CN117157054A - 包含干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用组合物及其用途 - Google Patents
包含干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用组合物及其用途 Download PDFInfo
- Publication number
- CN117157054A CN117157054A CN202280028858.1A CN202280028858A CN117157054A CN 117157054 A CN117157054 A CN 117157054A CN 202280028858 A CN202280028858 A CN 202280028858A CN 117157054 A CN117157054 A CN 117157054A
- Authority
- CN
- China
- Prior art keywords
- stem cells
- urine
- composition
- exosomes
- derived stem
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000001808 exosome Anatomy 0.000 title claims abstract description 114
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 106
- 239000000203 mixture Substances 0.000 title claims abstract description 73
- 230000002087 whitening effect Effects 0.000 title claims abstract description 22
- 239000004480 active ingredient Substances 0.000 title claims abstract description 19
- 239000003963 antioxidant agent Substances 0.000 title claims abstract description 8
- 230000003078 antioxidant effect Effects 0.000 title claims abstract description 6
- 230000001172 regenerating effect Effects 0.000 title description 4
- 239000002537 cosmetic Substances 0.000 claims abstract description 33
- 206010052428 Wound Diseases 0.000 claims abstract description 26
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 230000036560 skin regeneration Effects 0.000 claims abstract description 14
- 230000003064 anti-oxidating effect Effects 0.000 claims abstract description 12
- 210000002700 urine Anatomy 0.000 claims description 63
- 238000012258 culturing Methods 0.000 claims description 27
- 239000001963 growth medium Substances 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 23
- 239000006210 lotion Substances 0.000 claims description 21
- 150000002632 lipids Chemical class 0.000 claims description 20
- 239000013028 medium composition Substances 0.000 claims description 18
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 claims description 14
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims description 13
- 239000007640 basal medium Substances 0.000 claims description 13
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 11
- -1 astringent Substances 0.000 claims description 11
- 241000283690 Bos taurus Species 0.000 claims description 10
- 229940098773 bovine serum albumin Drugs 0.000 claims description 10
- 239000006071 cream Substances 0.000 claims description 10
- 210000002966 serum Anatomy 0.000 claims description 10
- 102000004042 Fibroblast Growth Factor-23 Human genes 0.000 claims description 9
- 108090000569 Fibroblast Growth Factor-23 Proteins 0.000 claims description 9
- 230000002485 urinary effect Effects 0.000 claims description 9
- 239000000839 emulsion Substances 0.000 claims description 8
- 230000001605 fetal effect Effects 0.000 claims description 8
- 102000055006 Calcitonin Human genes 0.000 claims description 7
- 108060001064 Calcitonin Proteins 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 7
- 238000002266 amputation Methods 0.000 claims description 7
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 7
- 229960004015 calcitonin Drugs 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 208000034656 Contusions Diseases 0.000 claims description 6
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims description 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 6
- 208000034693 Laceration Diseases 0.000 claims description 6
- 230000009519 contusion Effects 0.000 claims description 6
- 230000001815 facial effect Effects 0.000 claims description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 6
- 235000016709 nutrition Nutrition 0.000 claims description 6
- 230000035764 nutrition Effects 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 208000002847 Surgical Wound Diseases 0.000 claims description 5
- 229940035722 triiodothyronine Drugs 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003995 emulsifying agent Substances 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- MIJPAVRNWPDMOR-ZAFYKAAXSA-N L-ascorbic acid 2-phosphate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OP(O)(O)=O)=C1O MIJPAVRNWPDMOR-ZAFYKAAXSA-N 0.000 claims description 3
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 3
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 claims description 3
- 229960005084 calcitriol Drugs 0.000 claims description 3
- 235000020964 calcitriol Nutrition 0.000 claims description 3
- 239000011612 calcitriol Substances 0.000 claims description 3
- 239000000686 essence Substances 0.000 claims description 3
- 229960000890 hydrocortisone Drugs 0.000 claims description 3
- 230000003020 moisturizing effect Effects 0.000 claims description 3
- 229930002330 retinoic acid Natural products 0.000 claims description 3
- 229960001727 tretinoin Drugs 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000344 soap Substances 0.000 claims description 2
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 claims 3
- 101001051973 Homo sapiens Fibroblast growth factor 23 Proteins 0.000 claims 3
- 210000001161 mammalian embryo Anatomy 0.000 claims 2
- 239000000523 sample Substances 0.000 claims 2
- 239000008269 hand cream Substances 0.000 claims 1
- 230000003716 rejuvenation Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 43
- 230000000694 effects Effects 0.000 description 21
- 108010035532 Collagen Proteins 0.000 description 19
- 102000008186 Collagen Human genes 0.000 description 17
- 229920001436 collagen Polymers 0.000 description 17
- 210000001626 skin fibroblast Anatomy 0.000 description 17
- 235000019197 fats Nutrition 0.000 description 13
- 210000003491 skin Anatomy 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 12
- 239000002609 medium Substances 0.000 description 11
- 102000003425 Tyrosinase Human genes 0.000 description 10
- 108060008724 Tyrosinase Proteins 0.000 description 10
- 210000002510 keratinocyte Anatomy 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 235000013305 food Nutrition 0.000 description 9
- 230000005012 migration Effects 0.000 description 9
- 238000013508 migration Methods 0.000 description 9
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 8
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 8
- 229940126864 fibroblast growth factor Drugs 0.000 description 8
