KR20130055505A - Novel peptide derivative capable of synthesizing collagen and use thereof - Google Patents
Novel peptide derivative capable of synthesizing collagen and use thereof Download PDFInfo
- Publication number
- KR20130055505A KR20130055505A KR1020120066864A KR20120066864A KR20130055505A KR 20130055505 A KR20130055505 A KR 20130055505A KR 1020120066864 A KR1020120066864 A KR 1020120066864A KR 20120066864 A KR20120066864 A KR 20120066864A KR 20130055505 A KR20130055505 A KR 20130055505A
- Authority
- KR
- South Korea
- Prior art keywords
- peptide
- yigsr
- peptide derivative
- present
- acid sequence
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 80
- 108010035532 Collagen Proteins 0.000 title abstract description 35
- 102000008186 Collagen Human genes 0.000 title abstract description 35
- 229920001436 collagen Polymers 0.000 title abstract description 34
- 230000002194 synthesizing effect Effects 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 108010052768 tyrosyl-isoleucyl-glycyl-seryl-arginine Proteins 0.000 claims abstract description 24
- 239000000945 filler Substances 0.000 claims abstract description 21
- 150000001413 amino acids Chemical class 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 239000002537 cosmetic Substances 0.000 claims abstract description 12
- 125000001312 palmitoyl group Chemical group O=C([*])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 claims abstract description 12
- MWOGMBZGFFZBMK-LJZWMIMPSA-N (2s)-2-[[(2s)-2-[[2-[[(2s,3s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWOGMBZGFFZBMK-LJZWMIMPSA-N 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 7
- 230000002500 effect on skin Effects 0.000 claims description 18
- 206010052428 Wound Diseases 0.000 claims description 11
- 208000027418 Wounds and injury Diseases 0.000 claims description 11
- 230000037303 wrinkles Effects 0.000 claims description 9
- 230000009759 skin aging Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 23
- 238000003786 synthesis reaction Methods 0.000 abstract description 22
- 230000000694 effects Effects 0.000 abstract description 10
- 230000029663 wound healing Effects 0.000 abstract description 3
- 230000003712 anti-aging effect Effects 0.000 abstract 2
- 238000002360 preparation method Methods 0.000 description 19
- 210000003491 skin Anatomy 0.000 description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- -1 pack Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000003755 preservative agent Substances 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 238000007796 conventional method Methods 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 210000002950 fibroblast Anatomy 0.000 description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 235000019634 flavors Nutrition 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000004040 coloring Methods 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 229920001214 Polysorbate 60 Polymers 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 229940057995 liquid paraffin Drugs 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 4
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 4
- 229940113124 polysorbate 60 Drugs 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (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-carboxylic acid Chemical compound 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 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
- 239000006180 TBST buffer Substances 0.000 description 3
- 235000013871 bee wax Nutrition 0.000 description 3
- 239000012166 beeswax Substances 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 229940014259 gelatin Drugs 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 229920002674 hyaluronan Polymers 0.000 description 3
- 229960003160 hyaluronic acid Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- 238000009010 Bradford assay Methods 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000012422 Collagen Type I Human genes 0.000 description 2
- 108010022452 Collagen Type I Proteins 0.000 description 2
- 108010056543 CosmoDerm Proteins 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000000501 collagen implant Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 2
- GSGDTSDELPUTKU-UHFFFAOYSA-N nonoxybenzene Chemical compound CCCCCCCCCOC1=CC=CC=C1 GSGDTSDELPUTKU-UHFFFAOYSA-N 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000002374 sebum Anatomy 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 210000001626 skin fibroblast Anatomy 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 229940032094 squalane Drugs 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- DENIQPHQUIGDJZ-IBGZPJMESA-N (2s)-5-(diaminomethylideneamino)-2-(hexadecanoylamino)pentanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCCNC(N)=N DENIQPHQUIGDJZ-IBGZPJMESA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- QGJZLNKBHJESQX-UHFFFAOYSA-N 3-Epi-Betulin-Saeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(=C)C)C5C4CCC3C21C QGJZLNKBHJESQX-UHFFFAOYSA-N 0.000 description 1
- CLOUCVRNYSHRCF-UHFFFAOYSA-N 3beta-Hydroxy-20(29)-Lupen-3,27-oic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C(O)=O)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C CLOUCVRNYSHRCF-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000486679 Antitype Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- DIZWSDNSTNAYHK-XGWVBXMLSA-N Betulinic acid Natural products CC(=C)[C@@H]1C[C@H]([C@H]2CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(=O)O DIZWSDNSTNAYHK-XGWVBXMLSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241001340526 Chrysoclista linneella Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920002675 Polyoxyl Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 229920001954 Restylane Polymers 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000001153 anti-wrinkle effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- QGJZLNKBHJESQX-FZFNOLFKSA-N betulinic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C QGJZLNKBHJESQX-FZFNOLFKSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000004956 cell adhesive effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000571 coke Substances 0.000 description 1
- 102000021124 collagen binding proteins Human genes 0.000 description 1
- 108091011142 collagen binding proteins Proteins 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 108010089886 dermicol-P35 27G Proteins 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- PZXJOHSZQAEJFE-UHFFFAOYSA-N dihydrobetulinic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(C)C)C5C4CCC3C21C PZXJOHSZQAEJFE-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 108010020199 glutaraldehyde-cross-linked collagen Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000003915 liquefied petroleum gas Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- MQYXUWHLBZFQQO-UHFFFAOYSA-N nepehinol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C MQYXUWHLBZFQQO-UHFFFAOYSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 125000001117 oleyl 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])=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])[H] 0.000 description 1
- 235000015927 pasta Nutrition 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001289 polyvinyl ether Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 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
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 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
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940087126 wild yam extract Drugs 0.000 description 1
- 239000003357 wound healing promoting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Birds (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
본 발명은 펩타이드 유도체 및 그의 용도에 관한 것으로서, 더 상세하게는 콜라겐 합성능이 있는 신규 펩타이드 유도체 및 그의 용도에 관한 것이다.The present invention relates to peptide derivatives and uses thereof, and more particularly to novel peptide derivatives with collagen synthesis ability and uses thereof.
사람은 나이가 들면서 피부노화가 일어나게 되는데 그 대표적인 증상이 주름(Wrinkle)이다. 주름은 나이를 나타내는 하나의 현상으로서, 주름이 생기는 대표적인 원인은 피부의 진피에서 매트릭스를 형성하는 콜라겐의 분해에 기인한다. 피부의 콜라겐은 노화가 진행됨에 따라 생성이 저하된다.As a person ages, skin aging occurs. The main symptom is wrinkles. Wrinkles are a phenomenon of age, and the most common cause of wrinkles is the degradation of collagen that forms the matrix in the dermis of the skin. Collagen in the skin decreases as aging progresses.
콜라겐 합성을 촉진하는 종래의 물질로는 레티노이드(RE36068), TGF-β(Transforming growth factor), 베툴린산(JP8-208424), 야생 참마 추출물(대한민국 공개특허 제2009-0055079) 등이 알려져 있다.Conventional materials for promoting collagen synthesis include retinoids (RE36068), transforming growth factor (TGF-β), betulinic acid (JP8-208424), wild yam extract (Korean Patent Publication No. 2009-0055079), and the like.
한편, 팔미토일기(palmitoyl group)가 N-말단에 부착된 올리고펩타이드(oligopeptide) 중 일부가 콜라겐 합성을 촉진시켜 주름개선제로 사용되고 있다(Robinson et al., Int. J. Cosmet. Sci. (2005) 27(3): 155-160).Meanwhile, some of oligopeptides having a palmitoyl group attached to the N-terminus promote collagen synthesis and are used as antiwrinkle agents (Robinson et al ., Int. J. Cosmet. Sci . (2005). ) 27 (3): 155-160).
그러나 이러한 종래의 콜라겐 합성 증진제는 그 효율이 떨어지거나, 재조합 단백질로서 고가의 비용이 소요되며, 천연 추출물의 경우 재현성이 떨어지는 단점이 있었다.However, such a conventional collagen synthesis enhancer has a disadvantage of low efficiency, high cost as a recombinant protein, and a natural extract has a disadvantage of poor reproducibility.
본 발명은 상기와 같은 문제점을 포함하여 여러 문제점들을 해결하기 위한 것으로서, 비교적 저렴한 비용으로 효과적으로 콜라겐 합성을 증진함시킴으로써, 피부노화 경감 또는 주름개선용 화장료 조성물 또는 창상치료제 등으로 사용이 가능한 신규 펩타이드 및 그의 용도를 제공하는 것을 목적으로 한다. 그러나 이러한 과제는 예시적인 것으로, 이에 의해 본 발명의 범위가 한정되는 것은 아니다.The present invention is to solve a number of problems including the above problems, by effectively promoting collagen synthesis at a relatively low cost, new peptides that can be used as a cosmetic composition or wound treatment for reducing skin aging or improving wrinkles and Its purpose is to provide its use. However, these problems are exemplary and do not limit the scope of the present invention.
본 발명의 일 관점에 따르면, 서열번호 1로 기재되는 아미노산 서열(YIGSR)을 포함하는 5 내지 100 아미노산으로 구성되는 펩타이드의 N-말단에 팔미토일기(palmitoyl group) 부가된 펩타이드 유도체가 제공된다.According to one aspect of the invention, there is provided a peptide derivative having a palmitoyl group added to the N-terminus of a peptide consisting of 5 to 100 amino acids comprising the amino acid sequence (YIGSR) as set forth in SEQ ID NO: 1.
상기 펩타이드는 5 내지 20개의 아미노산으로 구성될 수 있고, 서열번호 1로 기재되는 아미노산 서열로 구성되는 펩타이드일 수 있다.The peptide may be composed of 5 to 20 amino acids and may be a peptide composed of the amino acid sequence set forth in SEQ ID NO: 1.
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체를 유효성분으로 포함하는 피부노화 경감용 조성물이 제공된다.According to another aspect of the invention, there is provided a composition for reducing skin aging comprising the peptide derivative as an active ingredient.
상기 피부노화 경감용 조성물은 화장료 조성물의 형태로 제공될 수 있다.The composition for reducing skin aging may be provided in the form of a cosmetic composition.
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체를 유효성분으로 포함하는 주름개선용 화장료 조성물이 제공된다.According to another aspect of the invention, there is provided a cosmetic composition for improving wrinkles comprising the peptide derivative as an active ingredient.
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체를 유효성분으로 함유하는 창상 치료제가 제공된다.According to another aspect of the invention, there is provided a wound healing agent containing the peptide derivative as an active ingredient.
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체를 유효성분으로 함유하는 피부 충전제가 제공된다.According to another aspect of the present invention, a dermal filler containing the peptide derivative as an active ingredient is provided.
상기한 바와 같이 이루어진 본 발명의 일 실시예에 따르면, 피부 상의 콜라겐의 합성을 촉진하여, 피부노화를 예방하고 주름을 개선할 수 있으며, 더 나아가 상처치유를 촉진할 수 있다. 물론 이러한 효과에 의해 본 발명의 범위가 한정되는 것은 아니다.According to one embodiment of the present invention made as described above, by promoting the synthesis of collagen on the skin, it is possible to prevent skin aging and improve wrinkles, and further promote wound healing. Of course, the scope of the present invention is not limited by these effects.
도 1은 본 발명의 펩타이드 유도체의 농도 의존적인 콜라겐 합성 활성을 보여주는 면역블롯팅 분석 결과이다.
도 2는 본 발명의 펩타이드 유도체 및 비교예의 콜라겐 합성 활성을 비교하는 면역블롯팅 분석 결과이다.
도 3은 본 발명의 펩타이드 유도체 및 비교예의 펩타이드의 Erk 인산화 활성을 비교한 면역블롯팅 분석 결과이다.
도 4는 본 발명의 펩타이드 유도체의 농도 의존적인 피부 섬유아세포 증식 활성을 보여주는 그래프이다.
도 5는 본 발명의 펩타이드 유도체 및 비교예에 따른 펩타이드의 노출 시간에 따른 콜라겐 합성 활성을 비교한 면역블롯팅 분석 결과이다.1 is an immunoblotting analysis showing the concentration-dependent collagen synthesis activity of the peptide derivative of the present invention.
Figure 2 is an immunoblotting analysis comparing the collagen synthesis activity of the peptide derivative of the present invention and the comparative example.
3 is an immunoblotting analysis result comparing the Erk phosphorylation activity of the peptide derivative of the present invention and the peptide of the comparative example.
4 is a graph showing the concentration-dependent skin fibroblast proliferation activity of the peptide derivative of the present invention.
5 is a result of immunoblotting analysis comparing the collagen synthesis activity according to the exposure time of the peptide derivative of the present invention and the peptide according to the comparative example.
발명의 상세한 설명DETAILED DESCRIPTION OF THE INVENTION
이하, 본 발명을 보다 상세히 설명하기로 한다.Hereinafter, the present invention will be described in more detail.
서열번호 1로 기재되는 아미노산 서열(YIGSR)을 포함하는 5 내지 100 아미노산으로 구성되는 펩타이드의 N-말단에 팔미토일기(palmitoyl group) 부가된 펩타이드 유도체가 제공된다.Peptide derivatives having a palmitoyl group added to the N-terminus of a peptide consisting of 5 to 100 amino acids comprising the amino acid sequence (YIGSR) set forth in SEQ ID NO: 1 are provided.
상기 펩타이드는 5 내지 20개의 아미노산으로 구성될 수 있고, 서열번호 1로 기재되는 아미노산 서열로 구성되는 펩타이드일 수 있다.The peptide may be composed of 5 to 20 amino acids and may be a peptide composed of the amino acid sequence set forth in SEQ ID NO: 1.
상기 펩타이드 유도체는 펩타이드 합성에 의해 제조될 수 있다. 상기 펩타이드 합성 방법은 당업계에 잘 알려져 있다(Merrifield, J. Am. Chem. Soc. (1963) 85(14): 2149??2154)The peptide derivative can be prepared by peptide synthesis. Such peptide synthesis methods are well known in the art (Merrifield, J. Am. Chem. Soc . (1963) 85 (14): 2149 ?? 2154)
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체 또는 서열번호 1로 기재되는 아미노산 서열로 구성되는 YIGSR 펩타이드를 유효성분으로 포함하는 피부노화 경감용 조성물이 제공된다.According to another aspect of the invention, there is provided a composition for reducing skin aging comprising the peptide derivative or YIGSR peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
상기 피부노화 경감용 조성물은 화장료 조성물의 형태로 제공될 수 있다.The composition for reducing skin aging may be provided in the form of a cosmetic composition.
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체 또는 서열번호 1로 기재되는 아미노산 서열로 구성되는 YIGSR 펩타이드를 유효성분으로 포함하는 주름개선용 화장료 조성물이 제공된다.According to another aspect of the present invention, there is provided a cosmetic composition for improving wrinkles comprising the peptide derivative or YIGSR peptide consisting of the amino acid sequence described in SEQ ID NO: 1 as an active ingredient.
본 발명의 다른 관점에 따르면, 상기 펩타이드 유도체 또는 서열번호 1로 기재되는 아미노산 서열로 구성되는 YIGSR 펩타이드를 유효성분으로 함유하는 창상 치료용 조성물이 제공된다.According to another aspect of the present invention, there is provided a composition for treating wounds, comprising as an active ingredient the YIGSR peptide consisting of the peptide derivative or the amino acid sequence described in SEQ ID NO: 1.
원래, YIGSR 펩타이드는 Laminin 등 콜라겐 결합 단백질에 잘 보존된 부위로서 콜라겐 결합 모티프로 알려져 있다. 상기 YIGSR 펩타이드는 leukemia 세포의 성장을 억제하는 등(Yoshida et al., (1999) Br. J. Cancer, 80(12): 1898-1904), 항암제로서의 가능성이 보고된 바 있다(Graf et al., (1987) Cell, 48: 989-996). 그러나, 상기 YIGSR 펩타이드의 콜라겐 합성능에 대하여는 보고된 바 없으며, 본 발명자들은 콜라겐 합성능을 증진시키는 펩타이드를 찾기 위해 예의 노력한 결과 YIGSR 펩타이드 및 이의 팔미토일화 유도체인 Pal-YIGSR 펩타이드가 향상된 콜라겐 합성을 가짐을 확인함으로써, 본 발명을 완성하였다.Originally, YIGSR peptides are known as collagen binding motifs as sites well conserved in collagen binding proteins such as Laminin. The YIGSR peptide inhibits the growth of leukemia cells (Yoshida et al ., (1999) Br. J. Cancer, 80 (12): 1898-1904), and has been reported to be an anticancer agent (Graf et al . (1987) Cell, 48: 989-996). However, the collagen synthesis ability of the YIGSR peptide has not been reported, and the present inventors have diligently tried to find a peptide that enhances the collagen synthesis ability, and as a result, the YIGSR peptide and its palmitoylated derivative Pal-YIGSR peptide have improved collagen synthesis. By confirming that the present invention was completed, the present invention was completed.
본 발명의 조성물에서 Pal-YIGSR 펩타이드 또는 YiGSR 펩타이드의 유효량은 환자의 환부의 종류, 적용부위, 처리회수, 처리시간, 제형, 환자의 상태, 보조제의 종류 등에 따라 변할 수 있다. 사용량은 특별히 한정되지 않지만, 0.01μg/kg/day 내지 10 mg/kg/day일일 수 있다. 상기 1일량은 1일에 1회, 또는 적당한 간격을 두고 하루에 2~3회에 나눠 투여해도 되고, 수일(數日) 간격으로 간헐(間歇)투여해도 된다. The effective amount of Pal-YIGSR peptide or YiGSR peptide in the composition of the present invention may vary depending on the type of affected part, the site of application, the number of treatments, the treatment time, the dosage form, the condition of the patient, the type of adjuvant, and the like. The amount used is not particularly limited, but may be 0.01 μg / kg / day to 10 mg / kg / day. The daily dose may be administered once or in two or three times a day at appropriate intervals or may be administered intermittently at intervals of several days.
본 발명의 조성물에서 상기 펩타이드 유도체 또는 서열번호 1로 기재되는 아미노산 서열로 구성되는 YIGSR 펩타이드는, 조성물 총 중량에 대하여 0.1-100 중량%로 함유될 수 있다.YIGSR peptide consisting of the peptide derivative or the amino acid sequence of SEQ ID NO: 1 in the composition of the present invention, may be contained in 0.1-100% by weight relative to the total weight of the composition.
본 발명의 조성물은 약학적 조성물 또는 화장료 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 또한, 약학 조성물 또는 화장료 조성물의 제조에는 고체 또는 액체의 제제용 첨가물을 사용할 수 있다. 제제용 첨가물은 유기 또는 무기 중 어느 것이어도 된다. Compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical or cosmetic compositions. In addition, for the preparation of pharmaceutical compositions or cosmetic compositions, additives for the preparation of solid or liquid may be used. The preparation additive may be either organic or inorganic.
부형제로서는 예를 들면 유당, 자당, 백당, 포도당, 옥수수 전분(corn starch), 전분, 탈크, 소르비트, 결정 셀룰로오스, 덱스트린, 카올린, 탄산칼슘, 이산화규소 등을 들 수 있다. 결합제로서는 예를 들면 폴리비닐알코올, 폴리비닐에테르, 에틸셀룰로오스, 메틸셀룰로오스, 아라비아고무, 트래거캔스(tragacanth), 젤라틴, 셀락(shellac), 히드록시프로필셀룰로오스, 히드록시프로필메틸셀룰로오스, 구연산칼슘, 덱스트린, 펙틴(pectin) 등을 들 수 있다. 활택제로서는 예를 들면 스테아린산마그네슘, 탈크, 폴리에틸렌글리콜, 실리카, 경화식물유 등을 들 수 있다. 착색제로서는 통상 의약품에 첨가하는 것이 허가되어 있는 것이라면 모두 사용할 수 있다. 이들의 정제, 과립제에는 당의(糖衣), 젤라틴코팅, 기타 필요에 따라 적절히 코팅할 수 있다. 또한, 필요에 따라 방부제, 항산화제 등을 첨가할 수 있다.Examples of the excipient include lactose, sucrose, saccharin, glucose, corn starch, starch, talc, sorbit, crystalline cellulose, dextrin, kaolin, calcium carbonate and silicon dioxide. Examples of the binder include polyvinyl alcohol, polyvinyl ether, ethylcellulose, methylcellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropylcellulose, hydroxypropylmethylcellulose, calcium citrate, Dextrin, pectin, and the like. Examples of the lubricant include magnesium stearate, talc, polyethylene glycol, silica, and hydrogenated vegetable oil. Any coloring agent may be used as long as it is usually allowed to be added to pharmaceuticals. These tablets and granules can be suitably coated with sugar (sugar coating), gelatin coating, and others as required. If necessary, preservatives, antioxidants and the like may be added.
본 발명의 약학적 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며(예: 문헌 [Remington's Pharmaceutical Science, 최신판; Mack Publishing Company, Easton PA), 제제의 형태는 특별히 한정되는 것은 아니나, 바람직하게는 외용제일 수 있다. 본 발명의 외용제에는 시트제, 액상도포제, 분무제, 로션제, 크림제, 파프제, 분제, 침투 패드제, 분무제, 수화겔을 포함한 겔제, 파스타제, 리니멘트제, 연고제, 에어로졸, 분말제, 현탁액제, 경피흡수제 등의 통상적인 외용제의 형태가 포함될 수 있다. 이들 제형은 모든 제약 화학에 일반적으로 공지된 처방서인 문헌[Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania 18042(Chapter 87: Blaug, Seymour)에 기술되어 있다.The pharmaceutical compositions of the present invention may be prepared in any formulation conventionally prepared in the art (e.g., Remington's Pharmaceutical Science, latest edition; Mack Publishing Company, Easton PA), although the form of the formulation is not particularly limited. Preferably, it may be an external preparation. The external preparation of the present invention includes a sheet, a liquid coating, a spray, a lotion, a cream, a pape, a powder, a penetrating pad, a spray, a gel including a hydrogel, a pasta, a liniment, an ointment, an aerosol, a powder, a suspension. Formulations may include conventional external preparations such as transdermal absorbents. These formulations are described in Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania 18042 (Chapter 87: Blaug, Seymour), a prescription generally known for all pharmaceutical chemistry.
본 발명의 일례로, 상기 조성물을 피부 또는 창상 부위에 직접 적용될 수 있다. 즉, 창상부위에 산포될 수 있다. 시트의 형태인 경우는 창상 부위에 도포하는데 이때 도포한 부위에 적절히 드레싱하여 창상을 보호하면서 활성 성분의 치료 효과가 감소하는 것을 방지한다. 드레싱은 시판되고 있거나 통상적으로 알려져 있는 어떠한 것도 사용 가능하다. 시판되고 있는 드레싱의 예로는 컴필(Compeel), 듀우덤(Duoderm), 타가덤(Tagaderm) 및 옵사이트(Opsite)를 들 수 있다.In one example of the invention, the composition may be applied directly to the skin or wound site. That is, it may be scattered on the wound site. In the form of a sheet, it is applied to the wound site, where appropriate dressing is applied to the applied site to protect the wound while preventing the therapeutic effect of the active ingredient from decreasing. The dressing can be any commercially available or commonly known. Examples of commercially available dressings include Compeel, Duoderm, Tagaderm and Opsite.
본 발명의 펩타이드 유도체가 화장료 조성물에 사용될 경우, 그 제형에 있어서 특별히 한정되는 바가 없으며 예를 들면, 유연화장수, 영양화장수, 마사지크림, 영양크림, 팩, 젤 또는 피부 점착타입 화장료의 제형을 갖는 화장료 조성물 일 수 있으며, 로션, 연고, 겔, 크림, 패취 또는 분무제와 같은 경피 투여형 제형일 수 있다.When the peptide derivative of the present invention is used in the cosmetic composition, there is no particular limitation in the formulation, for example, a cosmetic having a formulation of softening longevity, nourishing longevity, massage cream, nourishing cream, pack, gel or skin adhesive cosmetic It may be a composition and may be a transdermal dosage form such as a lotion, ointment, gel, cream, patch or spray.
본 발명의 조성물에서, 약제학상 또는 화장품 공전상 허용되는 담체로는 그의 제형에 따라 다르나, 바셀린, 유동 파라핀, 겔화 탄화수소(별명: 플라스티베이스) 등의 탄화수소류; 중쇄지방산 트리글리세라이드, 돈지, 하드 팻트, 카카오지 등의 동식물성 오일; 세탄올, 스테아릴알코올, 스테아린산, 팔미틴산이소프로필 등의 고급지방산 알코올 및 지방산 및 그의 에스테르류; 마크로골(폴리에틸렌글리콜), 1,3-부틸렌글리콜, 글리세롤, 젤라틴, 백당, 당알코올 등의 수용성 기제; 글리세린 지방산에스테르, 스테아린산폴리옥실, 폴리옥시에틸렌경화 피마자유 등의 유화제; 아크릴산에스테르, 알긴산나트륨 등의 점착제; 액화석유가스, 이산화탄소 등의 분사제; 파라옥시벤조산에스테르류 등의 방부제 등을 들 수 있으며, 본 발명의 외용제는 이들을 사용하여 통상의 방법에 따라 제조할 수 있다. 또한, 이들 이외에도 안정제, 향료, 착색제, pH 조정제, 희석제, 계면활성제, 보존제, 항산화제 등을 필요에 따라 배합할 수도 있다. 본 발명의 외용제는 사용은 통상의 방법에 의해 국소창상부에 도포 될 수 있다.In the composition of the present invention, pharmaceutically or cosmetically orbitally acceptable carriers may be hydrocarbons such as petrolatum, liquid paraffin, gelled hydrocarbons (also called plastibases), depending on the formulation thereof; Animal and vegetable oils such as medium chain fatty acid triglyceride, lard, hard fat and cacao butter; Higher fatty acid alcohols and fatty acids such as cetanol, stearyl alcohol, stearic acid and isopropyl palmitate and esters thereof; Water-soluble bases such as macrogol (polyethylene glycol), 1,3-butylene glycol, glycerol, gelatin, white sugar and sugar alcohol; Emulsifiers such as glycerin fatty acid esters, polyoxyl stearic acid and polyoxyethylene-cured castor oil; Pressure-sensitive adhesives such as acrylate ester and sodium alginate; Propellants such as liquefied petroleum gas and carbon dioxide; Preservatives, such as paraoxybenzoic acid ester, etc. are mentioned, The external preparation of this invention can be manufactured according to a conventional method using these. In addition to these, stabilizers, flavors, colorants, pH adjusters, diluents, surfactants, preservatives, antioxidants and the like may be blended as necessary. The external preparation of the present invention can be applied to the topical wounds by conventional methods.
또한, 본 발명에 따른 약학적 조성물은 통상적인 반창고의 창상 박리 커버 등과 같은 고체 지지체상에 점착되어 사용될 수 있다. 본 발명의 양태로서, 고체 지지체를 먼저 점착층으로 피복하여 고체 지지체에 펩타이드 유도체의 부착을 향상시킨다. 점착제의 예로는 폴리아크릴레이트 및 시아노아크릴레이트가 포함될 수 있다.In addition, the pharmaceutical composition according to the present invention may be used adhered to a solid support such as a wound peeling cover of a conventional band-aid. In an aspect of the present invention, the solid support is first coated with an adhesive layer to enhance the attachment of the peptide derivative to the solid support. Examples of the pressure-sensitive adhesive may include polyacrylate and cyanoacrylate.
이러한 형태의 제형은 시판되고 있는 것이 많으며 예로는 천공된 플라스틱 필름 형태의 비부착성 창상 박리 커버를 갖는 반창고(Smith & Nephew Ltd.), Johnson & Johnson의 얇은 스트립(strip), 패취(patch), 스포트(spot), 가소성 스트립 형태의 밴드-에이드(BAND-AID); Colgate-Palmolive Co.(Kendall)의 큐리티 큐러드(Curity CURAD, 오우취리스(Ouchless)) 반창고; 및 American WhiteCross Laboratories, Inc.의 스틱-타이트(STIK-TITE) 탄성 스트립 등을 들 수 있다.Many formulations of this type are commercially available, such as Smith & Nephew Ltd. with a non-adhesive wound release cover in the form of perforated plastic films, thin strips, patches, BAND-AIDs in the form of spots, plastic strips; Curity CURAD (Ouchless) Band-Aid from Colgate-Palmolive Co. (Kendall); And STIK-TITE elastic strips from American White Cross Laboratories, Inc .;
본 발명의 일례로, 본 발명에 따른 조성물은 상기 펩타이드 유도체와 생리식염수를 일정한 부피비로 혼합하고 액상 도포제의 형태로 제형화될 수 있다. 본 발명의 일례로서, 본 발명에 따른 약학 조성물은 상기한 본 발명의 펩타이드 유도체와 수용성 연고기제를 혼합하고 여기에 생리식염수를 첨가하여 연고제의 형태로 제형화될 수 있다. In one embodiment of the present invention, the composition according to the present invention may be formulated in the form of a liquid coating agent by mixing the peptide derivative and physiological saline in a constant volume ratio. As an example of the present invention, the pharmaceutical composition according to the present invention may be formulated in the form of an ointment by mixing the peptide derivative of the present invention with a water-soluble ointment and adding physiological saline thereto.
그러나, 본 발명의 약제학적 조성물의 상기 사용량은 투여 경로, 환자의 연령, 성별, 체중, 환자의 중증도, 창상 종류, 적용부위, 처리회수, 처리시간, 제형, 환자의 상태, 보조제의 종류 등의 여러 관련 인자에 비추어 결정되는 것이므로 상기 유효량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 이해되어서는 아니 된다. However, the amount of the pharmaceutical composition according to the present invention may be used in terms of the route of administration, the age, sex, weight of the patient, the severity of the patient, the type of wound, the site of application, the number of treatments, the treatment time, the dosage form, the condition of the patient, the type of supplement, and the like. The effective amount is not to be understood as limiting the scope of the present invention in any aspect because it is determined in view of various related factors.
아울러, 본 발명의 일 실시예에 따른 조성물은 피부 충전제의 제형으로 제공될 수 있다. '피부 충전제(dermal filler)' 또는 '필러(dermal filler)'는 피부조직과 유사한 성분으로 특정부위에 삽입되어 연부조직을 확장시킴으로써 주름개선이나 윤곽교정 등에 사용되는 물질을 의미한다. 연조직 확장에는 주사가능한 물질로서 콜라겐이 흔히 사용된다. 또한, 단백질, 지방, 히알루론산 (HA), 폴리알코올 및 카르복시메틸셀룰로오스, 덱스트란과 같은 기타 폴리머를 비롯한 수많은 다른 물질들이 주사용 피부 충전물로서 사용되어 오고 있다. 콜라겐을 주성분으로 하는 피부 충전제로는, 돼지 콜라겐을 주성분으로 하는 EVOLENCE 30(ColBar LifeScience사 피부 충전제의 상표명), 소 콜라겐을 주성분으로 하는 Zyderm이나 Zyplast(이상 Inamed사 피부 충전제의 상표명), 인간 콜라겐을 주성분으로 하는 CosmoDerm이나 CosmoPlast(이상 Inamed사 피부 충전제의 상표명) 등이 알려져 있다. 히알루론산을 주성분으로 하는 것으로는 Rofilan(Rofil/Philoderm사 피부 충전제의 상표명), Perlane, Restylane(이상 Medicis/Q-Med AB사 피부 충전제의 상표명), Teosyal(Teoxane SA사 피부 충전제의 상표명), Surgiderm(Corneal Laboratoire사 피부 충전제의 상표명) 등이 있다. 본 발명의 일 실시태양에 따른 피부 충전제는 공지의 피부 충전제에 본 발명의 일 실시예에 따른 펩타이드를 적량 적재하거나 상기 펩타이드를 피부 충전제의 골격이 되는 고분자에 공유결합 또는 비공유결합에 의해 결합시킴으로써 제조될 수 있다.In addition, the composition according to an embodiment of the present invention may be provided in the formulation of a dermal filler. The term 'dermal filler' or 'dermal filler' refers to a substance similar to skin tissue and is used in wrinkle improvement or contour correction by inserting in a specific area and expanding soft tissue. Collagen is commonly used as an injectable substance in soft tissue expansion. In addition, numerous other substances have been used as dermal fillers for injection, including proteins, fats, hyaluronic acid (HA), polyalcohols and other polymers such as carboxymethylcellulose, dextran. Examples of skin fillers based on collagen include EVOLENCE 30 (brand name of ColBar LifeScience skin filler), pig collagen as a main ingredient, Zyderm and Zyplast (above brand names of Inamed skin filler), and human collagen based on bovine collagen. CosmoDerm and CosmoPlast (trade name of skin fillers of Inamed Co., Ltd.) as main components are known. Main ingredients of hyaluronic acid include Rofilan (trade name of skin filler of Rofil / Philoderm), Perlane, Restylane (trade name of dermal filler of Medicis / Q-Med AB), Teosyal (trade name of dermal filler of Teoxane SA), Surgiderm (Trade name of dermal fillers of Corneal Laboratoire). Dermal filler according to an embodiment of the present invention is prepared by loading a suitable amount of the peptide according to an embodiment of the present invention in a known skin filler or by covalently or non-covalently binding the peptide to a polymer that is a skeleton of the skin filler. Can be.
이하, 실시예 및 실험예를 통해 본 발명을 상세히 설명한다. 그러나 본 발명은 이하에서 개시되는 실시예 및 실험예에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 수 있는 것으로, 이하의 실시예 및 실험예는 본 발명의 개시가 완전하도록 하며, 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이다. Hereinafter, the present invention will be described in detail through Examples and Experimental Examples. It should be understood, however, that the invention is not limited to the disclosed embodiments and examples, but may be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, It is provided to fully inform the owner of the scope of the invention.
실시예Example
실시예 1: YIGSR의 제조Example 1: Preparation of YIGSR
YIGSR 펩타이드(서열번호 1)를 펩타이드 제조업체(Anygen, Korea)에 의뢰하여 제조하였다.YIGSR peptide (SEQ ID NO: 1) was prepared by the peptide manufacturer (Anygen, Korea).
실시예 2: palmitoyl-YIGSR의 제조Example 2: Preparation of palmitoyl-YIGSR
상기 실시예 1의 YIGSR 펩타이드(서열번호 1)의 N-말단에 팔미토일기가 부착된 펩타이드 유도체(Pal-YIGSR, 분자량: 846)를 palmitoyl-tyrosine을 이용하여 실시예 1의 방법과 동일한 방법으로 제조하였다(Anygen, Korea). Peptide derivative (Pal-YIGSR, molecular weight: 846) having a palmitoyl group attached to the N-terminus of the YIGSR peptide (SEQ ID NO: 1) of Example 1 in the same manner as in Example 1 using palmitoyl-tyrosine It was prepared (Anygen, Korea).
비교예 1: Pal-RGD의 제조Comparative Example 1: Preparation of Pal-RGD
팔미토일기가 N-말단에 부착된 RGD 펩타이드를 palmitoyl-arginine을 이용하여 상기 실시예 1과 동일한 방법으로 제조하였다. RGD는 인테그린 결합 활성을 가진 펩타이드로서 세포부착제 등으로 사용되고 있는 물질이다.An RGD peptide having a palmitoyl group attached to the N-terminus was prepared in the same manner as in Example 1 using palmitoyl-arginine. RGD is a peptide having integrin binding activity and is used as a cell adhesive.
비교예 2: oleyl-YIGSR의 제조Comparative Example 2: Preparation of oleyl-YIGSR
팔미토일기 대신 올레일기가 N-말단에 부가된 YIGSR 펩타이드를 oleyl-tyrosine을 이용하여 상기 실시예 1과 동일한 방법으로 제조하였다.A YIGSR peptide having an oleyl group added to the N-terminus instead of a palmitoyl group was prepared in the same manner as in Example 1 using oleyl-tyrosine.
실험예Experimental Example
실험예 1: 콜라겐 합성 및 Erk 인산화 분석Experimental Example 1: Collagen Synthesis and Erk Phosphorylation
상기 실시예 1 및 2 및 비교예 2에서 제조한 펩타이드 유도체를 배양중인 Hs27 피부 섬유아세포에 처리한 후, 상기 세포에서의 제1형 콜라겐 발현양을 면역블롯팅 분석법으로 측정하였다. 상기 Hs27 피부 섬유아세포는 10% FBS(Lonza, USA)를 첨가한 DMEM 배지(Lonza, USA)를 이용하여 습도 95%, 5% CO2, 37℃의 조건에서 배양하였다. 각 농도(0, 2, 25, 50 및 100 μM)의 펩타이드들을 24시간 혹은 100 μM의 펩타이드를 각 시간(0, 0.5, 6, 12 및 24 시간)에 따라대로 상기 Hs27 피부 섬유아세포에 처리한 후, 처리된 세포를 용해 완충액(150 mM NaCl, 1% Triton X-100, 10mM Tris, 1mM EDTA, pH 7.4)에서 초음파 분쇄한 후, 원심분리하여 상층액을 분리한 뒤 브래드포드 방법(Bradford assay)으로 정량하였다. 동량의 단백질을 5x 시료 완충액에 혼합하여 95℃에서 5분간 가열한 다음 6~15% 농도구배 SDS-PAGE(SDS-Polyacrylamide gel electrophoresis)에서 전기 영동시킨 후 니트로셀룰로오스 막에 흡착시켰다. 항-제1형 콜라겐 1차 항체(Rockland, USA), 항-인산화-ERK 1차 항체(Cell Signaling, USA) 및 항-액틴 1차 항체(Santa Cruz, USA)를 5% 스킴 밀크를 포함하는 TBST 완충액(Tris buffered saline with 0.05% Tween 20, pH 7.6)에 희석시켜 16시간 동안 반응시킨 후, TBST로 10분간 6차례 세척하였다. 그런 다음, 항-마우스 래빗 퍼옥시다제-결합 2차 항체(KPL, USA)를 처리하고 실온에서 1시간 반응시킨 후 다시 TBST로 10분간 6차례 세척하였고, ECL(enhanced chemiluminescent) 용액(Amersham, USA)으로 발색하여 확인하였다.After treating the peptide derivatives prepared in Examples 1 and 2 and Comparative Example 2 to the cultured Hs27 dermal fibroblasts, the
그 결과, 피부섬유아세포에서 Pal-YIGSR이 콜라겐 형성에 미치는 영향은 농도가 증가할수록 콜라겐 합성량이 증가하며, 노출시간이 증가할수록 교원질 합성량이 증가하는 양상을 보였다(도 1). YIGSR 역시 Pal-YIGSR 보다는 그 정도가 약하지만 콜라겐 합성을 증가시켰다. 그러나, oleyl-YIGSR의 경우에는 콜라겐 합성 정도에 있어서, 대조군과 큰 차이가 없었다(도 2). As a result, the effect of Pal-YIGSR on collagen formation in dermal fibroblasts was increased collagen synthesis with increasing concentration, collagen synthesis was increased with increasing exposure time (Fig. 1). YIGSR was also weaker than Pal-YIGSR but increased collagen synthesis. However, in the case of oleyl-YIGSR, there was no significant difference in the degree of collagen synthesis from the control (Fig. 2).
뿐만 아니라, 피부섬유아세포에서 Pal-YIGSR에 의한 ERK 인산화 유도 역시 관찰할 수 있었다(도 3). 그러나, YIGSR 및 oleyl-YIGSR의 경우 ERK 인산화에 미치는 영향이 미미하였다.In addition, induction of ERK phosphorylation by Pal-YIGSR in dermal fibroblasts was also observed (Fig. 3). However, YIGSR and oleyl-YIGSR had little effect on ERK phosphorylation.
실험예 2: 팔미토일기의 영향 분석Experimental Example 2: Analysis of the Effect of Palmitoyl Group
본 발명자들은 Pal-YIGSR에 의한 콜라겐 합성 증가가 순전히 팔미토일기에 의한 영향인지 확인하기 위하여, 세포부착능이 알려진 RGD 펩타이드를 이용하여 실험을 수행하였다.The inventors carried out experiments using RGD peptides known cell adhesion capacity to determine whether the collagen synthesis increased by Pal-YIGSR is purely palmitoyl.
구체적으로 비교예 1에서 제조한 Pal-RGD 펩타이드와 팔미토일기가 부착되지 않은 RGD 펩타이드를 이용하여 상시 실험예 1과 동일하게 실험을 수행하였다.Specifically, the experiment was performed in the same manner as in Experimental Example 1 using the Pal-RGD peptide prepared in Comparative Example 1 and the RGD peptide to which the palmitoyl group was not attached.
그 결과, RGD 펩타이드와 Pal-RGD 펩타이드 모두 콜라간 합성 정도에 있어서 대조군과 큰 차이가 없었다(도 5). 이는 본 발명의 펩타이드 유도체에 의한 콜라게 합성 증가가 단순히 팔미토일기 자체의 기능에 의한 것만이 아님을 시사하는 것이다.As a result, the RGD peptide and Pal-RGD peptide did not show a significant difference from the control group in the degree of coke synthesis (FIG. 5). This suggests that the increased collagen synthesis by the peptide derivative of the present invention is not simply due to the function of palmitoyl group itself.
실험예 3: 세포증식의 측정Experimental Example 3: Measurement of Cell Proliferation
상기 Hs27 피부 섬유아세포를 24-웰 배양용기에 40,000개씩 뿌린 후 5%의 CO2, 37℃하에서 24시간 배양하여 세포가 배양용기 바닥에 부착할 수 있도록 하였다. 다음날 FBS를 포함한 배지로 교환한 다음 다시 24 시간을 배양한 후 상기 실시예 1 및 2 그리고 비교예 1 및 2의 펩타이드 유도체를 농도별로 처리하고 다시 72시간 배양하여 크리스탈 바이올렛 법(crystal violet assay)으로 세포의 증식을 측정하였다. The Hs27 skin fibroblasts were sprinkled 40,000 in 24-well culture vessels and incubated at 5% CO 2 at 37 ° C. for 24 hours to allow the cells to adhere to the culture vessel bottom. The next day after exchange with a medium containing FBS and incubated again for 24 hours, the peptide derivatives of Examples 1 and 2 and Comparative Examples 1 and 2 were treated by concentration and incubated again for 72 hours, followed by crystal violet assay. Proliferation of the cells was measured.
구체적으로 먼저 각각의 웰의 배지를 제거한 후 한 웰당 500 ml의 0.1% 크리스탈 바이올렛 용액을 첨가하여 5분간 염색한 후, 크리스탈 바이올렛 용액을 제거하고, 3차 증류수로 웰이 맑아질 때까지 4회 세척하였다. 세척되는 증류수가 맑아지면, 증류수를 제거하고, 95% 에탄올을 1 ml 첨가하여 20분간 교반하면서 세포에 염색된 크리스탈 바이올렛을 녹여낸다. 이 용액을 96-웰 용기에 200 ml씩 분주하고 ELISA 판독기를 사용하여 590 nm에서 흡광도를 측정한 후, 시험할 물질을 처리하지 않은 군을 대조군으로 하여 상대적인 세포증식을 계산하였다.Specifically, the medium of each well is first removed, and then stained for 5 minutes by adding 500 ml of 0.1% crystal violet solution per well, and then the crystal violet solution is removed and washed four times until the wells are cleared with distilled water. It was. When the washed distilled water is cleared, the distilled water is removed, and 1 ml of 95% ethanol is added to dissolve the stained crystal violet on the cells while stirring for 20 minutes. 200 ml of this solution was dispensed in a 96-well container and absorbance was measured at 590 nm using an ELISA reader, and relative cell proliferation was calculated using the untreated group as a control.
그 결과 Pal-YIGSR는 0.5 ?? 50 μM 농도 범위 에서 세포 증식이 나타났고, 특히 100 및 500 μM 농도범위에서 각각 13% 및 23%의 세포증식을 나타내었다(도 4). As a result, Pal-YIGSR is 0.5 ?? Cell proliferation was observed in the 50 μM concentration range, and especially 13% and 23% cell proliferation in the 100 and 500 μM concentration range, respectively (Fig. 4).
상기에서 살펴본 바와 같이, 본 발명의 Pal-YIGSR 펩타이드 유도체는 배양한 피부섬유아세포에서 제1형 콜라겐 생성을 증가시켰으며, 섬유아세포의 증식을 촉진하였는데, 이는 향후 항노화 및 상처재생 제제 개발 시 본 발명의 펩타이드 유도체가 유효 물질로 사용될 수 있음을 입증하는 것이다. As described above, the Pal-YIGSR peptide derivative of the present invention increased the production of
제조예 Manufacturing example
제조예 1: 주사액제Preparation Example 1 Injection Solution
Pal-YIGSR 펩타이드 유도체 10 mg을 함유하는 주사액제는 다음과 같은 방법으로 제조하였다. Injection solution containing 10 mg of Pal-YIGSR peptide derivative was prepared by the following method.
Pal-YIGSR 펩타이드 유도체 10 mg, 염화나트륨 0.6 g을 정제수에 용해시켜서 100 ㎖을 만들었다. 이 용액을 0.2 μm 필터로 걸러서 멸균시켰다. 10 mg of Pal-YIGSR peptide derivative and 0.6 g of sodium chloride were dissolved in purified water to make 100 ml. This solution was sterilized by filtering with a 0.2 μm filter.
상기 주사액제의 구성성분은 하기와 같다.The components of the injection solution are as follows.
성분 함량(중량%)Component content (% by weight)
정제수 To 100Purified Water To 100
Pal-YIGSR 펩타이드 0.01 Pal-YIGSR Peptide 0.01
염화나트륨 0.6 Sodium Chloride 0.6
제조예 2: 유연화장수(스킨로션)Preparation Example 2: Softener (Skin Lotion)
하기와 같이 Pal-YIGSR 펩타이드를 함유하는 유연화장수를 통상의 방법에 따라 제조하였다.A flexible longevity containing Pal-YIGSR peptide was prepared according to a conventional method as follows.
성분 함량(중량%)Component Content (wt%)
정제수 To 100Purified water To 100
Pal-YIGSR 펩타이드 0.01Pal-YIGSR Peptide 0.01
부틸렌글리콜 2.0Butylene Glycol 2.0
프로필렌글리콜 2.0Propylene Glycol 2.0
카르복시비닐 폴리머 0.1Carboxyvinyl Polymer 0.1
피이지-12 노닐페닐에테르 0.2Fiji-12 nonylphenyl ether 0.2
폴리솔베이트 80 0.4
에탄올 10.0Ethanol 10.0
트리에탄올아민 0.1Triethanolamine 0.1
방부제, 색소, 향료 적량Preservatives, colorings, flavors
제조예 3: 영양화장수(밀크로션)Preparation Example 3: Nutrients (Milk Lotion)
하기와 같이 Pal-YIGSR 펩타이드를 함유하는 영양화장수를 통상의 방법에 따라 제조하였다.Nutrients containing Pal-YIGSR peptides were prepared according to a conventional method as follows.
성분 함량(중량%)Component Content (wt%)
정제수 To 100Purified water To 100
Pal-YIGSR 펩타이드 0.01Pal-YIGSR Peptide 0.01
밀납 4.0Beeswax 4.0
폴리솔베이트 60 1.5
솔비탄세스퀴올레이트 1.5Solbitan Sesquioleate 1.5
유동파라핀 0.5Liquid Paraffin 0.5
카프릴릭/카프릭트리글리세라이드 5.0Caprylic / Capric Triglycerides 5.0
글리세린 3.0Glycerin 3.0
부틸렌글리콜 3.0Butylene Glycol 3.0
프로필렌글리콜 3.0Propylene Glycol 3.0
카르복시비닐폴리머 0.1Carboxy Vinyl Polymer 0.1
트리에탄올아민 0.2Triethanolamine 0.2
방부제, 색소, 향료 적량Preservatives, colorings, flavors
제조예 4: 영양크림Preparation Example 4 Nutrition Cream
하기와 같이 Pal-YIGSR 펩타이드를 함유하는 영양크림을 통상의 방법에 따라 제조하였다.A nutritive cream containing Pal-YIGSR peptide was prepared according to a conventional method as follows.
성분 함량(중량%)Component Content (wt%)
정제수 To 100Purified water To 100
Pal-YIGSR 펩타이드 0.01Pal-YIGSR Peptide 0.01
밀납 10.0Beeswax 10.0
폴리솔베이트 60 1.5
피이지 60 경화피마자유 2.0
솔비탄세스퀴올레이트 0.5Solbitan Sesquioleate 0.5
유동파라핀 10.0Liquid Paraffin 10.0
스쿠알란 5.0Squalane 5.0
카프릴릭/카프릭트리글리세라이드 5.0Caprylic / Capric Triglycerides 5.0
글리세린 5.0Glycerin 5.0
부틸렌글리콜 3.0Butylene Glycol 3.0
프로필렌글리콜 3.0Propylene Glycol 3.0
트리에탄올아민 0.2Triethanolamine 0.2
방부제, 색소, 향료 적량Preservatives, colorings, flavors
제조예 5: 마사지크림Preparation Example 5 Massage Cream
하기와 같이 Pal-YIGSR 펩타이드를 함유하는 마사지크림을 통상의 방법에 따라 제조하였다.A massage cream containing Pal-YIGSR peptide was prepared according to a conventional method as follows.
성분 함량(중량%)Component Content (wt%)
정제수 To 100Purified water To 100
Pal-YIGSR 펩타이드 0.01Pal-YIGSR Peptide 0.01
밀납 10.0Beeswax 10.0
폴리솔베이트 60 1.5
피이지 60 경화피마자유 2.0
솔비탄세스퀴올레이트 0.8Solbitan Sesquioleate 0.8
유동파라핀 40.0Liquid Paraffin 40.0
스쿠알란 5.0Squalane 5.0
카프릴릭/카프릭트리글리세라이드 4.0Caprylic / Capric Triglycerides 4.0
글리세린 5.0Glycerin 5.0
부틸렌글리콜 3.0Butylene Glycol 3.0
프로필렌글리콜 3.0Propylene Glycol 3.0
트리에탄올아민 0.2Triethanolamine 0.2
방부제, 색소, 향료 적량Preservatives, colorings, flavors
제조예 6: 팩Preparation Example 6: Pack
하기와 같이 Pal-YIGSR 펩타이드를 함유하는 팩을 통상의 방법에 따라 제조하였다.Packs containing Pal-YIGSR peptides were prepared according to conventional methods as follows.
성분 함량(중량%)Component Content (wt%)
정제수 To 100Purified water To 100
Pal-YIGSR 펩타이드 0.01Pal-YIGSR Peptide 0.01
폴리비닐알콜 13.0Polyvinyl Alcohol 13.0
소듐카르복시메틸셀룰로오스 0.2Sodium Carboxymethylcellulose 0.2
글리세린 5.0Glycerin 5.0
알라토인 0.1Allatoin 0.1
에탄올 6.0Ethanol 6.0
피이지-12 노닐페닐에테르 0.3Fiji-12 Nonylphenyl Ether 0.3
폴리솔베이트 60 0.3
방부제, 색소, 향료 적량Preservatives, colorings, flavors
제조예Manufacturing example 7: 피부 충전제( 7: dermal filler ( dermaldermal fillerfiller ))
하기의 표와 같이 Pal-YIGSR 펩타이드를 함유하는 피부 충전제를 통상의 방법에 따라 제조하였다.Dermal fillers containing Pal-YIGSR peptides were prepared according to conventional methods as shown in the table below.
성분 함량(중량%)Component content (% by weight)
정제수 To 100Purified Water To 100
Pal-YIGSR 펩타이드 0.01Pal-YIGSR Peptide 0.01
인간 콜라겐 3.5Human Collagen 3.5
염화칼륨(KCl) 0.02Potassium Chloride (KCl) 0.02
제일인산칼륨(KH2PO4) 0.024Potassium phosphate mono (KH 2 PO 4 ) 0.024
염화나트륨(NaCl) 0.8Sodium Chloride (NaCl) 0.8
제이인산나트륨(Na2HPO4) 0.1145Sodium diphosphate (Na 2 HPO 4 ) 0.1145
방부제 적량Preservative
본 발명은 상기 실시예, 실험예 및 제조예를 참고로 설명되었으나 이는 예시적인 것에 불과하며, 당해 기술분야에서 통상의 지식을 가진 자라면 이로부터 다양한 변형 및 균등한 다른 실시예가 가능하다는 점을 이해할 것이다. 따라서 본 발명의 진정한 기술적 보호 범위는 첨부된 특허청구범위의 기술적 사상에 의하여 정해져야 할 것이다.Although the present invention has been described with reference to the above Examples, Experimental Examples and Preparation Examples, these are merely exemplary, and it will be understood by those skilled in the art that various modifications and equivalent other embodiments are possible. will be. Therefore, the true technical protection scope of the present invention will be defined by the technical spirit of the appended claims.
<110> NOVACELL TECHNOLOGY INC.
<120> Novel peptide derivative capable of synthesizing collagen and use
thereof
<130> PD12-0436
<160> 1
<170> KopatentIn 2.0
<210> 1
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> YIGSR petide
<400> 1
Tyr Ile Gly Ser Arg
1 5
<110> NOVACELL TECHNOLOGY INC.
<120> Novel peptide derivative capable of synthesizing collagen and use
the
<130> PD12-0436
<160> 1
<170> Kopatentin 2.0
<210> 1
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> YIGSR petide
<400> 1
Tyr Ile
Claims (7)
상기 펩타이드는 5 내지 20개의 아미노산으로 구성되는, 펩타이드 유도체. The method of claim 1,
The peptide is a peptide derivative, consisting of 5 to 20 amino acids.
상기 펩타이드는 서열번호 1로 기재되는 아미노산 서열로 구성되는, 펩타이드 유도체.The method of claim 1,
The peptide consists of an amino acid sequence set forth in SEQ ID NO: 1.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020110118177 | 2011-11-14 | ||
KR20110118177 | 2011-11-14 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20130055505A true KR20130055505A (en) | 2013-05-28 |
KR101472476B1 KR101472476B1 (en) | 2014-12-15 |
Family
ID=48663978
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020120066864A KR101472476B1 (en) | 2011-11-14 | 2012-06-21 | Novel peptide derivative capable of synthesizing collagen and use thereof |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR101472476B1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160184385A1 (en) * | 2013-01-08 | 2016-06-30 | Novacell Technology Inc. | Novel peptide having ability to synthesize collagen and use thereof |
KR101715599B1 (en) * | 2016-10-04 | 2017-03-13 | (주)셀트리온 | Tripeptide combined with fatty acid and anti-wrinkle cosmetic composition comprising the same |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021251728A1 (en) * | 2020-06-08 | 2021-12-16 | 나인바이오팜 주식회사 | Composition comprising regentide-012 or regentide-013 for improving skin condition |
WO2021251727A1 (en) * | 2020-06-08 | 2021-12-16 | 나인바이오팜 주식회사 | Regentide-041 and composition comprising regentide-041 for improving skin condition |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060247165A1 (en) * | 2005-01-21 | 2006-11-02 | Stupp Samuel I | Methods and compositions for encapsulation of cells |
KR100879239B1 (en) * | 2007-04-19 | 2009-01-16 | (주)케어젠 | Peptide and Its Uses |
KR101001158B1 (en) * | 2009-04-14 | 2010-12-15 | (주)케어젠 | Peptides Having Activities of Transforming Growth Factor-Beta and Their Uses |
-
2012
- 2012-06-21 KR KR1020120066864A patent/KR101472476B1/en active IP Right Grant
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160184385A1 (en) * | 2013-01-08 | 2016-06-30 | Novacell Technology Inc. | Novel peptide having ability to synthesize collagen and use thereof |
US9999649B2 (en) * | 2013-01-08 | 2018-06-19 | Novacell Technology Inc. | Peptide having ability to synthesize collagen and use thereof |
KR101715599B1 (en) * | 2016-10-04 | 2017-03-13 | (주)셀트리온 | Tripeptide combined with fatty acid and anti-wrinkle cosmetic composition comprising the same |
WO2018066914A1 (en) * | 2016-10-04 | 2018-04-12 | ㈜셀트리온 | Tripeptide having fatty acids bonded thereto, and anti-wrinkle cosmetic composition comprising same |
Also Published As
Publication number | Publication date |
---|---|
KR101472476B1 (en) | 2014-12-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9458197B2 (en) | Elastin digest compositions and methods utilizing same | |
EP1768500B1 (en) | Compositions suitable for treating cutaneous signs of aging | |
JP5118018B2 (en) | Plant-derived elastin-binding protein ligand and method of use thereof | |
KR101988675B1 (en) | Peptides useful in the treatment and/or care of the skin and/or mucous membranes and their use in cosmetic or pharmaceutical compositions | |
KR20200024235A (en) | Compounds useful for the treatment and / or care of skin, hair, nails and / or mucous membranes | |
Yang et al. | Effects of oral administration of peptides with low molecular weight from Alaska Pollock (Theragra chalcogramma) on cutaneous wound healing | |
WO2023015533A1 (en) | Synthetic peptide, and cosmetic composition or pharmaceutical composition and application thereof | |
AU2012215805B2 (en) | Skin collagen production promoter | |
KR101472476B1 (en) | Novel peptide derivative capable of synthesizing collagen and use thereof | |
US20130157949A1 (en) | Novel Peptides for Wound Healing | |
KR101721028B1 (en) | Compsition for promotion of wound healing | |
US20060293227A1 (en) | Cosmetic compositions and methods using transforming growth factor-beta mimics | |
US9999649B2 (en) | Peptide having ability to synthesize collagen and use thereof | |
KR101753874B1 (en) | A cosmetic composition comprising a decapeptide as an active ingredient | |
KR20140072291A (en) | Anti-wrinkle pharmaceutical and cosmetic composition | |
KR20140090755A (en) | Composition for wound-healing or inhibiting wrinkle formation on skin | |
JP2023519935A (en) | Polypeptides derived from the C-terminus of acetylcholinesterase for use in skin conditions | |
US20240226233A1 (en) | Composition comprising zag-derived peptide for improving scars and keloids | |
KR20170061084A (en) | Pharmaceutical composition for wound healing containing Humanin or analogue thereof as an active ingredient | |
KR102120981B1 (en) | Gentisic acid derivative, method for production thereof and external skin composition containing the same | |
KR20190085413A (en) | Use of a SIS-1 peptide as a therapeutic agent for wound healing |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
AMND | Amendment | ||
E601 | Decision to refuse application | ||
AMND | Amendment | ||
X701 | Decision to grant (after re-examination) | ||
GRNT | Written decision to grant |