ASB1-포스페이트(naphthol-AS-B1-phosphate) 및 ECF (enhanced chemifluorescence)와 같은 발색반응 기질이 이용되고, 호스 래디쉬 퍼옥시다아제가 이용되는 경우에는 클로로나프톨, 아미노에틸카바졸, 디아미노벤지딘, D-루시페린, 루시게닌(비스-N-메틸아크리디늄 니트레이트), 레소루핀 벤질 에테르, 루미놀, 암플렉스 레드 시약(10-아세틸-3,7-디하이드록시페녹사진), TMB(3,3,5,5-tetramethylbenzidine), ABTS(2,2'-Azine-di[3-ethylbenzthiazoline sulfonate]) 및 o-페닐렌디아민(OPD)과 같은 기질이 이용될 수 있다.Suitable solid substrates are hydrocarbon polymers (such as polystyrene and polypropylene), glass, metals or gels, most preferably microtiter plates. The enzyme bound to the secondary antibody includes, but is not limited to, an enzyme that catalyzes a color reaction, a fluorescence reaction, a luminescence reaction, or an infrared reaction, for example, alkaline phosphatase, β-galactosidase, hose Radish peroxidase, luciferase and cytochrome P450. When alkaline phosphatase is used as the enzyme that binds to the secondary antibody, bromochloroindolyl phosphate (BCIP), nitro blue tetrazolium (NBT), naphthol-ASB1-phosphate (naphthol-AS-B1) is used as the substrate. Color reaction substrates such as -phosphate) and ECF (enhanced chemifluorescence) are used, and when hose-radish peroxidase is used, chloronaphthol, aminoethylcarbazole, diaminobenzidine, D-luciferin, and lucigenin (bis-N -Methylacridinium nitrate), resorphine benzyl ether, luminol, Amplex red reagent (10-acetyl-3,7-dihydroxyphenoxazin), TMB (3,3,5,5-tetramethylbenzidine), ABTS Substrates such as (2,2'-Azine-di[3-ethylbenzthiazoline sulfonate]) and o-phenylenediamine (OPD) can be used.
분석 결과, 도 1에 나타낸 바와 같이, 본 발명의 실시예 1 내지 3이 성분함량이 10배가 많은 비교예 1 내지 4에 비해서도 PGD2의 생성량이 감소된 것으로 나타났다. 따라서, 상기 결과를 통해 본 발명자들은 아멘토플라본과 백자인 추출물, 제니스테인 및 비오카닌 A로 구성된 군에서 선택된 하나 이상의 성분을 조합한 조성물이 상기 성분 물질을 단독으로 이용했을 때에 비해서 PTGDS 활성 억제능이 우수하다는 것을 알 수 있었다.As a result of the analysis, as shown in FIG. 1, it was found that the production amount of PGD2 was reduced in Examples 1 to 3 of the present invention compared to Comparative Examples 1 to 4 in which the component content was 10 times higher. Therefore, through the above results, the present inventors have excellent ability to inhibit PTGDS activity compared to when the composition combining one or more components selected from the group consisting of amentoflavones and white porcelain extracts, genistein and biokanin A, when using the component materials alone. I could see.
본 발명의 일 실시예에 따른 조성물의 제형예를 아래에서 설명하나, 이들 제형예 외에도 여러 가지 제형으로 응용 가능하며, 이는 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 제형예에 의해 한정되는 것은 아니다.Formulation examples of the composition according to an embodiment of the present invention are described below, but can be applied to various formulations in addition to these formulation examples, which are intended to illustrate the present invention, and the scope of the present invention is limited by these formulation examples It does not work.
<제형예 1> 정제<Formulation Example 1> Tablet
본 발명의 실시예 1 내지 3에 따라 제조된 조성물 100mg, 락토오스 400mg, 옥수수 전분 400mg 및 스테아린산 마그네슘 2mg을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing 100 mg of the composition prepared according to Examples 1 to 3 of the present invention, 400 mg of lactose, 400 mg of corn starch, and 2 mg of magnesium stearate, tablets were prepared by tableting according to a conventional tablet manufacturing method.
<제형예 2> 캡슐제<Formulation Example 2> Capsule
본 발명의 실시예 1 내지 3에 따라 제조된 조성물 100mg, 락토오스 400mg, 옥수수 전분 400mg 및 스테아린산 마그네슘 2mg을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing 100 mg of the composition prepared according to Examples 1 to 3 of the present invention, 400 mg of lactose, 400 mg of corn starch, and 2 mg of magnesium stearate, the capsules were prepared by filling the gelatin capsules according to a conventional capsule preparation method.
<제형예 3> 과립제<Formulation Example 3> Granules
본 발명의 실시예 1 내지 3에 따라 제조된 조성물 50mg, 무수결정 포도당 250mg 및 전분 550mg을 혼합하고, 유동층 과립기를 사용하여 과립으로 성형한 후 포에 충진하였다.50 mg of the composition prepared according to Examples 1 to 3 of the present invention, 250 mg of anhydrous crystalline glucose, and 550 mg of starch were mixed, molded into granules using a fluidized bed granulator, and then filled into the fabric.
<제형예 4> 드링크제<Formulation Example 4> Drink
본 발명의 실시예 1 내지 3에 따라 제조된 조성물 50mg, 포도당 10g, 구연산 0.6g 및 액상 올리고당 25g을 혼합한 후 정제수 300ml를 가하여 각 병에 200ml씩 충진한 후 130℃에서 4~5초간 살균하여 드링크제를 제조하였다.After mixing 50 mg of the composition prepared according to Examples 1 to 3 of the present invention, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide, 300 ml of purified water was added to each bottle, and 200 ml of each bottle was added thereto, followed by sterilization at 130°C for 4 to 5 seconds. Drinks were prepared.
<제형예 5> 주사제<Formulation Example 5> Injection
하기 표 2에 기재된 조성에 따라 통상적인 방법으로 주사제를 제조하였다.Injections were prepared by conventional methods according to the composition shown in Table 2.
배합 성분Ingredients 함량content
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 10-50 mg10-50 mg
주사용 멸균 증류수Sterile distilled water for injection 적량Proper
pH 조절제pH adjuster 적량Proper
<제형예 6> 유연화장수(스킨로션)<Formulation Example 6> Flexible cosmetic (skin lotion)
하기 표 3에 기재된 조성에 따라 통상적인 방법으로 유연화장수를 제조하였다.According to the composition shown in Table 3, a softening agent was prepared by a conventional method.
배합 성분Ingredients 함량 (중량%)Content (% by weight)
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 0.20.2
글리세린glycerin 3.03.0
부틸렌글리콜Butylene glycol 2.02.0
프로필렌글리콜Propylene glycol 2.02.0
카르복시비닐폴리머Carboxyvinyl polymer 0.10.1
피이지-12 노닐페닐에테르PG-12 nonylphenyl ether 0.20.2
폴리솔베이트 80Polysorbate 80 0.40.4
에탄올ethanol 10.010.0
트리에탄올아민Triethanolamine 0.10.1
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water 잔량Balance
<제형예 7> 영양화장수(밀크로션)<Formulation Example 7> Nutrient makeup (Milk lotion)
하기 표 4에 기재된 조성에 따라 통상적인 방법으로 영양화장수를 제조하였다.According to the composition shown in Table 4, nutrient makeup was prepared by a conventional method.
배합 성분Ingredients 함량 (중량%)Content (% by weight)
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 1.01.0
글리세린glycerin 3.03.0
부틸렌글리콜Butylene glycol 3.03.0
프로필렌글리콜Propylene glycol 3.03.0
카르복시비닐폴리머Carboxyvinyl polymer 0.10.1
밀납Wax 4.04.0
폴리솔베이트 60Polysorbate 60 1.51.5
카프릴릭/카프릭 트리글리세라이드Caprylic/Capric Triglyceride 5.05.0
스쿠알란Squalane 5.05.0
솔비타세스퀴올레이트Solvitasesquioleate 1.51.5
유동파라핀Floating paraffin 0.50.5
세테아릴 알코올Cetearyl alcohol 1.01.0
트리에탄올아민Triethanolamine 0.20.2
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water 잔량Balance
<제형예 8> 마사지 크림<Formulation Example 8> Massage cream
하기 표 5에 기재된 조성에 따라 통상적인 방법으로 마사지 크림을 제조하였다.Massage creams were prepared in a conventional manner according to the composition shown in Table 5.
배합 성분Ingredients 함량(중량%)Content (% by weight)
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 2.02.0
글리세린glycerin 8.08.0
부틸렌글리콜Butylene glycol 4.04.0
유동파라핀Floating paraffin 45.045.0
베타글루칸Beta glucan 7.07.0
카보머Carbomer 0.10.1
카프릴릭/카프릭 트리글리세라이드Caprylic/Capric Triglyceride 3.03.0
밀납Wax 4.04.0
세테아릴 글루코사이드Cetearyl Glucoside 1.51.5
세스퀴 올레인산 소르비탄Sesqui oleic acid sorbitan 0.90.9
바세린Vaseline 3.03.0
파라핀paraffin 1.51.5
방부제, 색소, 향료Preservatives, pigments, flavors 적량Proper
정제수Purified water 잔량Balance
<제형예 9> 헤어 로션의 제조<Formulation Example 9> Preparation of hair lotion
하기 표 6에 기재된 조성으로 통상의 방법에 따라 헤어 로션을 제조하였다.A hair lotion was prepared according to a conventional method with the composition shown in Table 6 below.
성분ingredient 함량(중량%)Content (% by weight)
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 2.02.0
정제수Purified water 잔량Balance
글리세린glycerin 3.03.0
부틸렌그리콜Butylene glycol 3.03.0
유동파라핀Floating paraffin 7.07.0
베타글루칸Beta glucan 7.07.0
카보머Carbomer 0.10.1
에델바이스 추출물Edelweiss extract 2.02.0
카프릴릭 카프릭 트리글리세라이드Caprylic capric triglyceride 3.03.0
스쿠알렌Squalene 5.05.0
세테아릴 그루코사이드Cetearyl Glucoside 1.51.5
소르비탄 스테아레이트Sorbitan stearate 0.40.4
폴리솔베이트Polysorbate 1.21.2
방부제antiseptic 적량Proper
향incense 적량Proper
색소Coloring 적량Proper
트리에탄올 아민Triethanol amine 0.10.1
<제형예 10> 샴푸 조성물의 제조<Formulation Example 10> Preparation of shampoo composition
하기 표 7에 기재된 조성으로 통상의 방법에 따라 샴푸 조성물을 제조하였다.A shampoo composition was prepared according to a conventional method with the composition shown in Table 7 below.
성분(중량%)Ingredient (% by weight) 함량(중량%)Content (% by weight)
폴리쿼터늄-10Polyquaternium-10 0.50.5
소듐라우레스설페이트Sodium laureth sulfate 2020
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 0.30.3
향incense 1.01.0
메틸파라벤Methylparaben 0.10.1
세틸알콜Cetyl alcohol 0.50.5
염화나트륨Sodium chloride 0.80.8
정제수Purified water To 100To 100
<제형예 11> 헤어 트리트먼트의 제조<Formulation Example 11> Preparation of hair treatment
하기 표 8에 기재된 조성으로 통상의 방법에 따라 헤어 트리트먼트를 제조하였다.A hair treatment was prepared according to a conventional method with the composition shown in Table 8 below.
구분(중량%)Category (% by weight) 함량(중량%)Content (% by weight)
실시예 1 내지 3에 따라 제조된 조성물Compositions prepared according to Examples 1 to 3 0.50.5
스테아라미도프로필디메틸아민Stearamidopropyldimethylamine 22
글리세린glycerin 0.50.5
향료Spices 0.50.5
방부제antiseptic 0.030.03
세토스테아릴알코올Cetostearyl alcohol 55
락트산Lactic acid 1One
증류수Distilled water to 100to 100

Claims (15)

  1. 아멘토플라본(Amentoflavone); 및Amentoflavone; And
    백자인 추출물, 제니스테인(Genistein) 및 비오카닌 A(Biochanin A)로 구성된 군에서 선택된 하나 이상의 성분;을 포함하는 탈모 또는 피부 염증 억제용 조성물.A composition for inhibiting hair loss or skin inflammation, including; at least one component selected from the group consisting of white porcelain extract, Genistein and Biochanin A.
  2. 제1항에 있어서,According to claim 1,
    상기 아멘토플라본(Amentoflavone)은 상기 조성물 총 중량에 대하여 0.1 내지 1,000 ppm 함유되는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The amentoflavone (Amentoflavone) is a composition for inhibiting hair loss or skin inflammation, characterized in that it contains 0.1 to 1,000 ppm based on the total weight of the composition.
  3. 제1항에 있어서,According to claim 1,
    상기 아멘토플라본(Amentoflavone)은 부처손, 바위손, 권백, 편백 및 은행으로 구성된 군에서 선택된 하나 이상으로부터 추출된 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The amentoflavone (Amentoflavone) is a composition for inhibiting hair loss or skin inflammation, characterized in that it is extracted from one or more selected from the group consisting of Buddha hands, rock hands, baekbaek, cypress and ginkgo.
  4. 제1항에 있어서,According to claim 1,
    상기 백자인 추출물은 상기 조성물 총 중량에 대하여 10 내지 10,000 ppm 함유되는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The white porcelain extract is a composition for inhibiting hair loss or skin inflammation, characterized in that it contains 10 to 10,000 ppm based on the total weight of the composition.
  5. 제1항에 있어서,According to claim 1,
    상기 제니스테인(Genistein)은 상기 조성물 총 중량에 대하여 1 내지 1,000 ppm 함유되는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The genistein (Genistein) is a composition for inhibiting hair loss or skin inflammation, characterized in that it contains 1 to 1,000 ppm based on the total weight of the composition.
  6. 제1항에 있어서,According to claim 1,
    상기 제니스테인(Genistein)은 콩 및 이소플라본(Isoflavone)으로 구성된 군에서 선택된 하나 이상으로부터 추출된 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The genistein (Genistein) is a composition for inhibiting hair loss or skin inflammation, characterized in that extracted from one or more selected from the group consisting of soybean and isoflavone (Isoflavone).
  7. 제1항에 있어서,According to claim 1,
    상기 비오카닌 A(Biochanin A)는 상기 조성물 총 중량에 대하여 10 내지 1,000 ppm 함유되는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The biochanin A (Biochanin A) is a composition for inhibiting hair loss or skin inflammation, characterized in that it contains 10 to 1,000 ppm based on the total weight of the composition.
  8. 제1항에 있어서,According to claim 1,
    상기 비오카닌 A(Biochanin A)는 강진향, 콩, 붉은토끼풀 및 이소플라본(Isoflavone)으로 구성된 군에서 선택된 하나 이상으로부터 추출된 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The biochanin A (Biochanin A) is a composition for inhibiting hair loss or skin inflammation, characterized in that extracted from one or more selected from the group consisting of Gangjinhyang, soybean, red shamrock, and isoflavone (Isoflavone).
  9. 제1항에 있어서,According to claim 1,
    상기 조성물은 생체 내 PTGDS(Prostagladin D2 Synthase)의 활성을 억제하는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The composition for inhibiting hair loss or skin inflammation, characterized in that to inhibit the activity of PTGDS (Prostagladin D2 Synthase) in vivo.
  10. 제1항에 있어서,According to claim 1,
    상기 탈모 또는 피부 염증 억제용 조성물은 화장료인 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The composition for inhibiting hair loss or skin inflammation is a cosmetic composition for inhibiting hair loss or skin inflammation.
  11. 제10항에 있어서,The method of claim 10,
    상기 화장료의 제형은 용액, 크림, 로션, 샴푸, 헤어토닉, 스프레이 및 겔 중 선택되는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The cosmetic formulation is a composition for inhibiting hair loss or skin inflammation, characterized in that selected from solutions, creams, lotions, shampoos, hair tonics, sprays and gels.
  12. 제1항에 있어서,According to claim 1,
    상기 탈모 또는 피부 염증 억제용 조성물은 경피주사 또는 피하주사를 통해 인체에 투여되는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The composition for inhibiting hair loss or skin inflammation is a composition for inhibiting hair loss or skin inflammation, characterized in that it is administered to the human body through transdermal or subcutaneous injection.
  13. 제1항에 있어서,According to claim 1,
    상기 탈모 또는 피부 염증 억제용 조성물은 피부 외용제 또는 경구 투여제인 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The composition for inhibiting hair loss or skin inflammation is a composition for inhibiting hair loss or skin inflammation, characterized in that it is an external preparation for skin or oral administration.
  14. 제1항에 있어서,According to claim 1,
    상기 피부는 모낭 및 두피를 포함하는 것을 특징으로 하는 탈모 또는 피부 염증 억제용 조성물.The skin is a composition for inhibiting hair loss or skin inflammation, characterized in that it comprises a hair follicle and scalp.
  15. 제1항 내지 제14항 중 어느 한 항의 조성물을 이용한 탈모 또는 피부 염증 억제 방법.A method for inhibiting hair loss or skin inflammation using the composition of any one of claims 1 to 14.
PCT/KR2019/015797 2018-11-29 2019-11-19 Composition for inhibiting hair loss or skin inflammation WO2020111621A1 (en)

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