WO2023018315A1 - Cosmetic composition for skin moisturizing and skin soothing comprising improved cell-permeable nuclear import inhibitor - Google Patents
Cosmetic composition for skin moisturizing and skin soothing comprising improved cell-permeable nuclear import inhibitor Download PDFInfo
- Publication number
- WO2023018315A1 WO2023018315A1 PCT/KR2022/012185 KR2022012185W WO2023018315A1 WO 2023018315 A1 WO2023018315 A1 WO 2023018315A1 KR 2022012185 W KR2022012185 W KR 2022012185W WO 2023018315 A1 WO2023018315 A1 WO 2023018315A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- skin
- cosmetic composition
- icp
- lotion
- present
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 239000002537 cosmetic Substances 0.000 title claims abstract description 36
- 230000003020 moisturizing effect Effects 0.000 title claims abstract description 20
- 229940122981 Nuclear import inhibitor Drugs 0.000 title claims abstract description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 36
- 208000003251 Pruritus Diseases 0.000 claims abstract description 34
- 230000007803 itching Effects 0.000 claims abstract description 24
- 206010015150 Erythema Diseases 0.000 claims abstract description 22
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 239000006210 lotion Substances 0.000 claims description 23
- 239000006071 cream Substances 0.000 claims description 16
- -1 foundation Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 238000009472 formulation Methods 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000007921 spray Substances 0.000 claims description 7
- 239000000499 gel Substances 0.000 claims description 6
- 235000015097 nutrients Nutrition 0.000 claims description 5
- 239000002674 ointment Substances 0.000 claims description 4
- 239000000344 soap Substances 0.000 claims description 4
- 239000000865 liniment Substances 0.000 claims description 3
- 229940040145 liniment Drugs 0.000 claims description 3
- 235000015927 pasta Nutrition 0.000 claims description 3
- 239000006260 foam Substances 0.000 claims description 2
- 239000008269 hand cream Substances 0.000 claims description 2
- 235000013336 milk Nutrition 0.000 claims description 2
- 239000008267 milk Substances 0.000 claims description 2
- 210000004080 milk Anatomy 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 235000016709 nutrition Nutrition 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 231100000321 erythema Toxicity 0.000 abstract description 7
- 210000003491 skin Anatomy 0.000 description 84
- 238000012360 testing method Methods 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 230000006872 improvement Effects 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 210000000434 stratum corneum Anatomy 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000036572 transepidermal water loss Effects 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000004909 Moisturizer Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 210000002615 epidermis Anatomy 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000001333 moisturizer Effects 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000004761 scalp Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 238000005406 washing Methods 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
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 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
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000007787 solid 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
- 239000003381 stabilizer Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 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
- 229940015975 1,2-hexanediol Drugs 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-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
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000699800 Cricetinae Species 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
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 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 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001034 Frostbite Diseases 0.000 description 1
- 208000006877 Insect Bites and Stings Diseases 0.000 description 1
- 150000007649 L alpha amino acids Chemical class 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
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010027627 Miliaria Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010039793 Seborrhoeic dermatitis 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
- 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
- 208000024780 Urticaria Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 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
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- BQMNFPBUAQPINY-UHFFFAOYSA-N azane;2-methyl-2-(prop-2-enoylamino)propane-1-sulfonic acid Chemical compound [NH4+].[O-]S(=O)(=O)CC(C)(C)NC(=O)C=C BQMNFPBUAQPINY-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 108010085685 cSN50.1 peptide Proteins 0.000 description 1
- 235000001046 cacaotero Nutrition 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
- 239000000969 carrier Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 229940086555 cyclomethicone Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 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
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- XJNUECKWDBNFJV-UHFFFAOYSA-N hexadecyl 2-ethylhexanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(CC)CCCC XJNUECKWDBNFJV-UHFFFAOYSA-N 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical class C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 230000005722 itchiness Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 235000011929 mousse Nutrition 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
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 230000025308 nuclear transport Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229940100460 peg-100 stearate Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase 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
- 230000000704 physical effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000007788 roughening Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036620 skin dryness Effects 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007790 solid phase Substances 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
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
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
- 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
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/18—Antioxidants, e.g. antiradicals
Definitions
- the present invention relates to a composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide, and more specifically, SEQ ID NO: It relates to a cosmetic composition or an external preparation for skin comprising 1 as an active ingredient.
- iCP-NI cell-permeable nuclear import inhibitor
- the skin is largely divided into three layers: epidermis, dermis, and subcutaneous fat tissue, and functions to protect the human body from physical and chemical stimuli from the external environment.
- the skin carries about 65-70% of the water that the human body has, that is, various physiologically active substances necessary for the human body, and plays a role in helping the skin to maintain a soft and moist state.
- the epidermis is divided into the stratum corneum, the granular layer, the spinous layer, and the basal layer in order from the outside. (J. Invest. Dermatol. 80 (Suppl.), 44-49. 1983).
- the stratum corneum of the epidermis contains about 10 to 20% of water and exists in the outermost layer of the human body, suppressing the evaporation of water to the outside of the body while blocking excessive penetration of substances from the outside.
- the surface of the stratum corneum is covered with a thin natural protective film made of sebum from the sebaceous glands and sweat from the sweat glands, which prevents moisture from evaporating.
- the cells that make up the stratum corneum of the skin contain a high concentration of Natural Moisturizing Factor (NMF), a water-soluble component, which helps the skin to show flexibility and maintain appropriate moisture.
- NMF Natural Moisturizing Factor
- the same substance is not only water-soluble, but also effectively binds to water and inhibits the drying of water from the skin (J. Invest. Dermatol. 54, 24-31, 1970).
- the present inventors introduced an advanced macromolecule transduction domain (aMTD) based on TSDT (therapeutic molecule systemic delivery technology) to a cell-permeable nuclear import inhibitor (CP-NI, cSN50.1 peptide) to obtain a peptide with improved solubility and stability.
- aMTD advanced macromolecule transduction domain
- CP-NI cell-permeable nuclear import inhibitor
- cSN50.1 peptide cell-permeable nuclear import inhibitor
- iCP-NI cell-permeable nuclear import inhibitor
- the iCP-NI not only has excellent biocompatibility, but also has skin moisturizing effects, itching improvement and erythema relief effects. confirmed and came to complete this invention.
- the present invention provides a cosmetic composition for skin moisturizing and skin soothing comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 as an active ingredient. aims to do
- iCP-NI cell-permeable nuclear import inhibitor
- the skin soothing may include reducing skin itching, improving skin erythema sensitivity and skin redness.
- the iCP-NI peptide may be contained in a concentration of 0.001 to 20 mM in the cosmetic composition.
- the formulation of the cosmetic composition is lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, eye cream, moisture
- lotion skin lotion
- skin softener skin toner
- astringent lotion
- milk lotion moisture lotion
- nutrient lotion massage cream
- nutrient cream eye cream
- moisture One or more may be selected from the group consisting of cream, hand cream, foundation, essence, nutrient essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, and body cleanser.
- the present invention also provides an external skin preparation for skin moisturizing and skin soothing, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 as an active ingredient.
- iCP-NI cell-permeable nuclear import inhibitor
- the formulation of the external preparation may be one or more selected from the group consisting of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta and cataplasma. there is.
- the present invention also provides a skin moisturizing and skin soothing method comprising the step of applying an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 to the subject. is intended to provide
- iCP-NI cell-permeable nuclear import inhibitor
- the iCP-NI peptide according to the present invention not only has excellent biocompatibility, but also has a skin moisturizing effect and relieves itching due to skin dryness, and exhibits excellent skin care effects such as skin erythema relief, so it is effective as a cosmetic composition or external skin application. expected to be usable.
- Figure 2 shows the erythema improvement effect of the cosmetic composition containing iCP-NI according to the present invention.
- Figure 3 shows the skin redness improvement effect of the cosmetic composition containing iCP-NI according to the present invention.
- a cosmetic composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide according to a specific embodiment of the present invention will be described in detail.
- iCP-NI cell-permeable nuclear import inhibitor
- the term "include” or “comprise” means to include a specific component (or element) without particular limitation unless otherwise stated throughout this specification, and other components (or elements) may not be construed as precluding the addition of
- amino acid in its broadest sense includes naturally occurring L ⁇ -amino acids or residues thereof as well as D-amino acids and chemically modified amino acids.
- amino acids may include mimetics and analogs of the aforementioned amino acids.
- mimetics and analogues may include functional equivalents.
- skin refers to a tissue covering the body surface of an animal, and is a concept in the broadest sense that includes not only the tissue covering the body surface such as the face or body, but also the scalp and hair.
- skin itching means an unpleasant sensation that causes a desire to scratch or rub the skin, and as one example, itching due to dry skin; itching caused by hives; itching caused by insect bites; itching caused by heat rash, acne, sores, frostbite, contact dermatitis, seborrheic dermatitis or psoriasis; Itching caused by various skin diseases; Including scalp itching and the like.
- skin itching of various causes other than the skin itching listed above is not excluded.
- the present invention covers all pruritus known in the art, such as pruritus of dermatological origin, pruritus of systemic origin, pruritus of neuropathic origin and pruritus of psychogenic origin.
- moistureturizing the skin means to prevent skin moisture from evaporating out of the body and block excessive penetration of external substances, thereby maintaining moisture in the stratum corneum and preventing the skin from drying out or roughening the surface. , which means keeping the skin soft and moist.
- skin soothing means to alleviate and soothe erythema or irritated skin areas and the like.