- 239000013642 negative control Substances 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000005299 abrasion Methods 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 239000012679 serum free medium Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000006143 cell culture medium Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 230000009759 skin aging Effects 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000037303 wrinkles Effects 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 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 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 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
- 239000011230 binding agent Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000004088 foaming agent Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- JWUBBDSIWDLEOM-UHFFFAOYSA-N 25-Hydroxycholecalciferol Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CCC1=C JWUBBDSIWDLEOM-UHFFFAOYSA-N 0.000 description 1
- MOMKYJPSVWEWPM-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-methylphenyl)-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=NC(CCl)=CS1 MOMKYJPSVWEWPM-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102100025222 CD63 antigen Human genes 0.000 description 1
- 102100027221 CD81 antigen Human genes 0.000 description 1
- 235000021318 Calcifediol Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 240000006432 Carica papaya Species 0.000 description 1
- 235000009467 Carica papaya Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 235000001809 DL-alpha-tocopherylacetate Nutrition 0.000 description 1
- 239000011626 DL-alpha-tocopherylacetate Substances 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 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
- QZKRHPLGUJDVAR-UHFFFAOYSA-K EDTA trisodium salt Chemical compound [Na+].[Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O QZKRHPLGUJDVAR-UHFFFAOYSA-K 0.000 description 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 101150112014 Gapdh gene Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 1
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 1
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- MLSJBGYKDYSOAE-DCWMUDTNSA-N L-Ascorbic acid-2-glucoside Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1O MLSJBGYKDYSOAE-DCWMUDTNSA-N 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000021319 Palmitoleic acid Nutrition 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 229960000271 arbutin Drugs 0.000 description 1
- 229940067599 ascorbyl glucoside Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000012754 barrier agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- JWUBBDSIWDLEOM-DTOXIADCSA-N calcidiol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)CCC1=C JWUBBDSIWDLEOM-DTOXIADCSA-N 0.000 description 1
- 229960004361 calcifediol Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 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
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 229940117373 dl-alpha tocopheryl acetate Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000019305 fibroblast migration Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- LBQIJVLKGVZRIW-ZDUSSCGKSA-N glabridin Chemical compound C1([C@H]2CC3=CC=C4OC(C=CC4=C3OC2)(C)C)=CC=C(O)C=C1O LBQIJVLKGVZRIW-ZDUSSCGKSA-N 0.000 description 1
- 229940093767 glabridin Drugs 0.000 description 1
- PMPYOYXFIHXBJI-ZDUSSCGKSA-N glabridin Natural products C1([C@H]2CC=3C=CC4=C(C=3OC2)CCC(O4)(C)C)=CC=C(O)C=C1O PMPYOYXFIHXBJI-ZDUSSCGKSA-N 0.000 description 1
- LBQIJVLKGVZRIW-UHFFFAOYSA-N glabridine Natural products C1OC2=C3C=CC(C)(C)OC3=CC=C2CC1C1=CC=C(O)C=C1O LBQIJVLKGVZRIW-UHFFFAOYSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000035990 intercellular signaling Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
- 229960004705 kojic acid Drugs 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940078752 magnesium ascorbyl phosphate Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-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
- 230000017074 necrotic cell death Effects 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 229940056211 paraffin Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 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
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 238000013424 sirius red staining Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000019983 sodium metaphosphate Nutrition 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- HTJNEBVCZXHBNJ-XCTPRCOBSA-H trimagnesium;(2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;diphosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O HTJNEBVCZXHBNJ-XCTPRCOBSA-H 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 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
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/22—Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- 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
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0607—Non-embryonic pluripotent stem cells, e.g. MASC
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Birds (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Cosmetics (AREA)
Abstract
本发明涉及一种包含皮肤再生、美白或者抗氧化功能提高的干细胞来源的外泌体作为有效成分的组合物。更具体地,本发明涉及一种包含尿源干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用化妆品组合物或者药物组合物。
Description
技术领域
本发明涉及一种包含皮肤再生、美白或抗氧化功能提高的干细胞来源的外泌体作为有效成分的组合物。更具体地,本发明涉及一种作为有效成分包含尿源干细胞来源的外泌体的皮肤再生、美白、抗氧化或治疗伤口用化妆品组合物或药物组合物。
背景技术
尿源干细胞是能够通过简单分离过程从人体尿液中获得干细胞的新干细胞源,与其他间叶干细胞相比,完全不会诱发患者疼痛和后遗症,且可以多次获得干细胞,因此与现有的细胞源相比能够获得更多初期培养所需的干细胞数量。另外,尿源干细胞增殖率高,短期内能够获得较多细胞数,因此商用化可能性高,HLA-DR的表达低,可以用作体内移植时不会诱发免疫反应的自体细胞治疗剂,因此具有非常容易接近临床的优点。此外,尿源干细胞在适宜的培养环境下分泌包括各种生长因子在内的细胞因子等,其治疗潜力得到了认可。
最近有研究报道,细胞分泌的分泌物(Secretome)中包含调节细胞活动的生物活性因子。外泌体(Exosome)是从细胞中分泌的30~150nm大小的纳米内质网[1,2]。已知外泌体包括mRNA、miRNA等遗传物质和细胞因子等蛋白质运输物质,根据细胞类型不同,根据分泌的环境进行不同的调节。外泌体作为细胞间信号传输介质,通过其传输的各种细胞信号调节靶细胞的激活、生长、迁移、分化、去分化、死亡、坏死等。另外,外泌体根据细胞来源的性质和状态包含特异性遗传物质和生物活性因子。尤其是干细胞外泌体根据干细胞的特性,含有与干细胞的细胞增殖、分化、再生相关的基因、蛋白质、生长因子等,在组织再生中起着重要作用[3,4,5]。
最近,随着老龄化人口的增加和多种皮肤美容技术的增加,消费者对改善皮肤老化的需求日益提高。另外,随着对干细胞外泌体的研究活跃进行,开发安全、功效优秀的功能性外泌体化妆品是化妆品行业主要关注的课题。干细胞外泌体能够用作改善皮肤老化现象的抗老化化妆品原料,对此的研究正活跃进行。
因此,本发明人等通过有效地分离和纯化尿源干细胞增殖时分泌的外泌体,并证明尿源干细胞外泌体的伤口再生、改善皱纹、皮肤美白等功效,开发对人体无副作用、功效优秀的新功能性化妆品。
现有文件
非专利文献1:S,E.L.A.,Mager,I.,Breakefield,X.O.&Wood,M.J.Extracellularvesicles:biology and emerging therapeutic opportunities.Nature reviews.Drugdiscovery 2013.12,347-357.
非专利文献2:Sahoo,S.et al.Exosomes from human CD34(+)stem cellsmediate their proangiogenic paracrine activity.Circulation research,2011.109,724-728.
非专利文献3:Schorey,J.S.&Bhatnagar,S.Exosome function:from tumorimmunology to pathogen biology.Traffic,2008,9,871-881.
非专利文献4:Thery,C.,Zitvogel,L.&Amigorena,S.Exosomes:composition,biogenesis and function.Nature reviews.Immunology,2002.2,569-579.
非专利文献5:Vishnubhatla,I.,Corteling,R.,Stevanato,L.,Hicks,C.&Sinden,J.The Development of Stem Cell-derived Exosomes as a Cell-freeRegenerative Medicine.Journal of Circulating Biomarkers,2014.1.
发明内容
技术课题
本发明人等在韩国专利申请第10-2019-0139702号中公开了用于培养尿源干细胞的培养基组合物以及利用其培养尿源干细胞的方法。本发明人等在持续进行对所述尿源干细胞的研究的过程中,发现尿源干细胞中分泌的外泌体具有伤口再生、改善皱纹、皮肤美白等改善皮肤老化功效,并完成了本发明。
解决课题方法
本发明的目的在于提供一种包含尿源干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用化妆品组合物。
本发明的另一目的在于提供一种包含尿源干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用药物组合物。
本发明又一目的在于提供一种包含尿源干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用食品组合物。
本发明又一目的在于提供一种用于皮肤再生、美白、抗氧化或治疗伤口的尿源干细胞来源的外泌体的制备方法。
本说明书中使用的术语“干细胞”是指能够分化成个体的所有组织细胞的具有多能性(pluripotent)或全能性(totipotent)的自我再生能力(self-renewal)的细胞,包括胚胎干细胞、诱导多功能干细胞以及成体干细胞。
本说明书中使用的术语干细胞的“增殖”是指干细胞不分化成具体的细胞,而是维持干细胞的特性直接进行细胞分裂,从而细胞总数增加。
本说明书中使用的术语“培养液”是指包含在体外(in vitro)维持细胞生长和存活所需的营养物质的组合物。
本说明书中使用的术语“细胞治疗剂”是指由个体通过分离、培养及特殊操作制备的细胞和组织,用于治疗、诊断和预防目的的药品,是指为了恢复细胞或组织的功能,通过体外增殖筛选自体、同种或异种细胞或通过其他方式改变细胞的生物学特性等的一系列行为,将这些细胞用于治疗、诊断和预防疾病的药品。
本说明书中使用的术语“外泌体”是指由细胞分泌,包括mRNA、miRNA等遗传物质和细胞因子等蛋白质运载物质的30~150nm大小的纳米内质网。
发明效果
本发明的包含尿源干细胞来源的外泌体作为有效成分的组合物无细胞毒性,且安全(实施例3),具有优秀的细胞增殖率(实施例4),具有治疗伤口(实施例5)、改善皮肤皱纹(实施例6)以及皮肤美白(实施例8)的效果。因此,本发明的包含尿源干细胞来源的外泌体作为有效成分的组合物有望作为皮肤再生、美白、抗氧化或治疗伤口用化妆品组合物、药物组合物以及食品组合物使用。
附图说明
图1表示根据实施例1通过TFF方法分离的外泌体内蛋白质的浓度。
图2表示根据实施例1分离的外泌体的颗粒大小。
图3表示根据实施例1分离的外泌体内存在的标记物。
图4表示根据实施例1分离的外泌体的细胞毒性。
图5表示根据实施例1分离的外泌体的细胞增殖率。
图6表示根据实施例1分离的外泌体对人皮肤成纤维细胞以及人角质形成细胞的迁移的影响效果。
图7表示根据实施例1分离的外泌体的改善皱纹效果。
图8表示根据实施例1分离的外泌体的美白效果。
具体实施方式
根据第一实施方案,本发明提供一种作为有效成分包含尿源干细胞来源的外泌体的皮肤再生、美白、抗氧化或治疗伤口用化妆品组合物。
本发明的化妆品组合物中,所述外泌体能够在培养尿源干细胞的过程中分离和纯化,用于培养所述尿源干细胞的培养基组合物如本发明人等的韩国专利申请第10-2019-0139702号所记载。例如,用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基(Dulbecco's Modified Eagle's Medium,DMEM)和哈姆F-12(Ham's F12)的基础培养基、2.5%以下的牛胎血清以及添加剂,所述添加剂为选自由牛血清白蛋白、脂质混合物(chemically defined lipids)、成纤维细胞成长因子23(fibroblast growth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol)组成的组中的一种以上。优选地,用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’sF12)的基础培养基、2.5%以下的牛胎血清、牛血清白蛋白、脂质混合物(chemicallydefined lipids)、成纤维细胞成长因子23(fibroblast growth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol),或者以上成分组成。用于从所述尿源干细胞中提取外泌体的培养基组合物是无血清、无抗生素培养基组合物。所述无血清、无抗生素培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’s F12)的基础培养基、成纤维细胞生长因子2(FGF2)、皮质醇、三碘甲状腺原氨酸(triiodothyronine,T3)、骨化三醇、胰岛素-转铁蛋白-硒-乙醇胺、L-抗坏血酸-2-磷酸酯以及视黄酸,或者以上成分组成。
本发明的化妆品组合物中,所述尿源干细胞来源于自体、异体或者异种。
本发明的化妆品组合物中,所述伤口包括割伤(cut)、切口(incisions)(例如,手术切口)、擦伤(abrasions)、撕裂伤或者撕裂(lacerations)、骨折(fracture)、挫伤(contusions)、烧伤(burns)或者截肢(amputations)。
本发明的化妆品组合物中,所述化妆品组合物除所述有效成分外,包括通常用于化妆品组合物的成分,包括例如脂肪物质、有机溶剂、溶解剂、浓缩剂和凝胶化剂、软化剂、抗氧化剂、悬浮剂、稳定剂、发泡剂(foaming agent)、芳香剂、表面活性剂、水、离子型或非离子型乳化液、填充剂、金属离子封锁剂和螯合剂、保存剂、维生素、阻隔剂、润湿剂、必需油类、染料、颜料、亲水性或亲油性活性剂、脂质囊等通常助剂以及载体。
本发明的化妆品组合物中,所述化妆品组合物在本领域中可制备成通常制备的任何剂型,可制备成例如溶液、悬浮液、乳浊液、膏状物、凝胶、霜、乳液、粉末、油、粉末粉底液、乳浊液粉底液、蜡粉底液、喷雾等,但不限于此。更详细而言,可制备成爽肤水、柔肤水、护肤水、收敛剂、乳液、润肤乳、保湿乳、营养乳、按摩霜、营养霜、眼霜、保湿霜、护手霜、精华液、营养精华液、面膜、洗面奶、卸妆水、卸妆乳、洁面霜、身体乳、沐浴露、皂以及粉末的化妆品剂型。
所述化妆品组合物的剂型为膏状物、霜或者凝胶的情况下,作为载体成分可使用动物油、植物油、蜡、石蜡、淀粉、黄蓍胶、纤维素衍生物、聚乙二醇、硅、膨润土、二氧化硅、滑石或氧化锌等。
所述化妆品组合物的剂型为粉末或喷雾的情况下,作为载体成分可使用乳糖、滑石、二氧化硅、氢氧化铝、硅酸钙或聚酰胺粉末,尤其是在喷雾的情况下,可以进一步包括氟氯烃(chlorofluoro hydrocarbon)、丙烷/丁烷或二甲醚等推进剂。
所述化妆品组合物的剂型为溶液或者乳浊液的情况下,作为载体成分,使用溶剂、溶解剂或者乳浊剂,包括例如水、乙醇、异丙醇、碳酸乙酯、乙酸乙酯、苄醇、苯甲酸苄酯、丙二醇、1,3-丁二醇油、甘油脂肪族酯、聚乙二醇或山梨糖醇的脂肪酸酯。
所述化妆品组合物的剂型为悬浮液的情况下,作为载体成分,可使用水、乙醇或者丙二醇等液体稀释剂,乙氧基化异硬脂醇、聚氧乙烯山梨醇酯、聚氧乙烯山梨糖醇酯等悬浮剂、微晶纤维素、偏氢氧化铝(aluminum metahydroxide)、膨润土、琼脂或黄蓍胶等。
根据第二实施方案,本发明还提供一种包含尿源干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用药物组合物。
本发明的药物组合物中,所述外泌体能够在培养尿源干细胞的过程中分离和纯化,用于培养所述尿源干细胞的培养基组合物如本发明人等的韩国专利申请第10-2019-0139702号所记载。例如,用于培养所述尿源干细胞的培养基组合物的特征为,包括以3:1的比例包含杜尔贝科改良伊格尔培养基(Dulbecco's Modified Eagle's Medium,DMEM)和哈姆F-12(Ham's F12)的基础培养基、2.5%以下的牛胎血清以及添加剂,所述添加剂为选自由牛血清白蛋白、脂质混合物(chemically defined lipids)、成纤维细胞成长因子23(fibroblast growth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol)组成的组中的一种以上。优选地,用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’sF12)的基础培养基、2.5%以下的牛胎血清、牛血清白蛋白、脂质混合物(chemicallydefined lipids)、成纤维细胞成长因子(fibroblast growth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol),或者以上成分组成。
本发明的药物组合物中,所述尿源干细胞来源于自体、异体或者异种。
本发明的药物组合物中,所述伤口包括割伤(cut)、切口(incisions)(例如,手术切口)、擦伤(abrasions)、撕裂伤或者撕裂(lacerations)、骨折(fracture)、挫伤(contusions)、烧伤(burns)或者截肢(amputations)。
本发明的药物组合物中,所述药物组合物可包括药剂学上可接受的稀释剂或者载体。所述稀释剂可以是乳糖、玉米淀粉、大豆油、微晶纤维素或者甘露醇,润滑剂可以是硬脂酸镁、滑石、或者其组合。所述载体可以是赋形剂、崩解剂、结合剂、润滑剂或其组合。所述赋形剂可以是微晶纤维素、乳糖、低取代度羟基纤维素或其组合。所述崩解剂可以是羧甲基纤维素钙、羟基乙酸淀粉钠、无水磷酸氢钙或其组合。所述结合剂可以是聚乙烯吡咯烷酮、低取代度羟丙基纤维素、羟丙基纤维素或其组合。所述润滑剂可以是硬脂酸镁、二氧化硅、滑石或其组合。
本发明的药物组合物中,所述药物组合物可以制备成非口服给药剂型。非口服给药剂型可以是注射剂或者皮肤外用剂。皮肤外用剂可以是霜、凝胶、软膏、皮肤乳化剂、皮肤悬浮液、透皮贴剂、面膜、含药物绷带、乳液、或者其组合。所述皮肤外用剂可根据通常用于化妆品或药品等皮肤外用剂的成分,例如水性成分、油性成分、粉末成分、醇类、保湿剂、增稠剂、紫外线吸收剂、美白剂、防腐剂、抗氧化剂、表面活性剂、香料、色素、各种皮肤营养剂、或其组合和需要适当地配制。所述皮肤外用剂也可以适当地配制乙二胺四乙酸二钠、乙二胺四乙酸三钠、柠檬酸钠、聚磷酸钠、偏磷酸钠、葡萄糖酸等螯合剂、咖啡因、单宁、维拉帕米、甘草提取物、光甘草定、木瓜的果实的热水提取物、各种生药、生育酚乙酸酯、甘草酸、氨甲环酸及其衍生物或其盐等药剂、维生素C、抗坏血酸磷酸镁、抗坏血酸葡萄糖苷、熊果苷、曲酸、葡萄糖、果糖、海藻糖等糖类。
根据第三实施方案,本发明还提供一种包含尿源干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或者伤口的预防或缓解用食品组合物。
本发明的食品组合物中,所述外泌体能够在培养尿源干细胞的过程中分离和纯化,用于培养所述尿源干细胞的培养基组合物如本发明人等的韩国专利申请第10-2019-0139702号所记载。例如,用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’s F12)的基础培养基、2.5%以下的牛胎血清以及添加剂,所述添加剂选自由牛血清白蛋白、脂质混合物(chemically definedlipids)、成纤维细胞成长因子23(fibroblast growth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol)组成的组中的一种以上。优选地,用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’s F12)的基础培养基、2.5%以下的牛胎血清、牛血清白蛋白、脂质混合物(chemically defined lipids)、成纤维细胞成长因子23(fibroblastgrowth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol),或者以上成分组成。
本发明的食品组合物中,所述尿源干细胞来源于自体、异体或者异种。
本发明的食品组合物中,所述伤口包括割伤(cut)、切口(incisions)(例如,手术切口)、擦伤(abrasions)、撕裂伤或者撕裂(lacerations)、骨折(fracture)、挫伤(contusions)、烧伤(burns)或者截肢(amputations)。
本发明的食品组合物除所述有效成分外,还可包括甜味剂、风味剂、生理活性成分、矿物质等。
本发明的食品组合物根据需要可包括保存剂、乳化剂、酸味剂、增稠剂等。优选这些保存剂、乳化剂等以可实现其添加用途的极微量添加使用。极微量是指从数值上表示,以食品组合物的总重量为基准的0.0005重量%~约0.5重量%的范围。
根据第四实施方案,本发明提供一种用于皮肤再生、美白、抗氧化或治疗伤口的尿源干细胞来源的外泌体的制备方法,所述方法包括:
在包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’sF12)的基础培养基、2.5%以下的牛胎血清以及添加剂的培养基组合物中培养尿源干细胞的步骤;以及
在无血清、无抗生素培养基组合物中培养所培养的所述尿源干细胞并提取外泌体的步骤。
本发明的方法的特征为,所述添加剂包括牛血清白蛋白、脂质混合物(chemicallydefined lipids)、成纤维细胞成长因子23(fibroblast growth factor 23,FGF23)、三碘甲状腺原氨酸(triiodothyronine,T3)以及骨化二醇(calcifediol),或者以上成分组成。
本发明的方法中,所述无血清和无抗生素培养液包括以3:1的比例包含杜尔贝科改良伊格尔培养基(DMEM)和哈姆F-12(Ham’s F12)的基础培养基、成纤维细胞生长因子2(FGF2)、皮质醇、三碘甲状腺原氨酸(triiodothyronine,T3)、骨化三醇、胰岛素-转铁蛋白-硒-乙醇胺、L-抗坏血酸-2-磷酸酯以及视黄酸,或者以上成分组成。
以下,参照实施例和试验例,对本发明进行更详细的说明。但是,这些实施例和试验例用于例示本发明,本发明并非由这些实施例和试验例所限定。
<实施例>
实施例1.由人体尿源干细胞提取外泌体
将人体尿源干细胞传代(passage)培养至2至7代之后,更换为用于提取外泌体的无血清、无抗生素培养基后提取外泌体。具体地,本发明人等通过韩国专利申请第10-2019-0139702号的用于培养尿源干细胞的培养基组合物专利中公开的用于培养尿源干细胞的培养基组合物(参照以下的表1和表2),对人体尿源干细胞进行传代培养2代至7代后,更换为用于提取外泌体的无血清、无抗生素培养基(参照以下的表3),并培养24小时至96小时。
[表1]
[表2]
脂质混合物 | 浓度 |
花生四烯酸 | 2-20ng/ml |
胆固醇 | 220-2200ng/ml |
DL-α-生育酚乙酸酯 | 70-700ng/ml |
亚油酸 | 10-100ng/ml |
肉豆蔻酸 | 10-100ng/ml |
油酸 | 10-100ng/ml |
棕榈酸 | 10-100ng/ml |
棕榈油酸 | 10-100ng/ml |
嵌段式聚醚F-68(Pluronic F-68) | 90-900μg/ml |
硬脂酸 | 10-100ng/ml |
吐温80 | 2.2-22μg/ml |
[表3]
之后,回收细胞培养上清液,以300xg至500xg离心分离5分钟至15分钟以去除细胞,然后以12000xg至20000xg高速离心分离30分钟至60分钟以去除细胞残留物。之后,对于去除了细胞和细胞残留物的培养液,使用0.22μm过滤器进行过滤、或者使用具有500kDa至1000kDa的MWCO的TFF过滤器进行过滤以获得其过滤物,从而去除100nm至300nm以上大小的物质。之后,为了分离外泌体,使用具有30kDa至100kDa的MWCO的TFF过滤器进行过滤以获得其浓缩物,从而去除10nm至30nm以下大小的物质。进行所述过滤步骤,直到浓缩物体积浓缩至1/50至1/100体积。使用磷酸盐缓冲液(PBS)清洗所浓缩的外泌体。此时,以浓缩物体积的10倍至20倍体积添加PBS,并使用TFF过滤器进行浓缩。所述清洗过程进行了1次至10次。使用通过所述过程分离和纯化的外泌体来制备化妆品组合物,并用于以下试验。为了比较人体尿源干细胞外泌体的功效,作为对照组,从人体脂肪源干细胞中提取外泌体,通过与上述方法相同的方法提取外泌体。
实施例2.分离的外泌体的特性分析(BCA定量、NTA、Exo-check)
利用BCA显色法(赛默飞世尔科技,ThermoFisher Scientific)测定从所述实施例1的人体尿源干细胞中提取的外泌体(UD-exo)和作为对照组从脂肪源干细胞中提取的外泌体(AD-exo)的蛋白质的量。通过TFF方法分离、浓缩外泌体,采用蛋白质定量法测定蛋白质、脂质、核酸、小分子化合物等被去除的程度。其结果显示,通过实施例1的TFF方法非常有效地去除培养液中存在的蛋白质(图1)。
对于通过实施例1的方法分离的外泌体的颗粒大小,使用纳米颗粒跟踪分析(nanoparticle tracking analysis,NTA)重复5次测定。其结果显示,分离的外泌体大小分布均匀(图2)。
另外,对通过实施例1的方法分离的外泌体,使用Exo-check(系统生物学,systembioscience)试剂盒进行外泌体标记物分析。其结果显示,CD63、CD81和EpCAM标记物存在于所分离的外泌体中(图3)。
实施例3.基于外泌体处理的细胞毒性测定
为了评估通过所述实施例1的分离方法获得的外泌体的毒性,对人皮肤成纤维细胞和人角质形成细胞以不同浓度处理外泌体并确认细胞毒性。将人皮肤成纤维细胞和人角质形成细胞悬浮在含有10%FBS的DMEM中,然后以具有80%至90%的密集度的方式进行分注,并在37℃、5%CO2培养箱中培养24小时。24小时后,去除培养液,将不含FBS的DMEM分注之后,分别以不同浓度处理从实施例1准备的人体尿源干细胞中提取的外泌体和作为对照组从人体脂肪源干细胞提取的外泌体,培养24小时至48小时,并评估细胞存活率。细胞存活率采用CCK-8(细胞计数试剂盒-8,cat#CK04-11)、MTT(abcam,cat#ab211091)和酶标仪进行测定。
其结果显示,以未经外泌体处理的DMEM中培养相同时间的细胞组为基准,在试验的浓度范围内未出现从人体尿源干细胞中提取的外泌体和从人体脂肪源干细胞中提取的外泌体引起的细胞毒性(图4)。
实施例4.基于外泌体处理的细胞增殖率测定
为了评估通过所述实施例1的分离方法获得的外泌体对人皮肤成纤维细胞和人角质形成细胞增殖率,对人皮肤成纤维细胞和人角质形成细胞进行不同浓度的外泌体处理,并确认细胞的增殖率。将人皮肤成纤维细胞和人角质形成细胞悬浮在含有10%FBS的DMEM中,然后以具有80%至90%的密集度的方式进行分注,并在37℃、5%CO2培养箱中培养24小时。24小时后,去除培养液,将不含FBS的DMEM分注之后,分别以不同浓度处理从实施例1准备的人体尿源干细胞中提取的外泌体和作为对照组从人体脂肪源干细胞提取的外泌体,培养48至72小时后评估不同外泌体浓度的细胞增殖率。细胞增殖率采用台盼蓝(trypanblue)的细胞计数(Cell counting)、CCK-8(细胞计数试剂盒-8,cat#CK04-11)、MTT(abcam,cat#ab211091)和酶标仪进行测定。
其结果显示,以未经外泌体处理的DMEM中培养相同时间的细胞组为基准,试验的外泌体的整体浓度下,从人体尿源干细胞中提取的外泌体的细胞增殖率比从人体脂肪源干细胞中提取的外泌体更优秀(图5)。
实施例5.利用从人体尿源干细胞中提取的外泌体的人皮肤成纤维细胞和人角质
形成细胞的迁移效果
为了了解从人体尿源干细胞中提取的外泌体(UD-exo)对人皮肤成纤维细胞和人角质形成细胞迁移的影响,使用了分别包含从人体尿源干细胞培养基中提取的外泌体和从人体脂肪源干细胞中提取的外泌体(AD-exo)的培养基组合物。所述培养基组合物中,UD-exo是以250μg/mL的浓度添加到DMEM无血清培养基中来使用,AD-exo是以250μg/mL的浓度添加到DMEM无血清培养基中来使用。作为阴性对照组,使用DMEM无血清培养基。人皮肤成纤维细胞和人角质形成细胞分别以2×105个细胞/孔分注至设置于24孔板的划痕试验(scratch assay)用框架内,在培养基(含有10%胎牛血清、1%青霉素/链霉素的DMEM)中培养24小时。培养后,小心地去除所设置的框架以制作一定间隔的伤口(wound),用含有外泌体的所述培养基组合物处理各细胞。在用含外泌体的培养基处理各细胞后0、6、12和18小时后拍照,并通过Image J对细胞的迁移程度进行数值化。
其结果显示,经过12小时开始,用含UD-exo的培养基处理的细胞(88.12%)比阴性对照组(26.44%)和用AD-exo(50.66%)处理的细胞迁移(migration)程度更高,经过18小时后与含AD-exo的培养基相比,在含UD-exo的培养基中迁移速度更快,成纤维细胞的迁移效果更优秀。在人角质形成细胞中,经含UD-exo的培养基处理的细胞(80.75%)也在经过12小时后开始迁移(migration)程度高于阴性对照组(36.53%)和经AD-exo(46.51%)处理的细胞(图6)。由此证明,从人体尿源干细胞中提取的外泌体比从人体脂肪源干细胞中提取的外泌体有更好的伤口恢复效果。
实施例6.从人体尿源干细胞中提取的外泌体的改善皱纹效果
为了了解从人体尿源干细胞中提取的外泌体对人皮肤成纤维细胞的胶原合成的影响,使用了分别包含从尿源干细胞培养基中提取的外泌体(UD-exo)和从脂肪源干细胞培养基中提取的外泌体(AD-exo)的培养基组合物。含UD-exo的培养基组合物通过在DMEM无血清培养基中添加250μg/mL浓度的UD-exo来使用,含AD-exo的培养基组合物通过在DMEM无血清培养基中添加250μg/mL浓度的AD-exo来使用,作为阴性对照组,使用DMEM无血清培养基。人皮肤成纤维细胞分别以3×105个/孔分注至6孔板中,在培养基(含有10%胎牛血清、1%青霉素/链霉素的DMEM)中培养24小时后,确认细胞是否粘附良好,然后用磷酸盐缓冲盐水清洗细胞,用含外泌体的所述培养基组合物处理各细胞。外泌体处理48小时后,为了确认胶原基因表达水平,分别回收各孔的人皮肤成纤维细胞和培养液,皮肤成纤维细胞是以25℃、2000rpm离心分离5分钟来获得,培养液是以25℃、3000rpm离心分离10分钟来获得。从回收的皮肤成纤维细胞获得的总RNA制备cDNA,然后使用以下的表4所示的引物进行实时PCR,测定胶原基因的mRNA变化量,回收的培养液是在离心分离后取所获得的上清液而用于水溶性胶原蛋白(soluble collagen)的提取和定量。作为用于胶原基因定量的标准基因,使用GAPDH基因。
[表4]
其结果可确认,当用含AD-exo的培养液和含UD-exo的培养液处理人皮肤成纤维细胞时,与阴性对照组相比,胶原的mRNA表达量增加,且显示与含AD-exo的培养液相比,在含UD-exo的培养液中胶原的mRNA表达量的增加更为显著(图7a)。
另外,为了从各经外泌体处理的人皮肤成纤维细胞获得的培养液内的胶原的定量,使用天狼星红总胶原检测试剂盒(Sirius Red Total Collagen Detection AssayKit,Cat#.9062P,Woodinville,USA)。将所述获得的上清液用0.05M乙酸缓冲液(aceticacid buffer)进行处理并在4℃保持12小时以上。之后,将所提供的胶原吸附染料(天狼星红染色液,sirius red solution)添加到添加有所述0.05M乙酸缓冲液的上清液中,以12,000rpm离心分离10分钟以浓缩胶原。之后,去除上清液以去除未吸附的染料,沉淀(pellet)用洗涤缓冲液清洗之后,离心分离10分钟以再一次浓缩胶原。之后,用碱性试剂(alkalireagent)处理,将吸附在胶原上的染料溶解,在530nm波长下测定吸光度。将吸光度代入标准曲线公式,计算添加UD-exo、AD-exo和阴性对照物质的孔中水溶性胶原的量。
其结果显示,UD-exo剂量组的水溶性胶原合成率比阴性对照组(190μg)有所提高,尤其是250μg/mL的UD-exo剂量组的胶原合成量为457μg,与同等量的AD-exo(211μg)相比其胶原合成量显著增加(图8b)。
由此证明从人体脂肪源干细胞中提取的外泌体具有促进皮肤成纤维细胞的胶原合成的效果。
实施例7.利用黑素细胞(melanocyte)的从人体尿源干细胞中提取的外泌体的酪
氨酸酶活性抑制效果
为了了解从人体尿源干细胞中提取的外泌体对酪氨酸酶活性抑制的影响,利用从人体尿源干细胞培养基中提取的外泌体(UD-exo)、从人体脂肪源干细胞培养基中提取的外泌体(AD-exo)进行酪氨酸酶活性抑制确认试验(Tyrosi nase inhibition assay、abcam、cat#2015)。使用250μg/mL的从人体尿源干细胞提取的外泌体和250μg/mL的从人体脂肪源干细胞提取的外泌体作为酪氨酸酶抑制样品。之后,在酪氨酸酶和酪氨酸酶底物反应后,添加每个外泌体样品,利用酶标仪,以未添加任何物质反应的阴性对照组为基准,每隔3分钟比较酪氨酸酶的活性,时间为30至60分钟。
其结果显示,用从人体尿源干细胞中提取的外泌体处理的组抑制34%的酪氨酸酶,用从人体脂肪源干细胞中提取的外泌体的组抑制16%的酪氨酸酶。由此证明从人体尿源干细胞中提取的外泌体的抑制酪氨酸酶活性的功效比从人体脂肪源干细胞中提取的外泌体更优异。
Claims (15)
1.一种皮肤再生、美白、抗氧化或治疗伤口用化妆品组合物,其包含尿源干细胞来源的外泌体作为有效成分。
2.根据权利要求1所述的化妆品组合物,其特征在于,
用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基即DMEM和哈姆F-12的基础培养基、2.5%以下的牛胎血清以及添加剂,
所述添加剂为选自由牛血清白蛋白、脂质混合物、成纤维细胞成长因子23即FGF23、三碘甲状腺原氨酸即T3以及骨化二醇组成的组中的一种以上。
3.根据权利要求2所述的化妆品组合物,其特征在于,
用于从所培养的所述尿源干细胞中提取外泌体的培养基组合物是无血清、无抗生素培养基组合物。
4.根据权利要求1所述的化妆品组合物,其特征在于,
所述尿源干细胞来源于自体、异体或者异种。
5.根据权利要求1所述的化妆品组合物,其特征在于,
所述伤口包括割伤、例如手术切口的切口、擦伤、撕裂伤或者撕裂、骨折、挫伤、烧伤或者截肢。
6.根据权利要求1所述的化妆品组合物,其特征在于,
所述化妆品组合物的剂型为爽肤水、柔肤水、护肤水、收敛剂、乳液、润肤乳、保湿乳、营养乳、按摩霜、营养霜、眼霜、保湿霜、护手霜、精华液、营养精华液、面膜、洗面奶、卸妆水、卸妆乳、洁面霜、身体乳、沐浴露、皂或者粉末。
7.一种皮肤再生、美白、抗氧化或治疗伤口用药物组合物,其包含尿源干细胞来源的外泌体作为有效成分。
8.根据权利要求7所述的药物组合物,其特征在于,
用于培养所述尿源干细胞的培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基即DMEM和哈姆F-12的基础培养基、2.5%以下的牛胎血清以及添加剂,
所述添加剂为选自由牛血清白蛋白、脂质混合物、成纤维细胞成长因子23即FGF23、三碘甲状腺原氨酸即T3以及骨化二醇组成的组中的一种以上。
9.根据权利要求8所述的药物组合物,其特征在于,
用于从所培养的所述尿源干细胞中提取外泌体的培养基组合物是无血清、无抗生素培养基组合物。
10.根据权利要求7所述的药物组合物,其特征在于,
所述尿源干细胞来源于自体、异体或者异种。
11.根据权利要求7所述的药物组合物,其特征在于,
所述伤口包括割伤、例如手术切口的切口、擦伤、撕裂伤或者撕裂、骨折、挫伤、烧伤或者截肢。
12.根据权利要求7所述的药物组合物,其特征在于,
所述药物组合物是选自霜、凝胶、软膏、皮肤乳化剂、皮肤悬浮液、透皮贴剂、面膜、含药物绷带或者乳液的皮肤外用剂。
13.一种用于皮肤再生、美白、抗氧化或治疗伤口的尿源干细胞来源的外泌体的制备方法,其中,所述方法包括:
在包括以3:1的比例包含杜尔贝科改良伊格尔培养基即DMEM和哈姆F-12的基础培养基、2.5%以下的牛胎血清以及添加剂的培养基组合物中培养尿源干细胞的步骤;以及
在无血清、无抗生素培养基组合物中培养所培养的所述尿源干细胞并提取外泌体的步骤。
14.根据权利要求13所述的方法,其特征在于,
所述添加剂包括牛血清白蛋白、脂质混合物、成纤维细胞成长因子23即FGF23、三碘甲状腺原氨酸即T3以及骨化二醇。
15.根据权利要求13所述的方法,其特征在于,
所述无血清、无抗生素培养基组合物包括以3:1的比例包含杜尔贝科改良伊格尔培养基即DMEM和哈姆F-12的基础培养基、成纤维细胞生长因子2即FGF2、皮质醇、三碘甲状腺原氨酸即T3、骨化三醇、胰岛素-转铁蛋白-硒-乙醇胺、L-抗坏血酸-2-磷酸酯以及视黄酸。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20200046808 | 2020-04-17 | ||
KR10-2021-0021026 | 2021-02-17 | ||
KR1020210021026A KR102341375B1 (ko) | 2020-04-17 | 2021-02-17 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피부재생, 미백, 항산화 또는 상처 치료용 조성물 및 이의 용도 |
PCT/KR2022/001851 WO2022177217A2 (ko) | 2020-04-17 | 2022-02-07 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피부재생, 미백, 항산화 또는 상처 치료용 조성물 및 이의 용도 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117157054A true CN117157054A (zh) | 2023-12-01 |
Family
ID=78286980
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202280028858.1A Pending CN117157054A (zh) | 2020-04-17 | 2022-02-07 | 包含干细胞来源的外泌体作为有效成分的皮肤再生、美白、抗氧化或治疗伤口用组合物及其用途 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20240216435A1 (zh) |
KR (1) | KR102341375B1 (zh) |
CN (1) | CN117157054A (zh) |
WO (1) | WO2022177217A2 (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102341375B1 (ko) * | 2020-04-17 | 2021-12-21 | 주식회사 이에이치엘바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피부재생, 미백, 항산화 또는 상처 치료용 조성물 및 이의 용도 |
CN115105494A (zh) * | 2022-07-27 | 2022-09-27 | 西安臻融生物科技有限公司 | 一种有美白功效的外泌体包裹的光甘草定及其制备方法和应用 |
KR102623104B1 (ko) | 2023-08-23 | 2024-01-11 | 에프아이씨씨주식회사 | 보툴리눔톡신 결합체와 줄기세포 엑소좀 복합체를 유효성분으로 함유하는 피부 재생 및 주름 개선용 화장료 조성물 및 그의 제조 방법 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101663912B1 (ko) * | 2015-01-08 | 2016-10-10 | 한양대학교 에리카산학협력단 | 줄기세포로부터 추출된 엑소좀을 함유하는 피부 미백, 주름개선 또는 재생용 화장료 조성물 |
KR101863344B1 (ko) * | 2016-07-15 | 2018-06-01 | 주식회사 엔바이오텍 | 줄기세포의 무혈청 배양액을 유효성분으로 함유하는 피부 항노화용 화장료 조성물 |
KR101894229B1 (ko) * | 2016-11-02 | 2018-09-04 | (주)프로스테믹스 | 녹용 줄기세포 배양액을 포함하는 탈모 치료용 기능성 조성물 |
KR102341375B1 (ko) * | 2020-04-17 | 2021-12-21 | 주식회사 이에이치엘바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피부재생, 미백, 항산화 또는 상처 치료용 조성물 및 이의 용도 |
-
2021
- 2021-02-17 KR KR1020210021026A patent/KR102341375B1/ko active IP Right Grant
-
2022
- 2022-02-07 WO PCT/KR2022/001851 patent/WO2022177217A2/ko active Application Filing
- 2022-02-07 US US18/546,831 patent/US20240216435A1/en active Pending
- 2022-02-07 CN CN202280028858.1A patent/CN117157054A/zh active Pending
Also Published As
Publication number | Publication date |
---|---|
KR102341375B1 (ko) | 2021-12-21 |
WO2022177217A3 (ko) | 2022-10-13 |
KR20210128902A (ko) | 2021-10-27 |
WO2022177217A2 (ko) | 2022-08-25 |
US20240216435A1 (en) | 2024-07-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6847080B2 (ja) | 皮膚美白またはしわ改善用組成物 | |
KR102341375B1 (ko) | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피부재생, 미백, 항산화 또는 상처 치료용 조성물 및 이의 용도 | |
KR101894229B1 (ko) | 녹용 줄기세포 배양액을 포함하는 탈모 치료용 기능성 조성물 | |
KR101885501B1 (ko) | 녹용 줄기세포 배양액을 포함하는 피부 재생용 기능성 조성물 | |
KR101336474B1 (ko) | 지방 유래 성체줄기세포 배양액의 나노섬유 또는 나노캡슐을 포함하는 화장료 조성물 및 그 제조방법 | |
US20230151331A1 (en) | Method for preparing culture medium containing high levels of high-potency exosomes secreted by cord blood stem cells, and use thereof | |
KR20100096447A (ko) | 돼지 태반 조직 유래 줄기세포의 배양물 및 그 추출 단백질을 함유한 화장료용 조성물 | |
JP6583679B2 (ja) | 酵母抽出物を用いた幹細胞の未分化状態維持剤及び増殖促進剤 | |
JP6535505B2 (ja) | マンネンタケ抽出物を用いた幹細胞の未分化状態維持剤及び増殖促進剤 | |
JP6159183B2 (ja) | 幹細胞由来成長因子産生促進剤 | |
JP6571494B2 (ja) | アイヌワカメを用いた幹細胞の未分化状態維持剤及び増殖促進剤 | |
JP6411778B2 (ja) | 幹細胞の未分化状態維持剤及び増殖促進剤 | |
JP2017108671A (ja) | 幹細胞の未分化状態維持剤及び増殖促進剤 | |
KR20200016183A (ko) | 피부 필링과 줄기세포 유래의 엑소좀 처리를 병용한 피부 미용방법 | |
JP6649050B2 (ja) | 幹細胞の未分化状態維持剤及び増殖促進剤 | |
JP2014214094A (ja) | ヒト由来幹細胞培養液抽出物を包接させたリポソームを含有する化粧料組成物 | |
KR102260713B1 (ko) | 로리오라이드 또는 세네데스무스 속 hs4를 포함하는 탈모 방지 또는 발모 촉진용 조성물 | |
KR102682677B1 (ko) | 제대혈 줄기세포에 의해 고효능의 엑소좀이 고함량으로 분비된 배양액의 제조 방법 및 이의 용도 | |
JP7202610B2 (ja) | 幹細胞の未分化状態維持剤及び増殖促進剤 | |
KR102368442B1 (ko) | 생리활성이 강화된 엑소좀의 생산방법 및 이의 응용 | |
KR101589869B1 (ko) | 단백질 키나아제 C 억제제(Protein Kinase C Inhibitor)로 인한 인간 지방 유래 중간엽 줄기세포의 미백효과 및 항산화효과 관련 성장인자 발현 제어 및 분비를 촉진하는 성장인자 대량 생산방법 | |
JP7178087B2 (ja) | 幹細胞の未分化状態維持剤及び増殖促進剤 | |
KR20240096413A (ko) | 폴리감마글루탐산 및 지방조직 유래 줄기세포 엑소좀을 함유하는 화장료 조성물 | |
JP6200713B2 (ja) | 幹細胞由来成長因子産生促進剤 | |
KR20230132190A (ko) | 식물줄기세포 배양추출물과 유산균 엑소좀을 내포하는 오스모셀을 유효성분으로 함유하는 화장료 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |