KR20240069119A - peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same - Google Patents
peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same Download PDFInfo
- Publication number
- KR20240069119A KR20240069119A KR1020220150296A KR20220150296A KR20240069119A KR 20240069119 A KR20240069119 A KR 20240069119A KR 1020220150296 A KR1020220150296 A KR 1020220150296A KR 20220150296 A KR20220150296 A KR 20220150296A KR 20240069119 A KR20240069119 A KR 20240069119A
- Authority
- KR
- South Korea
- Prior art keywords
- peptide
- acne
- 2ip5mp
- inflammatory
- antibacterial
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 58
- 239000000203 mixture Substances 0.000 title claims abstract description 40
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 22
- 239000002537 cosmetic Substances 0.000 title claims abstract description 22
- 230000003255 anti-acne Effects 0.000 title claims abstract description 19
- 230000000845 anti-microbial effect Effects 0.000 title 1
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 43
- 150000001412 amines Chemical class 0.000 claims abstract description 14
- 108010011723 polytryptophan Proteins 0.000 claims abstract description 11
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims abstract description 9
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 9
- LZDNBBYBDGBADK-KBPBESRZSA-N Val-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-KBPBESRZSA-N 0.000 claims abstract description 5
- -1 (isopropyl methylphenoxy) acetyl group Chemical group 0.000 claims description 22
- 241000894006 Bacteria Species 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 241000186427 Cutibacterium acnes Species 0.000 claims description 7
- 241000191963 Staphylococcus epidermidis Species 0.000 claims description 7
- 125000000524 functional group Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims description 6
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 claims description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 4
- 239000004474 valine Substances 0.000 claims description 4
- 108010016626 Dipeptides Proteins 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 229940055019 propionibacterium acne Drugs 0.000 claims description 3
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 230000002757 inflammatory effect Effects 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 32
- 206010000496 acne Diseases 0.000 description 30
- 208000002874 Acne Vulgaris Diseases 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- 238000009472 formulation Methods 0.000 description 25
- 239000011347 resin Substances 0.000 description 21
- 229920005989 resin Polymers 0.000 description 21
- 230000000052 comparative effect Effects 0.000 description 17
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 238000012360 testing method Methods 0.000 description 12
- 238000011156 evaluation Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000006071 cream Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 210000003491 skin Anatomy 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000006210 lotion Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- DYWUPCCKOVTCFZ-LBPRGKRZSA-N (2s)-2-amino-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoic acid Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=C(C[C@H](N)C(O)=O)C2=C1 DYWUPCCKOVTCFZ-LBPRGKRZSA-N 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 239000003708 ampul Substances 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 210000002374 sebum Anatomy 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- ADOHASQZJSJZBT-SANMLTNESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoic acid Chemical compound C12=CC=CC=C2N(C(=O)OC(C)(C)C)C=C1C[C@@H](C(O)=O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ADOHASQZJSJZBT-SANMLTNESA-N 0.000 description 4
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 4
- OSCJHTSDLYVCQC-UHFFFAOYSA-N 2-ethylhexyl 4-[[4-[4-(tert-butylcarbamoyl)anilino]-6-[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)NC(C)(C)C)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 OSCJHTSDLYVCQC-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 229940015975 1,2-hexanediol Drugs 0.000 description 3
- NCZPCONIKBICGS-UHFFFAOYSA-N 3-(2-ethylhexoxy)propane-1,2-diol Chemical compound CCCCC(CC)COCC(O)CO NCZPCONIKBICGS-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LZDNBBYBDGBADK-UHFFFAOYSA-N L-valyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101800005149 Peptide B Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 229940100524 ethylhexylglycerin Drugs 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 108010091748 peptide A Proteins 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 108010005636 polypeptide C Proteins 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229940104261 taurate Drugs 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- MURZAHIYMVFXCF-UHFFFAOYSA-N 2-(5-methyl-2-propan-2-ylphenoxy)acetic acid Chemical compound CC(C)C1=CC=C(C)C=C1OCC(O)=O MURZAHIYMVFXCF-UHFFFAOYSA-N 0.000 description 2
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 2
- SJVGFKBLUYAEOK-SFHVURJKSA-N 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile Chemical compound FC=1C=C(C=C(C=1)F)[C@@H]1CC=NN1C(=O)C1CCN(CC1)C1=CC(=NC=N1)C#N SJVGFKBLUYAEOK-SFHVURJKSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- NTOPKICPEQUPPH-UHFFFAOYSA-N IPMP Natural products COC1=NC=CN=C1C(C)C NTOPKICPEQUPPH-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 2
- 229920002385 Sodium hyaluronate Polymers 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 229960000458 allantoin Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 2
- 229960000735 docosanol Drugs 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000013020 final formulation Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N icosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- NFIDBGJMFKNGGQ-UHFFFAOYSA-N isopropylmethylphenol Natural products CC(C)CC1=CC=CC=C1O NFIDBGJMFKNGGQ-UHFFFAOYSA-N 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229940101267 panthenol Drugs 0.000 description 2
- 235000020957 pantothenol Nutrition 0.000 description 2
- 239000011619 pantothenol Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000001732 sebaceous gland Anatomy 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940010747 sodium hyaluronate Drugs 0.000 description 2
- 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 2
- 239000007921 spray Substances 0.000 description 2
- 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 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- OYINILBBZAQBEV-UWJYYQICSA-N (17s,18s)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,22,23-tetrahydroporphyrin-2-carboxylic acid Chemical compound N1C2=C(C)C(C=C)=C1C=C(N1)C(C)=C(CC)C1=CC(C(C)=C1C(O)=O)=NC1=C(CC(O)=O)C([C@@H](CCC(O)=O)[C@@H]1C)=NC1=C2 OYINILBBZAQBEV-UWJYYQICSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- UGNIYGNGCNXHTR-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UGNIYGNGCNXHTR-SFHVURJKSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- DGSZGZSCHSQXFV-UHFFFAOYSA-N 2,3-bis(2-ethylhexanoyloxy)propyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCC(OC(=O)C(CC)CCCC)COC(=O)C(CC)CCCC DGSZGZSCHSQXFV-UHFFFAOYSA-N 0.000 description 1
- PBFGMXZRJIUGKU-UHFFFAOYSA-N 3-decanoyloxybutyl decanoate Chemical compound CCCCCCCCCC(=O)OCCC(C)OC(=O)CCCCCCCCC PBFGMXZRJIUGKU-UHFFFAOYSA-N 0.000 description 1
- LFESLSYSZQYEIZ-UHFFFAOYSA-N 3-octanoyloxybutyl octanoate Chemical compound CCCCCCCC(=O)OCCC(C)OC(=O)CCCCCCC LFESLSYSZQYEIZ-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- DHFUFHYLYSCIJY-WSGIOKLISA-N CCCCCCCCCCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O Chemical compound CCCCCCCCCCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DHFUFHYLYSCIJY-WSGIOKLISA-N 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 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
- 239000004166 Lanolin Substances 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical compound OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 229940114374 butylene glycol dicaprylate Drugs 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical class C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-M sarcosinate Chemical compound CNCC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-M 0.000 description 1
- 229940071089 sarcosinate Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- 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
-
- 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
- A61Q19/008—Preparations for oily 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
-
- 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
본 발명은 항균, 항염증 또는 항여드름용 펩타이드 및 이를 포함하는 화장료 조성물에 관한 것으로, 상기 펩타이드는 트립토판, 폴리트립토판 또는 발린-트립토판 다이펩타이드의 아민 말단에 특정 화합물의 아실기가 결합된 것으로 항균, 항염증 또는 항여드름 효과를 가지므로, 이를 포함하는 화장료 조성물로 활용될 수 있다.The present invention relates to an antibacterial, anti-inflammatory or anti-acne peptide and a cosmetic composition containing the same. The peptide is an acyl group of a specific compound bound to the amine terminal of tryptophan, polytryptophan or valine-tryptophan dipeptide, and is an antibacterial, antibacterial, and anti-acne peptide. Since it has an inflammatory or anti-acne effect, it can be used as a cosmetic composition containing it.
Description
본 발명은 항균, 항염증 또는 항여드름용 펩타이드 및 이를 포함하는 화장료 조성물에 관한 것이다.The present invention relates to antibacterial, anti-inflammatory or anti-acne peptides and cosmetic compositions containing the same.
여드름은 아크네(acne)라는 그리스어로, 심상성좌창 및 면포라 하며 모공으로부터 화농반응이 일어나 피부의 구조가 파괴되고 손상되는 만성피지선 염증 질환을 말한다. 피지의 생산에 비해 배출작용이 따르지 못하고 모공에 피지가 남아서 여드름이 되고 모낭의 휴지기인 곳에서만 생기게 되는데 대부분 남성호르몬인 안드로젠 분비가 가장 현저하게 증가하는 사춘기 10대에서 약 80%가 감염되고 피지선이 많이 분포하는 얼굴, 가슴, 등 부분에 흔하게 나타나며, 성인은 20%정도가 여드름 증세가 보이는데 남성보다 여성이 많고, 육식을 하는 서양인들이 동양인에 비해 발생빈도가 높다.Acne is a Greek word meaning acne, which means acne vulgaris and comedo. It refers to a chronic sebaceous gland inflammatory disease in which a purulent reaction occurs in the pores and the structure of the skin is destroyed and damaged. The excretion action does not keep up with the production of sebum, and sebum remains in the pores, resulting in acne. It occurs only in the dormant part of the hair follicle. In most adolescent teenagers, when the secretion of androgen, a male hormone, increases most significantly, about 80% of people are infected and the sebaceous glands are infected. It commonly appears on the face, chest, and back, where it is widely distributed. Approximately 20% of adults show signs of acne, with more women than men, and Westerners who eat meat have a higher incidence of acne than Asians.
여드름을 일으키는 여러 가지 유발인자로는 내적요인에 피지과잉분비를 대표적으로 들 수 있는데 성호르몬의 불균형으로 안드로겐에 의해 피지분비 촉진과 각질비후 작용을 하며 프로게스테론에 의해 월경 후 여드름이 악화되고 부신피질호르몬 분비 뿐만 아니라 혈당치 상승으로도 분비가 촉진된다. 또한 비타민 등 영양 부족으로도 촉진되어 여드름이 발생한다. 외부자극에 의해서도 여드름 발생하는데 여드름에 가장 무서운 적인 스트레스와 세포분열을 증가시키고 피부 뿐 만 아니라 난포 내 세포가지도 분열을 촉진시키는 태양광선 및 계절, 기후, 화학약품, 다이어트, 약, 월경요소, 임신, 피임약, 화장품, 압력과 마찰, 손으로 쥐어뜯기 등으로 여드름 증상을 악화시키는 요인으로 볼 수 있다.Among the various triggers that cause acne, a representative example is internal factors and excessive sebum secretion. Due to an imbalance in sex hormones, androgens promote sebum secretion and act as keratin thickening, and progesterone worsens acne after menstruation and adrenocortical hormones. In addition to secretion, secretion is also promoted by increased blood sugar levels. Acne is also promoted by lack of nutrients such as vitamins. Acne can also occur due to external stimuli, including stress, which is the most dangerous enemy of acne, as well as sunlight, which increases cell division and promotes cell division not only in the skin but also in the follicles, as well as season, climate, chemicals, diet, medicine, menstrual factors, and pregnancy. , birth control pills, cosmetics, pressure, friction, and picking with hands can be seen as factors that worsen acne symptoms.
의학적 측면에서 여드름의 치료는 항생제나 부신피질 호르몬제를 투여하여 우선적으로 염증발생과 진행 그리고 미생물 형성 억제를 기본 방향으로 하지만 이는 항생제에 대한 내성과 소화 장애, 2차 감염, 체중증가, 고혈압 등 부작용이 나타날 수 있다는 문제가 있다.From a medical perspective, the treatment of acne is primarily directed at suppressing the occurrence and progression of inflammation and the formation of microorganisms by administering antibiotics or corticosteroids, but this has side effects such as resistance to antibiotics, digestive problems, secondary infections, weight gain, and high blood pressure. There is a problem that may appear.
한편, 미용학적 측면에서는 항염, 항균작용, 세정, 각질제거작용, 피지 조절하는 작용이 있는 성분을 함유한 화장품의 사용으로 여드름 관리를 하고 있다. 그러나 기존의 화장품의 여드름 개선 효과는 크지 않은 실정이며, 피부에 자극을 주지 않으면서도 효과적으로 여드름성 피부를 개선하고 여드름을 예방할 수 있는 화장품에 대한 연구 및 개발이 더 필요한 실정이다.Meanwhile, from a cosmetic perspective, acne is managed through the use of cosmetics containing ingredients with anti-inflammatory, antibacterial, cleansing, exfoliating, and sebum controlling effects. However, the effect of existing cosmetics on improving acne is not significant, and there is a need for more research and development on cosmetics that can effectively improve acne-prone skin and prevent acne without irritating the skin.
본 발명이 이루고자 하는 기술적 과제는 항균, 항염증 또는 항여드름용 펩타이드를 제공하는 것이다.The technical problem to be achieved by the present invention is to provide peptides for antibacterial, anti-inflammatory or anti-acne purposes.
또한, 본 발명이 이루고자 하는 기술적 과제는 상기 펩타이드를 포함하는 항균, 항염증 또는 항여드름용 화장료 조성물을 제공하는 것이다.In addition, the technical problem to be achieved by the present invention is to provide an antibacterial, anti-inflammatory or anti-acne cosmetic composition containing the above peptide.
본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 기술적 과제로 제한되지 않으며, 언급되지 않은 또 다른 기술적 과제들은 아래의 기재로부터 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.The technical problem to be achieved by the present invention is not limited to the technical problem mentioned above, and other technical problems not mentioned can be clearly understood by those skilled in the art from the description below. There will be.
상기 기술적 과제를 달성하기 위하여, 본 발명의 일실시예는 트립토판, 폴리트립토판 및 발린-트립토판 다이펩타이드 중 어느 하나의 펩타이드를 포함하고, 상기 펩타이드의 아민 말단에 하기 화학식1의 아실(acyl) 작용기가 결합되며, 상기 폴리트립토판은 트립토판이 2 내지 6개 연결된, 항균, 항염증 또는 항여드름용 펩타이드를 제공한다.In order to achieve the above technical problem, an embodiment of the present invention includes a peptide selected from tryptophan, polytryptophan, and valine-tryptophan dipeptide, and the amine terminal of the peptide has an acyl functional group of the following formula (1): Combined, the polytryptophan provides an antibacterial, anti-inflammatory or anti-acne peptide in which 2 to 6 tryptophans are linked.
[화학식 1][Formula 1]
여기서, R1은 C1~C14 알킬, C2~C14 알케닐, C2~C14 알키닐이다.Here, R 1 is C1~C14 alkyl, C2~C14 alkenyl, and C2~C14 alkynyl.
본 발명의 실시예에 있어서 상기 트립토판의 아민 말단에 (아이소프로필 메틸페녹시)아세틸기가 결합된 것일 수 있다.In an embodiment of the present invention, an (isopropyl methylphenoxy) acetyl group may be bonded to the amine terminal of the tryptophan.
본 발명의 실시예에 있어서, 상기 폴리트립토판의 아민 말단에 (아이소프로필 메틸페녹시)아세틸기가 결합된 것일 수 있다.In an embodiment of the present invention, an (isopropyl methylphenoxy) acetyl group may be bonded to the amine terminal of the polytryptophan.
본 발명의 실시예에 있어서, 상기 다이펩타이드는 발린의 아민 말단에 (아이소프로필 메틸페녹시)아세틸기가 결합된 것일 수 있다.In an embodiment of the present invention, the dipeptide may be one in which an (isopropyl methylphenoxy) acetyl group is bonded to the amine terminal of valine.
본 발명의 실시예에 있어서, 상기 균은 스타필로코커스 에피더미디스(Staphylococcus epidermidis) 또는 프로피오니박테리움 아크네스(propionibacterium acnes)일 수 있다.In an embodiment of the present invention, the bacteria may be Staphylococcus epidermidis or propionibacterium acnes.
본 발명의 실시예에 있어서, 상기 항염증은 NO생성 억제 또는 iNOS 발현 억제에 의한 것일 수 있다.In an embodiment of the present invention, the anti-inflammation may be due to inhibition of NO production or inhibition of iNOS expression.
상기 기술적 과제를 달성하기 위하여, 본 발명의 다른 실시예는 상기 타이드를 포함하는 항균, 항염증 또는 항여드름용 화장료 조성물을 제공한다.In order to achieve the above technical problem, another embodiment of the present invention provides an antibacterial, anti-inflammatory or anti-acne cosmetic composition containing the Tide.
본 발명은 항균, 항염증 또는 항여드름용 펩타이드 및 이를 포함하는 화장료 조성물에 관한 것으로, 상기 펩타이드는 트립토판, 폴리트립토판 또는 발린-트립토판 다이펩타이드의 아민 말단에 특정 화합물의 아실기가 결합된 것으로 항균, 항염증 또는 항여드름 효과를 가지므로, 이를 포함하는 화장료 조성물로 활용될 수 있다.The present invention relates to an antibacterial, anti-inflammatory or anti-acne peptide and a cosmetic composition containing the same. The peptide is an acyl group of a specific compound bound to the amine terminal of tryptophan, polytryptophan or valine-tryptophan dipeptide, and is an antibacterial, antibacterial, and anti-acne peptide. Since it has an inflammatory or anti-acne effect, it can be used as a cosmetic composition containing it.
본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 설명 또는 청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the configuration of the invention described in the description or claims of the present invention.
도 1 내지 6은 본 발명의 신규 펩타이드인 IPMP-Ac-VW의 여드름균에 대한 항균력을 평가한 것이다.
도 7 및 8은 본 발명의 신규 펩타이드인 IPMP-Ac-VW의 S. epidermidis에 대한 항균력을 평가한 것이다.
도 9 및 10은 본 발명의 신규 펩타이드인 2IP5MP-Ac-peptide 및 IPMP-AA의 여드름균에 대한 항균력을 평가한 것이다.
도 11 및 12는 각각 본 발명의 신규 펩타이드인 2IP5MP-Ac-VW 및 2IP5MP-Ac-WW의 HaCat cell(피부세포)와 Raw 264.7 cell(면역세포)에 대한 세포 독성을 확인한 것이다.
도 13 내지 16은 각각 본 발명의 신규 펩타이드인 2IP5MP-Ac-VW 및 2IP5MP-Ac-WW의 항염증 효과를 확인한 것이다.Figures 1 to 6 evaluate the antibacterial activity of IPMP-Ac-VW, a new peptide of the present invention, against acne bacteria.
Figures 7 and 8 evaluate the antibacterial activity of IPMP-Ac-VW, a new peptide of the present invention, against S. epidermidis.
Figures 9 and 10 evaluate the antibacterial activity of 2IP5MP-Ac-peptide and IPMP-AA, which are new peptides of the present invention, against acne bacteria.
Figures 11 and 12 confirm the cytotoxicity of the new peptides of the present invention, 2IP5MP-Ac-VW and 2IP5MP-Ac-WW, against HaCat cells (skin cells) and Raw 264.7 cells (immune cells), respectively.
Figures 13 to 16 confirm the anti-inflammatory effects of 2IP5MP-Ac-VW and 2IP5MP-Ac-WW, the new peptides of the present invention, respectively.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 항균, 항염증 또는 항여드름용 펩타이드에 관한 것이다.The present invention relates to peptides for antibacterial, anti-inflammatory or anti-acne use.
본 발명의 펩타이드는 트립토판, 폴리트립토판 및 발린-트립토판 다이펩타이드 중 어느 하나의 펩타이드를 포함한다.The peptide of the present invention includes any one of tryptophan, polytryptophan, and valine-tryptophan dipeptide.
본 발명에서 임의의 펩타이드에 존재하는 아미노산은 L-아미노산 또는 D-아미노산일 수 있다. 바람직하게는 L-아미노산일 수 있다.In the present invention, amino acids present in any peptide may be L-amino acids or D-amino acids. Preferably it may be L-amino acid.
상기 펩타이드는 아민 말단에 하기 화학식1의 아실(acyl) 작용기(IPMP(Isopropyl methylphenoxy)-R1CO-)가 결합된다.The peptide has an acyl functional group (IPMP (Isopropyl methylphenoxy)-R 1 CO-) of the following formula 1 attached to the amine terminal.
[화학식 1][Formula 1]
상기 아실 작용기의 R1은 C1~C14 알킬, C2~C14 알케닐, C2~C14 알키닐일 수 있다. 상기 아실 작용기의 R1은 아이소프로필 메틸페놀과 반응하여 아실 작용기를 도입하기 위해 사용되는 화합물의 종류에 따라 다양하게 변경될 수 있다. R 1 of the acyl functional group may be C1~C14 alkyl, C2~C14 alkenyl, or C2~C14 alkynyl. R 1 of the acyl functional group may vary depending on the type of compound used to introduce the acyl functional group by reacting with isopropyl methylphenol.
예를 들어, 아이소프로필 메틸페놀과 에틸 브로모마세테이트가 반응한다면, 상기 아실 작용기는 2-(아이소프로필 메틸페녹시)아세틸기일 수 있다. For example, if isopropyl methylphenol reacts with ethyl bromoacetate, the acyl functional group may be a 2-(isopropyl methylphenoxy)acetyl group.
상기 펩타이드는 이에 제한되지 않으나, 예를 들어, 상기 트립토판의 아민 말단에 (아이소프로필 메틸페녹시)아세틸기가 결합된 것일 수 있다. 또한, 상기 폴리트립토판의 아민 말단에 (아이소프로필 메틸페녹시)아세틸기가 결합된 것일 수 있다. 또한, 상기 다이펩타이드는 발린의 아민 말단에 (아이소프로필 메틸페녹시)아세틸기가 결합된 것일 수 있다.The peptide is not limited thereto, but may be, for example, one in which an (isopropyl methylphenoxy) acetyl group is bonded to the amine terminal of the tryptophan. Additionally, an (isopropyl methylphenoxy) acetyl group may be bonded to the amine terminal of the polytryptophan. Additionally, the dipeptide may be one in which an (isopropyl methylphenoxy) acetyl group is bonded to the amine terminal of valine.
상기 폴리트립토판은 트립토판이 2 내지 6개 연결된 것이다. 바람직하게는 2 내지 4개 연결된 것일 수 있고, 더욱 바람직하게는 2 내지 3개 연결된 것일 수 있다.The polytryptophan is one in which 2 to 6 tryptophans are connected. Preferably, it may be 2 to 4 connected, and more preferably, it may be 2 to 3 connected.
본 발명의 일 실시예에 따른 펩타이드는 당 분야에 공지된 방법 및 조건으로 공지된 수단을 이용하여 합성될 수 있다. 상기 펩타이드의 합성 방법은 크게 화학적 합성 방법과 생물학적 합성 방법이 있으며, 예를 들어, 상기 펩타이드는 화학적 합성 방법, 보다 구체적인 예를 들면, 고체상 합성 방법(solid phase synthesis method)에 따라 제조될 수 있다. 생물학적 합성 방법은, 유전공학적 기법에 의해, 예컨대 원하는 펩타이드를 코딩하는 염기 서열을 단백질 발현 벡터에 도입하여 박테리아에서 발현을 유도 후 분리하는 방법 등을 포함한다.The peptide according to one embodiment of the present invention can be synthesized using known means and under conditions known in the art. Methods for synthesizing the peptide include largely chemical synthesis and biological synthesis. For example, the peptide may be produced according to a chemical synthesis method, for example, a solid phase synthesis method. Biological synthesis methods include, for example, introducing a base sequence encoding a desired peptide into a protein expression vector, inducing expression in bacteria, and then isolating the protein using genetic engineering techniques.
본 발명에서 '항균'이란, 미생물, 예컨대 피부질환 관련 세균의 생장을 억제하는 효능을 의미할 수 있다.In the present invention, 'antibacterial' may mean the effect of inhibiting the growth of microorganisms, such as bacteria related to skin diseases.
상기 균은 예를 들어, 스타필로코커스 에피더미디스(Staphylococcus epidermidis) 또는 프로피오니박테리움 아크네스(propionibacterium acnes)일 수 있으나, 이에 제한되지 않고, 피부 상재균과 피부오염(질환)을 유발할 가능성이 있는 미생물을 포함할 수 있다.The bacteria may be, for example, Staphylococcus epidermidis or propionibacterium acnes, but are not limited thereto, and have the potential to cause skin contamination (disease). May contain microorganisms.
본 발명에서 '항염증'이란, “염증 억제 또는 개선”과 혼용될 수 있으며, 본 발명의 펩타이드에 의한 항염증은 예를 들어, NO생성 억제 또는 iNOS 발현 억제에 의한 것일 수 있다.In the present invention, ‘anti-inflammatory’ may be used interchangeably with “inhibition or improvement of inflammation,” and anti-inflammation by the peptide of the present invention may be due, for example, to inhibition of NO production or inhibition of iNOS expression.
본 발명은 상기 펩타이드를 포함하는 항균, 항염증 또는 항여드름용 화장료 조성물에 관한 것이다.The present invention relates to an antibacterial, anti-inflammatory or anti-acne cosmetic composition containing the above peptide.
펩타이드 및 그 효능에 관련된 구체적인 설명은 전술한 바와 같다.Specific descriptions related to the peptide and its efficacy are as described above.
상기 조성물은 예를 들어, 상기 펩타이드를 0.1 μM 내지 1000 μM 포함하는 것일 수 있고, 바람직하게는 50 μM 내지 300 μM 포함하는 것일 수 있다. 상기 조성물 내에 상기 펩타이드가 너무 적은 양이 포함되는 경우, 전술한 상기 펩타이드에 의한 피부 항균, 항염증, 항여드름 효과를 충분히 갖지 못할 수 있고, 지나치게 과량 포함될 경우, 세포 독성을 가질 수 있으므로, 그 양을 적절히 조절하는 것이 바람직하다.For example, the composition may contain 0.1 μM to 1000 μM of the peptide, preferably 50 μM to 300 μM. If the composition contains too little of the peptide, it may not have sufficient skin antibacterial, anti-inflammatory, and anti-acne effects due to the above-mentioned peptide, and if it contains too much, it may have cytotoxicity. It is desirable to adjust appropriately.
상기 조성물은 스킨, 로션, 토너제, 미용비누, 바디워시, 세럼, 클렌징로션, 에센스, 영양크림, 팩, 마사지크림 등으로 제형화 될 수 있고, 그 외 유연화장수, 수렴화장수, 영양화장수, 아이크림, 아이에센스, 클렌징폼, 클레징 워터, 파우더, 바디로션, 바디크림, 바디오일, 바디에센스, 메이크업 베이스, 파운데이션, 샴푸 또는 린스 등으로 제형화 될 수 있으나, 이에 한정되는 것은 아니다.The composition can be formulated into skin, lotion, toner, beauty soap, body wash, serum, cleansing lotion, essence, nutritional cream, pack, massage cream, etc., and other cosmetic products such as softening lotion, astringent lotion, nourishing lotion, and eye lotion. It can be formulated as cream, eye essence, cleansing foam, cleansing water, powder, body lotion, body cream, body oil, body essence, makeup base, foundation, shampoo or rinse, but is not limited to this.
또한, 화장료 조성물로 사용시, 피부 외용제 또는 화장료의 제형에 맞게 물질을 더 첨가할 수 있다. 예를 들어, 이에 한정되는 것은 아니나 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있고, 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있으며, 특히, 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다. 또한 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되는데, 바람직하게는 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르일 수 있으나 이에 한정되는 것은 아니다. 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소 결정성 셀룰로오스, 알루 미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있으며, 제 형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이 트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설 페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아 미드, 식물성유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이 용될 수 있으나 이에 한정되는 것은 아니다.Additionally, when used as a cosmetic composition, additional substances can be added to suit the formulation of the skin external agent or cosmetic. For example, but not limited to this, if the formulation is a paste, cream or gel, the carrier ingredients may include animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or Zinc oxide, etc. can be used, and when the formulation is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as a carrier ingredient. Especially, in the case of a spray, additional It may contain propellants such as chlorofluorohydrocarbons, propane/butane or dimethyl ether. Additionally, when the formulation is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, preferably water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or sorbitan fatty acid ester, but is not limited thereto. If the formulation is a suspension, the carrier ingredients include water, liquid diluents such as ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, Aluminum metahydroxide, bentonite, agar or tracant can be used, and when the formulation is a cleansing agent containing a surfactant, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, Isethionate, imidazolinium derivatives, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated Glycerol fatty acid ester, etc. may be used, but are not limited thereto.
이하, 본 발명을 구체적으로 설명하기 위해 실시예를 들어 상세하게 설명하기로 한다.Hereinafter, the present invention will be described in detail with reference to examples.
제조예Manufacturing example
1. 2-(2-isopropyl-5-methylphenoxy)acetic acid의 합성1. Synthesis of 2-(2-isopropyl-5-methylphenoxy)acetic acid
2-Isopropyl-5-methylphenol 15.0g(0.1mol)과 potassium carbonate 27.6g(0.2mol)을 acetone 330mL에 넣고, 이어서 ethyl bromoacetate 18.4g(0.11mol)을 투입 후 상온에서 12시간 동안 교반하였다. 반응 후 여과하였고, 얻어진 여액에 증류수 50mL를 넣은 뒤 50% sodium hydroxide solution 16.0g(0.2mol)을 넣고 상온에서 2시간 교반하였다. 반응이 완료된 후 3M HCl을 넣어 중화한 뒤 감압농축하였고, 얻어진 농축액을 EA에 녹인 후 0.1N HCl 수용액으로 씻고 물로 1회 씻어주었다. 유기층을 magnesium sulfate로 건조한 뒤 감압농축하여 17.7g(85%)의 고체화합물을 얻었다.15.0 g (0.1 mol) of 2-Isopropyl-5-methylphenol and 27.6 g (0.2 mol) of potassium carbonate were added to 330 mL of acetone, followed by 18.4 g (0.11 mol) of ethyl bromoacetate and stirred at room temperature for 12 hours. After the reaction was filtered, 50 mL of distilled water was added to the obtained filtrate, and then 16.0 g (0.2 mol) of 50% sodium hydroxide solution was added and stirred at room temperature for 2 hours. After the reaction was completed, it was neutralized by adding 3M HCl and concentrated under reduced pressure. The resulting concentrate was dissolved in EA, washed with 0.1N HCl aqueous solution, and washed once with water. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure to obtain 17.7 g (85%) of a solid compound.
2. H-(Trp(Boc))n-CTC resin의 합성2. Synthesis of H-(Trp(Boc))n-CTC resin
(a) H-Trp(Boc)-CTC resin(a) H-Trp(Boc)-CTC resin
2-Chloro trityl chloride resin 40g(1.25mmo/g)을 반응 용기에 넣고 DCM 300mL를 가하여 30분 동안 교반하였다. 용액을 제거하고 DMF 300mL를 넣어 30분 교반 후 다시 용매를 제거하였다. 반응 용기에 Fmoc-Trp(Boc)-OH 26.3g(0.05mol)과 DMF 300mL, DIPEA 17.4mL(0.1mol)를 넣어 4시간 반응시킨 후 여과 및 DCM 300mL로 세척한 다음 MC:MeOH:DIPEA(17:2:1)의 용액 300mL를 넣어 15분씩 2회 반응(capping)시켰다. 이후 반응 용액을 여과한 다음 20% Piperidine/DMF 용액 300mL를 이용하여 15분씩 2회 탈보호 반응을 하였다. 반응액을 여과하고 DMF 300mL로 3회, DCM 300mL로 1회 세척하였다.40 g (1.25 mmo/g) of 2-Chloro trityl chloride resin was placed in a reaction vessel, 300 mL of DCM was added, and the mixture was stirred for 30 minutes. The solution was removed, 300 mL of DMF was added, stirred for 30 minutes, and the solvent was removed again. Add 26.3 g (0.05 mol) of Fmoc-Trp(Boc)-OH, 300 mL of DMF, and 17.4 mL (0.1 mol) of DIPEA to the reaction vessel, react for 4 hours, filter, wash with 300 mL of DCM, and add MC:MeOH:DIPEA (17). :2:1) solution was added and reacted (capping) twice for 15 minutes each. Afterwards, the reaction solution was filtered and deprotection reaction was performed twice for 15 minutes each using 300 mL of 20% Piperidine/DMF solution. The reaction solution was filtered and washed three times with 300 mL of DMF and once with 300 mL of DCM.
(b) H- Trp(Boc)Trp(Boc)-CTC resin(b) H- Trp(Boc)Trp(Boc)-CTC resin
상기 (a)에서 합성된 H-Trp(Boc)-CTC resin에 Fmoc-Trp(Boc)-OH 39.5g(0.075mol)과 HOBt 11.1g(0.825mol) 및 DMF 300mL, DIC 11.7mL(0.075mol)을 넣어 반응시켰다. 4시간 반응 후 Kaiser test로 반응의 완결을 확인 후 반응 용액을 여과해 제거한 다음 20% Piperidine/DMF 용액 300mL를 이용하여 15분씩 2회 탈보호 반응을 하였다. 반응액을 여과하고 DMF 300mL로 3회, DCM 300mL로 1회 세척하여 H- Trp(Boc)-Trp(Boc)-CTC resin을 합성하였다. To the H-Trp(Boc)-CTC resin synthesized in (a) above, 39.5 g (0.075 mol) of Fmoc-Trp(Boc)-OH, 11.1 g (0.825 mol) of HOBt, 300 mL of DMF, and 11.7 mL (0.075 mol) of DIC was added and reacted. After 4 hours of reaction, completion of the reaction was confirmed by Kaiser test, the reaction solution was removed by filtration, and then deprotection reaction was performed twice for 15 minutes each using 300 mL of 20% Piperidine/DMF solution. The reaction solution was filtered and washed three times with 300 mL of DMF and once with 300 mL of DCM to synthesize H-Trp(Boc)-Trp(Boc)-CTC resin.
(c) H- Trp(Boc)Trp(Boc)Trp(Boc)Trp(Boc)-CTC resin(c) H- Trp(Boc)Trp(Boc)Trp(Boc)Trp(Boc)-CTC resin
상기 (b)에서 합성된 H-Trp(Boc)Trp(Boc)-CTC resin에 Fmoc-Trp(Boc)-OH 39.5g(0.075mol)과 HOBt 11.1g(0.825mol) 및 DMF 300mL, DIC 11.7mL(0.075mol)을 넣어 반응시켰다. 4시간 반응 후 Kaiser test로 반응의 완결을 확인 후 반응 용액을 여과해 제거한 다음 20% Piperidine/DMF 용액 300mL를 이용하여 15분씩 2회 탈보호 반응을 하였다. 반응액을 여과하고 DMF 300mL로 3회, DCM 300mL로 1회 세척하여 H-Trp(Boc)-Trp(Boc)-CTC resin을 합성하였다. 합성된 H-Trp(Boc)Trp(Boc)Trp(Boc)-CTC resin에 Fmoc-Trp(Boc)-OH을 1회 반복 반응한 후 20% Piperidine/DMF 용액 300mL를 이용하여 15분씩 2회 탈보호 반응하여 H- Trp(Boc)Trp(Boc)Trp(Boc)Trp(Boc)-CTC resin을 합성하였다.To the H-Trp(Boc)Trp(Boc)-CTC resin synthesized in (b) above, 39.5 g (0.075 mol) of Fmoc-Trp(Boc)-OH, 11.1 g (0.825 mol) of HOBt, 300 mL of DMF, 11.7 mL of DIC (0.075 mol) was added and reacted. After 4 hours of reaction, completion of the reaction was confirmed by Kaiser test, the reaction solution was removed by filtration, and then deprotection reaction was performed twice for 15 minutes each using 300 mL of 20% Piperidine/DMF solution. The reaction solution was filtered and washed three times with 300 mL of DMF and once with 300 mL of DCM to synthesize H-Trp(Boc)-Trp(Boc)-CTC resin. After repeating the reaction of Fmoc-Trp(Boc)-OH with the synthesized H-Trp(Boc)Trp(Boc)Trp(Boc)-CTC resin once, dehydration was performed twice for 15 minutes each using 300 mL of 20% Piperidine/DMF solution. Through the protection reaction, H- Trp(Boc)Trp(Boc)Trp(Boc)Trp(Boc)-CTC resin was synthesized.
3. 2IP5MP-Ac-(Trp(Boc))n-CTC resin의 합성3. Synthesis of 2IP5MP-Ac-(Trp(Boc))n-CTC resin
상기 제조예 2에서 합성된 H-(Trp(Boc))n-CTC resin에 상기 제조예 1에서 합성된 2-(2-isopropyl-5-methylphenoxy)acetic acid 13.5g(0.065mol), HOBt 11.4g(0.083mol) 및 DMF 300mL, DIC 11.7mL(0.075mol)을 넣어 DMF 300mL하에서 반응시켰다. 4시간 반응 후 Kaiser test로 반응의 완결을 확인 후 반응 용액을 여과해 제거한 후 DMF 300mL로 3회, DCM 300mL로 3회 세척하였다.To the H-(Trp(Boc))n-CTC resin synthesized in Preparation Example 2, 13.5 g (0.065 mol) of 2-(2-isopropyl-5-methylphenoxy)acetic acid synthesized in Preparation Example 1 and 11.4 g of HOBt (0.083 mol), 300 mL of DMF, and 11.7 mL (0.075 mol) of DIC were added and reacted under 300 mL of DMF. After 4 hours of reaction, completion of the reaction was confirmed by Kaiser test, and the reaction solution was filtered and washed three times with 300 mL of DMF and three times with 300 mL of DCM.
4. 2IP5MP-Ac-(Trp)n-OH의 합성4. Synthesis of 2IP5MP-Ac-(Trp)n-OH
상기 제조예 3에서 합성된 2IP5MP-Ac-(Trp(Boc))n-CTC resin에 50% TFA/DCM 350mL를 가하여 2시간 동안 resin으로부터 탈루 반응 및 탈보호 반응을 진행하였다. 2회 반응한 여액을 모아 반응물을 농축한 후 ether에 분산시켜 crude 2IP5MP-Ac-(Trp)n-OH를 회수하였다. Crude 펩타이드에 증류수를 가하여 녹인 다음 prep-LC(column ID 8cm)를 이용하여 정제 후 동결 건조하여 백색의 분말을 얻었다. 350 mL of 50% TFA/DCM was added to the 2IP5MP-Ac-(Trp(Boc))n-CTC resin synthesized in Preparation Example 3, and release and deprotection reactions were performed from the resin for 2 hours. The filtrate reacted twice was collected, concentrated, and dispersed in ether to recover crude 2IP5MP-Ac-(Trp)n-OH. The crude peptide was dissolved in distilled water, purified using prep-LC (column ID 8cm), and then freeze-dried to obtain a white powder.
2IP5MP-Ac-Trp-OH은 하기 화학식 2와 같으며, 11.5g(순도: 97.5%(HPLC), 수율: 58.5%)을 LC-MS에 의한 분자량은 395.20(M+1), (이론값: M = 394.19)로 측정되었다.2IP5MP-Ac-Trp-OH has the following formula (2), and the molecular weight of 11.5 g (purity: 97.5% (HPLC), yield: 58.5%) was determined by LC-MS to be 395.20 (M+1), (theoretical value: M = 394.19).
[화학식 2][Formula 2]
2IP5MP-Ac-TrpTrp-OH은 하기 화학식 3과 같으며, 14.3g(순도: 96.5%(HPLC), 수율49.3%)을 LC-MS에 의한 분자량은581.24 (M+1), (이론값: M = 580.27)로 측정되었다.2IP5MP-Ac-TrpTrp-OH has the following formula (3), and the molecular weight of 14.3g (purity: 96.5% (HPLC), yield 49.3%) was determined by LC-MS to be 581.24 (M+1), (theoretical value: M = 580.27).
[화학식 3][Formula 3]
2IP5MP-Ac-TrpTrpTrpTrt-OH은 하기 화학식 4와 같으며, 24.5g(순도: 97.4%(HPLC), 수율: 51.4%)을 LC-MS에 의한 분자량은 953.45(M+1), (이론값: M = 952.43)로 측정되었다.2IP5MP-Ac-TrpTrpTrpTrt-OH has the following formula 4, and the molecular weight of 24.5 g (purity: 97.4% (HPLC), yield: 51.4%) was determined by LC-MS to be 953.45 (M+1), (theoretical value: M = 952.43).
[화학식 4][Formula 4]
5. 2IP5MP-Ac-(Val)-(Trp)-OH의 합성5. Synthesis of 2IP5MP-Ac-(Val)-(Trp)-OH
(a) H-Val-Trp(Boc)-CTC resin(a) H-Val-Trp(Boc)-CTC resin
상기 제조예2(a)에서 합성된 H-Trp(Boc)-CTC resin에 Fmoc-Val-OH 25.5g(0.075mol)과 HOBt 11.1g(0.825mol) 및 DMF 300mL, DIC 11.7mL(0.075mol)을 넣어 반응시켰다. 4시간 반응 후 Kaiser test로 반응의 완결을 확인 후 반응 용액을 여과해 제거한 다음 20% Piperidine/DMF 용액 300mL를 이용하여 15분씩 2회 탈보호 반응을 하였다. 반응액을 여과하고 DMF 300mL로 3회, DCM 300mL로 1회 세척하여 H- Val-Trp(Boc)-CTC resin을 합성하였다.25.5 g (0.075 mol) of Fmoc-Val-OH, 11.1 g (0.825 mol) of HOBt, 300 mL of DMF, and 11.7 mL (0.075 mol) of DIC to the H-Trp(Boc)-CTC resin synthesized in Preparation Example 2(a). was added and reacted. After 4 hours of reaction, completion of the reaction was confirmed by Kaiser test, the reaction solution was removed by filtration, and then deprotection reaction was performed twice for 15 minutes each using 300 mL of 20% Piperidine/DMF solution. The reaction solution was filtered and washed three times with 300 mL of DMF and once with 300 mL of DCM to synthesize H-Val-Trp(Boc)-CTC resin.
(b) 2IP5MP-Ac-Val-Trp(Boc)-CTC resin(b) 2IP5MP-Ac-Val-Trp(Boc)-CTC resin
상기 (a)에서 합성된 H-Val-Trp(Boc)-CTC resin에 HOBt 11.4g(0.083mol) 및 DMF 300mL를 가한 뒤 제조예 1에서 합성된 2-(2-isopropyl-5-methylphenoxy)acetic acid 13.5g(0.065mol) 및 DIC 11.7mL(0.075mol)을 넣어 반응시켰다. 4시간 반응 후 Kasiser test로 반응의 완결을 확인 후 반응 용액을 여과 제거한 후 DMF 300mL로 3회, DCM 300mL로 3회 세척하였다.11.4 g (0.083 mol) of HOBt and 300 mL of DMF were added to the H-Val-Trp(Boc)-CTC resin synthesized in (a) above, and then 2-(2-isopropyl-5-methylphenoxy)acetic synthesized in Preparation Example 1. 13.5g (0.065mol) of acid and 11.7mL (0.075mol) of DIC were added and reacted. After 4 hours of reaction, completion of the reaction was confirmed by Kasiser test, and the reaction solution was filtered out and washed three times with 300 mL of DMF and three times with 300 mL of DCM.
(c) 2IP5MP-Ac-Val-Trp-OH의 합성(c) Synthesis of 2IP5MP-Ac-Val-Trp-OH
상기 (b)에서 합성된 2IP5MP-Ac-Val-Trp(Boc)-CTC resin에 50% TFA/DCM 350mL를 가하여 30분 동안 resin으로부터 탈루 반응 및 탈보호 반응을 진행하였다. 2회 반응한 여액을 모아 반응물을 농축한 후 ether에 분산시켜 crude 2IP5MP-Ac-Val-Trp-OH를 회수하였다. Crude 펩타이드에 증류수를 가하여 녹인 다음 prep-LC(column ID 8cm)를 이용하여 정제 후 동결 건조하여 백색의 분말 15.1g(순도: %(HPLC), 수율: 61.2%)을 얻었으며 LC-MS에 의한 분자량은 (M+1), (이론값: M = 493.26)로 측정되었다.350 mL of 50% TFA/DCM was added to the 2IP5MP-Ac-Val-Trp(Boc)-CTC resin synthesized in (b) above, and the release and deprotection reactions were performed from the resin for 30 minutes. The filtrate from two reactions was collected, concentrated, and dispersed in ether to recover crude 2IP5MP-Ac-Val-Trp-OH. The crude peptide was dissolved in distilled water, purified using prep-LC (column ID 8cm), and then freeze-dried to obtain 15.1 g of white powder (purity: % (HPLC), yield: 61.2%), which was obtained by LC-MS. The molecular weight was measured as (M+1), (theoretical value: M = 493.26).
[화학식 5][Formula 5]
실험예Experiment example
1. 신규 펩타이드의 항균 효능 평가1. Evaluation of antibacterial efficacy of new peptides
하기 표 1의 시험물질을 이용하여 P. acnes 및 S. epidermidis에 대한 항균 효능을 평가하였다. 구체적으로, P. acnes는 Reinforced Clostridial Medium (RCM)에서 37℃, 1.5x106 CFU/mL, 96 well plate 72 시간 배양(물질처리 동시진행), anaerobic condition으로 실시하였고, S. epidermidis는 Nutrient Medium에서 37℃, 1.5x106 CFU/mL, 96 well plate 24 시간 배양(물질처리 동시진행), aerobic condition으로 실시하였다. 시험법은 Ryu, AR., Han, CS., Oh, HK. et al. Chlorin e6-mediated photodynamic inactivation with halogen light against microbes and fungus. Toxicol. Environ. Health Sci. 7, 231-238 (2015). https://doi.org/10.1007/s13530-015- 0243-z를 참고하였다.Antibacterial efficacy against P. acnes and S. epidermidis was evaluated using the test substances shown in Table 1 below. Specifically, P. acnes was cultured in Reinforced Clostridial Medium (RCM) at 37°C, 1.5x10 6 CFU/mL, 96 well plate for 72 hours (simultaneous material treatment), anaerobic condition, and S. epidermidis was cultured in Nutrient Medium. Culture was carried out at 37°C, 1.5x10 6 CFU/mL, 96 well plate for 24 hours (simultaneous material treatment), aerobic conditions. The test method was described by Ryu, AR., Han, CS., and Oh, HK. et al. Chlorin e6-mediated photodynamic inactivation with halogen light against microbes and fungus. Toxicol. Environ. Health Sci. 7, 231-238 (2015). Refer to https://doi.org/10.1007/s13530-015-0243-z.
(MW 493.60)2IP5MP-Ac-VW
(MW 493.60)
(MW 493.60)4IP3MP-Ac-VW
(MW 493.60)
(MW 563.74)2IP5MP-Ac-KVK
(MW 563.74)
(MW 563.74)4IP3MP-Ac-KVK
(MW 563.74)
(MW 530.63)2IP5MP-Ac-GHK
(MW 530.63)
(MW 530.63)4IP3MP-Ac-GHK
(MW 530.63)
여기서, V, W, G, H, K는 아미노산 약자로, V(발린), W(트립토판), G(글리신), H(히스티딘), K(라이신)이다. IPMP는 (Isopropyl methylphenoxy)acetyl기로, 예를 들어, 2IP5MP-Ac-VW는 2-(2-isopropyl-5-methylphenoxy)acetyl-VW이고, 4IP3MP-Ac-VW는 2-(4-isopropyl-3-methylphenoxy)acetyl-VW이다.Here, V, W, G, H, and K are abbreviations for amino acids, which are V (valine), W (tryptophan), G (glycine), H (histidine), and K (lysine). IPMP is an (Isopropyl methylphenoxy)acetyl group. For example, 2IP5MP-Ac-VW is 2-(2-isopropyl-5-methylphenoxy)acetyl-VW, and 4IP3MP-Ac-VW is 2-(4-isopropyl-3- It is methylphenoxy)acetyl-VW.
그 결과, IPMP-Ac-VW의 여드름균에 대해 우수한 항균력을 보였다(도 1, 5 및 6). 125μM 농도에서 50% 내외, 250 μM 농도에서 70~80%의 항균력을 보였다. 또한, 여드름균 성장을 50% 억제하는 농도(IC50)는 2IP5MP-Ac-VW가 130 μM, 4IP3MP-Ac-VW가 164 μM, 5IP2MP-Ac-VW가 146 μM 이였다(도 2). 그에 비해 IPMP-Ac-KVK 및 IPMP-Ac-GHK는 여드름균에 대한 항균력이 매우 미미하였다(도 3 및 4).As a result, IPMP-Ac-VW showed excellent antibacterial activity against acne bacteria (Figures 1, 5, and 6). It showed antibacterial activity of around 50% at a concentration of 125 μM and 70-80% at a concentration of 250 μM. In addition, the concentration (IC 50 ) that inhibits acne bacteria growth by 50% was 130 μM for 2IP5MP-Ac-VW, 164 μM for 4IP3MP-Ac-VW, and 146 μM for 5IP2MP-Ac-VW (Figure 2). In comparison, IPMP-Ac-KVK and IPMP-Ac-GHK had very little antibacterial activity against acne bacteria (Figures 3 and 4).
또한, 본 실험조건에서 VW, KVK, GHK 자체는 여드름균에 대한 항균력을 거의 보이지 않았다. 본 실험조건에서 2IP5MP, 4IP3MP, 5IP2MP 자체는 여드름균에 대한 항균력이 미미하였다. 125μM의 2IP5MP, 4IP3MP, 5IP2MP는 여드름균에 대한 항균력이 10% 내외, 250μM의 2IP5MP, 4IP3MP, 5IP2MP는 20% 내외의 여드름균에 대한 항균력을 보였다.Additionally, under these experimental conditions, VW, KVK, and GHK themselves showed little antibacterial activity against acne bacteria. In this experimental condition, 2IP5MP, 4IP3MP, and 5IP2MP themselves had minimal antibacterial activity against acne bacteria. 125μM of 2IP5MP, 4IP3MP, and 5IP2MP showed an antibacterial activity against acne bacteria of about 10%, and 250μM of 2IP5MP, 4IP3MP, and 5IP2MP showed an antibacterial effect against acne bacteria of about 20%.
IPMP-Ac-VW는 S. epidermidis에 대해서도 항균력을 보였으며, 250μM 농도에서 30% 내외의 항균력을 보였다(도 7 및 8).IPMP-Ac-VW also showed antibacterial activity against S. epidermidis, with an antibacterial activity of approximately 30% at a concentration of 250 μM (Figures 7 and 8).
2. 2IP5MP-Ac-W, 2IP5MP-Ac-WW, 2IP5MP-Ac-WWWW의 여드름균에 대한 항균력 평가2. Evaluation of antibacterial activity against acne bacteria of 2IP5MP-Ac-W, 2IP5MP-Ac-WW, and 2IP5MP-Ac-WWWW
2IP5MP-Ac-VW을 기준으로 2IP5MP-Ac-W, 2IP5MP-Ac-WW, 2IP5MP-Ac-WWWW의 여드름균에 대한 항균력을 3개 농도(62.5 μM, 125 μM, 250 μM)에서 비교하였다. 항균 효능 평가 시험법은 상기 실험예 1과 같다.Based on 2IP5MP-Ac-VW, the antibacterial activity against acne bacteria of 2IP5MP-Ac-W, 2IP5MP-Ac-WW, and 2IP5MP-Ac-WWWW was compared at three concentrations (62.5 μM, 125 μM, 250 μM). The antibacterial efficacy evaluation test method was the same as Experiment 1 above.
시험물질은 하기 표 2와 같다.The test substances are listed in Table 2 below.
그 결과, 2IP5MP 기반 펩타이드 중 2IP5MP-Ac-VW와 2IP5MP-Ac-W의 P. acnes균에 대한 항균력은 3개 농도에서 서로 비슷하였다. 2IP5MP-Ac-WW의 P. acnes균에 대한 항균력은 3개 농도에서 2IP5MP-Ac-VW(혹은 2IP5MP-Ac-W)보다 더 우수한 결과를 보였다. 2IP5MP-Ac-WWWW는 농도의존적 항균력 변화를 보이지 않았으나 항균력이 있음을 알 수 있다(도 9).As a result, among the 2IP5MP-based peptides, the antibacterial activity of 2IP5MP-Ac-VW and 2IP5MP-Ac-W against P. acnes was similar at three concentrations. The antibacterial activity of 2IP5MP-Ac-WW against P. acnes showed better results than 2IP5MP-Ac-VW (or 2IP5MP-Ac-W) at three concentrations. 2IP5MP-Ac-WWWW did not show a concentration-dependent change in antibacterial activity, but it was found to have antibacterial activity (Figure 9).
이에 반해, 3종의 AA중간체 및 GA-VW는 3개 농도에서 항균력의 유의한 변화를 보이지 않았다(도 10).In contrast, the three AA intermediates and GA-VW did not show significant changes in antibacterial activity at the three concentrations (Figure 10).
3. 세포독성 및 항염증 효능 평가3. Evaluation of cytotoxic and anti-inflammatory efficacy
(1) 세포 독성 평가(1) Cytotoxicity evaluation
2IP5MP-Ac-VW와 2IP5MP-Ac-WW를 500μM에서 2배 연속 희석한 시험물질을 이용하여 MTT assay를 수행하였다. RAW 264.7(대식세포 유래) 세포와 HaCaT cell (피부각질세포)에 시험물질을 처리하여 세포의 생존율을 확인하였다.MTT assay was performed using 2IP5MP-Ac-VW and 2IP5MP-Ac-WW serially diluted 2-fold at 500 μM. RAW 264.7 (macrophage-derived) cells and HaCaT cells (skin keratinocytes) were treated with test substances to confirm cell survival.
그 결과, 피부세포와 면역세포의 2종 세포에서 2IP5MP-Ac-VW 보다 2IP5MP-Ac-WW가 세포 독성이 강하였다. 2IP5MP-Ac-VW보다 2IP5MP-Ac-WW가 피부자극성이 더 클 가능성을 보여준다. 이는 2IP5MP-Ac-VW보다 2IP5MP-Ac-WW가 여드름균에 대한 항균력이 우수한 결과와 직접적인 관련성이 있을 것으로 판단된다(도 11 및 12)As a result, 2IP5MP-Ac-WW had stronger cytotoxicity than 2IP5MP-Ac-VW in two types of cells, skin cells and immune cells. 2IP5MP-Ac-WW shows greater potential for skin irritation than 2IP5MP-Ac-VW. This is believed to be directly related to the result that 2IP5MP-Ac-WW has superior antibacterial activity against acne bacteria than 2IP5MP-Ac-VW (Figures 11 and 12)
(2) 항염증 효능 평가(2) Evaluation of anti-inflammatory efficacy
RAW 264.7(대식세포 유래) 세포에 LPS로 염증 유도 후 시험물질을 처리하였다.RAW 264.7 (macrophage-derived) cells were treated with test substances after inducing inflammation with LPS.
NO 측정은 2IP5MP-Ac-VW와 2IP5MP-Ac-WW을 500μM에서 2배 연속 희석한 시험물질을 이용하여 Griess reagent 사용법으로 실시하였다. NO measurement was performed using the Griess reagent using test substances serially diluted 2-fold at 500 μM of 2IP5MP-Ac-VW and 2IP5MP-Ac-WW.
염증인자 발현 억제는 2IP5MP-Ac-VW와 2IP5MP-Ac-WW을 세포독성 없는 농도에서 Western transfer로 측정하였고, 1차 항체로 iNOS, COX-2, IL-1β항체를 사용하여 iNOS, COX-2, IL-1β발현 억제능을 평가하였다.Inhibition of inflammatory factor expression was measured by Western transfer for 2IP5MP-Ac-VW and 2IP5MP-Ac-WW at non-cytotoxic concentrations, using iNOS, COX-2, and IL-1β antibodies as primary antibodies. , the ability to suppress IL-1β expression was evaluated.
그 결과, 2IP5MP-Ac-VW와 2IP5MP-Ac-WW는 Raw cell에서 LPS가 유도한 NO생성과 iNOS발현을 서로 비슷한 수준에서 억제하였지만 COX-2와 IL-1β를 억제하지는 못하였다. 이 두 펩타이드는 다양한 염증기전 중 NO생성과 iNOS발현 억제를 통해 항염증 효능을 나타내는 것으로 판단된다(도 13 내지 16).As a result, 2IP5MP-Ac-VW and 2IP5MP-Ac-WW inhibited LPS-induced NO production and iNOS expression at similar levels in raw cells, but did not inhibit COX-2 and IL-1β. These two peptides are believed to exhibit anti-inflammatory effects through inhibition of NO production and iNOS expression among various inflammatory mechanisms (Figures 13 to 16).
4. 제형 평가4. Formulation evaluation
(1) Peptide Solution 제조(1) Peptide solution manufacturing
본 발명의 신규 펩타이드들은 순수한 물에는 잘 용해되지 않는 난용성을 보여 가용화 제형에 바로 투입은 어렵고, 칭량과 제조의 편이성을 위해서 폴리올에 고농도로 선 용해시킨 후 제형에 투입하는 공정으로 진행하였다. 하기 표 3은 상기 제조된 펩타이드 중 3종류의 펩타이드를 각 1,000 ppm으로 Solution 시킨 것이다.The new peptides of the present invention show poor solubility in pure water, so it is difficult to add them directly into the solubilized formulation. For convenience of weighing and manufacturing, the process was carried out by first dissolving them in polyol at a high concentration and then adding them into the formulation. Table 3 below shows the solution of three types of peptides among the peptides prepared above at 1,000 ppm each.
SolutionPeptide A
Solution
SolutionPeptide B
Solution
SolutionPeptide C
Solution
(2) 앰플 제형(2) Ampoule formulation
1) 제조 방법 1) Manufacturing method
통상의 알려진 방법으로 앰플 제형을 제조하였으며, 본 발명의 신규 펩타이드는 1,000 pppm Solution 상태로 제조 맨 마지막 공정에 투입하였다. An ampoule formulation was prepared by a commonly known method, and the new peptide of the present invention was introduced into the final manufacturing process as a 1,000 ppm solution.
표 4와 같이, 실시예 1과 2는 최종 제형 내 2IP5MP-Ac-VW가 35 ppm(= 70uM), 65 ppm(= 131 uM) 각각 함유된 것이며, 비교예 1은 펩타이드를 무첨가한 제형, 비교예 2는 2IP5MP가 65 ppm(= 131 um), 비교예 3은 VW가 65ppm(= 131 uM) 함유되어 있는 것이다. As shown in Table 4, Examples 1 and 2 contain 35 ppm (= 70 uM) and 65 ppm (= 131 uM) of 2IP5MP-Ac-VW in the final formulation, respectively, and Comparative Example 1 is a formulation without peptide added. Example 2 contains 65 ppm (= 131 um) of 2IP5MP, and Comparative Example 3 contains 65 ppm (= 131 uM) of VW.
2) 제형 안정성 평가2) Formulation stability evaluation
상기 펩타이드가 함유된 앰플 제형의 상온과 고온 안정성을 확인하였다. The room temperature and high temperature stability of the ampoule formulation containing the above peptide was confirmed.
Appearance, pH, 점도 등 화장품 규격에 의거해서 제조된 화장품 제형을 시간에 따라서 평가하였으며 전체적으로 큰 차이가 없는 것으로 확인되었다(표 5). 이는 함유된 펩타이드들이 앰플 제형을 이루는 주요 조성비들 (점증제, 폴리올 등)과 별도 상호작용 없이 안정함을 확인하여 앰플 제형에 사용되는데 크게 어려움이 없을 것으로 예상된다.Cosmetic formulations manufactured according to cosmetic standards such as appearance, pH, and viscosity were evaluated over time, and it was confirmed that there was no significant difference overall (Table 5). This confirms that the contained peptides are stable without any interaction with the main components (thickener, polyol, etc.) that make up the ampoule formulation, so it is expected that there will be no major difficulties in using it in the ampoule formulation.
* 평가 : Appearance / pH / 점도* Evaluation: Appearance / pH / Viscosity
(3) 크림 제형(3) Cream formulation
1) 제조방법1) Manufacturing method
통상의 알려진 방법으로 크림 제형을 제조하였으며, 본 발명의 신규 펩타이드는 1,000 pppm Solution 상태로 제조 맨 마지막 공정에 투입하였다.A cream formulation was prepared by a commonly known method, and the new peptide of the present invention was introduced into the final manufacturing process as a 1,000 ppm solution.
표 6과 같이 실시예 3과 4는 최종 제형 내 2IP5MP-Ac-VW가 35 ppm(= 70uM), 65 ppm(= 131 uM) 각각 함유된 것이며, 비교예 4는 펩타이드가 무첨가한 제형, 비교예 5는 2IP5MP가 65 ppm(= 131 um), 비교예 6은 VW가 65ppm(= 131 uM) 함유되어 있는 것이다.As shown in Table 6, Examples 3 and 4 contain 35 ppm (= 70 uM) and 65 ppm (= 131 uM) of 2IP5MP-Ac-VW, respectively, in the final formulation, and Comparative Example 4 is a formulation without peptide added, Comparative Example. 5 contains 65 ppm (= 131 um) of 2IP5MP, and Comparative Example 6 contains 65 ppm (= 131 uM) of VW.
2) 제형 안정성 평가2) Formulation stability evaluation
상기 펩타이드가 함유된 크림 제형의 상온과 고온 안정성을 확인하였다. The room temperature and high temperature stability of the cream formulation containing the above peptide was confirmed.
Appearance, pH, 점도 등 화장품 규격에 의거해서 제조된 화장품 제형을 시간에 따라서 평가하였으며 전체적으로 큰 차이가 없는 것으로 확인되었다(표 7). 이는 함유된 펩타이드들이 크림 제형을 이루는 주요 조성비들 (점증제, 폴리올 등)과 별도 상호작용 없이 안정함을 확인하여 크림 제형에 사용되는데 크게 어려움이 없을 것으로 예상된다.Cosmetic formulations manufactured according to cosmetic standards such as appearance, pH, and viscosity were evaluated over time, and it was confirmed that there was no significant difference overall (Table 7). This confirms that the contained peptides are stable without any interaction with the main ingredients (thickener, polyol, etc.) that make up the cream formulation, so it is expected that there will be no major difficulties in using it in cream formulations.
* 평가 : Appearance / pH / 점도* Evaluation: Appearance / pH / Viscosity
Claims (7)
상기 펩타이드의 아민 말단에 하기 화학식1의 아실(acyl) 작용기가 결합되며,
상기 폴리트립토판은 트립토판이 2 내지 6개 연결된, 항균, 항염증 또는 항여드름용 펩타이드.
[화학식 1]
여기서, R1은 C1~C14 알킬, C2~C14 알케닐, C2~C14 알키닐이다.Contains any one of tryptophan, polytryptophan, and valine-tryptophan dipeptide,
An acyl functional group of the following formula (1) is bound to the amine terminal of the peptide,
The polytryptophan is an antibacterial, anti-inflammatory or anti-acne peptide in which 2 to 6 tryptophans are linked.
[Formula 1]
Here, R 1 is C1~C14 alkyl, C2~C14 alkenyl, and C2~C14 alkynyl.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020220150296A KR20240069119A (en) | 2022-11-11 | 2022-11-11 | peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same |
| PCT/KR2023/017694 WO2024101830A1 (en) | 2022-11-11 | 2023-11-06 | Antibacterial, anti-inflammatory, or anti-acne peptide and cosmetic composition containing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020220150296A KR20240069119A (en) | 2022-11-11 | 2022-11-11 | peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20240069119A true KR20240069119A (en) | 2024-05-20 |
Family
ID=91033275
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020220150296A KR20240069119A (en) | 2022-11-11 | 2022-11-11 | peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR20240069119A (en) |
| WO (1) | WO2024101830A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102115668B1 (en) | 2018-11-09 | 2020-06-17 | (주)하이메디코스 | Cosmetic composition having anti-acne activity comprising probiotics fermentation product |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101689878B1 (en) * | 2014-08-28 | 2016-12-26 | (주)셀아이콘랩 | Cosmetic composition for treating acne |
| KR102093209B1 (en) * | 2017-05-11 | 2020-03-25 | (주)케어젠 | Conjugate of isotretinoin and peptide |
| CA3158582A1 (en) * | 2019-11-22 | 2021-05-27 | Critical Outcome Technologies Inc. | Peptides, compounds, compositions and methods for inhibiting sox9 dimerization |
-
2022
- 2022-11-11 KR KR1020220150296A patent/KR20240069119A/en unknown
-
2023
- 2023-11-06 WO PCT/KR2023/017694 patent/WO2024101830A1/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102115668B1 (en) | 2018-11-09 | 2020-06-17 | (주)하이메디코스 | Cosmetic composition having anti-acne activity comprising probiotics fermentation product |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024101830A1 (en) | 2024-05-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114269769A (en) | Novel peptide compound or pharmaceutically acceptable salt thereof | |
| US12005123B2 (en) | Conjugate of isotretinoin and peptide | |
| US5126327A (en) | Melanocyte-stimulating hormone inhibitor and external preparation containing the same | |
| KR102158036B1 (en) | Novel antimicrobial peptide derived from Pseudin-2 peptide and uses thereof | |
| KR101710486B1 (en) | Oligopeptide derivatives and skin wrinkle composition comprising it | |
| KR102678549B1 (en) | Peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same | |
| KR20240069119A (en) | peptide for antimicrobial, anti-inflammatory or anti-acne and cosmetic composition for comprising the same | |
| KR100702329B1 (en) | Compositiion for Inhibiting 5?-Reductase Activity and Cosmetic Composition for Inhibiting Secretion of Sebum containing Extract of Chelidonium majus as Active Ingredient | |
| KR101970465B1 (en) | Use of novel peptide derivatives derived from silkworm that coupled with caffeic acid | |
| KR101354915B1 (en) | Galloyl-peptide and cosmetic external preparation composition for skin using the same | |
| CA3053321C (en) | Conjugate of salicylic acid and peptide | |
| JPH04187618A (en) | Skin external preparation | |
| KR20000019981A (en) | Skin preparation containing extract of bamboosae calulis in taeniam for external use | |
| WO2018139885A1 (en) | Composition comprising acetoxychavicol acetate as active ingredient for preventing hair loss and promoting hair growth | |
| JP3874477B2 (en) | Melanin production promoter containing chitosan derivative | |
| KR20200101767A (en) | Peptide having anti-microbial activity and compositions for anti-microbial comprising the same | |
| JP2003327596A (en) | New polyphenol glycoside, and cosmetic, medicinal composition and food containing the same | |
| JP4106454B2 (en) | Compositions for treating acne containing phytandiolamine (Compositions for treating acne competing phytiodiolamine) | |
| KR20180125419A (en) | Conjugate of isotretinoin and peptide | |
| KR20240050560A (en) | Peptide Having Activity of Promoting Hair Growth and Inhibiting Hair Loss and Uses Thereof | |
| KR20240050564A (en) | Peptide Having Activity of Promoting Hair Growth and Inhibiting Hair Loss and Uses Thereof | |
| FR2582304A1 (en) | 5-OXOPROLINE AND 6-PIPERIDINO-2,4-DIAMINOPYRIMIDINE-3-OXIDE SALT AND COSMETIC-DERMATOLOGICAL COMPOSITIONS CONTAINING THE SAME | |
| KR101410589B1 (en) | Neuropeptide derivatives and Composition for Skin External Application Comprising the Same | |
| CN115322254A (en) | Lactoferrin, polypeptide derived from lactoferrin and application of polypeptide to inhibition and/or reduction of grease generation | |
| OA19680A (en) | Conjugate of Isotretinoin and Peptide. |