- skin erythema refers to a phenomenon in which the skin turns red due to external/internal stimuli, abnormal expansion of blood vessels, or redness in whole or in part in erythema caused by accumulation of blood in skin tissue.
- the term “improvement” or “treatment” refers to (a) inhibition of the development (b) alleviation and (c) elimination of a dermatitis disorder in a subject.
- prevention refers to inhibiting the occurrence of a disease or condition in a subject who has not been diagnosed as having the disease or condition, but is predisposed to the disease or condition.
- the term "application” means any method of contacting the composition according to the present invention to the skin of an individual by any suitable method, and through this, the composition is absorbed into the skin.
- the present invention provides a skin moisturizing and skin soothing cosmetic composition
- a skin moisturizing and skin soothing cosmetic composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 as an active ingredient.
- iCP-NI cell-permeable nuclear import inhibitor
- the iCP-NI peptide according to the present invention is preferably contained in a concentration of 0.01 to 10000 ppm in the cosmetic composition, more preferably in a concentration of 0.01 to 1000 ppm, but is not limited thereto. If the concentration of the peptide is less than 0.01ppm, it is difficult to obtain the desired skin moisturizing and skin soothing effects, and if it exceeds 10000ppm, there is a problem in that the production economy is poor because there is no significant increase in the effect due to the increase in the content.
- the iCP-NI peptide according to the present invention can be prepared by general chemical synthesis, for example, solid-phase peptide synthesis, and a microorganism transformed with a recombinant vector containing a nucleic acid encoding the peptide. After expressing the peptide by culturing, it may be prepared by purification by a conventional method, but is not limited thereto.
- the cosmetic composition according to the present invention may further contain other ingredients that can give a synergistic effect to the effect of the present invention, preferably within a range that does not impair the effect intended by the present invention.
- the cosmetic composition of the present invention may contain conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances, or carriers, as well as any other substances known to have skin moisturizing and skin soothing effects. can include
- the cosmetic composition according to the present invention is not particularly limited in its formulation, and may be prepared in any formulation commonly prepared in the art, for example, a solution, suspension, emulsion, paste, gel, cream, It can be formulated into lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like.
- scalp treatment agents, soaps, hair tonics, shampoos, rinses, hair packs, hair gels, lotions, conditioners, hair oils, mousses, creams, solids, solutions, emulsions, dispersants, micelles, liposomes, ointments It may be prepared in the form of lotion, essence, patch or spray.
- the formulation of the cosmetic composition is a paste, cream or gel
- animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier components
- lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane / propellants such as butane or dimethyl ether.
- a solvent, solubilizing agent or emulsifying agent may be used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate , propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.
- a liquid diluent such as water, ethanol or propylene glycol
- a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester
- Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanth may be used, and in the case of surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate as carrier components , imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol
- the iCP-NI peptide of the present invention has excellent biocompatibility, reduces skin itching, increases skin moisture content and permittivity, reduces transepidermal water loss, reduces skin erythema caused by ultraviolet rays, and improves skin redness.
- the iCP-NI peptide of the present invention can be usefully used as an active ingredient of a cosmetic composition for skin moisturizing and skin soothing.
- the present invention provides a pharmaceutical composition for skin moisturizing and skin soothing, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide composed of amino acids of SEQ ID NO: 1 as an active ingredient.
- iCP-NI cell-permeable nuclear import inhibitor
- the pharmaceutical composition according to the present invention includes dermal, buccal, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal administration, preferably oral or parenteral administration.
- parenteral administration includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.
- the pharmaceutical composition according to the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the iCP-NI peptide according to the present invention.
- the composition may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively.
- Solid preparations for oral administration of the pharmaceutical composition include powders, granules, tablets, capsules, soft capsules, pills, and the like.
- Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc.
- various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. .
- Formulations for parenteral administration include powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc., and sterile injection preparations according to conventional methods, respectively. It can be formulated and used in the form of a cream, gel, patch, spray, ointment, warning, lotion, liniment, pasta, or cataplasma. , but is not limited thereto. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.
- the pharmaceutical composition according to the present invention may further contain adjuvants such as preservatives, stabilizers, hydration agents or emulsification accelerators, salts and/or buffers for osmotic pressure control, and other therapeutically useful substances. It can be formulated according to mixing, granulating or coating methods.
- the pharmaceutical composition according to the present invention may vary depending on various factors including age, body weight, general health, sex, administration time, route of administration, excretion rate, drug combination, and severity of a specific disease.
- the pharmaceutical composition according to the present invention is formulated in a unit dose form containing the iCP-NI peptide as an active ingredient, the iCP-NI peptide as an active ingredient in a unit dose of about 0.01 to 1,500 mg It is preferable to contain, and the dosage required for adult treatment is usually in the range of about 1 to 500 mg per day depending on the frequency and strength of administration, but is not limited thereto. A total dose of about 5 to 300 mg per day will usually suffice for a single dose for intramuscular or intravenous administration to adults, although higher daily doses may be desirable in some patients.
- the composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
- the present invention comprises the step of treating or administering an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 in a cosmetically or pharmaceutically effective amount to a subject. It provides a method for moisturizing and soothing the skin.
- iCP-NI cell-permeable nuclear import inhibitor
- the cosmetically or pharmaceutically effective amount is 0.0001 to 100 mg/kg, preferably 0.001 to 10 mg/kg, but is not limited thereto.
- the treatment or dose may be adjusted according to the weight, age, sex, health condition, diet, administration period, administration method, removal rate, severity of disease, etc. of a specific patient. Treatment or administration may be administered once a day or divided into several times.
- the subject is a vertebrate animal, preferably a mammal, more preferably a human or an experimental animal such as a rat, rabbit, guinea pig, hamster, dog, or cat, and most preferably a human It may be, but is not limited thereto.
- the treatment or administration method may be applied, oral or parenteral administration, and in the case of parenteral administration, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine intrauterine injection It may be administered by injection, intracerebrovascular injection or intrathoracic injection.
- the iCP-NI peptide composed of the amino acid sequence of SEQ ID NO: 1 according to the present invention uses an advanced macromolecule transduction domain (aMTD) composed of amino acids of SEQ ID NO: 2 and an NF- ⁇ nuclear localization sequence (NLS) composed of amino acids of SEQ ID NO: 3 was prepared (Table 1).
- aMTD advanced macromolecule transduction domain
- NLS NF- ⁇ nuclear localization sequence
- NHDF cells were inoculated into a 24-well plate at a concentration of 2.0 ⁇ 10 4 cells/well and cultured for 24 hours, followed by iCP-NI peptide samples (diluted with medium to final concentrations of 1, 5, 10, 30, and 50 ⁇ M). ) was exchanged with serum-free FBM and cultured for 24 hours. After incubation, 50 ⁇ l of EZ-Cytox was added per well and further incubated for 1 hour. The cultured medium was transferred to a 96-well plate and absorbance was measured at 450 nm using a VERSA max microplate reader (Molecular devices, LCC., USA). The average absorbance value for each sample group was obtained, and cell viability was investigated by comparing with the absorbance value of the control group. As a result, it was confirmed that the iCP-NI peptide according to the present invention was not cytotoxic compared to the control group in the concentration range of 1 to 50 ⁇ M (FIG. 1).
- a lotion containing the iCP-NI peptide of the present invention as an active ingredient was prepared as shown in Table 2 below (content: parts by weight).
- a human application test was conducted to verify the functionality of the iCP-NI according to the present invention. After washing the cheeks of the face, wait for more than 30 minutes under constant temperature and humidity (22 ⁇ 2°C, 50 ⁇ 5%) conditions to sufficiently stabilize the skin before participating in the test.
- the itching score (Score) before and after using the test product, skin moisture content (A.U.), and average permittivity ( ⁇ transepidermal water loss (g/m2h)) were measured to evaluate the efficacy of relieving itchiness due to dryness.
- test subjects Before using the test product, after 2 weeks of use, and after 4 weeks of use, the test subjects were asked to self-evaluate the itching classification on a 10-point scale according to Table 3 below, and the average score was calculated to evaluate the degree of improvement in itching.
- score degree of itching 0 points no itching More than 1 point and less than 3 points Mild pruritus 3 or more and less than 7 Moderate pruritus 7 or more and less than 9 severe itching (severe pruritus) 10 points very severe pruritus
- the cosmetic composition containing the iCP-NI according to the present invention significantly decreased the itching score after 2 weeks and 4 weeks of use compared to before use.
- Corneometer CM825 Probe (Courage+Khazaka GmbH, Germany) was used to evaluate the skin moisture content by measuring the capacitance of the stratum corneum within 10 ⁇ m from the skin surface. As a result, it was confirmed that the cosmetic composition containing iCP-NI according to the present invention significantly increased skin moisture after 2 weeks and 4 weeks of use compared to before use.
- Epsilon E100 (Biox Systems Ltd., England) used a CMOS fingerprint recognition sensor with a special resolution of 50 ⁇ m to calculate the average permittivity ( ⁇ value) of the moisture content of the skin surface in contact with the sensor in the area of 12.8mm*15mm.
- ⁇ value average permittivity
- TEWL transepidermal water loss
- ICP-NI (0.01%) was applied to the erythema area formed by inducing stimulation through ultraviolet rays on the human skin, and 48 hours later, it was compared with the non-applied group.
- the a* value (red flag) of the test site was measured using a spectrophotometer CM-26dG (Konica Minolta).
- CM-26dG Konica Minolta
- a human application test was conducted on 20 test subjects. After washing the cheeks of the face, wait for more than 30 minutes under constant temperature and humidity (22 ⁇ 2°C, 50 ⁇ 5%) conditions to sufficiently stabilize the skin before participating in the test. Before and after 4 weeks of using the test product, pictures were taken using VISIA-CR and skin redness in the cheek area was evaluated using an image analysis program. As a result, it was confirmed that the cosmetic composition containing iCP-NI according to the present invention improved skin redness by about 42% after 4 weeks of use (FIG. 3).
- the iCP-NI peptide of the present invention has excellent biocompatibility, and has effects of reducing skin itching, increasing skin moisture content and permittivity, reducing transepidermal water loss, reducing skin erythema caused by ultraviolet rays, and improving skin redness. Therefore, the iCP-NI peptide of the present invention can be usefully used as an active ingredient of a cosmetic composition for skin moisturizing and skin soothing.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Biochemistry (AREA)
Abstract
The present invention relates to a composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide and, more specifically, to a cosmetic composition or an external preparation for skin comprising, as an active ingredient, SEQ ID NO: 1, which has effect in skin moisturizing, improving skin itching, and alleviating erythema.
Description
관련 출원에 대한 상호 참조CROSS REFERENCES TO RELATED APPLICATIONS
본 출원은 2021년 8월 13일에 출원된 미국 가특허출원 일련번호 63/232,766의 혜택과 우선권을 주장하며, 그 전체가 여기에 참조로 포함된다.This application claims the benefit and priority of U.S. Provisional Patent Application Serial No. 63/232,766, filed on August 13, 2021, which is hereby incorporated by reference in its entirety.
본 발명은 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 포함하는 조성물에 관한 것으로, 보다 상세하게는 피부 보습, 피부 가려움증 개선 및 홍반 완화 효과를 갖는 서열번호 1을 유효성분으로 포함하는 화장료 조성물 또는 피부 외용제에 관한 것이다. The present invention relates to a composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide, and more specifically, SEQ ID NO: It relates to a cosmetic composition or an external preparation for skin comprising 1 as an active ingredient.
피부는 표피, 진피, 피하지방 조직의 3개 층으로 크게 구분되며, 인체를 외부 환경으로부터의 물리적, 화학적인 자극으로부터 보호해 주는 기능을 한다. 특히 피부는 인체가 갖고 있는 약 65~70%의 수분, 즉 인체에 필요한 각종 생리 활성 물질을 운반하며, 피부가 부드럽고 촉촉한 상태를 유지할 수 있도록 도와주는 역할을 한다. 또한, 표피는 외부로부터 각질층, 과립층, 유극층, 기저층의 순서로 구분되는데, 각질층의 세포들은 벽돌과 같은 역할을 하고, 각질세포 사이의 세포간 지질들은 모르타르와 같은 역할로 작용하여 피부 장벽을 구성한다(J. Invest. Dermatol. 80(Suppl.), 44-49. 1983). 표피의 각질층은 약 10~20%의 수분을 함유하며 인체의 최외각에 존재함으로써 체외로의 수분 증발을 억제하는 한편 외부로부터의 물질 과잉 침투를 차단한다. 이들 각질층 표면은 피지선에서 나온 피지와 땀샘에서 나온 땀으로 만들어진 얇은 천연 보호막으로 감싸져 있어서 수분의 증발을 예방할 수 있다. 피부의 각질층을 구성하고 있는 세포에는 수용성 성분인 고농도의 자연보습인자(Natural Moisturizing Factor, NMF)가 존재하여 피부가 유연성을 나타내도록 작용함은 물론 적절한 수분을 유지할 수 있도록 돕는데, 예를 들면 아미노산과 같은 물질은 수용성일 뿐만 아니라 효과적으로 수분과 결합하여 피부에서 수분이 건조되는 것을 억제한다(J. Invest. Dermatol. 54, 24-31, 1970).The skin is largely divided into three layers: epidermis, dermis, and subcutaneous fat tissue, and functions to protect the human body from physical and chemical stimuli from the external environment. In particular, the skin carries about 65-70% of the water that the human body has, that is, various physiologically active substances necessary for the human body, and plays a role in helping the skin to maintain a soft and moist state. In addition, the epidermis is divided into the stratum corneum, the granular layer, the spinous layer, and the basal layer in order from the outside. (J. Invest. Dermatol. 80 (Suppl.), 44-49. 1983). The stratum corneum of the epidermis contains about 10 to 20% of water and exists in the outermost layer of the human body, suppressing the evaporation of water to the outside of the body while blocking excessive penetration of substances from the outside. The surface of the stratum corneum is covered with a thin natural protective film made of sebum from the sebaceous glands and sweat from the sweat glands, which prevents moisture from evaporating. The cells that make up the stratum corneum of the skin contain a high concentration of Natural Moisturizing Factor (NMF), a water-soluble component, which helps the skin to show flexibility and maintain appropriate moisture. The same substance is not only water-soluble, but also effectively binds to water and inhibits the drying of water from the skin (J. Invest. Dermatol. 54, 24-31, 1970).
그러나, 환경의 변화 또는 생활 패턴의 변화에 따른 인위적인 온도 조절, 사회 생활에서 발생되는 각종 스트레스와 환경오염으로 인한 피부 스트레스, 화장 습관에 따른 잦은 세안 및 연령 증가에 따른 자연적인 피부 노화 등의 여러 가지 원인으로 인하여 각질층의 수분이 감소하여 피부가 건조해지고 표면이 거칠게 되며 피부가 윤기를 잃어 칙칙하게 보이는 등의 현상이 발생하기 때문에 피부 보습제의 필요가 증가하고 있다.However, various factors such as artificial temperature control due to changes in the environment or lifestyle, skin stress due to various stresses and environmental pollution in social life, frequent face washing due to makeup habits, and natural skin aging due to age increase, etc. Due to the cause, the moisture of the stratum corneum is reduced, the skin becomes dry, the surface becomes rough, and the skin loses its luster and looks dull, so the need for a skin moisturizer is increasing.
한편, 이러한 피부 보습을 유지하기 위한 방안으로 수분 증발을 방지하는 폐쇄 보습제(occlusive moisturizer)를 사용하여 각질층에서의 수분 보유를 증가시키는 방식이 가장 널리 사용되고 있으나, 이들은 피부에 도포 시 폴리올의 고유 점성과 물성으로 인하여 끈적임이 심하거나 눅진한 느낌이 드는 단점이 있으며, 이외에도 종래 사용되고 있는 피부 보습제는 피부 트러블 등이 유발될 수 있어 피부 안전성에도 문제가 있다. 따라서 보다 안정적이면서도 우수한 보습 효과를 갖는 피부 보습제의 개발이 필요한 실정이다.On the other hand, as a way to maintain such skin moisture, a method of increasing moisture retention in the stratum corneum using an occlusive moisturizer that prevents moisture evaporation is most widely used, but these Due to physical properties, there is a disadvantage in that it feels sticky or wet, and in addition, conventionally used skin moisturizers may cause skin troubles, so there is a problem with skin safety. Therefore, it is necessary to develop a skin moisturizer having a more stable and excellent moisturizing effect.
본 발명자들은 위와 같은 배경 하에서 세포 투과성 핵 유입 억제제(CP-NI, cSN50.1 펩티드)에 TSDT(therapeuticmolecule systemic delivery technology)를 기반으로 하는 aMTD(advanced macromolecule transduction domain)을 도입해 용해성과 안정성이 향상된 펩티드로서 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI)를 제조하였으며, 상기 iCP-NI는 생체 적합성이 뛰어날 뿐만 아니라, 피부 보습 효과, 가려움증 개선 및 홍반 완화 효과가 있음을 확인하고, 본 발명을 완성하기에 이르렀다. Under the above background, the present inventors introduced an advanced macromolecule transduction domain (aMTD) based on TSDT (therapeutic molecule systemic delivery technology) to a cell-permeable nuclear import inhibitor (CP-NI, cSN50.1 peptide) to obtain a peptide with improved solubility and stability. As an improved cell-permeable nuclear import inhibitor (iCP-NI) was prepared, the iCP-NI not only has excellent biocompatibility, but also has skin moisturizing effects, itching improvement and erythema relief effects. confirmed and came to complete this invention.
본 발명은 서열번호 1로 표시되는 아미노산 서열로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 유효성분으로 포함하는 피부 보습 및 피부 진정용 화장료 조성물을 제공하는 것을 목적으로 한다. The present invention provides a cosmetic composition for skin moisturizing and skin soothing comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 as an active ingredient. aims to do
본 발명에 따른 화장료 조성물에 있어서, 상기 피부 진정은 피부 가려움증 감소, 피부 홍반 감성 및 피부 붉은기 개선을 포함할 수 있다. In the cosmetic composition according to the present invention, the skin soothing may include reducing skin itching, improving skin erythema sensitivity and skin redness.
본 발명에 따른 화장료 조성물에 있어서, 상기 iCP-NI 펩티드는 화장료 조성물 내 0.001 내지 20 mM의 농도로 함유될 수 있다. In the cosmetic composition according to the present invention, the iCP-NI peptide may be contained in a concentration of 0.001 to 20 mM in the cosmetic composition.
본 발명에 따른 화장료 조성물에 있어서, 상기 화장료 조성물의 제형은 화장수(스킨로션), 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양 로션, 마사지 크림, 영양 크림, 아이 크림, 모이스쳐 크림, 핸드크림, 파운데이션, 에센스, 영양 에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션 및 바디클렌저로 이루어진 군으로부터 하나 또는 그 이상 선택될 수 있다. In the cosmetic composition according to the present invention, the formulation of the cosmetic composition is lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, eye cream, moisture One or more may be selected from the group consisting of cream, hand cream, foundation, essence, nutrient essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, and body cleanser.
본 발명은 또한 서열번호 1로 표시되는 아미노산 서열로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 유효성분으로 포함하는 피부 보습 및 피부 진정용 피부 외용제를 제공하는 것을 목적으로 한다. The present invention also provides an external skin preparation for skin moisturizing and skin soothing, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 as an active ingredient. intended to provide
본 발명에 따른 피부 외용제에 있어서, 상기 외용제의 제형은 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제로 이루어진 군으로부터 하나 또는 그 이상 선택될 수 있다. In the skin external preparation according to the present invention, the formulation of the external preparation may be one or more selected from the group consisting of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta and cataplasma. there is.
본 발명은 또한 서열번호 1로 표시되는 아미노산 서열로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 개체에게 도포하는 단계를 포함하는 피부 보습 및 피부 진정 방법을 제공하는 것을 목적으로 한다. The present invention also provides a skin moisturizing and skin soothing method comprising the step of applying an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 to the subject. is intended to provide
본 발명에 따른 iCP-NI 펩티드는 생체 적합성이 뛰어날 뿐만 아니라 피부 보습 효과 및 피부 건조에 의한 가려움증을 완화시킬 뿐만 아니라 피부 홍반 완화 등의 피부 미용에 있어서 우수한 효과를 나타내므로 화장료 조성물 또는 피부 외용제로 유효하게 사용될 수 있을 것으로 기대된다. The iCP-NI peptide according to the present invention not only has excellent biocompatibility, but also has a skin moisturizing effect and relieves itching due to skin dryness, and exhibits excellent skin care effects such as skin erythema relief, so it is effective as a cosmetic composition or external skin application. expected to be usable.
한편, 전술한 바와 같은 효과들에 의해 본 발명의 범위가 제한되는 것은 아니다.On the other hand, the scope of the present invention is not limited by the effects as described above.
도 1은 본 발명에 따른 iCP-NI 펩티드의 생체 적합성을 나타낸다. 1 shows the biocompatibility of the iCP-NI peptide according to the present invention.
도 2는 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물의 홍반 개선 효과를 나타낸다. Figure 2 shows the erythema improvement effect of the cosmetic composition containing iCP-NI according to the present invention.
도 3은 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물의 피부 붉은기 개선 효과를 나타낸다. Figure 3 shows the skin redness improvement effect of the cosmetic composition containing iCP-NI according to the present invention.
이하, 본 발명의 구체적인 실시예에 따른 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 포함하는 화장료 조성물을 자세히 설명한다. 다만, 이는 예시를 위한 실시예에 불과하며, 본 발명의 범위가 이에 한정되는 것은 아니며, 본 발명의 범위 내에서 다양한 실시예에 대한 변형이 가능함은 당업자에게 자명하다.Hereinafter, a cosmetic composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide according to a specific embodiment of the present invention will be described in detail. However, these are only examples for illustrative purposes, and the scope of the present invention is not limited thereto, and it is obvious to those skilled in the art that modifications to various embodiments are possible within the scope of the present invention.
본 명세서에서 사용된 용어 "포함하다(include)" 또는 "포함하다(comprise)" 는 본 명세서 전체에 걸쳐 달리 언급되지 않는 한 특별한 제한 없이 특정한 구성(또는 요소)를 포함하는 것을 의미하며, 다른 구성(또는 요소)의 추가를 배제하는 것으로 해석될 수 없다.As used herein, the term "include" or "comprise" means to include a specific component (or element) without particular limitation unless otherwise stated throughout this specification, and other components (or elements) may not be construed as precluding the addition of
본 명세서에서 사용된 용어 "아미노산"은 가장 넓은 의미에서, 자연 발생한 L α-아미노산 또는 이의 잔기 뿐만 아니라 D-아미노산 및 화학적으로 변형된 아미노산을 포함한다. 예를 들어, 아미노산은 전술한 아미노산의 모방체 및 유사체를 포함할 수 있다. 본 개시에서, 모방체 및 유사체는 기능적 등가물을 포함할 수 있다.As used herein, the term “amino acid” in its broadest sense includes naturally occurring L α-amino acids or residues thereof as well as D-amino acids and chemically modified amino acids. For example, amino acids may include mimetics and analogs of the aforementioned amino acids. In the present disclosure, mimetics and analogues may include functional equivalents.
본 명세서에서 사용된 용어 "피부"는 동물의 체표를 덮는 조직을 의미하는 것으로서, 얼굴 또는 바디 등의 체표를 덮는 조직뿐만 아니라, 두피와 모발을 포함하는 최광의의 개념이다.As used herein, the term "skin" refers to a tissue covering the body surface of an animal, and is a concept in the broadest sense that includes not only the tissue covering the body surface such as the face or body, but also the scalp and hair.
본 명세서에서 사용된 용어 "피부 가려움증"은 피부를 긁거나 문지르고 싶은 욕망을 일으키는 불쾌한 감각을 의미하며, 하나의 예시로서, 피부건조에 의한 가려움증; 두드러기에 의한 가려움증; 벌레물림에 의한 가려움증; 땀띠, 여드름, 짓무름, 동상, 접촉성 피부염, 지루성 피부염 또는 건선 등으로 유발되는 가려움증; 각종 피부질환에 의한 가려움증; 두피 가려움증 등을 포함한다. 그러나, 본 발명에서는 이상에서 열거한 피부 가려움증 이외의 다양한 원인의 피부 가려움증을 배제하는 것이 아님은 물론이다. 본 발명은 당업계에 알려진 모든 가려움증, 예를 들어 피부과적 원인 가려움증, 전신성 원인 가려움증, 신경병증성 원인 가려움증 및 심인성 원인 가려움증 등을 포함한다.As used herein, the term "skin itching" means an unpleasant sensation that causes a desire to scratch or rub the skin, and as one example, itching due to dry skin; itching caused by hives; itching caused by insect bites; itching caused by heat rash, acne, sores, frostbite, contact dermatitis, seborrheic dermatitis or psoriasis; Itching caused by various skin diseases; Including scalp itching and the like. However, in the present invention, of course, skin itching of various causes other than the skin itching listed above is not excluded. The present invention covers all pruritus known in the art, such as pruritus of dermatological origin, pruritus of systemic origin, pruritus of neuropathic origin and pruritus of psychogenic origin.
본 명세서에서 사용된 용어 "피부 보습"은 피부의 수분이 체외로 증발되는 것을 억제하고 외부 물질의 과잉 침투를 차단함으로써, 피부 각질층의 수분을 유지하고 피부가 건조해지거나 표면이 거칠어지는 것을 방지하여, 피부가 부드럽고 촉촉한 상태를 유지할 수 있도록 하는 것 등을 의미한다.As used herein, the term "moisturizing the skin" means to prevent skin moisture from evaporating out of the body and block excessive penetration of external substances, thereby maintaining moisture in the stratum corneum and preventing the skin from drying out or roughening the surface. , which means keeping the skin soft and moist.
본 명세서에서 사용된 용어 "피부 진정"은 홍반 또는 자극 받은 피부 부위 등을 완화시키고 가라앉히는 것을 의미한다.As used herein, the term "skin soothing" means to alleviate and soothe erythema or irritated skin areas and the like.
상기 "피부 홍반"이란 피부가 외적/내적 자극으로 인해 피부가 붉게 변하거나 혈관의 비정상적 확장, 또는 피부 조직 등에 피가 고여 발색한 홍반에서 전체, 또는 부분적으로 붉은 색이 띄는 현상을 의미한다. The term "skin erythema" refers to a phenomenon in which the skin turns red due to external/internal stimuli, abnormal expansion of blood vessels, or redness in whole or in part in erythema caused by accumulation of blood in skin tissue.
본 명세서에서 사용된 용어 "개선" 또는 "치료"는 개체에서 피부염 질환의 (a) 발전의 억제 (b) 경감 및 (c) 제거를 의미한다.As used herein, the term "improvement" or "treatment" refers to (a) inhibition of the development (b) alleviation and (c) elimination of a dermatitis disorder in a subject.
본 명세서에서 사용된 용어 "예방"은 질환 또는 질병을 보유하고 있다고 진단된 적은 없으나, 이러한 질환 또는 질병에 걸리기 쉬운 경향이 있는 개체에서 질환 또는 질병의 발생을 억제하는 것을 의미한다.As used herein, the term “prevention” refers to inhibiting the occurrence of a disease or condition in a subject who has not been diagnosed as having the disease or condition, but is predisposed to the disease or condition.
본 명세서에서 사용된 용어 "도포"는 어떠한 적절한 방법으로 개체의 피부에 본 발명에 따른 조성물을 접촉시키는 모든 방법을 의미하며, 이를 통해 해당 조성물을 피부 내부로 흡수시키는 것을 목적으로 한다.As used herein, the term "application" means any method of contacting the composition according to the present invention to the skin of an individual by any suitable method, and through this, the composition is absorbed into the skin.
제1구현예에 따르면, According to the first embodiment,
본 발명은 서열번호 1의 아미노산으로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 유효성분으로 포함하는 피부 보습 및 피부 진정용 화장료 조성물을 제공한다. The present invention provides a skin moisturizing and skin soothing cosmetic composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 as an active ingredient.
본 발명에 따른 iCP-NI 펩티드는 화장료 조성물 내 0.01 내지 10000 ppm의 농도로 함유되는 것이 바람직하고, 0.01 내지 1000ppm의 농도로 함유되는 것이 더욱 바람직하나 이에 한정되지 않는다. 상기 펩티드의 농도가 0.01ppm 미만이면 원하는 피부 보습 및 피부 진정효과를 얻기 어렵고, 10000ppm을 초과하면 함유량 증가에 따른 뚜렷한 효과의 증가가 나타나지 않아서 생산 경제성이 떨어지는 문제점이 있다.The iCP-NI peptide according to the present invention is preferably contained in a concentration of 0.01 to 10000 ppm in the cosmetic composition, more preferably in a concentration of 0.01 to 1000 ppm, but is not limited thereto. If the concentration of the peptide is less than 0.01ppm, it is difficult to obtain the desired skin moisturizing and skin soothing effects, and if it exceeds 10000ppm, there is a problem in that the production economy is poor because there is no significant increase in the effect due to the increase in the content.
본 발명에 따른 iCP-NI 펩티드는 일반적인 화학합성, 예를 들어 고체상 펩티드 합성기술(solid-phase peptide synthesis)에 의해 제조될 수 있고, 상기 펩티드를 코딩하는 핵산을 함유하는 재조합 벡터로 형질전환된 미생물을 배양하여 상기 펩티드를 발현시킨 다음, 통상의 방법으로 정제하여 제조할 수도 있으나, 이에 한정되지 않는다.The iCP-NI peptide according to the present invention can be prepared by general chemical synthesis, for example, solid-phase peptide synthesis, and a microorganism transformed with a recombinant vector containing a nucleic acid encoding the peptide. After expressing the peptide by culturing, it may be prepared by purification by a conventional method, but is not limited thereto.
본 발명에 따른 화장료 조성물은 상기 펩티드 외에 본 발명이 목적으로 하는 효과를 손상시키지 않는 범위 내에서, 바람직하게는 상기 펩티드의 효과에 상승 효과를 줄 수 있는 다른 성분 등을 추가로 함유할 수 있다. 예를 들면, 본 발명의 화장료 조성물은 피부 보습 및 피부 진정 효과가 알려져 있는 임의의 다른 물질들 뿐만 아니라, 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 또는 담체를 포함할 수 있다.In addition to the peptide, the cosmetic composition according to the present invention may further contain other ingredients that can give a synergistic effect to the effect of the present invention, preferably within a range that does not impair the effect intended by the present invention. For example, the cosmetic composition of the present invention may contain conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances, or carriers, as well as any other substances known to have skin moisturizing and skin soothing effects. can include
본 발명에 따른 화장료 조성물은 그 제형에 있어서 특별히 한정되지 않고, 본 기술분야에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들면, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있다. 다른 한편으로, 두피 트리트먼트제, 비누, 헤어토닉, 샴푸, 린스, 헤어팩, 헤어젤, 로션, 컨디셔너, 헤어오일, 무스, 크림, 고형제, 용액제, 유제, 분산제, 미셀, 리포좀, 연고제, 화장수, 에센스, 패취 또는 분무제의 제형으로 제조될 수도 있다.The cosmetic composition according to the present invention is not particularly limited in its formulation, and may be prepared in any formulation commonly prepared in the art, for example, a solution, suspension, emulsion, paste, gel, cream, It can be formulated into lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like. On the other hand, scalp treatment agents, soaps, hair tonics, shampoos, rinses, hair packs, hair gels, lotions, conditioners, hair oils, mousses, creams, solids, solutions, emulsions, dispersants, micelles, liposomes, ointments, It may be prepared in the form of lotion, essence, patch or spray.
상기 화장료 조성물의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있고, 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 디메틸에테르와 같은 추진체를 포함할 수 있다.When the formulation of the cosmetic composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier components In the case of a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane / propellants such as butane or dimethyl ether.
상기 화장료 조성물의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용될 수 있고, 예를 들어 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸아세테이트, 벤질알코올, 벤질벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the cosmetic composition is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent may be used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate , propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.
상기 화장료 조성물의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌글리콜과 같은 액상의 희석제, 에톡실화이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있으며, 계면활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the cosmetic composition is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester; Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanth may be used, and in the case of surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate as carrier components , imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters. can be used
본 발명의 구체적인 구현예에 따르면, 본 발명의 iCP-NI 펩티드는 생체 적합성이 뛰어나며, 피부 가려움 감소, 피부 수분량 및 유전율 증가, 경피수분손실량 감소, 자외선에 의한 피부 홍반 감소 및 피부 붉은기 개선 효과를 갖는다. 따라서, 본 발명의 iCP-NI 펩티드는 피부 보습 및 피부 진정을 위한 화장료 조성물의 유효성분으로서 유용하게 사용될 수 있다.According to a specific embodiment of the present invention, the iCP-NI peptide of the present invention has excellent biocompatibility, reduces skin itching, increases skin moisture content and permittivity, reduces transepidermal water loss, reduces skin erythema caused by ultraviolet rays, and improves skin redness. have Therefore, the iCP-NI peptide of the present invention can be usefully used as an active ingredient of a cosmetic composition for skin moisturizing and skin soothing.
제2구현예에 따르면, According to the second embodiment,
본 발명은 서열번호 1의 아미노산으로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 유효성분으로 포함하는 피부 보습 및 피부 진정용 약제학적 조성물을 제공한다. The present invention provides a pharmaceutical composition for skin moisturizing and skin soothing, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide composed of amino acids of SEQ ID NO: 1 as an active ingredient.
본 발명에 따른 약제학적 조성물은 피부, 구강, 정맥내, 근육내, 동맥내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장 투여가 포함되고, 경구 또는 비경구 투여가 바람직하나 이에 한정되지 않는다. 상기 비경구 투여는 피하, 피내, 정맥내, 근육내, 병소내 주사 또는 주입기술을 포함한다.The pharmaceutical composition according to the present invention includes dermal, buccal, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal administration, preferably oral or parenteral administration. However, it is not limited to this. The parenteral administration includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.
본 발명에 따른 약제학적 조성물은 본 발명에 따른 iCP-NI 펩티드에 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다. 상기 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the iCP-NI peptide according to the present invention. The composition may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively.
상기 약제학적 조성물의 경구투여를 위한 고형제제에는 산제, 과립제, 정제, 캡슐제, 연질캅셀제, 환 등이 포함된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제로는 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 멸균된 수용액, 액제, 비수성용제, 현탁제, 에멀젼, 시럽, 좌제, 에어로졸 등의 외용제 및 멸균 주사제제의 형태로 제형화하여 사용될 수 있으며, 바람직하게는 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제의 피부 외용 약학적 조성물을 제조하여 사용할 수 있으나, 이에 한정하는 것은 아니다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Solid preparations for oral administration of the pharmaceutical composition include powders, granules, tablets, capsules, soft capsules, pills, and the like. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Formulations for parenteral administration include powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc., and sterile injection preparations according to conventional methods, respectively. It can be formulated and used in the form of a cream, gel, patch, spray, ointment, warning, lotion, liniment, pasta, or cataplasma. , but is not limited thereto. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.
본 발명에 따른 약제학적 조성물은 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제, 및 기타 치료적으로 유용한 물질을 추가로 함유할 수 있으며, 통상적인 방법인 혼합, 과립화 또는 코팅 방법에 따라 제형화할 수 있다.The pharmaceutical composition according to the present invention may further contain adjuvants such as preservatives, stabilizers, hydration agents or emulsification accelerators, salts and/or buffers for osmotic pressure control, and other therapeutically useful substances. It can be formulated according to mixing, granulating or coating methods.
본 발명에 따른 약제학적 조성물은 개체의 연령, 체중, 일반적인 건강, 성별, 투여시간, 투여 경로, 배출률, 약물 배합 및 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있다.The pharmaceutical composition according to the present invention may vary depending on various factors including age, body weight, general health, sex, administration time, route of administration, excretion rate, drug combination, and severity of a specific disease.
본 발명에 따른 약제학적 조성물이 상기 iCP-NI 펩티드를 유효성분으로 함유하는 약제학적 조성물을 단위 용량 형태로 제형화하는 경우, 유효성분으로서 상기 iCP-NI 펩티드를 약 0.01 내지 1,500 ㎎의 단위용량으로 함유되는 것이 바람직하고, 성인 치료에 필요한 투여량은 투여의 빈도와 강도에 따라 하루에 약 1 내지 500 ㎎ 범위가 보통이나 이에 한정되지 않는다. 성인에게 근육 내 또는 정맥 내 투여 시 일 회 투여량으로는 하루에 보통 약 5 내지 300 ㎎의 전체 투여량이면 충분할 것이나, 일부 환자의 경우 더 높은 일일 투여량이 바람직할 수 있다. 본 발명의 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.When the pharmaceutical composition according to the present invention is formulated in a unit dose form containing the iCP-NI peptide as an active ingredient, the iCP-NI peptide as an active ingredient in a unit dose of about 0.01 to 1,500 mg It is preferable to contain, and the dosage required for adult treatment is usually in the range of about 1 to 500 mg per day depending on the frequency and strength of administration, but is not limited thereto. A total dose of about 5 to 300 mg per day will usually suffice for a single dose for intramuscular or intravenous administration to adults, although higher daily doses may be desirable in some patients. The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
제3구현예에 따르면, According to the third embodiment,
본 발명은 화장품학적 또는 약제학적으로 유효한 양의 서열번호 1의 아미노산으로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 개체에 처리 또는 투여하는 단계를 포함하는 피부 보습 및 피부 진정 방법을 제공한다.The present invention comprises the step of treating or administering an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 in a cosmetically or pharmaceutically effective amount to a subject. It provides a method for moisturizing and soothing the skin.
본 발명에 따른 방법에 있어서, 상기 화장품학적 또는 약제학적으로 유효한 양이란 0.0001 내지 100 ㎎/㎏이고, 바람직하게는 0.001 내지 10 ㎎/㎏이며, 이에 제한되는 것은 아니다. 처리 또는 투여량은 특정 환자의 체중, 연령, 성별, 건강상태, 식이, 투여기간, 투여방법, 제거율, 질환의 중증도 등에 따라 조절될 수 있다. 처리 또는 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 실시할 수도 있다.In the method according to the present invention, the cosmetically or pharmaceutically effective amount is 0.0001 to 100 mg/kg, preferably 0.001 to 10 mg/kg, but is not limited thereto. The treatment or dose may be adjusted according to the weight, age, sex, health condition, diet, administration period, administration method, removal rate, severity of disease, etc. of a specific patient. Treatment or administration may be administered once a day or divided into several times.
본 발명에 따른 방법에 있어서, 상기 개체는 척추동물이고 바람직하게는 포유동물이며, 보다 바람직하게는 인간 또는 쥐, 토끼, 기니아피그, 햄스터, 개, 고양이와 같은 실험동물이고, 가장 바람직하게는 인간일 수 있으나 이에 한정되는 것은 아니다.In the method according to the present invention, the subject is a vertebrate animal, preferably a mammal, more preferably a human or an experimental animal such as a rat, rabbit, guinea pig, hamster, dog, or cat, and most preferably a human It may be, but is not limited thereto.
본 발명에 따른 방법에 있어서, 상기 처리 또는 투여 방법은 도포, 경구 또는 비경구 투여할 수 있으며, 비경구 투여시 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사, 자궁내 경막 주사, 뇌혈관내 주사 또는 흉부내 주사에 의해 투여될 수 있다.In the method according to the present invention, the treatment or administration method may be applied, oral or parenteral administration, and in the case of parenteral administration, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine intrauterine injection It may be administered by injection, intracerebrovascular injection or intrathoracic injection.
이하, 실시예 및 실험예를 통하여 본 발명을 더욱 상세하게 설명한다. 다만, 하기 실시예 및 실험예는 본 발명을 예시하기 위한 것으로, 본 발명의 내용이 하기 실시예 및 실험예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples and experimental examples. However, the following Examples and Experimental Examples are intended to illustrate the present invention, and the contents of the present invention are not limited to the following Examples and Experimental Examples.
<제조예><Production Example>
1. 개선된 세포 투과성 핵 수송 억제제(iCP-NI)의 제조1. Preparation of an improved cell permeable nuclear transport inhibitor (iCP-NI)
본 발명에 따른 서열번호 1의 아미노산 서열로 이루어진 iCP-NI 펩티드는 서열번호 2의 아미노산으로 이루어진 aMTD(advanced macromolecule transduction domain) 및 서열번호 3의 아미노산으로 이루어진 NF-κ핵 위치 서열(NLS)을 이용하여 제조하였다(표 1). The iCP-NI peptide composed of the amino acid sequence of SEQ ID NO: 1 according to the present invention uses an advanced macromolecule transduction domain (aMTD) composed of amino acids of SEQ ID NO: 2 and an NF-κ nuclear localization sequence (NLS) composed of amino acids of SEQ ID NO: 3 was prepared (Table 1).
| 명칭designation | 서열order | SEQ No.SEQ No. |
| iCP-NIiCP-NI | IAAVLAAPALVPCVQRKRQKLMPCIAAVLAAPALVPCVQRKRQKLMPC | 서열번호 1SEQ ID NO: 1 |
| aMTDaMTD | IAAVLAAPALVPIAAVLAAPALVP | 서열번호 2SEQ ID NO: 2 |
| NLSNLS | CVQRKRQKLMPCCVQRKRQKLMPC | 서열번호 3SEQ ID NO: 3 |
2. iCP-NI 펩티드의 생체적합성에 대한 in-vitro 효능 평가2. In-vitro efficacy evaluation for biocompatibility of iCP-NI peptides
NHDF 세포를 24-well plate에 2.0×104cells/well의 농도로 접종하여 24시간 배양한 뒤, iCP-NI 펩티드 시료(최종농도가 1, 5, 10, 30 및 50 μM이 되도록 배지로 희석됨)가 포함된 serum-free FBM로 교환한 후 24시간 배양하였다. 배양 후 EZ-Cytox을 한 well당 50 μl씩 첨가하고 1시간 동안 더 배양하였다. 배양한 배지를 96well plate에 옮겨 담고 VERSA max microplate reader (Molecular devices, LCC., USA)를 사용하여 450nm에서 흡광도를 측정하였다. 각 시료군에 대한 평균 흡광도 값을 구하였으며, 대조군의 흡광도 값과 비교하여 세포 생존율을 조사하였다. 그 결과, 본 발명에 따른 iCP-NI 펩티드는 1 ~ 50 μM 농도 범위에서 대조군 대비 세포 독성이 없는 것으로 확인되었다(도 1).NHDF cells were inoculated into a 24-well plate at a concentration of 2.0×10 4 cells/well and cultured for 24 hours, followed by iCP-NI peptide samples (diluted with medium to final concentrations of 1, 5, 10, 30, and 50 μM). ) was exchanged with serum-free FBM and cultured for 24 hours. After incubation, 50 μl of EZ-Cytox was added per well and further incubated for 1 hour. The cultured medium was transferred to a 96-well plate and absorbance was measured at 450 nm using a VERSA max microplate reader (Molecular devices, LCC., USA). The average absorbance value for each sample group was obtained, and cell viability was investigated by comparing with the absorbance value of the control group. As a result, it was confirmed that the iCP-NI peptide according to the present invention was not cytotoxic compared to the control group in the concentration range of 1 to 50 μM (FIG. 1).
3. iCP-NI 펩티드를 포함하는 화장품의 제조3. Preparation of Cosmetics Containing the iCP-NI Peptide
본 발명의 iCP-NI 펩티드를 유효성분으로 함유하는 로션을 하기 표 2와 같이 제조하였다(함량: 중량부).A lotion containing the iCP-NI peptide of the present invention as an active ingredient was prepared as shown in Table 2 below (content: parts by weight).
| 구분division | 성분명ingredient name | 제형예formulation example | 비교예comparative example |
| 수상Awards | WATERWATER | To. 100To. 100 | To. 100To. 100 |
|
GLYCERIN |
55 | 55 | |
| 1,3-BUTYLENE GLYCOL1,3-BUTYLENE GLYCOL | 88 | 88 | |
| 1,2-Hexanediol1,2-Hexanediol | 22 | 22 | |
| EDTA-2NaEDTA-2Na | 0.020.02 | 0.020.02 | |
| AMMONIUM ACRYLOYLDIMETHYLTAURATE/VP COPOLYMERAMMONIUM ACRYLOYLDIMETHYLTAURATE/VP COPOLYMER | 0.50.5 | 0.50.5 | |
| 유상Paid | CETEARYL ALCOHOLCETEARYL ALCOHOL | 2.02.0 | 2.02.0 |
| PEG-100 STEARATEPEG-100 STEARATE | 1.51.5 | 1.51.5 | |
| GLYCERYL STEARATEGLYCERYL STEARATE | 0.70.7 | 0.70.7 | |
| BEESWAXBEESWAX | 1One | 1One | |
|
CETYLETHYLHEXANOATE |
55 | 55 | |
|
SQUALANE |
33 | 33 | |
| C14-22 ALCOHOLC14-22 ALCOHOL | 2.02.0 | 2.02.0 | |
|
POLYSORBATE 20 |
0.50.5 | 0.50.5 | |
| SOLBITAN ISOSTEARATESOLBITAN ISOSTEARATE | 1.21.2 | 1.21.2 | |
| C12-20 ALKYLGLUCOSIDEC12-20 ALKYLGLUCOSIDE | 0.50.5 | 0.50.5 | |
| CYCLOMETHICONECYCLOMETHICONE | 22 | 22 | |
| DIMETHICONEDIMETHICONE | 1One | 1One | |
| DIMETHICONOLDIMETHICONOL | 0.50.5 | 0.50.5 | |
| iCP-NI 상iCP-NI Award | WATERWATER | 1One | -- |
| iCP-NIiCP-NI | 0.010.01 | -- | |
| 첨가제상additive phase | FRAGRANCEFRAGRANCE | 적량Appropriate amount | 적량Appropriate amount |
<실험예> <Experimental example>
1. 본 발명에 따른 iCP-NI의 가려움증 완화 효능 평가1. Evaluation of itching relieving efficacy of iCP-NI according to the present invention
본 발명에 따른 iCP-NI의 기능성 검증을 위한 인체적용시험을 진행하였다. 얼굴 뺨 부위를 세안 후 항온항습(22±2°C, 50±5%) 조건에서 30분 이상 대기하여 충분히 피부 안정을 취한 다음 시험에 참여하였다. 시험제품 사용 전 후의 가려움 점수(Score), 뺨 부위의 피부 수분량(A.U.), 평균 유전율(ε경피수분손실량(g/m2h)을 측정하여 건조함에 의한 가려움 완화 효능을 평가하였다. A human application test was conducted to verify the functionality of the iCP-NI according to the present invention. After washing the cheeks of the face, wait for more than 30 minutes under constant temperature and humidity (22±2°C, 50±5%) conditions to sufficiently stabilize the skin before participating in the test. The itching score (Score) before and after using the test product, skin moisture content (A.U.), and average permittivity (ε transepidermal water loss (g/m2h)) were measured to evaluate the efficacy of relieving itchiness due to dryness.
(1) 가려움 점수(1) itch score
시험제품 사용 전과 2주 사용 후, 4주 사용 후에 시험대상자가 하기의 표 3에 따른 10점 척도의 가려움의 분류를 스스로 평가하도록 하여 점수의 평균을 계산하여 가려움의 개선 정도를 평가하였다.Before using the test product, after 2 weeks of use, and after 4 weeks of use, the test subjects were asked to self-evaluate the itching classification on a 10-point scale according to Table 3 below, and the average score was calculated to evaluate the degree of improvement in itching.
| 점수score | 가려움의 정도degree of itching |
| 0점0 points | 가려움이 없음no itching |
| 1점 이상 3점 미만More than 1 point and less than 3 points |
경증의 가려움(mild pruritus) |
| 3점 이상 7점 미만3 or more and less than 7 | 중등도의 가려움(moderate pruritus)Moderate pruritus |
| 7점 이상 9점 미만7 or more and less than 9 | 중증 가려움(severe pruritus)severe itching (severe pruritus) |
| 10점10 points | 매우 중증 가려움(very severe pruritus)very severe pruritus |
그 결과, 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물은 사용 전과 비교하여 2주 사용 후, 4주 사용 후 가려움 점수(Score)가 모두 유의하게 감소시키는 것으로 확인되었다. As a result, it was confirmed that the cosmetic composition containing the iCP-NI according to the present invention significantly decreased the itching score after 2 weeks and 4 weeks of use compared to before use.
| 구분division | 평균 ± 표준편차mean ± standard deviation | 개선율improvement rate | p-valuep-value | |
| 시험 부위test site | 시험전before exam | 4.95±1.764.95±1.76 | -- | <0.001<0.001 |
| 시험 2주 후2 weeks after exam | 2.73±1.702.73±1.70 | 44.95%44.95% | ||
| 시험 4주 후4 weeks after exam | 1.59±0.731.59±0.73 | 67.89%67.89% | ||
(2) 피부 수분량(A.U.)(2) Skin moisture content (A.U.)
Corneometer CM825 Probe (Courage+Khazaka GmbH, Germany)를 이용하여 피부 표면으로부터 10∼㎛ 이내의 각질층 전기용량(Capacitance)을 측정하여 피부 수분량을 평가하였다. 그 결과, 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물은 사용 전과 비교하여 2주 사용 후, 4주 사용 후 피부 수분량을 모두 유의하게 증가시키는 것으로 확인되었다. Corneometer CM825 Probe (Courage+Khazaka GmbH, Germany) was used to evaluate the skin moisture content by measuring the capacitance of the stratum corneum within 10 μm from the skin surface. As a result, it was confirmed that the cosmetic composition containing iCP-NI according to the present invention significantly increased skin moisture after 2 weeks and 4 weeks of use compared to before use.
| 구분division | 평균 ± 표준편차mean ± standard deviation | 개선율improvement rate | p-valuep-value | |
| 시험 부위test site | 시험전before exam | 27.00±2.2527.00±2.25 | -- | <0.001<0.001 |
| 시험 2주 후2 weeks after exam | 31.42±3.5931.42±3.59 | 16.37%16.37% | ||
| 시험 4주 후4 weeks after exam | 34.40±3.4634.40±3.46 | 27.42%27.42% | ||
(3) 평균 유전율 (3) average permittivity
Epsilon E100 (Biox Systems Ltd., England)은 50㎛ 특수 해상도를 가진 CMOS 지문 인식 센서를 이용하여 12.8mm*15mm 영역의 센서에 접촉된 피부 표면 수분량을 평균 유전율(ε값으로 산출하였다. 그 결과, 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물은 사용 전과 비교하여 2주 사용 후, 4주 사용 후 피부 유전율을 모두 유의하게 증가시키는 것으로 확인되었다. Epsilon E100 (Biox Systems Ltd., England) used a CMOS fingerprint recognition sensor with a special resolution of 50㎛ to calculate the average permittivity (ε value) of the moisture content of the skin surface in contact with the sensor in the area of 12.8mm*15mm. As a result, It was confirmed that the cosmetic composition containing iCP-NI according to the present invention significantly increased skin permittivity after 2 weeks and 4 weeks of use compared to before use.
| 구분division | 평균 ± 표준편차mean ± standard deviation | 개선율improvement rate | p-valuep-value | |
| 시험 부위test site | 시험전before exam | 18.99±5.9018.99±5.90 | -- | <0.001<0.001 |
| 시험 2주 후2 weeks after exam | 22.28±5.9022.28±5.90 | 17.31%17.31% | ||
| 시험 4주 후4 weeks after exam | 24.88±5.7624.88±5.76 | 31.01%31.01% | ||
(4) 경피수분손실량(4) Transepidermal water loss amount
Vapometer (Delfin Technologies Ltd., Finland)는 표피를 통한 수분의 손실 지표인 경피수분손실량 (TEWL, Transepidermal Water Loss)을 평가하였다. 그 결과, 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물은 사용 전과 비교하여 2주 사용 후, 4주 사용 후 피부 유전율을 모두 유의하게 감소시키는 것으로 확인되었다. Vapometer (Delfin Technologies Ltd., Finland) evaluated transepidermal water loss (TEWL), which is an indicator of water loss through the epidermis. As a result, it was confirmed that the cosmetic composition containing iCP-NI according to the present invention significantly reduced the skin dielectric constant after 2 weeks and 4 weeks of use compared to before use.
| 구분division | 평균 ± 표준편차mean ± standard deviation | 개선율improvement rate | p-valuep-value | |
| 시험 부위test site | 시험전before exam | 18.96±5.0518.96±5.05 | -- | <0.001<0.001 |
| 시험 2주 후2 weeks after exam | 16.86±4.5416.86±4.54 | 11.10%11.10% | ||
| 시험 4주 후4 weeks after exam | 15.47±4.7115.47±4.71 | 18.42%18.42% | ||
2. 본 발명에 따른 iCP-NI의 자외선 자극에 의한 피부 진정 효능 평가2. Evaluation of skin soothing efficacy of iCP-NI according to the present invention by ultraviolet stimulation
인체의 피부에 자외선을 통한 자극을 유도하고 이로 인해 형성된 홍반 부위에 iCP-NI (0.01%)를 도포한 후, 48 시간 뒤 무도포군과 비교하였다. 분광측색계 Spectrophotometer CM-26dG (Konica Minolta)를 이용하여 시험 부위의 a* value (붉은 기)를 측정하였다. 그 결과, 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물은 자외선으로부터 유도된 최소홍반정도 (minimum erythema degree, MED)을 48 시간 뒤 감소시키는 것으로 확인되었다(도 2). ICP-NI (0.01%) was applied to the erythema area formed by inducing stimulation through ultraviolet rays on the human skin, and 48 hours later, it was compared with the non-applied group. The a* value (red flag) of the test site was measured using a spectrophotometer CM-26dG (Konica Minolta). As a result, it was confirmed that the cosmetic composition containing iCP-NI according to the present invention reduced the minimum erythema degree (MED) induced by ultraviolet rays after 48 hours (FIG. 2).
3. 본 발명에 따른 iCP-NI의 피부 붉은기 개선 효능 평가3. Evaluation of skin redness improvement efficacy of iCP-NI according to the present invention
시험 대상자 20명을 대상으로 인체적용시험을 진행함. 얼굴 볼 부위를 세안 후 항온항습(22±2°C, 50±5%) 조건에서 30분 이상 대기하여 충분히 피부 안정을 취한 다음 시험에 참여하였다. 시험제품 사용 전과 4주 사용 후 VISIA-CR을 이용한 사진촬영 및 이미지 분석 프로그램을 이용한 볼 부위의 피부 붉은기 평가하였다. 그 결과, 본 발명에 따른 iCP-NI를 포함하는 화장료 조성물은 피부 붉은기를 사용 4주 후 약 42% 개선시키는 것으로 확인되었다 (도 3).A human application test was conducted on 20 test subjects. After washing the cheeks of the face, wait for more than 30 minutes under constant temperature and humidity (22±2°C, 50±5%) conditions to sufficiently stabilize the skin before participating in the test. Before and after 4 weeks of using the test product, pictures were taken using VISIA-CR and skin redness in the cheek area was evaluated using an image analysis program. As a result, it was confirmed that the cosmetic composition containing iCP-NI according to the present invention improved skin redness by about 42% after 4 weeks of use (FIG. 3).
본 발명의 iCP-NI 펩티드는 생체 적합성이 뛰어나며, 피부 가려움 감소, 피부 수분량 및 유전율 증가, 경피수분손실량 감소, 자외선에 의한 피부 홍반 감소 및 피부 붉은기 개선 효과를 갖는다. 따라서, 본 발명의 iCP-NI 펩티드는 피부 보습 및 피부 진정을 위한 화장료 조성물의 유효성분으로서 유용하게 사용될 수 있다.The iCP-NI peptide of the present invention has excellent biocompatibility, and has effects of reducing skin itching, increasing skin moisture content and permittivity, reducing transepidermal water loss, reducing skin erythema caused by ultraviolet rays, and improving skin redness. Therefore, the iCP-NI peptide of the present invention can be usefully used as an active ingredient of a cosmetic composition for skin moisturizing and skin soothing.
Claims (7)
- 서열번호 1로 표시되는 아미노산 서열로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 유효성분으로 포함하는 피부 보습 및 피부 진정용 화장료 조성물.A cosmetic composition for skin moisturizing and skin soothing, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 as an active ingredient.
- 제1항에 있어서,According to claim 1,상기 피부 진정은 피부 가려움증 감소, 피부 홍반 감성 및 피부 붉은기 개선을 포함하는 것을 특징으로 하는 것인, 화장료 조성물. The skin soothing is characterized in that it comprises reducing skin itching, improving skin erythema sensitivity and skin redness, the cosmetic composition.
- 제1항에 있어서,According to claim 1,상기 iCP-NI 펩티드는 화장료 조성물 내 0.01 내지 10000 ppm 의 농도로 함유되는 것을 특징으로 하는 것인, 화장료 조성물 The iCP-NI peptide is characterized in that it is contained in a concentration of 0.01 to 10000 ppm in the cosmetic composition, a cosmetic composition
- 제1항에 있어서,According to claim 1,상기 화장료 조성물의 제형은 화장수(스킨로션), 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양 로션, 마사지 크림, 영양 크림, 아이 크림, 모이스쳐 크림, 핸드크림, 파운데이션, 에센스, 영양 에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션 및 바디클렌저로 이루어진 군으로부터 하나 또는 그 이상 선택되는 것을 특징으로 하는 것인, 화장료 조성물. The formulation of the cosmetic composition is lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, eye cream, moisture cream, hand cream, foundation, essence, A cosmetic composition characterized in that one or more is selected from the group consisting of nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser.
- 서열번호 1로 표시되는 아미노산 서열로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 유효성분으로 포함하는 피부 보습 및 피부 진정용 피부 외용제.An external skin preparation for skin moisturizing and skin soothing, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 as an active ingredient.
- 제5항에 있어서, According to claim 5,상기 외용제의 제형은 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제로 이루어진 군으로부터 하나 또는 그 이상 선택되는 것을 특징으로 하는 것인, 피부 외용제. The formulation of the external preparation is characterized in that one or more selected from the group consisting of creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents, skin external preparations.
- 서열번호 1로 표시되는 아미노산 서열로 이루어진 개선된 세포 투과성 핵 수송 억제제(improved cell-permeable nuclear import inhibitor, iCP-NI) 펩티드를 개체에게 도포하는 단계를 포함하는 피부 보습 및 피부 진정 방법.A skin moisturizing and skin soothing method comprising the step of applying an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence represented by SEQ ID NO: 1 to a subject.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020247000047A KR20240019215A (en) | 2021-08-13 | 2022-08-16 | Cosmetic composition for skin moisturizing and skin soothing comprising an improved cell-permeable nuclear transport inhibitor |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163232766P | 2021-08-13 | 2021-08-13 | |
| US63/232,766 | 2021-08-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023018315A1 true WO2023018315A1 (en) | 2023-02-16 |
Family
ID=85200200
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2022/012186 WO2023018316A1 (en) | 2021-08-13 | 2022-08-16 | Cosmetic composition containing improved cell-permeable nuclear import inhibitor for preventing skin aging or reducing skin wrinkles |
| PCT/KR2022/012185 WO2023018315A1 (en) | 2021-08-13 | 2022-08-16 | Cosmetic composition for skin moisturizing and skin soothing comprising improved cell-permeable nuclear import inhibitor |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2022/012186 WO2023018316A1 (en) | 2021-08-13 | 2022-08-16 | Cosmetic composition containing improved cell-permeable nuclear import inhibitor for preventing skin aging or reducing skin wrinkles |
Country Status (2)
| Country | Link |
|---|---|
| KR (2) | KR20240019216A (en) |
| WO (2) | WO2023018316A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040235746A1 (en) * | 1994-06-13 | 2004-11-25 | Hawiger Jack J. | Cell permeable peptides for inhibition of inflammatory reactions and methods of use |
| US20140309159A1 (en) * | 2013-04-11 | 2014-10-16 | Vanderbilt University | Compositions and methods for targeting nuclear import shuttles and treating inflammatory disorders |
| WO2017026779A1 (en) * | 2015-08-10 | 2017-02-16 | Cellivery Therapeutics, Inc. | Improved cell-permeable cre (icp-cre) recombinant protein and use thereof |
| KR20170031243A (en) * | 2014-08-17 | 2017-03-20 | (주)셀리버리 | Advanced macromolecule transduction domain (amtd) sequences for improvement of cell-permeability, polynucleotides encoding the same, method to identify the unique features of amtds comprising the same, method to develop the amtd sequences comprising the same |
| WO2020056250A1 (en) * | 2018-09-14 | 2020-03-19 | Vanderbilt University | Methods and compositions for treating skin diseases |
-
2022
- 2022-08-16 KR KR1020247000048A patent/KR20240019216A/en unknown
- 2022-08-16 WO PCT/KR2022/012186 patent/WO2023018316A1/en active Application Filing
- 2022-08-16 WO PCT/KR2022/012185 patent/WO2023018315A1/en active Application Filing
- 2022-08-16 KR KR1020247000047A patent/KR20240019215A/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040235746A1 (en) * | 1994-06-13 | 2004-11-25 | Hawiger Jack J. | Cell permeable peptides for inhibition of inflammatory reactions and methods of use |
| US20140309159A1 (en) * | 2013-04-11 | 2014-10-16 | Vanderbilt University | Compositions and methods for targeting nuclear import shuttles and treating inflammatory disorders |
| KR20170031243A (en) * | 2014-08-17 | 2017-03-20 | (주)셀리버리 | Advanced macromolecule transduction domain (amtd) sequences for improvement of cell-permeability, polynucleotides encoding the same, method to identify the unique features of amtds comprising the same, method to develop the amtd sequences comprising the same |
| WO2017026779A1 (en) * | 2015-08-10 | 2017-02-16 | Cellivery Therapeutics, Inc. | Improved cell-permeable cre (icp-cre) recombinant protein and use thereof |
| WO2020056250A1 (en) * | 2018-09-14 | 2020-03-19 | Vanderbilt University | Methods and compositions for treating skin diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2023018316A1 (en) | 2023-02-16 |
| KR20240019215A (en) | 2024-02-14 |
| KR20240019216A (en) | 2024-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO1996014085A1 (en) | External preparation for skin protection | |
| NO341897B1 (en) | Preparation for the treatment and / or improvement of a skin disease | |
| TWI682782B (en) | Methods and compositions for topical delivery for skin care | |
| KR102140652B1 (en) | Composition Comprising Vitamin C | |
| EP1765278A1 (en) | Skin aging treatment comprising paeoniflorin | |
| WO2012002730A2 (en) | Skin-whitening and skin-moisturizing composition containing bee venom extracts | |
| WO2018174453A1 (en) | Composition containing cirsium japonicum extract as active ingredient for stimulating melanogenesis | |
| WO2019027132A1 (en) | Composition for preventing or treating scars | |
| JP2006327967A (en) | Skin care preparation containing flavonoid | |
| WO2018203668A1 (en) | External-use skin preparation composition for alleviating atopic skin, and cosmetic containing same | |
| WO2012020989A9 (en) | Pharmaceutical or cosmetic composition containing nicotinic acid adenine dinucleotide phosphate or derivative thereof | |
| WO2011053007A2 (en) | Composition for suppressing pore shrinkage or sebum secretion which comprises potentilla chinensis extract | |
| WO2012173382A2 (en) | Skin composition for external use containing tanshinone ii a as active ingredient | |
| WO2023018315A1 (en) | Cosmetic composition for skin moisturizing and skin soothing comprising improved cell-permeable nuclear import inhibitor | |
| KR20140055155A (en) | Salidroside improving skin aging or inflammation with protecting skin from external harmful materials such as ultraviolet ray etc | |
| KR100340185B1 (en) | Anti-wrinkle cosmetic composition containing PAECILOMYCES JAPONICA extract | |
| JP2006327965A (en) | Skin care preparation and application of the same | |
| WO2021145699A1 (en) | Composition for treating skin diseases, comprising colchicine | |
| WO2024136592A1 (en) | Skin improvement compositions containing carnitine salicylate (ca-sa) as active ingredient | |
| KR101550727B1 (en) | Composition containing polygalacic acid for improving skin aging and inflammation | |
| WO2023167537A1 (en) | Pharmaceutical composition for preventing or treating skin diseases caused by radiation irradiation comprising darapladib or pharmaceutically acceptable salt thereof as active ingredient | |
| KR20120075766A (en) | Composition for preventing hair loss or promoting hair growth | |
| WO2009082185A1 (en) | Skin-whitening agent containing platycodin d | |
| WO2020004696A1 (en) | Composition for skin moisturizing and skin soothing, containing plant extract | |
| WO2023090781A1 (en) | Composition for preventing and improving skin rosacea comprising isochlorogenic acid or salt thereof as active ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22856308 Country of ref document: EP Kind code of ref document: A1 |
|
| ENP | Entry into the national phase |
Ref document number: 20247000047 Country of ref document: KR Kind code of ref document: A |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1020247000047 Country of ref document: KR |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |