WO2021125484A1 - 아릴 탄화수소 수용체의 활성을 억제하는 폡타이드 및 이를 이용하는 화장료 조성물 - Google Patents
아릴 탄화수소 수용체의 활성을 억제하는 폡타이드 및 이를 이용하는 화장료 조성물 Download PDFInfo
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- WO2021125484A1 WO2021125484A1 PCT/KR2020/009499 KR2020009499W WO2021125484A1 WO 2021125484 A1 WO2021125484 A1 WO 2021125484A1 KR 2020009499 W KR2020009499 W KR 2020009499W WO 2021125484 A1 WO2021125484 A1 WO 2021125484A1
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- peptide
- acid
- fine dust
- cosmetic composition
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- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- ZUFONQSOSYEWCN-UHFFFAOYSA-M sodium;2-(methylamino)acetate Chemical compound [Na+].CNCC([O-])=O ZUFONQSOSYEWCN-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940117986 sulfobetaine Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 229940104261 taurate Drugs 0.000 description 1
- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011747 thiamine hydrochloride Substances 0.000 description 1
- 235000019190 thiamine hydrochloride Nutrition 0.000 description 1
- 229960000344 thiamine hydrochloride Drugs 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 1
- LOIYMIARKYCTBW-UHFFFAOYSA-N trans-urocanic acid Natural products OC(=O)C=CC1=CNC=N1 LOIYMIARKYCTBW-UHFFFAOYSA-N 0.000 description 1
- 229960003500 triclosan Drugs 0.000 description 1
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- SZEMGTQCPRNXEG-UHFFFAOYSA-M trimethyl(octadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)C SZEMGTQCPRNXEG-UHFFFAOYSA-M 0.000 description 1
- 229940118594 trimethylolpropane triisostearate Drugs 0.000 description 1
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
- APVVRLGIFCYZHJ-UHFFFAOYSA-N trioctyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCC)CC(=O)OCCCCCCCC APVVRLGIFCYZHJ-UHFFFAOYSA-N 0.000 description 1
- COXJMKGEQAWXNP-UHFFFAOYSA-N tris(14-methylpentadecyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)CCCCCCCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCCCCCCCC(C)C)CC(=O)OCCCCCCCCCCCCCC(C)C COXJMKGEQAWXNP-UHFFFAOYSA-N 0.000 description 1
- RHNXTZDKMRCKKT-UHFFFAOYSA-N tris(6-methylheptyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)CCCCCOC(=O)CC(O)(C(=O)OCCCCCC(C)C)CC(=O)OCCCCCC(C)C RHNXTZDKMRCKKT-UHFFFAOYSA-N 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 235000013799 ultramarine blue Nutrition 0.000 description 1
- 239000006097 ultraviolet radiation absorber Substances 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000011912 vitamin B7 Nutrition 0.000 description 1
- 239000011735 vitamin B7 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- CPYIZQLXMGRKSW-UHFFFAOYSA-N zinc;iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+3].[Fe+3].[Zn+2] CPYIZQLXMGRKSW-UHFFFAOYSA-N 0.000 description 1
- 229910001928 zirconium oxide Inorganic materials 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
- 229930007845 β-thujaplicin Natural products 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0819—Tripeptides with the first amino acid being acidic
-
- 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
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1019—Tetrapeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1021—Tetrapeptides with the first amino acid being acidic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention relates to a phatide that inhibits the activity of an aryl hydrocarbon receptor and a cosmetic composition using the same.
- Fine dust which has recently increased in frequency, refers to dust with a diameter of 10 ⁇ m or less, and is generated through exhaust gas from automobiles and factories, and is mainly composed of carbon particles.
- the carbon particles contained in the fine dust combine with organic substances such as polyaromatic hydrocarbons and bind to an aryl hydrocarbon receptor (AhR) in the cell to induce active oxygen and inflammation, thereby causing skin troubles.
- AhR aryl hydrocarbon receptor
- the aryl hydrocarbon receptor is a type of transcription factor present in the cytoplasm, and has a Helix-loop-helix motif at the N-terminus, and in the inactivated state, hsp90, p23 , XAP2, etc., exist in a complex state, but when activated by binding to halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons in fine dust, it enters the nucleus and binds to Arnt and acts as a transcription factor, resulting in AHRE (AhR-response) element), DRE (Dioxin-response element), XRE (Xenobiotics-response element), etc. by binding to a specific DNA regulatory region to promote the expression of various genes located mainly downstream, thereby allowing the expression of various proteins, As a result, when gene expression progresses abnormally, cytotoxicity occurs.
- AHRE AhR-response
- DRE Dioxin-respons
- aryl hydrocarbon receptor activity inhibitors capable of preventing and treating diseases by inhibiting the activity of the aryl hydrocarbon receptor as shown in the following patent documents have been developed.
- Patent Publication No. 10-2019-0113902 published on Oct. 08, 2019
- Aryl hydrocarbon receptor (AhR) modulating compound Aryl hydrocarbon receptor (AhR) modulating compound
- the present invention has been devised to solve the above problems,
- An object of the present invention is to provide a ptide that inhibits the activity of an ethyl hydrocarbon receptor, which can be used to improve skin troubles caused by fine dust, and a cosmetic composition using the same.
- the present invention is implemented by an embodiment having the following configuration in order to achieve the above object.
- the peptide according to the present invention is characterized in that it consists of any one amino acid sequence of SEQ ID NOs: 1 to 4.
- the peptide according to the present invention is characterized in that it decreases the activity of the aryl hydrocarbon receptor.
- the peptide according to the present invention is characterized in that it is used to alleviate skin troubles caused by fine dust.
- the peptide according to the present invention is characterized in that it suppresses inflammation caused by fine dust.
- the cosmetic composition according to the present invention is characterized in that it comprises a peptide comprising the amino acid sequence of any one of SEQ ID NOs: 1 to 4.
- the cosmetic composition according to the present invention is characterized in that it provides an effect of alleviating skin troubles caused by fine dust.
- the present invention can obtain the following effects by the present embodiment above.
- the present invention has an effect of improving skin troubles caused by fine dust by inhibiting the activity of an aryl hydrocarbon receptor using a peptide consisting of any one of the amino acid sequences of SEQ ID NOs: 1 to 4.
- 1 is a graph showing the effect of a peptide according to an embodiment of the present invention on the interaction between AhR and POLII.
- Figure 2 is a graph for confirming the effect of the peptide according to an embodiment of the present invention on cytotoxicity caused by fine dust.
- FIG. 3 is a graph for confirming the effect of the peptide according to an embodiment of the present invention on the generation of active oxygen induced by fine dust.
- One embodiment of the present invention relates to a peptide that inhibits the activity of an aryl hydrocarbon receptor, wherein the peptide is SEQ ID NO: 1 (Asp-Arg-Leu-Asn), 2 (Asp-Arg-Leu), 3 (Asn-Thr- Glu-Leu) or 4 (Asn-Thr-Glu).
- the peptide inhibits the activity of the aryl hydrocarbon receptor, thereby alleviating skin troubles caused by fine dust binding to the aryl hydrocarbon receptor.
- the peptide inhibits the activity of the aryl hydrocarbon receptor, thereby inhibiting the generation of cytotoxicity, free radicals, and inflammatory cytokines caused by the binding of fine dust to the aryl hydrocarbon receptor, thereby alleviating skin troubles.
- Another embodiment of the present invention relates to a cosmetic composition
- a cosmetic composition comprising a peptide consisting of any one of the amino acid sequences of SEQ ID NOs: 1 to 4, wherein the cosmetic composition suppresses the production of cytotoxicity, active oxygen and inflammatory cytokines. It can alleviate skin troubles caused by fine dust.
- the cosmetic composition of the present invention may further include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight polysaccharides, sphingolipids, and seaweed extract.
- the water-soluble vitamin may be any type of vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, etc. and their salts (thiamine hydrochloride, sodium ascorbate salt, etc.) and derivatives (ascorbic acid-2-phosphate sodium salt, ascorbic acid-2-phosphate magnesium salt, etc.) are also water-soluble vitamins that can be used in the present invention. are included in The water-soluble vitamin can be obtained by a conventional method such as a microbial transformation method, a purification method from a microbial culture, an enzymatic method or a chemical synthesis method.
- the oil-soluble vitamins may be any as long as they can be formulated in cosmetics, but preferably include vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol). and their derivatives (ascorbine palmitate, ascorbine stearate, ascorbine dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinic acid, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl ether, etc.) are also included in the oil-soluble vitamins used in the present invention.
- the oil-soluble vitamin can be obtained by a conventional method such as a microbial transformation method, a purification method from a microbial culture, an enzyme or a chemical synthesis method, and the like.
- the high-molecular polysaccharide may be any one as long as it can be blended into a cosmetic.
- hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfuric acid or a salt thereof (sodium salt, etc.) is mentioned.
- chondroitin sulfate or a salt thereof can be used after purification from mammals or fish.
- the sphingolipid may be any as long as it can be blended into a cosmetic, and preferred examples include ceramide, phytosphingosine, and sphingoglycolipid.
- the sphingo lipid may be purified by a conventional method from mammals, fish, shellfish, yeast or plants, or may be obtained by chemical synthesis.
- the seaweed extract may be any one as long as it can be formulated in cosmetics, but preferably brown algae extract, red algae extract, green algae extract, etc., and calrageenan purified from these seaweed extracts, arginic acid, sodium alginate , potassium alginate, etc. are also included in the seaweed extract used in the present invention.
- the said seaweed extract can be obtained by refine
- the cosmetic composition of the present invention may contain other ingredients that are normally formulated in the cosmetic composition.
- oils and fats moisturizing agents, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, A cooling agent, an antiperspirant agent, purified water, etc. are mentioned.
- Examples of the fats and oils include ester fats and oils, hydrocarbon oils, silicone oils, fluorine oils, animal fats, and vegetable oils.
- Examples of the ester-based oils and fats include glyceryl tri-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, stearate.
- hydrocarbon-based fats and oils examples include hydrocarbon-based fats and oils such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybudene, microcrystalline wax, petrolatum.
- silicone-based oils and fats examples include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane/methylcetyloxysiloxane copolymer, dimethylsiloxane/methylstealloxysiloxane copolymer, Alkyl-modified silicone oil, amino-modified silicone oil, etc. are mentioned. As said fluorine-type fats and oils, perfluoro polyether etc. are mentioned.
- animal or vegetable oils and fats examples include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, bird flower oil, soybean oil, corn oil, rapeseed oil, passerine oil, palm kernel oil, palm oil, castor oil, sunflower oil, grapes. Seed oil, cottonseed oil, palm oil, kukui nut oil, wheat germ oil, rice germ oil, shea butter, cranberry colostrum, marcadeumia nut oil, meadow home oil, egg yolk oil, beef tallow, horse oil, mink oil, orange rafi oil, jojoba and animal or plant oils and fats, such as oil, candelabra wax, carnauba wax, liquid lanolin, and hydrogenated castor oil.
- avocado oil almond oil, olive oil, sesame oil, rice bran oil, bird flower oil, soybean oil, corn oil, rapeseed oil, passerine oil, palm kernel oil, palm oil, castor oil, sunflower oil, grapes.
- moisturizer examples include water-soluble low molecular weight moisturizing agents, fat-soluble molecular moisturizing agents, water-soluble polymers, and fat-soluble polymers.
- Cholesterol, cholesterol ester, etc. are mentioned as said fat-soluble low molecular weight moisturizing agent.
- the water-soluble polymer include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water-soluble chitin, chitosan, dextrin, and the like.
- the fat-soluble polymer examples include polyvinylpyrrolidone/eicosene copolymer, polyvinylpyrrolidone/hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and high molecular weight silicone.
- acyl glutamic acid cholesteryl ester As said emollient agent, long-chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, lanolin fatty acid cholesteryl ester, etc. are mentioned.
- Nonionic surfactants anionic surfactants, cationic surfactants, amphoteric surfactants, etc. are mentioned as said surfactant.
- the nonionic surfactant include self-emulsifying monostearic acid glycerin, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerol fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene), sorbitan fatty acid ester, POE sorbitan fatty acid ester , POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POEPOP (polyoxyethylene polyoxypropylene) copolymer, POEPOP alkyl ether, polyether-modified silicone, lauric acid alkanolamide , alkylamine oxide, hydrogenated soybean phospholipid, and the like.
- anionic surfactant examples include fatty acid soap, alpha-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkyl amide sulfate, alkyl phosphate, POE alkyl phosphate, and alkyl.
- Amide phosphate alkyloyl alkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfoacetate sodium, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate ester, etc.
- the cationic surfactant examples include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, Benzalkonium chloride, diethylaminoethyl stearate, dimethylaminopropyl stearate, quaternary ammonium salt of lanolin derivative, etc. are mentioned.
- amphoteric surfactant examples include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amidesulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amideamine type, etc. of amphoteric surfactants, and the like.
- organic and inorganic pigments examples include silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, oxide.
- inorganic pigments such as aluminum, calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine, and complexes thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene/styrene copolymer, and organic pigments such as silk powder, cellulose, CI pigment yellow and CI pigment orange, and composite pigments of these inorganic pigments and organic pigments.
- inorganic pigments such as aluminum, calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine, and complexe
- organic powder examples include metal soaps such as calcium stearate; alkyl phosphate metal salts such as sodium cetylate, zinc laurylate, and calcium laurylate; acylamino acid polyvalent metal salts such as calcium N-lauroyl-beta-alanine, zinc N-lauroyl-beta-alanine, and calcium N-lauroyl glycine; amidesulfonic acid polyvalent metal salts such as calcium N-lauroyl-taurine and calcium N-palmitoyl-taurine; N such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylizine, N-alpha-paritoylolnithine, N-alpha-lauroylarginine, N-alpha-hydrogenated beef fatty acid acylarginine, etc.
- metal soaps such as calcium stearate
- alkyl phosphate metal salts such as
- N-acyl polypeptides such as N-lauroyl glycyl glycine
- alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid
- Polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, a divinylbenzene-styrene copolymer, ethylene tetrafluoride, etc. are mentioned.
- Examples of the ultraviolet absorber include para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylate, cinnamic acid Benzyl, para-methoxycinnamic acid-2-ethoxyethyl, para-methoxycinnamic acid octyl, dipara-methoxycinnamic acid mono-2-ethylhexane glyceryl, para-methoxycinnamic acid isopropyl, diisopropyl diisopropyl cinnamic acid ester mixture; Urocanic acid, ethyl urocanate, hydroxymethoxybenzoph
- disinfectant examples include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincphyllithione, benzalkonium chloride, Photosensitizer No. 301, mononitroguaial sodium, undecyrenic acid, etc. are mentioned.
- antioxidant examples include butylhydroxyanisole, propyl gallic acid, and ellisorbic acid.
- pH adjuster examples include citric acid, sodium citrate, malic acid, sodium malate, fmalic acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, and the like.
- alcohols such as cetyl alcohol, are mentioned.
- blending components that may be added are not limited thereto, and any of the above components can be blended within a range that does not impair the object and effect of the present invention, but preferably 0.01 to 5% by weight relative to the total weight, more preferably 0.01 to 3% by weight.
- the cosmetic composition of the present invention may take the form of a solution, an emulsion, a viscous mixture, or the like.
- Components included in the cosmetic composition of the present invention may include components commonly used in cosmetic compositions in addition to the above compound as an active ingredient, for example, conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments and fragrances and carriers.
- conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments and fragrances and carriers.
- the cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, emulsion, cream, foundation, lotion, cosmetic liquid, hair cosmetics, and the like.
- the cosmetic composition of the present invention is a skin lotion, skin softener, moisture lotion, nourishing lotion, massage cream, nourishing cream, hand cream, moisture cream, essence, pack, soap, lotion, milk lotion, gel, ointment, patch, It includes formulations of cleansing foams, body cleansers, astringents, and sprays.
- the formulation of the present invention is a paste, cream or gel, animal fiber, vegetable fiber, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
- 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, additional chlorofluorohydrocarbon, propane /may contain propellants 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-butylglycol oil, glycerol fatty esters, fatty acid esters of polyethylene glycol or sorbitan.
- the formulation of the present invention is a suspension
- a carrier component water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or tracanth may be used.
- the formulation of the present invention is a surfactant-containing cleansing agent
- Ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolin derivative or ethoxylated glycerol fatty acid ester and the like can be used.
- the peptides of SEQ ID NOs: 1 to 4 described in Table 1 below were synthesized by the FMOC solid-phase method using an automated synthesizer (PeptrEx-R48, Peptron, Korea). The synthesized peptide was purified and analyzed by reverse-phase high-performance chromatography (Prominence LC-20AB, Shimadzu, Japan) using a C18 analytical RP column (Shiseido capcell pak), and mass spectrometry (HP 1100 Series LC/MSD, Hewlett-Packard) , USA) was used for identification.
- Peptide name SEQ ID NO: amino acid sequence AhR Pep1 SEQ ID NO: 1 Asp-Arg-Leu-Asn AhR Pep2 SEQ ID NO: 2 Asp-Arg-Leu AhR Pep3 SEQ ID NO: 3 Asn-Thr-Glu-Leu AhR Pep4 SEQ ID NO: 4 Asn-Thr-Glu
- Example 2 It was confirmed that the peptide prepared in Example 1 reversed the activity of the aryl hydrocarbon receptor and lowered the physical bond between AhR and POLII.
- Example 1 the peptide with AhR antagonist 3-MC (3-Methylcholanthrene) produced in human keratinocytes after (HaCaT) treatment on cells, in situ PLA (proximity ligation assay) AhR and RNA Polymerase II by the method ( POLII) on the physical binding was evaluated.
- AhR antagonist 3-MC 3-Methylcholanthrene
- the cells in each well were washed with PBS, fixed by treatment with 2% formaldehyde for 15 minutes, and then treated with 0.1% TritonX-100 for 5 minutes to increase the antibody permeability into the cells.
- Anti-AhR polyclonal antibody (abcam, UK) and anti-POLII monoclonal antibody (Santa cruz, USA) were added, and PLA probe was added using an in situ PLA kit (Sigma-Aldrich), followed by hybridization ( hybridization), ligation, amplification and mounting steps were performed.
- Example 3 Evaluation of cytotoxicity of the peptides prepared in Example 1
- MTT assay was performed.
- the cultured HaCaT cells were treated with each of the peptides (AhR Pep 1 to 4) prepared in Example 1 at concentrations of 0, 2, 20, and 50 uM, and cultured for 24 hours. Then, the MTT solution was added and cultured, and after removing the supernatant, DMSO was added, and absorbance was measured at 540 nm.
- Example 4 Evaluation that the peptide prepared in Example 1 inhibits cytotoxicity caused by fine dust
- Example 1 In order to confirm that the peptide prepared in Example 1 inhibited cytotoxicity caused by fine dust, 20 ug/ml fine dust (using diesel particulate matter purchased from Sigma Aldridge) was added to cultured HaCaT cells 2, Each of the peptides (AhR Pep 1 to 4) prepared in Example 1 at 20 uM was treated and incubated for 24 hours. Thereafter, MTT solution was added and cultured, DMSO was added, and absorbance was measured at 540 nm, and the cell viability was calculated and shown in FIG. 2 . As a control group, no treatment and only fine dust treatment were used.
- FIG. 2 it can be seen that the cell viability of human keratinocytes treated alone with fine dust sharply decreased.
- AhR Peps 1 to 4 were treated together, the cell viability was significantly higher than when fine dust was treated alone. large can be seen.
- Fine dust binds with AhR to generate cytotoxicity, and it can be seen that the peptide prepared in Example 1 inhibits the binding of fine dust and AhR, thereby reducing the occurrence of cytotoxicity. Due to this, it is possible to alleviate skin troubles (inflammation, etc.) due to reduced cytotoxicity.
- Example 5 Evaluation that the peptide prepared in Example 1 inhibits the generation of active oxygen caused by fine dust
- the cultured HaCaT cells were treated with 10 ug/ml of fine dust and 2 and 20 uM of each of the peptides (AhR Pep 1 to 4) prepared in Example 1, and incubated for 24 hours. Thereafter, dichlorofluorescein diacetate (DCF-DA) was reacted at 37° C. for 30 minutes, followed by analysis using a flow cytometer, and the results are shown in FIG. 3 .
- DCF-DA dichlorofluorescein diacetate
- FIG. 3 it can be seen that when fine dust is treated alone in human keratinocytes, the generation of active oxygen is remarkably increased.
- AhR Pep 1 to 4 are treated together, the amount of active oxygen increased by fine dust It can be seen that the production is suppressed.
- Fine dust binds to AhR to generate active oxygen, and it can be seen that the peptide prepared in Example 1 inhibits the bond between fine dust and AhR, thereby reducing the generation of active oxygen. Due to this, it is possible to alleviate skin troubles (inflammation, etc.) due to inhibition of active oxygen production.
- Example 6 Evaluation that the peptide prepared in Example 1 inhibits the generation of pro-inflammatory cytokines induced by fine dust
- Example 1 An ELISA method was used to confirm that the peptide prepared in Example 1 inhibited the generation of pro-inflammatory cytokines induced by fine dust.
- the cultured HaCaT cells were treated with 10 ug/ml of fine dust and 20 uM of each of the peptides (AhR Pep 1 to 4) prepared in Example 1 and incubated for 24 hours. Then, the amount of IL-6 and TNF- ⁇ using a mouse enzyme-linked immnunosorbent assay (ELISA) kit (R&D Systems Inc, Minneapolis, MN, USA), the results are shown in Table 2.
- ELISA enzyme-linked immnunosorbent assay
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Abstract
본 발명은 미세 먼지에 의한 피부 트러블을 개선하기 위해 사용할 수 있는 아틸 탄화수소 수용체의 활성을 억제하는 폡타이드 및 이를 이용하는 화장료 조성물에 대한 것이다.
Description
본 발명은 아릴 탄화수소 수용체의 활성을 억제하는 폡타이드 및 이를 이용하는 화장료 조성물에 대한 것이다.
최근 발생 빈도가 급격히 증가하고 있는 미세먼지는 지름이 10㎛ 이하의 먼지를 의미하는데, 자동차, 공장 등의 배출가스 등을 통해 발생하며, 주로 탄소입자들로 구성되게 된다. 상기 미세먼지에 포함된 탄소입자들은 다방향족 탄화수소 등의 유기물질과 결합하여, 세포 내 아릴 탄화수소 수용체(aryl hydrocarbon receptor, AhR)과 결합하여 활성산소 및 염증을 유발하여 피부 트러블을 일으키게 된다.
구체적으로, 상기 아릴 탄화수소 수용체는 세포질 내부에 존재하는 일종의 전사인자로, N-말단에 나선-고리-나선 DNA 결합 모티프(Helix-loop-helix motif)를 갖고 있으며, 비활성화된 상태의 경우 hsp90, p23, XAP2 등의 단백질과 결합하여 복합체 상태로 존재하나, 미세먼지의 할로겐화 방향족 탄화수소, 다중고리 방향족 탄화수소 등과 결합하여 활성화되면, 핵 내부로 들어가 Arnt와 결합하여 전사인자로 작용하여, AHRE(AhR-response element), DRE(Dioxin-response element), XRE(Xenobiotics-response element) 등과 같은 특정 DNA 조절 영역에 결합하여 주로 하류(Downstream)에 위치한 다양한 유전자의 발현을 촉진하고 이로 인해 다양한 단백질들이 발현되도록 하는데, 그 결과 유전자 발현이 비정상적으로 진행될 경우 세포 독성이 발생하게 된다.
따라서, 하기 특허문헌처럼 상기 아릴 탄화수소 수용체의 활성을 억제하여 질환을 예방 및 치료할 수 있는 아릴 탄화수소 수용체 활성 억제제가 개발되고 있다.
<특허문헌>
특허공개공보 제10-2019-0113902호(2019. 10. 08. 공개) "아릴 탄화수소 수용체(AhR)조절 화합물"
하지만, 종래의 아릴 탄화수소 수용체 활성 억제제는 대부분 화학 합성되어 질환의 치료시 부작용 발생하는 문제가 있다.
본 발명은 상기와 같은 문제점을 해결하기 위해 안출된 것으로,
본 발명은 미세 먼지에 의한 피부 트러블을 개선하기 위해 사용할 수 있는 아틸 탄화수소 수용체의 활성을 억제하는 폡타이드 및 이를 이용하는 화장료 조성물을 제공하는데 그 목적이 있다.
본 발명은 앞서 본 목적을 달성하기 위하여 다음과 같은 구성을 가진 실시예에 의해 구현된다.
본 발명의 일 실시예에 따르면, 본 발명에 따른 펩타이드는 서열번호 1 내지 4 중 어느 하나의 아미노산 서열로 구성되는 것을 특징으로 한다.
본 발명의 다른 실시예에 따르면, 본 발명에 따른 펩타이드는 아릴 탄화수소 수용체의 활성을 저하시키는 것을 특징으로 한다.
본 발명의 또 다른 실시예에 따르면, 본 발명에 따른 펩타이드는 미세먼지에 발생하는 피부 트러블을 완화하기 위해 사용되는 것을 특징으로 한다.
본 발명의 또 다른 실시예에 따르면, 본 발명에 따른 펩타이드는 미세먼지에 의한 염증 발생을 억제하는 것을 특징으로 한다.
본 발명의 또 다른 실시예에 따르면, 본 발명에 따른 화장료 조성물은 서열번호 1 내지 4 중 어느 하나의 아미노산 서열로 구성된 펩타이드를 포함하는 것을 특징으로 한다.
본 발명의 또 다른 실시예에 따르면, 본 발명에 따른 화장료 조성물은 미세먼지에 발생하는 피부 트러블을 완화하는 효과를 제공하는 것을 특징으로 한다.
본 발명은 앞서 본 실시예에 의해 다음과 같은 효과를 얻을 수 있다.
본 발명은 서열번호 1 내지 4 중 어느 하나의 아미노산 서열로 이루어진 펩타이드를 이용하여 아릴 탄화수소 수용체의 활성을 억제함으로써, 미세먼지에 의한 피부 트러블을 개선할 수 있는 효과가 있다.
도 1은 본 발명의 일 실시예에 따른 펩타이드가 AhR과 POLⅡ의 상호작용에 미치는 영향을 나타내는 그래프.
도 2는 본 발명의 일 실시예에 따른 펩타이드가 미세먼지에 의한 세포 독성에 미치는 영향을 확인하기 위한 그래프.
도 3은 본 발명의 일 실시예에 따른 펩타이드가 미세먼지에 의해 유발되는 활성산소의 생성에 미치는 영향을 확인하기 위한 그래프.
이하에서는 본 발명에 따른 아릴 탄화수소 수용체의 활성을 억제하는 폡타이드 및 이를 이용하는 화장료 조성물을 첨부된 도면을 참조하여 상세히 설명한다. 특별한 정의가 없는 한 본 명세서의 모든 용어는 본 발명이 속하는 기술분야의 통상의 지식을 가진 기술자가 이해하는 당해 용어의 일반적 의미와 동일하고 만약 본 명세서에 사용된 용어의 의미와 충돌하는 경우에는 본 명세서에 사용된 정의에 따른다. 또한, 본 발명의 요지를 불필요하게 흐릴 수 있는 공지 기능 및 구성에 대해 상세한 설명은 생략한다. 명세서 전체에서, 어떤 부분이 어떤 구성요소를 "포함"한다고 할 때 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성요소를 더 포함할 수 있는 것을 의미한다.
본 발명의 일 실시예는 아릴 탄화수소 수용체의 활성을 억제하는 펩타이드 대한 것으로, 상기 펩타이드는 서열번호 1(Asp-Arg-Leu-Asn), 2(Asp-Arg-Leu), 3(Asn-Thr-Glu-Leu) 또는 4(Asn-Thr-Glu)의 아미노산 서열로 구성되는 것을 특징으로 한다. 상기 펩타이드는 아릴 탄화수소 수용체의 활성을 억제하여 미세먼지가 아릴 탄화수소 수용체에 결합함으로 인해 발생하는 피부 트러블을 완화할 수 있다. 구체적으로, 상기 펩타이드는 아릴 탄화수소 수용체의 활성을 억제하여, 미세먼지가 아릴 탄화수소 수용체와 결합하여 생기는 세포독성, 활성산소, 염증성 사이토카인의 생성을 억제하여 피부 트러블을 완화시킬 수 있다.
본 발명의 또 다른 실시예는 서열번호 1 내지 4 중 어느 하나의 아미노산 서열로 이루어진 펩타이드를 포함하는 화장료 조성물에 대한 것으로, 상기 화장료 조성물은 세포 독성 완화, 활성 산소 및 염증성 사이토카인의 생성을 억제하여 미세먼지에 의해 발생하는 피부 트러블을 완화할 수 있다.
본 발명의 화장료 조성물은 수용성 비타민, 유용성 비타민, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 조성물을 추가로 포함할 수 있다.
상기 수용성 비타민으로서는 화장료에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 비타민B1, 비타민 B2, 비타민 B6, 피리독신, 염산피리독신, 비타민 B12, 판토텐산, 니코틴산, 니코틴산아미드, 엽산, 비타민 C, 비타민 H 등을 들 수 있으며, 그들의 염(티아민염산염, 아스코르빈산나트륨염 등)이나 유도체(아스코르빈산-2-인산나트륨염, 아스코르빈산-2-인산마그네슘염 등)도 본 발명에서 사용할 수 있는 수용성 비타민에 포함된다. 상기 수용성 비타민은 미생물 변환법, 미생물의 배양물로부터의 정제법, 효소법 또는 화학 합성법 등의 통상의 방법에 의해 수득할 수 있다.
상기 유용성 비타민으로서는 화장료에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 비타민A, 카로틴, 비타민 D2, 비타민 D3, 비타민 E(d1-알파 토코페롤, d-알파 토코페롤, d-알파 토코페롤) 등을 들 수 있으며, 그들의 유도체(팔미틴산아스코르빈, 스테아르산아스코르빈, 디팔미틴산아스코르빈, 아세트산dl-알파 토코페롤, 니코틴산dl-알파 토코페롤비타민 E, DL-판토테닐알코올, D-판토테닐알코올, 판토테닐에틸에테르 등) 등도 본 발명에서 사용되는 유용성 비타민에 포함된다. 상기 유용성 비타민은 미생물 변환법, 미생물의 배양물로부터의 정제법, 효소 또는 화학 합성법 등의 통상의 방법에 의해 취득할 수 있다.
상기 고분자 다당으로서는 화장료에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 히드록시에틸셀룰로오스, 크산탄검, 히알루론산나트륨, 콘드로이틴 황산 또는 그 염 (나트륨염 등) 등을 들 수 있다. 예를 들어, 콘드로이틴 황산 또는 그 염 등은 통상 포유 동물이나 어류로부터 정제하여 사용할 수 있다.
상기 스핑고 지질로서는 화장료에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 세라미드, 피토스핑고신, 스핑고당지질 등을 들 수 있다. 상기 스핑고 지질은 통상 포유류, 어류, 패류, 효모 또는 식물 등으로부터 통상의 방법에 의해 정제하거나 화학 합성법에 의해 취득할 수 있다.
상기 해초 엑기스로는 화장료에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 갈조 엑기스, 홍조 엑기스, 녹조 엑기스 등을 들 수 있으며, 또, 이들의 해초 엑기스로부터 정제된 칼라기난, 아르긴산, 아르긴산나트륨, 아르긴산칼륨 등도 본 발명에서 사용되는 해초 엑기스에 포함된다. 상기 해초 엑기스는 해초로부터 통상의 방법에 의해 정제하여 취득할 수 있다.
본 발명의 화장료 조성물에는 통상 화장료 조성물에 배합되는 다른 성분을 배합할 수 있다. 예를 들면, 유지 성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한(制汗)제, 정제수 등을 들 수 있다.
상기 유지 성분으로서는 에스테르계 유지, 탄화수소계 유지, 실리콘계 유지, 불소계 유지, 동물 유지, 식물 유지 등을 들 수 있다. 상기 에스테르계 유지로서는 트리2-에틸헥산산글리세릴, 2-에틸헥산산세틸, 미리스틴산이소프로필, 미리스틴산부틸, 팔미틴산이소프로필, 스테아르산에틸, 팔미틴산옥틸, 이소스테아르산이소세틸, 스테아르산부틸, 리놀레산에틸, 리놀레산이소프로필, 올레인산에틸, 미리스틴산이소세틸, 미리스틴산이소스테아릴, 팔미틴산이소스테아릴, 미리스틴산옥틸도데실, 이소스테아르산이소세틸, 세바신산디에틸, 아디핀산디이소프로필, 네오펜탄산이소알킬, 트리(카프릴, 카프린산)글리세릴, 트리2-에틸헥산산트리메틸롤프로판, 트리이소스테아르산트리메틸롤프로판, 테트라2-에틸헥산산펜타엘리슬리톨, 카프릴산세틸, 라우린산데실, 라우린산헥실, 미리스틴산데실, 미리스틴산미리스틸, 미리스틴산세틸, 스테아르산스테아릴, 올레인산데실, 리시노올레인산세틸, 라우린산이소스테아릴, 미리스틴산이소트리데실, 팔미틴산이소세틸, 스테아르산옥틸, 스테아르산이소세틸, 올레인산이소데실, 올레인산옥틸도데실, 리놀레산옥틸도데실, 이소스테아르산이소프로필, 2-에틸헥산산세토스테아릴, 2-에틸헥산산스테아릴, 이소스테아르산헥실, 디옥탄산에틸렌글리콜, 디올레인산에틸렌글리콜, 디카프린산프로필렌글리콜, 디(카프릴,카프린산)프로필렌글리콜, 디카프릴산프로필렌글리콜, 디카프린산네오펜틸글리콜, 디옥탄산네오펜틸글리콜, 트리카프릴산글리세릴, 트리운데실산글리세릴, 트리이소팔미틴산글리세릴, 트리이소스테아르산글리세릴, 네오펜탄산옥틸도데실, 옥탄산이소스테아릴, 이소노난산옥틸, 네오데칸산헥실데실, 네오데칸산옥틸도데실, 이소스테아르산이소세틸, 이소스테아르산이소스테아릴, 이소스테아르산옥틸데실, 폴리글리세린올레인산에스테르, 폴리글리세린이소스테아르산에스테르, 시트르산트리이소세틸, 시트르산트리이소알킬, 시트르산트리이소옥틸, 락트산라우릴, 락트산미리스틸, 락트산세틸, 락트산옥틸데실, 시트르산트리에틸, 시트르산아세틸트리에틸, 시트르산아세틸트리부틸, 시트르산트리옥틸, 말산디이소스테아릴, 히드록시스테아르산 2-에틸헥실, 숙신산디2-에틸헥실, 아디핀산디이소부틸, 세바신산디이소프로필, 세바신산디옥틸, 스테아르산콜레스테릴, 이소스테아르산콜레스테릴, 히드록시스테아르산콜레스테릴, 올레인산콜레스테릴, 올레인산디히드로콜레스테릴, 이소스테아르산피트스테릴, 올레인산피트스테릴, 12-스테알로일히드록시스테아르산이소세틸, 12-스테알로일히드록시스테아르산스테아릴, 12-스테알로일히드록시스테아르산이소스테아릴 등의 에스테르계 등을 들 수 있다. 상기 탄화 수소계 유지로서는 스쿠알렌, 유동 파라핀, 알파-올레핀올리고머, 이소파라핀, 세레신, 파라핀, 유동 이소파라핀, 폴리부덴, 마이크로크리스탈린왁스, 와셀린 등의 탄화 수소계 유지 등을 들 수 있다. 상기 실리콘계 유지로서는 폴리메틸실리콘, 메틸페닐실리콘, 메틸시클로폴리실록산, 옥타메틸폴리실록산, 데카메틸폴리실록산, 도데카메틸시클로실록산, 디메틸실록산ㆍ메틸세틸옥시실록산 공중합체, 디메틸실록산ㆍ메틸스테알록시실록산 공중합체, 알킬 변성 실리콘유, 아미노 변성 실리콘유 등을 들 수 있다. 상기 불소계 유지로서는 퍼플루오로폴리에테르 등을 들 수 있다. 상기 동물 또는 식물 유지로서는 아보카도유, 아르몬드유, 올리브유, 참깨유, 쌀겨유, 새플라워유, 대두유, 옥수수유, 유채유, 행인(杏仁)유, 팜핵유, 팜유, 피마자유, 해바라기유, 포도종자유, 면실유, 야자유, 쿠쿠이너트유, 소맥배아유, 쌀 배아유, 시아버터, 월견초유, 마커데이미아너트유, 메도홈유, 난황유, 우지(牛脂), 마유, 밍크유, 오렌지라피유, 호호바유, 캔데리러왁스, 카르나바왁스, 액상 라놀린, 경화피마자유 등의 동물 또는 식물 유지를 들 수 있다.
상기 보습제로서는 수용성 저분자 보습제, 지용성 분자 보습제, 수용성 고분자, 지용성 고분자 등을 들 수 있다. 상기 수용성 저분자 보습제로서는 세린, 글루타민, 솔비톨, 만니톨, 피롤리돈-카르복실산나트륨, 글리세린, 프로필렌글리콜, 1,3-부틸렌글리콜, 에틸렌글리콜, 폴리에틸렌글리콜B(중합도 n = 2 이상), 폴리프로필렌글리콜(중합도 n = 2 이상), 폴리글리세린B(중합도 n = 2 이상), 락트산, 락트산염 등을 들 수 있다. 상기 지용성 저분자 보습제로서는 콜레스테롤, 콜레스테롤에스테르 등을 들 수 있다. 상기 수용성 고분자로서는 카르복시비닐폴리머, 폴리아스파라긴산염, 트라가칸트, 크산탄검, 메틸셀룰로오스, 히드록시메틸셀룰로오스, 히드록시에틸셀룰로오스, 히드록시프로필셀룰로오스, 카르복시메틸셀룰로오스, 수용성 키틴, 키토산, 덱스트린 등을 들 수 있다. 상기 지용성 고분자로서는 폴리비닐피롤리돈ㆍ에이코센 공중합체, 폴리비닐피롤리돈ㆍ헥사데센 공중합체, 니트로셀룰로오스, 덱스트린지방산에스테르, 고분자 실리콘 등을 들 수 있다.
상기 에몰리엔트제로서는 장쇄아실글루타민산콜레스테릴에스테르, 히드록시스테아르산콜레스테릴, 12-히드록시스테아르산, 스테아르산, 로진산, 라놀린지방산콜레스테릴에스테르 등을 들 수 있다.
상기 계면 활성제로서는 비이온성 계면 활성제, 음이온성 계면 활성제, 양이온성 계면 활성제, 양성 계면 활성제 등을 들 수 있다. 상기 비이온성 계면 활성제로서는 자기 유화형 모노스테아르산글리세린, 프로필렌글리콜지방산에스테르, 글리세린지방산에스테르, 폴리글리세린지방산에스테르, 솔비탄지방산에스테르, POE (폴리옥시에틸렌), 솔비탄지방산에스테르, POE 솔비트지방산에스테르, POE 글리세린지방산에스테르, POE 알킬에테르, POE 지방산에스테르, POE 경화피마자유, POE 피마자유, POEPOP (폴리옥시에틸렌폴리옥시프로필렌) 공중합체, POEPOP 알킬에테르, 폴리에테르변성실리콘, 라우린산알카놀아미드, 알킬아민옥시드, 수소첨가대두인지질 등을 들 수 있다. 상기 음이온성 계면 활성제로서는 지방산비누, 알파-아실술폰산염, 알킬술폰산염, 알킬알릴술폰산염, 알킬나프탈렌술폰산염, 알킬황산염, POE 알킬에테르황산염, 알킬아미드황산염, 알킬인산염, POE 알킬인삼염, 알킬아미드인산염, 알킬로일알킬타우린염, N-아실아미노산염, POE 알킬에테르카르복실산염, 알킬술포숙신산염, 알킬술포아세트산나트륨, 아실화 가수분해 콜라겐펩티드염, 퍼플루오로알킬인산에스테르 등을 들 수 있다. 상기 양이온성 계면 활성제로서는 염화알킬트리메틸암모늄, 염화스테아릴트리메틸암모늄, 브롬화스테아릴트리메틸암모늄, 염화세토스테아릴트리메틸암모늄, 염화디스테아릴디메틸암모늄, 염화스테아릴디메틸벤질암모늄, 브롬화베헤닐트리메틸암모늄, 염화벤잘코늄, 스테아르산디에틸아미노에틸아미드, 스테아르산디메틸아미노프로필아미드, 라놀린 유도체 제 4급 암모늄염 등을 들 수 있다. 상기 양성 계면 활성제로서는 카르복시베타인형, 아미드베타인형, 술포베타인형, 히드록시술포베타인형, 아미드술포베타인형, 포스포베타인형, 아미노카르복실산염형, 이미다졸린 유도체형, 아미드아민형 등의 양성 계면활성제 등을 들 수 있다.
상기 유기 및 무기 안료로서는 규산, 무수규산, 규산마그네슘, 탤크, 세리사이트,마이카, 카올린, 벵갈라, 클레이, 벤토나이트, 티탄피막운모, 옥시염화비스무트, 산화지르코늄, 산화마그네슘, 산화아연, 산화티탄, 산화알루미늄, 황산칼슘, 황산바륨, 황산마그네슘, 탄산칼슘, 탄산마그네슘, 산화철, 군청, 산화크롬, 수산화크롬, 칼라민 및 이들의 복합체등의 무기 안료 ; 폴리아미드, 폴리에스테르, 폴리프로필렌, 폴리스티렌, 폴리우레탄, 비닐수지, 요소수지, 페놀수지, 불소수지, 규소수지, 아크릴수지, 멜라민수지, 에폭시수지, 폴리카보네이트수지, 디비닐벤젠ㆍ스티렌 공중합체, 실크파우더, 셀룰로오스, CI 피그먼트옐로우, CI 피그먼트오렌지 등의 유기 안료 및 이들의 무기 안료와 유기 안료의 복합 안료 등을 들 수 있다.
상기 유기 분체로서는 스테아르산칼슘 등의 금속비누 ; 세틸린산아연나트륨, 라우릴린산아연, 라우릴린산칼슘 등의 알킬인산금속염 ; N-라우로일-베타-알라닌칼슘, N-라우로일-베타-알라닌아연, N-라우로일글리신칼슘 등의 아실아미노산 다가금속염 ; N-라우로일-타우린칼슘, N-팔미토일-타우린칼슘 등의 아미드술폰산 다가금속염 ; N-엡실론-라우로일-L-리진, N-엡실론-팔미토일리진, N-알파-파리토일올니틴, N-알파-라우로일아르기닌, N-알파-경화우지지방산아실아르기닌 등의 N-아실염기성아미노산 ; N-라우로일글리실글리신 등의 N-아실폴리펩티드 ; 알파-아미노카프릴산, 알파-아미노라우린산 등의 알파-아미노지방산 ; 폴리에틸렌, 폴리프로필렌, 나일론, 폴리메틸메타크릴레이트, 폴리스티렌, 디비닐벤젠ㆍ스티렌 공중합체, 사불화에틸렌 등을 들 수 있다.
상기 자외선 흡수제로서는 파라아미노벤조산, 파라아미노벤조산에틸, 파라아미노벤조산아밀, 파라아미노벤조산옥틸, 살리실산에틸렌글리콜, 살리신산페닐, 살리신산옥틸, 살리신산벤질, 살리신산부틸페닐, 살리신산호모멘틸, 계피산벤질, 파라메톡시계피산-2-에톡시에틸, 파라메톡시계피산옥틸, 디파라메톡시계피산모노-2-에틸헥산글리세릴, 파라메톡시계피산이소프로필, 디이소프로필ㆍ디이소프로필계피산에스테르 혼합물, 우로카닌산, 우로카닌산에틸, 히드록시메톡시벤조페논, 히드록시메톡시벤조페논술폰산 및 그 염, 디히드록시메톡시벤조페논, 디히드록시메톡시벤조페논디술폰산나트륨, 디히드록시벤조페논, 테트라히드록시벤조페논, 4-tert-부틸-4'-메톡시디벤조일메탄, 2,4,6-트리아닐리노-p-(카르보-2'-에틸헥실-1'-옥시)-1,3,5-트리아진, 2-(2-히드록시-5-메틸페닐)벤조트리아졸 등을 들 수 있다.
상기 살균제로서는 히노키티올, 트리클로산, 트리클로로히드록시디페닐에테르, 크로르헥시딘글루콘산염, 페녹시에탄올, 레조르신, 이소프로필메틸페놀, 아줄렌, 살리칠산, 진크필리티온, 염화벤잘코늄, 감광소 301호, 모노니트로과이어콜나트륨, 운데시렌산 등을 들 수 있다.
상기 산화 방지제로서는 부틸히드록시아니솔, 갈릭산프로필, 엘리소르빈산 등을 들 수 있다.
상기 pH 조정제로서는 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등을 들 수 있다.
상기 알코올로서는 세틸알코올 등의 고급 알코올을 들 수 있다.
또한, 이외에 첨가해도 되는 배합 성분은 이에 한정되는 것은 아니며, 또, 상기 어느 성분도 본 발명의 목적 및 효과를 손상시키지 않는 범위 내에서 배합 가능하지만, 총중량에 대하여 바람직하게는 0.01 내지 5% 중량 백분율, 더욱 바람직하게는 0.01 내지 3% 중량 백분율로 배합된다.
본 발명의 화장료 조성물은 용액, 유화물, 점성형 혼합물 등의 형상을 취할 수 있다.
본 발명의 화장료 조성물에 포함되는 성분은 유효성분으로서 상기 화합물 이외에 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예를 들면, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제 및 담체를 포함한다.
본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어 유액, 크림, 파운데이션, 로션, 미용액, 모발화장료 등을 들 수 있다. 구체적으로, 본 발명의 화장료 조성물은 스킨로션, 스킨소프너, 모이스쳐 로션, 영양로션, 맛사지크림, 영양크림, 핸드크림, 모이스처크림, 에센스, 팩, 비누, 화장수, 밀크로션, 젤, 연고, 패취, 클렌징폼, 바디클린저, 아스트린젠트, 분무제의 제형을 포함한다. 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. 본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다. 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, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다. 본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다. 본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.
이하, 실시예를 통해서 본 발명을 보다 상세히 설명하기로 한다. 하지만, 이들은 본 발명을 보다 상세하게 설명하기 위한 것일 뿐, 본 발명의 권리범위가 이에 한정되는 것은 아니다.
<실시예 1> 펩타이드의 합성
하기 표 1에 기재된 서열번호 1 내지 4의 펩타이드는 자동화합성기(PeptrEx-R48, 펩트론, 대한민국)를 이용하여 FMOC 고체-상 방법(FMOC solid-phase method)으로 합성하였다. 합성된 펩타이드는 C18 분석용 RP 컬럼(Shiseido capcell pak)을 사용한 역상 고속액체크로마토그래피(Prominence LC-20AB, Shimadzu, 일본)로 정제 및 분석하였으며, 질량분석기(HP 1100 Series LC/MSD, Hewlett-Packard, 미국)를 이용하여 동정하였다.
펩타이드 명칭 | 서열번호 | 아미노산 서열 |
AhR Pep1 | 서열번호 1 | Asp-Arg-Leu-Asn |
AhR Pep2 | 서열번호 2 | Asp-Arg-Leu |
AhR Pep3 | 서열번호 3 | Asn-Thr-Glu-Leu |
AhR Pep4 | 서열번호 4 | Asn-Thr-Glu |
<실시예 2> 실시예 1에서 제조된 펩타이드가 아릴 탄화수소 수용체의 활성을 역제하여 AhR과 POLⅡ의 물리적 결합에 저하시키는 것을 확인
1. 실시예 1에서 제조된 펩타이드와 AhR 길항제인 3-MC(3-Methylcholanthrene)를 인간 각질(HaCaT) 세포에 처리한 후, in situ PLA(proximity ligation assay) 방법을 통하여 AhR과 RNA Polymerase II(POLII)의 물리적 결합에 대한 영향을 평가하였다.
2. 구체적으로, 24-웰 마이크로플레이트의 각 웰에 4.5X104개의 HaCaT 세포를 DMEM 혈청배지에 분주하고 37℃, 5% CO2 인큐베이터에서 24시간 배양하였다. 배양 후, 3-MC와 실시예 1에서 제조된 펩타이드(AhR Pep 1 내지 4) 각각을 처리하고 24시간 동안 동일한 조건에서 인큐베이션하였다. 배지 중 3-MC의 농도는 3uM이고 각 펩타이드의 농도는 2, 20uM이 되도록 하였으며, 대조군으로 아무 처리를 하지 않은 것과 3-MC만 단독 처리한 것을 사용하였다. 이후, 각 웰의 세포를 PBS로 세정하고 2% 포름알데히드로 15분 동안 처리하여 고정시킨 후, 0.1% TritonX-100을 5분간 처리하여 세포 안으로의 항체 투과성을 높였다. anti-AhR 다클론항체(abcam, UK) 및 anti-POLII 단일클론 항체(Santa cruz, USA)를 첨가하고, In situ PLA 키트(Sigma-Aldrich)를 사용하여 PLA 프로브를 가한 다음, 하이브리디제이션(hybridization), 라이게이션(ligation), 증폭(amplification) 및 마운팅 단계를 수행하였다.
3. 이후, 각각의 세포에서 검출되는 발광 신호(PLA signals)를 공초점 레이져 현미경(Olympus fluoview FW1000; Olympus, Japan)으로 측정하여 AhR 및 POLII 항체의 물리적인 상호작용을 정량하여, 그 결과를 도 1에 나타내었다.
4. 도 1을 보면, 인간 각질 세포에 3-MC를 처리하는 경우 AhR과 RNA POLⅡ의 상호작용이 증가하는데, AhR Pep 1 내지 4를 함께 처리한 경우 상기 AhR과 POLII의 상호작용 증가를 감소시킴을 확인할 수 있어, 상기 AR Pep 1 내지 4가 아릴 탄화수소 수용체의 활성을 억제함을 알 수 있다. 즉, AR Pep 1 내지 4가 아릴 탄화수소 수용체의 활성을 억제해, AR과 POLII의 상호작용 증가를 감소시킴으로 피부 트러블(염증 등)을 완화할 수 있게 된다.
<실시예 3> 실시예 1에서 제조된 펩타이드의 세포 독성 평가
1. 실시예 1에서 제조된 펩타이드의 세포 독성을 평가하기 위해 MTT assay를 실시하였다. 배양된 HaCaT 세포에 실시예 1에서 제조된 펩타이드(AhR Pep 1 내지 4) 각각을 0, 2, 20, 50uM의 농도로 처리하고 24시간 동안 배양하였다. 이후, MTT 용액을 넣고 배양하고, 상층액을 제거한 후 DMSO를 넣고, 540nm에서 흡광도를 측정하였다.
2. 측정 결과, AhR Pep 1 내지 4는 모두 세포 독성이 없음을 확인하였다.
<실시예 4> 실시예 1에서 제조된 펩타이드가 미세먼지에 의한 세포 독성을 억제함을 평가
1. 실시예 1에서 제조된 펩타이드가 미세먼지에 의한 세포 독성을 억제함을 확인하기 위해, 배양된 HaCaT 세포에 20ug/ml의 미세먼지(시그마 알드리지에서 구매한 diesel particulate matter 사용)와 2, 20uM의 실시예 1에서 제조된 펩타이드(AhR Pep 1 내지 4) 각각을 처리하고 24시간 동안 인큐베이션하였다. 이후, MTT solution을 넣고 배양하고, DMSO를 넣고, 540nm에서 흡광도를 측정한 후, 세포 생존율을 계산하여 도 2에 나타내었다. 대조군으로 아무 처리를 하지 않은 것과 미세먼지만 단독 처리한 것을 사용하였다.
2. 도 2를 보면, 인간 각질 세포 미세먼지를 단독 처리하는 세포 생존율이 급격하게 떨어지는 것을 알 수 있는데, AhR Pep 1 내지 4를 함께 처리한 경우 미세먼지를 단독 처리한 경우보다 세포 생존율을 현저하게 큼을 확인할 수 있다. 미세먼지는 AhR과 결합하여 세포 독성을 발생시키는데, 실시예 1에서 제조된 펩타이드는 미세먼지와 AhR의 결합을 억제하여 세포 독성의 발생을 저하시킴을 알 수 있다. 이로 인해, 세포 독성 감소로 인해 피부 트러블(염증 등)을 완화할 수 있게 된다.
<실시예 5> 실시예 1에서 제조된 펩타이드가 미세먼지에 의해 유발되는 활성산소의 생성을 억제함을 평가
1. 실시예 1에서 제조된 펩타이드가 미세먼지에 의해 유발되는 활성산소의 생성을 억제함을 확인하기 위해 DCF-DA 법을 이용하였다.
2. 구체적으로, 배양된 HaCaT 세포에 10ug/ml의 미세먼지와 2, 20uM의 실시예 1에서 제조된 펩타이드(AhR Pep 1 내지 4) 각각을 처리하고 24시간 동안 인큐베이션하였다. 이후, Dichlorofluorescein diacetate(DCF-DA)를 30분간 37℃에서 반응시킨 후, 유세포 분석기를 이용하여 분석하여 그 결과를 도 3에 나타내었다.
3. 도 3을 보면, 인간 각질 세포에 미세먼지를 단독 처리하는 경우 활성산소의 생성이 현저하게 증가함을 알 수 있는데, AhR Pep 1 내지 4를 함께 처리한 경우 미세먼지에 의해 증가한 활성산소의 생성이 억제됨을 확인할 수 있다. 미세먼지는 AhR과 결합하여 활성 산소를 발생시키는데, 실시예 1에서 제조된 펩타이드는 미세먼지와 AhR의 결합을 억제하여 활성 산소의 발생을 저하시킴을 알 수 있다. 이로 인해, 활성산소 생성 억제로 인해 피부 트러블(염증 등)을 완화할 수 있게 된다.
<실시예 6> 실시예 1에서 제조된 펩타이드가 미세먼지에 의해 유발되는 pro-inflammatory cytokines의 생성을 억제함을 평가
1. 실시예 1에서 제조된 펩타이드가 미세먼지에 의해 유발되는 pro-inflammatory cytokines의 생성을 억제함을 확인하기 위해 ELISA 방법을 이용하였다.
2. 구체적으로, 배양된 HaCaT 세포에 10ug/ml의 미세먼지와 20uM의 실시예 1에서 제조된 펩타이드(AhR Pep 1 내지 4) 각각을 처리하고 24시간 동안 인큐베이션하였다. 이후, IL-6 및 TNF-α 양을 mouse enzyme-linked immnunosorbent assay(ELISA) kit(R&D Systems Inc, Minneapolis, MN, USA)를 이용하여, 그 결과를 표 2에 나타내었다.
3. 표 2를 보면, 인간 각질 세포에 미세먼지를 단독 처리하는 경우 사이토카인의 생성이 증가함을 알 수 있는데, AhR Pep 1 내지 4를 함께 처리한 경우 미세먼지에 의해 증가한 사이토카인의 생성이 억제됨을 확인할 수 있다. 미세먼지는 AhR과 결합하여 사이토카인을 생성시키는데, 실시예 1에서 제조된 펩타이드는 미세먼지와 AhR의 결합을 억제하여 사이토카인의 발생을 저하시킴을 알 수 있다. 이로 인해, 사이토카인 생성 억제로 인해 피부 트러블(염증 등)을 완화할 수 있게 된다.
미처리 | 미세먼지 | 미세먼지+AhR Pep 1 | 미세먼지+AhR Pep 2 | 미세먼지+AhR Pep 3 | 미세먼지+AhR Pep 4 | |
IL-6 생성(%) | 0 | 100 | 76 | 87 | 83 | 74 |
TNF-α 생성(%) | 0 | 100 | 79 | 93 | 89 | 82 |
이상에서, 출원인은 본 발명의 바람직한 실시예들을 설명하였지만, 이와 같은 실시예들은 본 발명의 기술적 사상을 구현하는 일 실시예일 뿐이며 본 발명의 기술적 사상을 구현하는 한 어떠한 변경예 또는 수정예도 본 발명의 범위에 속하는 것으로 해석되어야 한다.
Claims (6)
- 서열번호 1 내지 4 중 어느 하나의 아미노산 서열로 구성된 펩타이드.
- 제1항에 있어서,상기 펩타이드는 아릴 탄화수소 수용체의 활성을 저하시키는 것을 특징으로 하는 펩타이드.
- 제1항에 있어서,상기 펩타이드는 미세먼지에 발생하는 피부 트러블을 완화하기 위해 사용되는 것을 특징으로 하는 펩타이드.
- 제3항에 있어서,상기 펩타이드는 미세먼지에 의한 염증 발생을 억제하는 것을 특징으로 하는 펩타이드.
- 서열번호 1 내지 4 중 어느 하나의 아미노산 서열로 구성된 펩타이드를 포함하는 것을 특징으로 하는 화장료 조성물.
- 제5항에 있어서,상기 화장료 조성물은 미세먼지에 발생하는 피부 트러블을 완화하는 효과를 제공하는 것을 특징으로 하는 화장료 조성물.
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JP2022536824A JP7422431B2 (ja) | 2019-12-17 | 2020-07-20 | アリール炭化水素受容体の活性を抑制するペプチド及びこれを用いる化粧料組成物 |
US17/605,774 US20220048945A1 (en) | 2019-12-17 | 2020-07-20 | Peptide inhibiting activity of aryl hydrocarbon receptor and cosmetic composition using same |
EP20903940.3A EP4079749A4 (en) | 2019-12-17 | 2020-07-20 | PEPTIDE INHIBITING THE ACTIVITY OF AN ARYL HYDROCARBON RECEPTOR AND COSMETIC COMPOSITION USING SAME |
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EP (1) | EP4079749A4 (ko) |
JP (1) | JP7422431B2 (ko) |
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KR20180112140A (ko) * | 2017-03-30 | 2018-10-12 | (주)케어젠 | 환경오염 물질에 대한 세포 보호 효과를 갖는 펩타이드 및 이의 용도 |
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KR102041561B1 (ko) * | 2018-02-23 | 2019-11-06 | 주식회사 메디쿼터스 | 미세먼지 차단용 피부화장료 조성물 및 겔 조성물 |
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CA2459796A1 (en) * | 2001-09-05 | 2003-03-13 | King's College London | Homing peptides |
EP1298210A1 (en) * | 2001-10-01 | 2003-04-02 | Societe Des Produits Nestle S.A. | Cocoa flavour precursor peptides |
WO2003064449A2 (en) * | 2002-01-28 | 2003-08-07 | Keraplast Technologies, Ltd. | Bioactive keratin peptides |
WO2004077058A1 (en) * | 2003-02-26 | 2004-09-10 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with aryl hydrocarbon receptor (ahr) |
WO2013036791A2 (en) * | 2011-09-09 | 2013-03-14 | Beth Israel Deaconess Medical Center, Inc. | Modified adenoviral vectors and methods of treatment using same |
WO2014200910A2 (en) * | 2013-06-10 | 2014-12-18 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
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- 2019-12-17 KR KR1020190168700A patent/KR102351515B1/ko active IP Right Grant
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2020
- 2020-07-20 JP JP2022536824A patent/JP7422431B2/ja active Active
- 2020-07-20 WO PCT/KR2020/009499 patent/WO2021125484A1/ko unknown
- 2020-07-20 EP EP20903940.3A patent/EP4079749A4/en active Pending
- 2020-07-20 US US17/605,774 patent/US20220048945A1/en not_active Abandoned
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KR20190113902A (ko) | 2017-02-01 | 2019-10-08 | 페넥스 파마슈티컬스 아게 | 아릴 탄화수소 수용체(AhR)조절 화합물 |
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US20220048945A1 (en) | 2022-02-17 |
JP2023507728A (ja) | 2023-02-27 |
KR102351515B1 (ko) | 2022-01-14 |
EP4079749A1 (en) | 2022-10-26 |
KR20210077261A (ko) | 2021-06-25 |
EP4079749A4 (en) | 2024-01-10 |
JP7422431B2 (ja) | 2024-01-26 |
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