WO2022145960A1 - Weissella cibaria strain and use thereof - Google Patents
Weissella cibaria strain and use thereof Download PDFInfo
- Publication number
- WO2022145960A1 WO2022145960A1 PCT/KR2021/020031 KR2021020031W WO2022145960A1 WO 2022145960 A1 WO2022145960 A1 WO 2022145960A1 KR 2021020031 W KR2021020031 W KR 2021020031W WO 2022145960 A1 WO2022145960 A1 WO 2022145960A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- strain
- skin
- composition
- oral
- culture medium
- Prior art date
Links
- 241000975185 Weissella cibaria Species 0.000 title claims abstract description 7
- 206010006326 Breath odour Diseases 0.000 claims abstract description 28
- 208000025157 Oral disease Diseases 0.000 claims abstract description 16
- 208000030194 mouth disease Diseases 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 91
- 239000001963 growth medium Substances 0.000 claims description 37
- 239000000284 extract Substances 0.000 claims description 30
- 241000894006 Bacteria Species 0.000 claims description 29
- 206010052428 Wound Diseases 0.000 claims description 27
- 208000027418 Wounds and injury Diseases 0.000 claims description 27
- 239000006166 lysate Substances 0.000 claims description 27
- 230000008591 skin barrier function Effects 0.000 claims description 18
- 201000001245 periodontitis Diseases 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 14
- 230000006872 improvement Effects 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 12
- 230000037303 wrinkles Effects 0.000 claims description 12
- 230000003020 moisturizing effect Effects 0.000 claims description 11
- 230000036560 skin regeneration Effects 0.000 claims description 11
- 239000002537 cosmetic Substances 0.000 claims description 10
- 208000007565 gingivitis Diseases 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000009759 skin aging Effects 0.000 claims description 10
- 230000006378 damage Effects 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 238000005728 strengthening Methods 0.000 claims description 8
- 208000002925 dental caries Diseases 0.000 claims description 7
- 206010013781 dry mouth Diseases 0.000 claims description 6
- 201000004328 Pulpitis Diseases 0.000 claims description 4
- 206010037464 Pulpitis dental Diseases 0.000 claims description 4
- 208000010266 Aggressive Periodontitis Diseases 0.000 claims description 3
- 208000006558 Dental Calculus Diseases 0.000 claims description 3
- 206010034016 Paronychia Diseases 0.000 claims description 3
- 241000029132 Paronychia Species 0.000 claims description 3
- 208000001143 Periodontal Abscess Diseases 0.000 claims description 3
- 206010044016 Tooth abscess Diseases 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 241000873388 Weissella sp. Species 0.000 claims description 3
- 201000009329 acute pericementitis Diseases 0.000 claims description 3
- 208000033608 aggressive 1 periodontitis Diseases 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 208000001277 chronic periodontitis Diseases 0.000 claims description 3
- 230000003054 hormonal effect Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 201000005128 suppurative periapical periodontitis Diseases 0.000 claims description 3
- 230000037394 skin elasticity Effects 0.000 claims description 2
- 206010017711 Gangrene Diseases 0.000 claims 1
- 244000005700 microbiome Species 0.000 abstract description 24
- 208000032139 Halitosis Diseases 0.000 abstract description 2
- 150000003568 thioethers Chemical class 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 52
- 239000000243 solution Substances 0.000 description 48
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 27
- 230000000694 effects Effects 0.000 description 25
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 18
- 210000000214 mouth Anatomy 0.000 description 17
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 16
- 241000202221 Weissella Species 0.000 description 11
- 235000014655 lactic acid Nutrition 0.000 description 11
- 239000004310 lactic acid Substances 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 150000003464 sulfur compounds Chemical class 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- 230000006698 induction Effects 0.000 description 10
- 238000012937 correction Methods 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 238000011084 recovery Methods 0.000 description 8
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 7
- 102100028314 Filaggrin Human genes 0.000 description 7
- 101710088660 Filaggrin Proteins 0.000 description 7
- 101710128038 Hyaluronan synthase Proteins 0.000 description 7
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 7
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 7
- 238000012258 culturing Methods 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000029663 wound healing Effects 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 235000013376 functional food Nutrition 0.000 description 6
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 210000003296 saliva Anatomy 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000012679 serum free medium Substances 0.000 description 6
- 102100033601 Collagen alpha-1(I) chain Human genes 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 108010029483 alpha 1 Chain Collagen Type I Proteins 0.000 description 5
- 235000013361 beverage Nutrition 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 5
- 108020004465 16S ribosomal RNA Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000032683 aging Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- -1 ascorbic acid glucoside Chemical class 0.000 description 4
- 230000003796 beauty Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 210000002615 epidermis Anatomy 0.000 description 4
- 235000019441 ethanol Nutrition 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
- 230000000813 microbial effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
- 102000003918 Hyaluronan Synthases Human genes 0.000 description 3
- 108090000320 Hyaluronan Synthases Proteins 0.000 description 3
- 244000199866 Lactobacillus casei Species 0.000 description 3
- 235000013958 Lactobacillus casei Nutrition 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 239000000645 desinfectant Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229940017800 lactobacillus casei Drugs 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000000434 stratum corneum Anatomy 0.000 description 3
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 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
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 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 2
- 239000005715 Fructose Substances 0.000 description 2
- 241000605986 Fusobacterium nucleatum Species 0.000 description 2
- 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 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 240000001046 Lactobacillus acidophilus Species 0.000 description 2
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 2
- 241000186869 Lactobacillus salivarius Species 0.000 description 2
- 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 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010067482 No adverse event Diseases 0.000 description 2
- 206010051246 Photodermatosis Diseases 0.000 description 2
- 241001135225 Prevotella nigrescens Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 241001134658 Streptococcus mitis Species 0.000 description 2
- 241000194019 Streptococcus mutans Species 0.000 description 2
- 241001135235 Tannerella forsythia Species 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 230000003712 anti-aging effect Effects 0.000 description 2
- 230000001153 anti-wrinkle effect Effects 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 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 2
- 239000011230 binding agent Substances 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
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000008103 glucose Substances 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
- 238000000338 in vitro Methods 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 235000021109 kimchi Nutrition 0.000 description 2
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 229940051866 mouthwash Drugs 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000006201 parenteral dosage form Substances 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000008845 photoaging Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 229940034610 toothpaste Drugs 0.000 description 2
- 239000000606 toothpaste Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 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
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-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
- 241000606749 Aggregatibacter actinomycetemcomitans Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-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
- 230000005971 DNA damage repair Effects 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium 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
- 241000194033 Enterococcus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241000555712 Forsythia Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 101000598906 Homo sapiens Olfactory receptor 6C2 Proteins 0.000 description 1
- 101710197055 Hyaluronan synthase 3 Proteins 0.000 description 1
- 102100029425 Hyaluronan synthase 3 Human genes 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
- 241000186660 Lactobacillus Species 0.000 description 1
- 241000194036 Lactococcus Species 0.000 description 1
- 241000192132 Leuconostoc Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 102100037748 Olfactory receptor 6C2 Human genes 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 241000605862 Porphyromonas gingivalis Species 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 241000605861 Prevotella Species 0.000 description 1
- 241001135221 Prevotella intermedia Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010043949 Tongue discolouration Diseases 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
- 241000589892 Treponema denticola Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 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 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
- 239000003708 ampul Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960000271 arbutin Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 238000010804 cDNA synthesis Methods 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
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 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
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940029329 intrinsic factor Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 201000006370 kidney failure Diseases 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
- 229940039696 lactobacillus Drugs 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 229940074358 magnesium ascorbate Drugs 0.000 description 1
- AIOKQVJVNPDJKA-ZZMNMWMASA-L magnesium;(2r)-2-[(1s)-1,2-dihydroxyethyl]-4-hydroxy-5-oxo-2h-furan-3-olate Chemical compound [Mg+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] AIOKQVJVNPDJKA-ZZMNMWMASA-L 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 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
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 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
- 239000013641 positive control Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000012423 response to bacterium Effects 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000037152 sensory function Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 230000037070 skin defense Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 239000000779 smoke Substances 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
- 229960001790 sodium citrate Drugs 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
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000013097 stability assessment Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 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
- 230000001052 transient effect Effects 0.000 description 1
- 229960005066 trisodium edetate Drugs 0.000 description 1
- 239000006097 ultraviolet radiation absorber Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 230000037330 wrinkle prevention Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Images
Classifications
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- 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
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- 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
- A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Definitions
- the skin ecosystem provides various types of habitat for microorganisms, and a wide range of microorganisms live there. They form a symbiotic relationship with the human host, and are known to have many positive effects on the host.
- the skin constitutes various types of habitats, such as depressions and specialized crevices, and helps a wide range of microorganisms to grow. Basically, the skin forms a physical barrier and helps to defend against potential hazards and toxic substances from the outside.
- the skin becomes a connection point with the external environment and is also a gathering place for various microorganisms (fungi, bacteria, viruses and small larvae). In accordance with the selection of physical and chemical functions, microorganisms adapt to specialized niches to prepare habitats.
- the skin is cold, acidic, and remains dry. Structurally, the epidermis forms a skin barrier, blocks the penetration of microorganisms and toxins, and plays an important role in maintaining moisture.
- the uppermost layer of the epidermis is composed of the stratum corneum.
- the epidermis has a so-called 'brick and mortar structure', and the skin tissue undergoes a continuous self-healing process, and the squames that have undergone the final differentiation process repeat the process of constantly being removed from the skin tissue.
- the lactic acid bacteria are used in the manufacturing process of fermented foods such as kimchi or yogurt, and the lactic acid bacteria used in food include Enterococcus genus, Lactobacillus genus, Lactococcus genus, Leukonostok ( Leuconostoc ) genus, Streptococcus genus, Weissella genus, and the like.
- these lactic acid bacteria have a problem in that when the lactic acid bacteria are administered to the oral cavity, they are swallowed directly into the esophagus while being diluted with saliva like metal salts or disinfectants, making it difficult to remain in the oral cavity.
- Lactobacillus acidophilus Lactobacillus acidophilus
- Lactobacillus casei Lactobacillus casei
- Lactobacillus salivarius Lactobacillus salivarius
- strong acids cause dental caries, there is a problem in that oral hygiene is not good if these bacteria are administered to the oral cavity for a long time. Therefore, there is a need for the development of microorganisms for reducing bad breath.
- One aspect is to provide a CXO-1 strain belonging to the Weissella sp .
- Another aspect is to provide a lysate or culture solution of the strain.
- Another aspect is to provide a cosmetic composition
- a cosmetic composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
- Another aspect is to provide a pharmaceutical composition for the treatment of wounds comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
- Another aspect is to provide an oral composition
- an oral composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
- Another aspect is to provide a pharmaceutical composition for the prevention or treatment of oral diseases comprising the above strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof.
- Another aspect is to provide a method of treating a wound comprising administering to a subject a composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
- Another aspect is to provide a method of treating oral diseases comprising administering to an individual a composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
- Another aspect is to provide a wound treatment, prevention or treatment of oral diseases of the composition comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof.
- the Weissella cibaria strain may be a strain deposited with accession number KCCM12889P.
- the Weissellacibaria strain may be a strain comprising 16s rRNA of SEQ ID NO: 1.
- the strain increases the expression of anti-aging and anti-wrinkle factors, for example, COL1A1 or decreases the expression of MMP-1, and hyaluronan synthase 3 (Hyaluronan synthase), which is a factor related to skin moisturizing and skin barrier 3, HSA3) was confirmed to increase the expression of or filaggrin.
- HSA3 hyaluronan synthase 3
- the strain according to an aspect may have a skin beauty improvement effect, for example, skin aging inhibition, skin barrier strengthening, skin wrinkle inhibition, or skin moisturizing effect.
- Another aspect provides a lysate of the strain, a culture solution, or an extract of the culture solution. Specific details of the strain are the same as described above.
- culture medium may be used interchangeably with “culture supernatant”, “conditioned culture medium” or “conditioned medium”, and may be used to provide nutrients so that the B. sibira strain can grow and survive in vitro. It may mean the entire medium including the strain obtained by culturing the strain for a certain period of time, its metabolites, and extra nutrients in a medium that can.
- the culture solution may refer to a culture solution obtained by culturing the strain in which the cells are removed from the culture solution.
- the liquid from which the cells have been removed among the above culture solution is also called “supernatant”, and the culture solution is left for a certain period of time to take only the liquid from the upper layer except for the part that has sunk to the lower layer, remove the cells through filtration, or centrifuge the culture solution to the lower part It can be obtained by removing the precipitation of and taking only the liquid at the top.
- the "cell” of the present invention refers to the strain itself of the present invention, and includes the strain isolated and selected from a skin sample, or the strain isolated from the culture solution by culturing the strain. The cells can be obtained by centrifuging the culture medium to take the part that has sunk to the lower layer, or by gravity sink to the lower layer of the culture solution, leaving it still for a certain period of time and then removing the upper liquid It can be obtained.
- the culture medium may include the culture medium itself obtained by culturing the strain, its concentrate, or a freeze-dried product or a culture supernatant obtained by removing the strain from the culture medium, its concentrate or freeze-dried product.
- the culture medium is obtained by culturing the Weissella sibaira strain in a medium (eg, R2A medium or TSA medium) at any temperature of more than 10° C. or less than 40° C. for a certain period of time, for example, 4 to 50 hours.
- a medium eg, R2A medium or TSA medium
- the culture supernatant of the strain can be obtained by centrifuging or filtering the strain culture solution to remove the strain.
- the concentrate may be obtained by concentrating the supernatant obtained after filtering the strain culture solution itself, or the culture solution using a centrifuge or filter.
- the culture medium and culture conditions for culturing the Weissella sibaira strain may be appropriately selected or modified by those of ordinary skill in the art.
- lysate may refer to a product obtained by disrupting the cell wall of the strain itself by chemical or physical force.
- culture solution extract means extraction from the culture solution or its concentrate, and includes an extract, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or these prepared or purified products, and fractions obtained by fractionation thereof. can do.
- Another aspect provides the use of the strain, a lysate of the strain, a culture solution, or an extract of the culture solution. Specifically, it provides a composition comprising a Weissella sibaira strain, a lysate thereof, a culture solution or an extract of the culture solution thereof.
- Uses of the strain may include improving skin condition, improving skin beauty, preventing, improving or treating skin diseases.
- the skin condition improvement or skin beauty improvement may be skin aging inhibition or improvement, anti-wrinkle, skin elasticity, skin regeneration, skin barrier strengthening, skin moisturizing or wound improvement.
- skin aging refers to the tangible and intangible changes that appear on the skin with age, for example, a phenomenon in which the thickness of the epidermis becomes thin, the number of cells or blood vessels in the dermis, DNA damage repair ability, cell replacement cycle , wound recovery, skin barrier function, epidermal moisture retention, sweat secretion, sebum secretion, vitamin D production, physical damage defense, chemical removal ability, immune response, sensory function, and decreased body temperature control.
- the strain or its culture medium may be for improving skin aging caused by extrinsic factors or intrinsic factors.
- the extrinsic factor refers to various external factors, such as ultraviolet light (light), and the intrinsic factor is also referred to as a chronological factor and refers to a factor mainly caused by the passage of time. That is, the skin aging specifically refers to not only the premature aging symptoms induced by external stimuli such as ultraviolet rays, pollution, cigarette smoke, chemical substances, etc., but also a natural aging phenomenon that occurs as the proliferation of skin cells decreases with aging. It is a concept that includes all of wrinkles, elasticity reduction, skin sagging and dryness. In addition, wrinkles include those that cause wrinkles by changing the components constituting the skin tissue by stimulation by changes in internal and external factors.
- the aging may be photoaging.
- photoaging is a phenomenon induced by external environmental factors, and the most representative factor is ultraviolet rays. Ultraviolet rays cause damage to biological components such as activation of proteolytic enzymes, chain cleavage of matrix proteins, and abnormal cross-linking, and repetition of these mechanisms leads to apparent skin aging.
- wrinkle refers to a state in which the elasticity of the skin is lost and loosened, and for example, the skin may be folded.
- skin wrinkle prevention or improvement may refer to any action of preventing or improving wrinkles by inhibiting the expression of factors related to wrinkles, or increasing the total amount of collagen.
- skin barrier strengthening may refer to any action that enhances the function of the skin barrier that is located at the outermost part of the skin and prevents loss of moisture and nutrients.
- damage to the skin barrier function may refer to any change that appears in the skin due to the deterioration or damage of the function of the skin barrier. For example, it may include increased skin wrinkles, dryness, dermatitis, atopic dermatitis, allergic dermatitis, acne, and the like.
- skin moisturizing may refer to any action of maintaining skin moisture or preventing moisture loss.
- wound is also called “wound” and means damage to the living body.
- the loss may be due to external factors such as, for example, physical damage, radiation, stimulation by chemical substances, etc., proliferation of microorganisms, or internal tolerance such as stress.
- the wounds may include all kinds of wounds, such as cleavage, puncture, cleavage, acne, fissure, bronchial, and school spear.
- Wound improvement may refer to any action that lightens or reduces the extent of a wound on the face or body
- wound healing may refer to a series of biological reactions to repair the wound.
- the strain may be used together with other strains belonging to the genus Weissella having a skin improvement effect to show a synergistic effect.
- the strain belonging to the genus Weissella is, for example, Weissella confuse ( Weissella confuse ), Weissella ubarum ) and the like.
- the composition comprises 0.001 wt% to 80 wt%, for example, 0.01 wt% to 60 wt%, 0.01 wt% to 40 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 20 wt%, based on the total weight of the composition %, 0.01% to 10%, 0.01% to 5%, 0.05% to 60%, 0.05% to 40%, 0.05% to 30%, 0.05% to 20% by weight, 0.05% to 10% by weight, 0.05% to 5% by weight, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight, 0.1% by weight % to 10% by weight, or 0.1% to 5% by weight of the strain, a lysate thereof, a culture medium, or an extract of the culture medium thereof.
- the composition may be a cosmetic composition.
- the cosmetic composition may have a cosmetic formulation of, for example, a softening lotion, a nourishing lotion, a massage cream, a nourishing cream, an essence, a pack, a gel, an ampoule, or a skin adhesion type.
- Components included in the cosmetic composition may include components commonly used in cosmetic compositions in addition to the composition as an active ingredient, for example, conventional adjuvants and carriers such as stabilizers, solubilizers, vitamins, pigments and fragrances. may include
- the composition may be a composition for external application to the skin.
- the external preparation for skin may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermally delivered patch, drug-containing bandage, lotion, or a combination thereof.
- the external preparation for skin is a component usually used in external preparations for skin such as cosmetics or pharmaceuticals, for example, an aqueous component, an oily component, a powder component, alcohol, a moisturizer, a thickener, an ultraviolet absorber, a whitening agent, a preservative, an antioxidant, a surfactant, a fragrance , colorant, various skin nutrients, or a combination thereof may be appropriately formulated as needed.
- the external preparation for skin includes metal-blocking agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belapamil, licorice extract, glablidine, and kaline.
- metal-blocking agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belapamil, licorice extract, glablidine, and kaline.
- Fruit hot water extracts, various herbal medicines, tocopherol acetate, glitylittic acid, tranexamic acid and derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars, such as trehalose, etc. can be mix
- the composition may be a pharmaceutical composition.
- the pharmaceutical composition may further include a pharmaceutically acceptable diluent or carrier.
- the diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and the lubricant may be magnesium stearate, talc, or a combination thereof.
- the carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof.
- the excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof.
- the disintegrant may be carboxymethyl cellulose calcium, sodium starch glycolate, anhydrous calcium monohydrogen phosphate, or a combination thereof.
- the binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof.
- the lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.
- the pharmaceutical composition may be formulated as an oral or parenteral dosage form.
- Oral dosage forms may be granules, powders, solutions, tablets, capsules, dry syrups, or a combination thereof.
- the parenteral dosage form may be an injection.
- the composition may be a health functional food composition.
- the health functional food composition may be used alone or in combination with other foods or food ingredients of the strain or its culture, and may be appropriately used according to a conventional method.
- the mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prophylactic, health or therapeutic treatment).
- the composition of the present specification may be added in an amount of 15 parts by weight or less based on the raw material.
- the beverage composition may contain various flavoring agents or natural carbohydrates as an additional component like a conventional beverage.
- the natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
- sweetener natural sweeteners such as taumartin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used.
- the health food composition may also be added to nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonated beverages carbonation agent used, or a combination thereof.
- the health functional food composition may also contain natural fruit juice, fruit juice beverage, fruit flesh for the production of vegetable beverage, or a combination thereof.
- Another aspect provides a method of preventing, ameliorating or treating a skin condition in a subject comprising treating or administering to the subject in need thereof an effective amount of the composition.
- Specific details of the skin condition are the same as described above.
- Another aspect provides a pharmaceutical composition for wound treatment comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient.
- Another aspect provides an external composition for wound treatment comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient.
- Another aspect provides a method for treating a wound comprising administering to a subject in need thereof an effective amount of the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof. The specific details of the wound are the same as described above.
- administering As used herein, the terms “administering”, “introducing”, and “implanting” are used interchangeably and into a subject by a method or route that results in at least partial localization of a composition according to one embodiment to a desired site. It may mean the arrangement of the composition according to one embodiment of the.
- Administration may be administered by methods known in the art. Administration may be administered directly to a subject by any means, for example, intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. can The administration may be systemically or locally.
- the subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat.
- the subject may be an individual in need of skin beauty improvement, for example, skin moisturizing, skin barrier strengthening, skin wrinkle improvement effect.
- the administration is 0.1 mg to 1,000 mg, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg , 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg may be administered.
- the dosage may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and reaction sensitivity, and those skilled in the art
- the dosage may be appropriately adjusted in consideration of these factors.
- the number of administration may be once a day or twice or more within the range of clinically acceptable side effects, and may be administered to one or two or more places for the site of administration, and total daily or at intervals of 2 to 5 days
- the number of days of administration may range from 1 to 30 days per treatment. If necessary, the same treatment can be repeated after a titration period.
- the dose is the same as that of a human per kg, or the above dose is converted, for example, by the volume ratio (for example, average value) of the target animal and the organ (heart, etc.) of the human One dose can be administered.
- the strain according to one aspect can increase the expression of skin moisturizing and skin barrier-related hyaluronic acid synthase 3 (Hyaluronan synthase 3, HAS3, filagrin) and regenerate damaged cells.
- the strain can increase the expression of COL1A1 reduced by ultraviolet light, and decrease the increased expression of MMP-1. That is, the increase in markers such as HAS3 and filaggrin means that filaggrin, a precursor of NMF, and intercellular lipids are normalized in keratinocytes through the formation of a normal stratum corneum. Therefore, to prevent skin aging and maintain skin health from external environmental changes such as atmospheric drying, ultraviolet rays and various pollutants, to strengthen the skin barrier to prevent moisture loss in the skin tissue while promoting the maintenance of moisture in the skin tissue It can form a stratum corneum.
- the strain promotes the proliferation of damaged fibroblasts and extracellular matrix to regenerate the skin and restore the epithelial layer, so it is useful for skin regeneration or wound healing.
- Another aspect provides an oral composition
- an oral composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof as an active ingredient.
- Specific details of the strain are the same as described above.
- the strain reduces the concentrations of volatile sulfur compounds (VSC), methyl mercaptan and dimethyl sulfide, which are volatile sulfur compounds (VSC) generated by bad breath-inducing microorganisms, and it was confirmed that the amount of oral microorganisms was reduced.
- the hydrogen sulfide (Hydrogen sulfide, H 2 S) may cause bad breath due to oral contamination and diseases related to mental and physiological causes.
- the methyl mercaptan (Methyl mercaptan, CH 3 SH) may cause bad breath due to oral diseases (periodontal disease).
- dimethyl sulfide Dimethyl sulfide, (CH 3 ) 2 S) may cause transient bad breath due to food metabolism.
- halitosis is a problem experienced in daily life, and 90% of it is derived from periodontitis, tongue discoloration, poor oral hygiene, and inadequate prosthetics in the oral cavity, and the remaining 10% is gastrointestinal disease, carcinoma, diabetes, liver failure, renal failure and from the same systemic disease. More than 600 types of bacteria live in the oral cavity, including disease-causing bacteria.
- the strain according to an aspect may have an effect of improving oral contamination and various diseases, or bad breath caused by food metabolism, reducing plaque, reducing tartar, reducing dry mouth, or inhibiting oral bacteria.
- the oral composition may be formulated as a mouthwash, mouthwash, toothpaste, oral spray, denture cleaner, toothpaste whitening agent, and the like.
- Another aspect provides a pharmaceutical composition for preventing or treating oral diseases comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient.
- Another aspect provides a method of treating an oral disease comprising administering to a subject in need thereof an effective amount of the composition.
- Another aspect provides a health functional food composition for preventing or improving oral diseases comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient. Specific details of the strain are the same as described above.
- the oral disease is, for example, invasive periodontitis, juvenile periodontitis, acute or chronic periodontitis, alveolar bone destruction, chronic or intractable periodontitis, gingivitis, ulcerative gingivitis, acute paronychia, acute lumpy gingivitis, hormonal periodontitis, complex infection, apical It may be a disease, periodontal abscess, dental caries, apical abscess, pulpitis, and the like.
- composition containing the strain in one embodiment, after 2 weeks of use of the composition containing the strain, representative oral microorganisms Tannerella forsythia , Fusobacterium nucleatum , Prevotella nigrescens ( Prevotella ) nigrescens ), Streptococcus mitis and Streptococcus mutans were significantly reduced compared to before use, and it was confirmed that no adverse reactions due to long-term use were observed.
- the strain according to one aspect has excellent oral microbial inhibitory effect as well as excellent stability for the human oral cavity, so even if used for a long period of time, it does not affect the resistance of bacteria in the oral cavity. effective in treatment.
- Weissella sibaira strain according to an aspect, it can be usefully used for preventing, improving or treating skin-related conditions. In addition, it can be usefully used for the prevention, improvement or treatment of oral diseases by reducing the sulfur compounds causing bad breath and inhibiting oral microorganisms.
- 1 is a graph showing the effect of a strain according to an embodiment on the expression of HAS3.
- FIG. 2 is a graph showing the effect of a strain according to an embodiment on the expression of filaggrin.
- FIG. 3 is a graph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
- FIG. 4 is a photograph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
- [Correction by Rule 91 24.02.2022] 5 is a graph showing the effect of a strain according to an embodiment on the expression of MMP-1.
- 6A is a graph comparing changes in the concentration of hydrogen sulfide before, immediately after, and after 2 weeks of use of the composition according to an aspect.
- 6B is a graph comparing changes in the concentration of methyl mercaptan before, immediately after, and 2 weeks after use of the composition according to an aspect.
- 6c is a graph comparing changes in the concentration of dimethyl sulfide before, immediately after, and after 2 weeks of use of the composition according to an aspect.
- Figure 7a is a graph comparing the amounts of bacteria Actinomycetem comitans ( Aa ) and gingivalis ( Pg ) before and 2 weeks after use of the composition according to an aspect.
- Figure 7b is a graph comparing the amounts of bacteria forsythia ( Tf ) and bacteria denticola ( Td ) before and 2 weeks after use of the composition according to an aspect.
- Figure 7c is a graph comparing the amounts of nucleatum bacteria ( Fn ) and intermediary bacteria ( Pi ) before and 2 weeks after use of the composition according to an aspect.
- Figure 7d is a graph comparing the amount of bacteria nigrescens ( Pn ) and Mytisbacterium ( Smi ) before and 2 weeks after use of the composition according to an aspect.
- Figure 7e is a graph comparing the amounts of bacteria mutans ( Smu ) and casei bacteria ( Lc ) before and 2 weeks after use of the composition according to an aspect.
- 7f is a graph comparing the total amount of microorganisms before and 2 weeks after use of the composition according to an aspect.
- FIG. 8 is a graph analyzing the results of a questionnaire evaluation regarding the efficacy and usability of a composition according to an aspect.
- Samples collected from human oral saliva and kimchi were inoculated into a liquid or solid medium (Becton Dickinson, Cockeysville, MD) containing MRS. After inoculation, 100 colonies formed after culturing for 48 hours in an incubator at 28°C were purely separated and cultured, and cultured in an incubator at 28°C for 48 hours. The cultured colonies were subjected to 16s rRNA gene sequence identification.
- the primers used were designed to amplify in response to bacteria only (27F, 5'-AGAGTTTGATCCTGGCTCAG-3'; 1492R, 5'-GGTTACCTTGTTACGACTT-3).
- PCR amplification was carried out in 30 cycles of 95°C for 1 minute, 55°C for 1 minute, 75°C for 1 minute and 30 seconds, and finally, after treatment at 72°C for 8 minutes, it was stored at 4°C.
- DNA sequences of the isolated and cultured species were determined using ABI-3730XL (ABI, USA). The nucleotide sequence of the 16S rRNA region determined from the isolated and cultured microbial colonies was compared with other strains registered in the BLAST program provided on the website of the National Center for Biotechnology Information (NCBI), and the homology of 97% or less was found.
- NCBI National Center for Biotechnology Information
- CXO-1 novel microorganism with 97% homology or less Weissella cibaria strain
- the selected CXO-1 strain was deposited with the Korea Microbial Conservation Center on December 3, 2020 and was given an accession number KCCM12889P, and the CXO-1 strain has a 16s rRNA sequence of SEQ ID NO: 1 (complementary DNA).
- HaCaT cells which are human keratinocytes, were cultured in DMEM medium (Dulbecco'smodified Eagle's Medium, Gibco 1210-0038) containing 10% fetal bovine serum, and all cultures were cultured at 37°C 5°C. % CO 2 in an incubator.
- the cultured cell line was treated with the culture solution of the CXO-1 strain (1%, 10% (w/w)) and further cultured for 24 hours.
- RNA was isolated from the cells of each sample using trizol (RNA iso, DAKARA, Japan), and RNA was quantified at 260 nm with nanodrops, and cDNA was synthesized in an amplifier using 2 ⁇ g of RNA each. (C1000 Thermal Cycler, Bio-Rad, USA).
- the target gene, HAS3 (hyaluronic acid synthase), a factor related to skin barrier strengthening and moisturizing, and primers and cDNA for filaggrin were added together with a real-time PCR machine (Step One Plus, Real-time polymerase chain reaction was performed in Applied Biosystems, USA).
- the expression level of the gene was finally analyzed through correction for the ⁇ -actin gene, and the results are shown in FIGS. 1 and 2 .
- 1 is a graph showing the effect of a strain according to an embodiment on the expression of HAS3.
- FIG. 2 is a graph showing the effect of a strain according to an embodiment on the expression of filaggrin.
- the strain according to one embodiment restores the damaged skin barrier by significantly increasing the expression of HAS3 and filaggrin in a concentration-dependent manner, and strengthens the skin barrier to increase skin defense. can give In addition, it is excellent in moisturizing the skin and is effective in preventing or treating moisture-related diseases.
- Example 2 In order to evaluate the skin regeneration and wound healing efficacy of the CXO-1 strain isolated in Example 1, a cell migration assay was performed. Specifically, Hs68 human fibroblasts were seeded in 96-well ImageLock plate (No. 4379; Essen BioScience) at 2 ⁇ 10 4 cells/well. Experiments were conducted at 90% cell confluent. On the second day, WoundMaker (Essen BioScience, USA) was washed with 45 ml of 70% ethanol solution for 5 minutes, and then washed with 45 ml of distilled water for 5 minutes. All cell layers in each well of the plate were scratched using the washed WoundMakerTM. Then, the medium was removed and washed with PBS.
- WoundMaker Essen BioScience, USA
- each test substance was treated.
- the degree of wound recovery was measured and graphed at 2-hour intervals for 8 hours.
- the degree of wound recovery was visually confirmed by checking the photograph of the cell measured with a microscope in the device.
- FIG. 3 is a graph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
- FIG. 4 is a photograph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
- the strain according to one embodiment promotes skin regeneration by activating cells in the wound site, and thus can be used as a material for skin regeneration or wound healing.
- Example 1 The effect of the CXO-1 strain culture medium isolated in Example 1 on factors related to aging skin aging and wrinkle generation by ultraviolet (UV) irradiation was analyzed.
- a human dermal fibroblast (Hs68) cell line was seeded in a 6-well plate at 3.5x10 5 cells/well, and then cultured in an incubator at 37° C. and 5% CO 2 condition for 24 hours. After removing the medium and adding DPBS, 20 mJ/cm2 of UVB was irradiated or not. Immediately after UVB irradiation, after removing DPBS and replacing it with a medium without FBS, the culture solution of the CXO-1 strain was treated by concentration (1% (w/w), 10% (w/w)) and added for 24 hours cultured. As a negative control group, UV-treated and strain culture untreated groups were used.
- Figure 5 is a graph showing the effect of the strain according to one embodiment on the expression of COL1A1
- Figure 5b is a graph showing the effect of the strain according to one embodiment on the expression of MMP-1.
- the strain according to one aspect has an excellent effect in preventing skin aging, such as reducing elasticity and inhibiting wrinkle production, by restoring collagen destroyed by ultraviolet rays by ultraviolet rays, and inhibiting the production of MMP-1 increased by ultraviolet rays .
- VSC Volatile Sulfur Compound
- 6A to 6C are graphs comparing changes in the concentration of volatile sulfur compounds (hydrogen sulfide, methyl mercaptan and dimethyl sulfide) before, immediately after, and after 2 weeks of use of the composition according to an aspect.
- the concentration of volatile sulfur compounds which is a parameter for bad breath, significantly decreased immediately after use and 2 weeks after use compared to before use (p ⁇ 0.05).
- the rate of change of volatile sulfur compounds is 89.41% and 87.80% for hydrogen sulfide, 68.46%, and 82.05% for methyl mercaptan, and 98.12% and 90.43% for dimethyl sulfide. After 2 weeks, it was confirmed that each concentration decreased by 80% or more.
- composition according to an aspect is effective in improving bad breath by significantly reducing the concentration of volatile sulfur compounds.
- the sample container was provided from the oral pathogenic microorganism test requesting institution (DENOMICS, Korea). After collecting a volunteer's saliva sample, changes in oral microorganisms and total amount of microorganisms in Table 2 below were analyzed using Oral Bacteria Dignosis (OBD) analysis service, and the results are shown in Table 3 below.
- OBD Oral Bacteria Dignosis
- 7A to 7E are graphs comparing the amount of microorganisms described in Table 2 before and after 2 weeks of use of a composition according to an aspect.
- 7f is a graph comparing the total amount of microorganisms before and 2 weeks after use of the composition according to an aspect.
- composition according to one aspect can prevent or treat oral diseases such as periodontitis, gingivitis, apical disease, dental caries, pulpitis, and the like, as well as prevent tartar formation by significantly reducing oral microorganisms.
- oral diseases such as periodontitis, gingivitis, apical disease, dental caries, pulpitis, and the like, as well as prevent tartar formation by significantly reducing oral microorganisms.
- the efficacy of improving bad breath, reducing plaque, and reducing dry mouth was evaluated according to the evaluation criteria 1 of Table 4 below, and the results were obtained. It is shown in Table 5 below.
- usability such as freshness, stimulation, flavor and taste were evaluated, and the results are shown in Table 6 below.
- FIG. 8 is a graph analyzing the results of a questionnaire evaluation regarding the efficacy and usability of a composition according to an aspect.
- the composition containing the strain culture solution of Example 1 was evaluated to have excellent effects of improving bad breath, reducing plaque, and reducing dry mouth.
- the composition was evaluated as being refreshing and having no irritation, so that the feeling of use was excellent overall.
- composition according to an aspect may provide an oral care product having excellent feeling of use as well as functionalities such as improving bad breath, reducing plaque, and reducing dry mouth.
- the 20 volunteers were allowed to use the composition containing the culture medium of Example 1 for 2 weeks, and then the test site of the volunteers was observed. Thereafter, the state of the test site was checked, recorded, and evaluated through Q&A. In the event of an adverse reaction, an adverse reaction report was prepared, and an expert judged the relationship between the adverse reaction and the composition.
- the composition according to one aspect has an advantage in that it has excellent oral microbial inhibitory effect as well as excellent stability to the human oral cavity, so that even when used for a long period of time, it does not affect the resistance of bacteria in the oral cavity.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- Dermatology (AREA)
- General Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Birds (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Cosmetics (AREA)
Abstract
The present invention relates to a Weissella cibaria strain and use thereof. The strain can be usefully used for the prevention, amelioration, or treatment of skin-related conditions, and reduces sulfide compounds causing halitosis and inhibits oral microorganisms, and thus can be usefully used for the prevention, amelioration, or treatment of oral diseases.
Description
본 출원은 2020년 12월 28일 출원된 대한민국 특허출원 제10-2020-0185220호를 우선권으로 주장하고, 상기 명세서 전체는 본 출원의 참고문헌이다. This application claims priority to Korean Patent Application No. 10-2020-0185220, filed on December 28, 2020, and the entire specification is a reference to the present application.
바이셀라 시바리아 균주 및 이의 용도에 관한 것이다.It relates to Weissella civaria strains and uses thereof.
피부의 생태계는 미생물에게 다양한 형태의 서식처를 제공하며, 광범위한 미생물들이 살고 있다. 이들은 숙주인 인간과 공생관계를 이루고 있으며, 숙주에 많은 긍정적인 영향을 미친다고 알려져 있다. 피부는 함입부, 특화되어있는 틈새 등 다양한 형태의 서식처를 구성하고 있으며, 넓은 분포의 미생물이 자랄 수 있도록 돕는다. 기본적으로 피부는 물리적인 막을 형성하며, 외부로부터 잠재적인 위험요소 및 독성물질들로부터 방어를 하도록 도와준다. 피부는 외부환경과의 접속지점이 되며, 다양한 미생물들(진균, 세균, 바이러스 및 작은 유충)의 집합소이기도 하다. 물리적, 화학적 기능의 선택에 맞게 미생물들은 특화된 틈새에 적응하여 서식처를 마련한다. 일반적으로 피부는 차갑고, 산성 성질을 나타내며, 건조된 상태로 유지된다. 구조적으로 표피(epidermis)는 피부장벽을 이루고 있으며, 미생물과 독소가 침투하는 것을 차단하고, 수분을 유지하는 중요한 역할을 한다. 표피의 최상위층은 각질층(stratum corneum)으로 구성되어있다. 표피는 일명 '벽돌과 몰탈 구조'라고 불리는 형태를 띠고 있는데, 피부 조직은 계속적인 자가 회복 과정을 거치고, 분화과정의 마지막을 거친 비늘(squames)은 끊임없이 피부조직에서 탈락되는 과정을 반복하게 된다. The skin ecosystem provides various types of habitat for microorganisms, and a wide range of microorganisms live there. They form a symbiotic relationship with the human host, and are known to have many positive effects on the host. The skin constitutes various types of habitats, such as depressions and specialized crevices, and helps a wide range of microorganisms to grow. Basically, the skin forms a physical barrier and helps to defend against potential hazards and toxic substances from the outside. The skin becomes a connection point with the external environment and is also a gathering place for various microorganisms (fungi, bacteria, viruses and small larvae). In accordance with the selection of physical and chemical functions, microorganisms adapt to specialized niches to prepare habitats. In general, the skin is cold, acidic, and remains dry. Structurally, the epidermis forms a skin barrier, blocks the penetration of microorganisms and toxins, and plays an important role in maintaining moisture. The uppermost layer of the epidermis is composed of the stratum corneum. The epidermis has a so-called 'brick and mortar structure', and the skin tissue undergoes a continuous self-healing process, and the squames that have undergone the final differentiation process repeat the process of constantly being removed from the skin tissue.
한편, 피부에 서식 하는 미생물 중에는 구강 및 인접기관에서 서식하며 구취를 유발하는 개체도 있으며, 이러한 미생물로부터 발생되는 휘발성 유황화합물에 발상해는 냄새를 구취라고 한다. 이러한 구취로 인해 일상 생활에서 불편을 호소하는 사람들이 존재한다. 구취를 억제하기 위해서는 구취의 주성분인 휘발성 유황화합물을 생성하는 혐기성세균의 증식을 억제하는 것이 가장 효과적이기 때문에, 종래에는 혀로부터 세균의 증식 기질을 제거하기 위하여 혀 세정기(tongue scraper)를 사용하여 설태를 제거하거나, 혐기성세균의 증식이나 혐기성세균에 의한 휘발성 유황화합물 생성을 억제하기 위하여 알코올 또는 염화아연(zinc chloride)과 같은 금속염 같은 소독제를 사용하였다. 그러나, 이러한 금속염이나 소독제는 구취를 발생시키는 혐기성세균뿐만 아니라 구강내 다른 미생물까지도 발생을 억제하며, 이러한 물질은 식도로 삼키지 않기 때문에 구취 발생에 있어서 중요한 장소인 혀의 뒤쪽까지 가지 못하고 구강 앞쪽에서 주로 가글링되고 입 밖으로 뱉어낸다. 또한, 이러한 물질은 타액에 의해서 희석되고 타액과 함께 식도로 삼켜져 구강에서의 효과는 20분 내지 2시간 정도로 짧은 편이며, 그 후 구강에는 미생물이 다시 증식하여 구취가 발생하게 된다. 또한, 구취 발생 혐기성 세균의 주요한 증식 장소인 혀 뒤쪽까지는 소독할 수 없다는 문제점이 있으며, 섭취하였을 경우에는 인체에 유해할 수 있다는 부분도 고려하여야 한다. 최근 유산균 및 유산균의 발효물을 이용하여 혐기성 세균의 증식을 억제하고자 하는 시도가 있었다. 유산균은 탄수화물을 발효하여 최종 대사 산물로 유산을 생산하는 세균을 지칭하며, 유산균은 인간과 동물의 구강 및 소화관에 존재한다. 통상적으로 상기 유산균은 김치 또는 요구르트 등 발효식품의 제조과정에 활용되는데, 식품에 활용되는 유산균으로는 엔테로코커스(Enterococcus)속, 락토바실러스 (Lactobacillus)속, 락토코커스(Lactococcus)속, 류코노스톡(Leuconostoc)속, 스트렙토코커스(Streptococcus)속, 바이셀라(Weissella)속 등이 있다. 그러나, 이러한 유산균은 상기 유산균을 구강에 투여하면 금속염이나 소독제와 같이 타액에 의해 희석이 되면서 식도로 바로 삼켜져 구강에 잔류하기가 어렵다는 문제점이 있다. 또한, 락토바실러스 애시도필러스(Lactobacillus acidophilus), 락토바실러스 카세이(Lactobacillus casei), 락토바실러스 살리바리우스(Lactobacillus salivarius)와 같은 유산균은 강산을 만들어 실험관에서 혐기성 세균의 증식을 억제할 수 있으나, 정상인의 구강에서는 타액의 완충작용으로 유산균이 만든 강산이 중화되어 다른 세균의 증식을 억제하기 어렵다. 더구나 강산은 치아 우식증을 일으키기 때문에 이러한 세균을 구강에 장기간 투여하면 구강 위생에 좋지 않다는 문제점이 있다. 따라서, 구취를 감소시키기 위한 미생물의 개발이 필요한 실정이다.On the other hand, some microorganisms that live on the skin live in the oral cavity and adjacent organs and cause bad breath. There are people who complain of discomfort in daily life due to such bad breath. In order to suppress bad breath, it is most effective to inhibit the growth of anaerobic bacteria that produce volatile sulfur compounds, which are the main components of bad breath. A disinfectant such as alcohol or a metal salt such as zinc chloride was used to remove or inhibit the growth of anaerobes or the generation of volatile sulfur compounds by anaerobes. However, these metal salts or disinfectants inhibit the occurrence of not only anaerobic bacteria that cause bad breath but also other microorganisms in the oral cavity. Gargling and spitting out of the mouth. In addition, these substances are diluted with saliva and swallowed together with saliva into the esophagus, so that the effect in the oral cavity is short, about 20 minutes to 2 hours, and thereafter, microorganisms multiply again in the oral cavity to cause bad breath. In addition, there is a problem that it cannot be disinfected to the back of the tongue, which is the main growth site of anaerobic bacteria causing bad breath. Recently, there has been an attempt to suppress the growth of anaerobic bacteria by using lactic acid bacteria and fermented products of lactic acid bacteria. Lactic acid bacteria refer to bacteria that ferment carbohydrates to produce lactic acid as final metabolites, and lactic acid bacteria exist in the oral cavity and digestive tract of humans and animals. Typically, the lactic acid bacteria are used in the manufacturing process of fermented foods such as kimchi or yogurt, and the lactic acid bacteria used in food include Enterococcus genus, Lactobacillus genus, Lactococcus genus, Leukonostok ( Leuconostoc ) genus, Streptococcus genus, Weissella genus, and the like. However, these lactic acid bacteria have a problem in that when the lactic acid bacteria are administered to the oral cavity, they are swallowed directly into the esophagus while being diluted with saliva like metal salts or disinfectants, making it difficult to remain in the oral cavity. In addition, Lactobacillus acidophilus ( Lactobacillus acidophilus ), Lactobacillus casei ( Lactobacillus casei ), Lactobacillus salivarius ( Lactobacillus salivarius ), such as lactic acid bacteria can suppress the growth of anaerobic bacteria in vitro by making strong acids, but In the oral cavity, the strong acid produced by lactic acid bacteria is neutralized by the buffering action of saliva, making it difficult to suppress the growth of other bacteria. Moreover, since strong acids cause dental caries, there is a problem in that oral hygiene is not good if these bacteria are administered to the oral cavity for a long time. Therefore, there is a need for the development of microorganisms for reducing bad breath.
일 양상은 바이셀라 속(Weissella sp.)에 속하는 바이셀라 시바이라(Weissellacibaria) CXO-1 균주를 제공하는 것이다. One aspect is to provide a CXO-1 strain belonging to the Weissella sp .
다른 양상은 상기 균주의 파쇄액 또는 배양액을 제공하는 것이다. Another aspect is to provide a lysate or culture solution of the strain.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 화장료 조성물을 제공하는 것이다. Another aspect is to provide a cosmetic composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 상처 치료용 약학적 조성물을 제공하는 것이다. Another aspect is to provide a pharmaceutical composition for the treatment of wounds comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 구강 조성물을 제공하는 것이다. Another aspect is to provide an oral composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 구강 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Another aspect is to provide a pharmaceutical composition for the prevention or treatment of oral diseases comprising the above strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 조성물을 개체에 투여하는 단계를 포함하는 상처 치료 방법을 제공하는 것이다. Another aspect is to provide a method of treating a wound comprising administering to a subject a composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 조성물을 개체에 투여하는 단계를 포함하는 구강 질환의 치료 방법을 제공하는 것이다.Another aspect is to provide a method of treating oral diseases comprising administering to an individual a composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 조성물의 상처 치료, 구강질환의 예방 또는 치료 용도를 제공하는 것이다. Another aspect is to provide a wound treatment, prevention or treatment of oral diseases of the composition comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof.
일 양상은 바이셀라 속(Weissella sp.)에 속하는 바이셀라 시바이라(Weissellacibaria) CXO-1 균주를 제공한다. 일 구체예에 있어서, 상기 바이셀라 시바이라(Weissellacibaria) 균주는 기탁번호 KCCM12889P로 기탁된 균주일 수 있다. 또한, 상기 바이셀라 시바이라(Weissellacibaria) 균주는 서열번호 1의 16s rRNA를 포함하는 균주일 수 있다. One aspect provides a CXO-1 strain belonging to Weissella sp . In one embodiment, the Weissella cibaria strain may be a strain deposited with accession number KCCM12889P. In addition, the Weissellacibaria strain may be a strain comprising 16s rRNA of SEQ ID NO: 1.
일 실시예에서는 상기 균주가 항노화 및 항주름 인자 예를 들어, COL1A1의 발현을 증가시키거나 또는 MMP-1의 발현을 감소시키고, 피부 보습 및 피부 장벽 관련 인자인 히알루론산 합성 효소 3(Hyaluronan synthase 3, HSA3) 또는 필라그린의 발현을 증가시킴을 확인하였다. 또한, 상기 균주의 상처 회복 효과가 우수함을 확인하였다. 따라서, 일 양상에 따른 균주는 피부 미용 개선 효과, 예를 들어, 피부 노화 억제, 피부 장벽 강화, 피부 주름 억제 또는 피부 보습 효과를 갖는 것일 수 있다. In one embodiment, the strain increases the expression of anti-aging and anti-wrinkle factors, for example, COL1A1 or decreases the expression of MMP-1, and hyaluronan synthase 3 (Hyaluronan synthase), which is a factor related to skin moisturizing and skin barrier 3, HSA3) was confirmed to increase the expression of or filaggrin. In addition, it was confirmed that the wound healing effect of the strain is excellent. Therefore, the strain according to an aspect may have a skin beauty improvement effect, for example, skin aging inhibition, skin barrier strengthening, skin wrinkle inhibition, or skin moisturizing effect.
다른 양상은 상기 균주의 파쇄물, 배양액, 또는 배양액의 추출물을 제공한다. 상기 균주의 구체적인 내용은 전술한 바와 같다. Another aspect provides a lysate of the strain, a culture solution, or an extract of the culture solution. Specific details of the strain are the same as described above.
본 명세서에서 용어,"배양액"은 "배양 상층액", "조건 배양액" 또는 "조정 배지"와 호환적으로 사용될 수 있고, 바이셀라 시바이라 균주가 시험관 내에서 성장 및 생존할 수 있도록 영양분을 공급할 수 있는 배지에 상기 균주를 일정기간 배양하여 얻는 상기 균주, 이의 대사물, 여분의 영양분 등을 포함하는 전체 배지를 의미할 수 있다. 또한, 상기 배양액은 균주를 배양하여 얻은 균체 배양액에서 균체를 제거한 배양액을 의미할 수 있다. 한편, 상기 배양액 중 균체를 제거한 액체를 "상등액"이라고도 하며, 배양액을 일정시간 가만히 두어 하층에 가라앉은 부분을 제외한 상층의 액체 만을 취하거나, 여과를 통해 균체를 제거하거나, 배양액을 원심분리하여 하부의 침전을 제거하고 상부의 액체 만을 취하여 획득할 수 있다. 상기 "균체"는 본 발명의 균주 자체를 의미하는 것으로 피부 샘플 등으로부터 분리하여 선별한 균주 자체 또는 상기 균주를 배양하여 배양액으로부터 분리한 균주를 포함한다. 상기 균체는 배양액을 원심분리하여 하층에 가라앉은 부분을 취하여 획득할 수 있고, 또는 중력에 의해 배양액의 하층으로 가라앉으므로 일정 시간 동안 가만히 두었다가 상부의 액체를 제거함으로써 획득할 수 있다.As used herein, the term "culture medium" may be used interchangeably with "culture supernatant", "conditioned culture medium" or "conditioned medium", and may be used to provide nutrients so that the B. sibira strain can grow and survive in vitro. It may mean the entire medium including the strain obtained by culturing the strain for a certain period of time, its metabolites, and extra nutrients in a medium that can. In addition, the culture solution may refer to a culture solution obtained by culturing the strain in which the cells are removed from the culture solution. On the other hand, the liquid from which the cells have been removed among the above culture solution is also called “supernatant”, and the culture solution is left for a certain period of time to take only the liquid from the upper layer except for the part that has sunk to the lower layer, remove the cells through filtration, or centrifuge the culture solution to the lower part It can be obtained by removing the precipitation of and taking only the liquid at the top. The "cell" of the present invention refers to the strain itself of the present invention, and includes the strain isolated and selected from a skin sample, or the strain isolated from the culture solution by culturing the strain. The cells can be obtained by centrifuging the culture medium to take the part that has sunk to the lower layer, or by gravity sink to the lower layer of the culture solution, leaving it still for a certain period of time and then removing the upper liquid It can be obtained.
상기 배양액은 균주를 배양하여 수득된 배양액 자체, 그의 농축물, 또는 동결 건조물 또는 배양액로부터 균주를 제거하여 수득된 배양 상층액, 그의 농축물 또는 동결건조물을 포함할 수 있다. The culture medium may include the culture medium itself obtained by culturing the strain, its concentrate, or a freeze-dried product or a culture supernatant obtained by removing the strain from the culture medium, its concentrate or freeze-dried product.
상기 배양액은 바이셀라 시바이라 균주를 배지(예를 들면, R2A 배지 또는 TSA 배지) 에서 10℃ 초과 또는 40℃ 미만 중 어느 온도에서 일정 시간, 예를 들면, 4 내지 50시간 동안 배양하여 수득된 것일 수 있다. The culture medium is obtained by culturing the Weissella sibaira strain in a medium (eg, R2A medium or TSA medium) at any temperature of more than 10° C. or less than 40° C. for a certain period of time, for example, 4 to 50 hours. can
일 구체예에 있어서, 균주의 배양 상층액은 균주 배양액을 원심분리나 여과시켜 균주를 제거하는 단계에 의해 수득될 수 있다.In one embodiment, the culture supernatant of the strain can be obtained by centrifuging or filtering the strain culture solution to remove the strain.
다른 구체예에 있어서, 농축물은 상기 균주 배양액 자체, 또는 상기 배양액을 원심분리나 필터를 이용하여 여과한 후 수득된 상층액을 농축하는 단계에 의해 수득될 수 있다. In another embodiment, the concentrate may be obtained by concentrating the supernatant obtained after filtering the strain culture solution itself, or the culture solution using a centrifuge or filter.
상기 바이셀라 시바이라 균주를 배양하기 위한 배양용 배지 및 배양 조건은 통상의 지식을 가진 자가 적절하게 선택하거나 변형하여 이용할 수 있다.The culture medium and culture conditions for culturing the Weissella sibaira strain may be appropriately selected or modified by those of ordinary skill in the art.
본 명세서에서 용어, "파쇄액"은 균주 자체를 화학적 또는 물리적 힘에 의하여 균주의 세포벽을 파쇄하여 얻은 산물을 의미할 수 있다.As used herein, the term “lysate” may refer to a product obtained by disrupting the cell wall of the strain itself by chemical or physical force.
본 명세서에서 용어, "배양액 추출물"은 상기 배양액 또는 그의 농축액로부터 추출한 것을 의미하며, 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들 조정제물 또는 정제물, 이를 분획한 분획물을 포함할 수 있다. As used herein, the term "culture solution extract" means extraction from the culture solution or its concentrate, and includes an extract, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or these prepared or purified products, and fractions obtained by fractionation thereof. can do.
다른 양상은 상기 균주, 상기 균주의 파쇄액, 배양액, 또는 배양액의 추출물의 용도를 제공한다. 구체적으로, 바이셀라 시바이라 균주, 그의 파쇄액, 배양액 또는 그의 배양액의 추출물을 포함하는 조성물을 제공한다. Another aspect provides the use of the strain, a lysate of the strain, a culture solution, or an extract of the culture solution. Specifically, it provides a composition comprising a Weissella sibaira strain, a lysate thereof, a culture solution or an extract of the culture solution thereof.
상기 균주의 용도는 피부 상태 개선, 피부 미용 개선, 피부 질환의 예방, 개선 또는 치료 등을 포함할 수 있다. Uses of the strain may include improving skin condition, improving skin beauty, preventing, improving or treating skin diseases.
상기 피부 상태 개선 또는 피부 미용 개선은 피부 노화 억제 또는 개선, 항 주름, 피부 탄력, 피부 재생, 피부 장벽 강화, 피부 보습 또는 상처 개선일 수 있다. The skin condition improvement or skin beauty improvement may be skin aging inhibition or improvement, anti-wrinkle, skin elasticity, skin regeneration, skin barrier strengthening, skin moisturizing or wound improvement.
본 명세서에서 용어, "피부 노화"란 나이가 들어가면서 피부에 나타나게 되는 유형과 무형상의 변화를 통틀어 말하는 것으로, 예컨대 표피 두께가 얇아지는 현상, 진피의 세포 수나 혈관 수, DNA 손상복구 능력, 세포교체주기, 상처 회복, 피부장벽기능, 표피의 수분 유지, 땀분비, 피지분비, 비타민D 생산, 물리적 손상방어, 화학물질 제거능력, 면역반응, 감각 기능, 체온조절의 감소를 말한다. As used herein, the term "skin aging" refers to the tangible and intangible changes that appear on the skin with age, for example, a phenomenon in which the thickness of the epidermis becomes thin, the number of cells or blood vessels in the dermis, DNA damage repair ability, cell replacement cycle , wound recovery, skin barrier function, epidermal moisture retention, sweat secretion, sebum secretion, vitamin D production, physical damage defense, chemical removal ability, immune response, sensory function, and decreased body temperature control.
상기 균주 또는 이의 배양액은 외인성 요인 또는 내인성 요인에 의해 유발되는 피부 노화 개선용일 수 있다. 상기 외인성 요인은 여러 가지 외부 요인, 예컨대 자외선(광)을 말하고 내인성 요인은 연대기적 요인이라고도 지칭되며 주로 시간의 흐름에 의해 발생하는 요인을 말한다. 즉, 상기 피부 노화는 구체적으로는 자외선, 공해, 담배연기, 화학물질 등에 의한 외부 자극에 의해 유도되는 조기 노화 증상 뿐만 아니라, 나이가 들어감에 의해 피부세포의 증식이 감소함에 따라 발생하는 자연 노화 현상을 포함하며 주름, 탄력 감소, 피부 쳐짐 및 건조 현상 등을 모두 포함하는 개념이다. 또한 주름은 내ㆍ외부 요인의 변화에 의한 자극이 피부조직을 구성하고 있는 성분을 변화시켜 주름을 유발하는 것을 포함한다. The strain or its culture medium may be for improving skin aging caused by extrinsic factors or intrinsic factors. The extrinsic factor refers to various external factors, such as ultraviolet light (light), and the intrinsic factor is also referred to as a chronological factor and refers to a factor mainly caused by the passage of time. That is, the skin aging specifically refers to not only the premature aging symptoms induced by external stimuli such as ultraviolet rays, pollution, cigarette smoke, chemical substances, etc., but also a natural aging phenomenon that occurs as the proliferation of skin cells decreases with aging. It is a concept that includes all of wrinkles, elasticity reduction, skin sagging and dryness. In addition, wrinkles include those that cause wrinkles by changing the components constituting the skin tissue by stimulation by changes in internal and external factors.
상기 노화는 광노화일 수 있다. 본 명세서에서 용어, "광노화(Photoaging)"는 외부 환경적인 요인에 의해 유발되는 현상으로, 가장 대표적인 인자로는 자외선이 있다. 자외선은 단백질 분해효소의 활성화와 기질단백질의 사슬절단 및 비정상적인 교차결합 등의 생체 구성 성분들의 손상을 가져오고, 이러한 메커니즘의 반복은 외관상으로도 확연한 피부노화를 초래하게 된다. The aging may be photoaging. As used herein, the term “photoaging” is a phenomenon induced by external environmental factors, and the most representative factor is ultraviolet rays. Ultraviolet rays cause damage to biological components such as activation of proteolytic enzymes, chain cleavage of matrix proteins, and abnormal cross-linking, and repetition of these mechanisms leads to apparent skin aging.
본 명세서에서 용어, "주름"은 피부의 탄력성이 상실되어 느슨해진 상태를 의미하며, 예를 들면 피부가 접히는 것일 수 있다. 상기 "피부 주름 예방 또는 개선"이란 주름과 관련된 인자의 발현을 억제하여 주름을 방지 또는 개선하거나, 콜라겐 총량을 증가시키는 모든 작용을 의미할 수 있다.As used herein, the term “wrinkle” refers to a state in which the elasticity of the skin is lost and loosened, and for example, the skin may be folded. The "skin wrinkle prevention or improvement" may refer to any action of preventing or improving wrinkles by inhibiting the expression of factors related to wrinkles, or increasing the total amount of collagen.
상기 "피부 장벽 강화"는 피부 가장 바깥쪽에 위치하여 수분과 영양 손실을 막아주는 피부 장벽의 기능이 증진되는 모든 작용을 의미할 수 있다. 또한, "피부 장벽 기능 손상"은 피부 장벽의 기능이 저하되거나 손상되어 피부에 나타나는 모든 변화를 의미할 수 있다. 예를 들어, 피부 주름 증가, 건조, 피부염, 아토피 피부염, 알레르기성 피부염, 여드름 등을 포함할 수 있다.The "skin barrier strengthening" may refer to any action that enhances the function of the skin barrier that is located at the outermost part of the skin and prevents loss of moisture and nutrients. In addition, "damage to the skin barrier function" may refer to any change that appears in the skin due to the deterioration or damage of the function of the skin barrier. For example, it may include increased skin wrinkles, dryness, dermatitis, atopic dermatitis, allergic dermatitis, acne, and the like.
상기 "피부 보습"은 피부 수분을 유지하거나 수분 손실을 방지하는 모든 작용을 의미할 수 있다.The "skin moisturizing" may refer to any action of maintaining skin moisture or preventing moisture loss.
상기 "상처"는 "창상"이라고도 하며, 생체의 손상을 의미한다. 상기 손산은 예를 들어, 물리적 손상, 방사선, 화학물질 등에 의한 자극, 미생물의 증식 등 외부 요인에 의한 것이거나 또는 스트레스 등의 내부 용인에 의한 것일 수 있다. 상기 상처는 절창, 자창, 할창, 좌창, 열창, 사창, 교창 등 모든 종류의 상처를 포함할 수 있다. “상처 개선"은 얼굴이나 신체의 상처를 옅어지게 하거나 정도를 감소시키는 모든 작용을 의미할 수 있고,"상처 치유"는 상처를 회복하는 일련의 생체 반응을 의미할 수 있다.The "wound" is also called "wound" and means damage to the living body. The loss may be due to external factors such as, for example, physical damage, radiation, stimulation by chemical substances, etc., proliferation of microorganisms, or internal tolerance such as stress. The wounds may include all kinds of wounds, such as cleavage, puncture, cleavage, acne, fissure, bronchial, and school spear. "Wound improvement" may refer to any action that lightens or reduces the extent of a wound on the face or body, and "wound healing" may refer to a series of biological reactions to repair the wound.
다른 구체예에 있어서, 상기 균주는 피부 개선 효과를 갖는 바이셀라 속에 속하는 다른 균주와 함께 사용되어 시너지 효과를 나타내는 것일 수 있다. 상기 바이셀라 속에 속하는 균주는 예를 들어, 바이셀라 콘푸세(Weissella confuse), 바이셀라 우바럼(Weissella uvarum) 등일 수 있다. In another embodiment, the strain may be used together with other strains belonging to the genus Weissella having a skin improvement effect to show a synergistic effect. The strain belonging to the genus Weissella is, for example, Weissella confuse ( Weissella confuse ), Weissella ubarum ) and the like.
상기 조성물은 조성물 총 중량에 대하여 0.001 중량% 내지 80 중량%, 예를 들면, 0.01 중량% 내지 60 중량%, 0.01 중량% 내지 40 중량%, 0.01 중량% 내지 30 중량%, 0.01 중량% 내지 20 중량%, 0.01 중량% 내지 10 중량%, 0.01 중량% 내지 5 중량%, 0.05 중량% 내지 60 중량%, 0.05 중량% 내지 40 중량%, 0.05 중량% 내지 30 중량%, 0.05 중량% 내지 20 중량%, 0.05 중량% 내지 10 중량%, 0.05 중량% 내지 5 중량%, 0.1 중량% 내지 60 중량%, 0.1 중량% 내지 40 중량%, 0.1 중량% 내지 30 중량%, 0.1 중량% 내지 20 중량%, 0.1 중량% 내지 10 중량%, 또는 0.1 중량% 내지 5 중량%의 균주, 이의 파쇄액, 배양액, 또는 이의 배양액의 추출물을 포함할 수 있다.The composition comprises 0.001 wt% to 80 wt%, for example, 0.01 wt% to 60 wt%, 0.01 wt% to 40 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 20 wt%, based on the total weight of the composition %, 0.01% to 10%, 0.01% to 5%, 0.05% to 60%, 0.05% to 40%, 0.05% to 30%, 0.05% to 20% by weight, 0.05% to 10% by weight, 0.05% to 5% by weight, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight, 0.1% by weight % to 10% by weight, or 0.1% to 5% by weight of the strain, a lysate thereof, a culture medium, or an extract of the culture medium thereof.
일 구체예에 있어서, 상기 조성물은 화장료 조성물일 수 있다. In one embodiment, the composition may be a cosmetic composition.
상기 화장료 조성물은 예를 들면, 유연화장수, 영양화장수, 마사지크림, 영양크림, 에센스, 팩, 젤, 앰플 또는 피부 점착 타입의 화장료 제형을 갖는 것일 수 있다.The cosmetic composition may have a cosmetic formulation of, for example, a softening lotion, a nourishing lotion, a massage cream, a nourishing cream, an essence, a pack, a gel, an ampoule, or a skin adhesion type.
상기 화장료 조성물에 포함되는 성분은 유효성분으로서 상기 조성물 이외에 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예를 들면, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제 및 담체를 포함할 수 있다.Components included in the cosmetic composition may include components commonly used in cosmetic compositions in addition to the composition as an active ingredient, for example, conventional adjuvants and carriers such as stabilizers, solubilizers, vitamins, pigments and fragrances. may include
다른 구체예에 있어서, 상기 조성물은 피부외용제용 조성물일 수 있다. In another embodiment, the composition may be a composition for external application to the skin.
본 명세서에서, 상기 피부외용제는 크림, 겔, 연고, 피부 유화제, 피부 현탁액, 경피전달성 패치, 약물 함유 붕대, 로션, 또는 그 조합일 수 있다. 상기 피부외용제는 통상 화장품이나 의약품 등의 피부외용제에 사용되는 성분, 예를 들면 수성성분, 유성성분, 분말성분, 알코올류, 보습제, 증점제, 자외선흡수제, 미백제, 방부제, 산화방지제, 계면활성제, 향료, 색제, 각종 피부 영양제, 또는 이들의 조합과 필요에 따라서 적절하게 배합될 수 있다. 상기 피부외용제는, 에데트산이나트륨, 에데트산삼나트륨, 시트르산나트륨, 폴리인산나트륨, 메타인산나트륨, 글루콘산 등의 금속봉쇄제, 카페인, 탄닌, 벨라파밀, 감초추출물, 글라블리딘, 칼린의 과실의 열수추출물, 각종생약, 아세트산토코페롤, 글리틸리틴산, 트라넥삼산 및 그 유도체 또는 그 염등의 약제, 비타민 C, 아스코르브산인산마그네슘, 아스코르브산글루코시드, 알부틴, 코지산, 글루코스, 프룩토스, 트레할로스 등의 당류 등도 적절하게 배합할 수 있다.In the present specification, the external preparation for skin may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermally delivered patch, drug-containing bandage, lotion, or a combination thereof. The external preparation for skin is a component usually used in external preparations for skin such as cosmetics or pharmaceuticals, for example, an aqueous component, an oily component, a powder component, alcohol, a moisturizer, a thickener, an ultraviolet absorber, a whitening agent, a preservative, an antioxidant, a surfactant, a fragrance , colorant, various skin nutrients, or a combination thereof may be appropriately formulated as needed. The external preparation for skin includes metal-blocking agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belapamil, licorice extract, glablidine, and kaline. Fruit hot water extracts, various herbal medicines, tocopherol acetate, glitylittic acid, tranexamic acid and derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars, such as trehalose, etc. can be mix|blended suitably.
다른 구체예에 있어서, 상기 조성물은 약학적 조성물일 수 있다. In another embodiment, the composition may be a pharmaceutical composition.
상기 약학적 조성물은 약제학적으로 허용 가능한 희석제 또는 담체를 추가적으로 포함할 수 있다. 상기 희석제는 유당, 옥수수 전분, 대두유, 미정질 셀룰로오스, 또는 만니톨, 활택제로는 스테아린산 마그네슘, 탈크, 또는 그 조합일 수 있다. 상기 담체는 부형제, 붕해제, 결합제, 활택제, 또는 그 조합일 수 있다. 상기 부형제는 미결정 셀룰로오즈, 유당, 저치환도 히드록시셀룰로오즈, 또는 그 조합일 수 있다. 상기 붕해제는 카르복시메틸셀룰로오스 칼슘, 전분글리콜산 나트륨, 무수인산일수소 칼슘, 또는 그 조합일 수 있다. 상기 결합제는 폴리비닐피롤리돈, 저치환도 히드록시프로필셀룰로오즈, 히드록시프로필셀룰로오즈, 또는 그 조합일 수 있다. 상기 활택제는 스테아린산 마그네슘, 이산화규소, 탈크, 또는 그 조합일 수 있다.The pharmaceutical composition may further include a pharmaceutically acceptable diluent or carrier. The diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and the lubricant may be magnesium stearate, talc, or a combination thereof. The carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be carboxymethyl cellulose calcium, sodium starch glycolate, anhydrous calcium monohydrogen phosphate, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.
상기 약학적 조성물은 경구 또는 비경구 투여 제형으로 제형화될 수 있다. 경구 투여 제형은 과립제, 산제, 액제, 정제, 캅셀제, 건조시럽제, 또는 그 조합일 수 있다. 비경구 투여 제형은 주사제일 수 있다.The pharmaceutical composition may be formulated as an oral or parenteral dosage form. Oral dosage forms may be granules, powders, solutions, tablets, capsules, dry syrups, or a combination thereof. The parenteral dosage form may be an injection.
다른 구체예에 있어서, 상기 조성물은 건강기능식품 조성물일 수 있다. In another embodiment, the composition may be a health functional food composition.
상기 건강기능식품 조성물은 상기 균주 또는 이의 배양액 단독 또는 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 명세서의 조성물은 원료에 대하여 15 중량부 이하의 양으로 첨가될 수 있다. 상기 건강기능식품의 종류에는 특별한 제한은 없다. 건강기능식품의 종류 중 음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 건강식품 조성물은 또한 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제, 또는 그 조합을 함유할 수 있다. 상기 건강기능식품 조성물은 또한, 천연 과일쥬스, 과일쥬스 음료, 야채 음료의 제조를 위한 과육, 또는 그 조합을 함유할 수 있다.The health functional food composition may be used alone or in combination with other foods or food ingredients of the strain or its culture, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prophylactic, health or therapeutic treatment). In general, in the production of food or beverage, the composition of the present specification may be added in an amount of 15 parts by weight or less based on the raw material. There is no particular limitation on the type of the health functional food. Among the types of health functional food, the beverage composition may contain various flavoring agents or natural carbohydrates as an additional component like a conventional beverage. The natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumartin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The health food composition may also be added to nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonated beverages carbonation agent used, or a combination thereof. The health functional food composition may also contain natural fruit juice, fruit juice beverage, fruit flesh for the production of vegetable beverage, or a combination thereof.
다른 양상은 유효한 양의 상기 조성물을 그를 필요로 하는 개체에 처리 또는 투여하는 단계를 포함하는 개체의 피부 상태를 예방, 개선 또는 치료하는 방법을 제공한다. 상기 피부 상태의 구체적인 내용은 전술한 바와 같다.Another aspect provides a method of preventing, ameliorating or treating a skin condition in a subject comprising treating or administering to the subject in need thereof an effective amount of the composition. Specific details of the skin condition are the same as described above.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 상처 치료용 약학적 조성물을 제공한다. 또 다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 상처 치료용 외용제 조성물을 제공한다. 또 다른 양상은 유효량의 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는 상처 치료 방법을 제공한다. 상기 상처의 구체적인 내용은 전술한 바와 같다. Another aspect provides a pharmaceutical composition for wound treatment comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient. Another aspect provides an external composition for wound treatment comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient. Another aspect provides a method for treating a wound comprising administering to a subject in need thereof an effective amount of the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof. The specific details of the wound are the same as described above.
본 명세서에서 용어, "투여하는", "도입하는", 및 "이식하는"은 상호교환적으로 사용되고 일 구체예에 따른 조성물의 원하는 부위로의 적어도 부분적 국소화를 초래하는 방법 또는 경로에 의한 개체 내로의 일 구체예에 따른 조성물의 배치를 의미할 수 있다. As used herein, the terms "administering", "introducing", and "implanting" are used interchangeably and into a subject by a method or route that results in at least partial localization of a composition according to one embodiment to a desired site. It may mean the arrangement of the composition according to one embodiment of the.
투여는 당업계에 알려진 방법에 의하여 투여될 수 있다. 투여는 예를 들면, 정맥내, 근육내, 경구, 경피 (transdermal), 점막, 코안 (intranasal), 기관내 (intratracheal) 또는 피하 투여와 같은 경로로, 임의의 수단에 의하여 개체로 직접적으로 투여될 수 있다. 상기 투여는 전신적으로 또는 국부적으로 투여될 수 있다.Administration may be administered by methods known in the art. Administration may be administered directly to a subject by any means, for example, intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. can The administration may be systemically or locally.
상기 개체는 포유동물, 예를 들면, 사람, 소, 말, 돼지, 개, 양, 염소, 또는 고양이일 수 있다. 상기 개체는 피부미용 개선, 예를 들어 피부 보습, 피부 장벽 강화, 피부 주름 개선 효과를 필요로 하는 개체일 수 있다.The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an individual in need of skin beauty improvement, for example, skin moisturizing, skin barrier strengthening, skin wrinkle improvement effect.
상기 투여는 일 구체예에 따른 조성물을 개체당 일당 0.1 ㎎ 내지 1,000 ㎎, 예를 들면, 0.1 ㎎ 내지 500 ㎎, 0.1 ㎎ 내지 100 ㎎, 0.1 ㎎ 내지 50 ㎎, 0.1 ㎎ 내지 25 ㎎, 1 ㎎ 내지 1,000 ㎎, 1 ㎎ 내지 500 ㎎, 1 ㎎ 내지 100 ㎎, 1 ㎎ 내지 50 ㎎, 1 ㎎ 내지 25 ㎎, 5 ㎎ 내지 1,000 ㎎, 5 ㎎ 내지 500 ㎎, 5 ㎎ 내지 100 ㎎, 5 ㎎ 내지 50 ㎎, 5 ㎎ 내지 25 ㎎, 10 ㎎ 내지 1,000 ㎎, 10 ㎎ 내지 500 ㎎, 10 ㎎ 내지 100 ㎎, 10 ㎎ 내지 50 ㎎, 또는 10 ㎎ 내지 25 ㎎을 투여하는 것일 수 있다. 다만, 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성별, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있고, 당업자라면 이러한 요인들을 고려하여 투여량을 적절히 조절할 수 있다. 투여 횟수는 1일 1회 또는 임상적으로 용인 가능한 부작용의 범위 내에서 2회 이상이 가능하고, 투여 부위에 대해서도 1개소 또는 2개소 이상에 투여할 수 있으며, 매일 또는 2 내지 5일 간격으로 총 투여 일수는 한번 치료 시 1일에서 30일까지 투여될 수 있다. 필요한 경우, 적정 시기 이후에 동일한 치료를 반복할 수 있다. 인간 이외의 동물에 대해서도, kg당 인간과 동일한 투여량으로 하거나, 또는 예를 들면 목적의 동물과 인간과의 기관(심장 등)의 용적비(예를 들면, 평균값) 등으로 상기의 투여량을 환산한 양을 투여할 수 있다.The administration is 0.1 mg to 1,000 mg, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg , 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg may be administered. However, the dosage may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and reaction sensitivity, and those skilled in the art The dosage may be appropriately adjusted in consideration of these factors. The number of administration may be once a day or twice or more within the range of clinically acceptable side effects, and may be administered to one or two or more places for the site of administration, and total daily or at intervals of 2 to 5 days The number of days of administration may range from 1 to 30 days per treatment. If necessary, the same treatment can be repeated after a titration period. For animals other than humans, the dose is the same as that of a human per kg, or the above dose is converted, for example, by the volume ratio (for example, average value) of the target animal and the organ (heart, etc.) of the human One dose can be administered.
상기한 바와 같이, 일 양상에 따른 균주는 피부 보습 및 피부 장벽 관련 히알루론산 합성 효소 3(Hyaluronan synthase 3, HAS3), 필라그린(filagrin))의 발현을 증가시키고 손상된 세포를 재생시킬 수 있다. 또한, 상기 균주는 자외선에 의해 감소된 COL1A1의 발현을 증가시키고, 증가된 MMP-1의 발현을 감소시킬 수 있다. 즉, HAS3 및 필라그린 등과 같은 마커의 증가는 정상적인 각질층의 형성을 통하여 각질세포 내에 NMF의 전구체인 필라그린과 세포간 지질이 정상화된 것을 의미한다. 따라서, 피부 노화를 방지하고 외부 환경 변화인 대기 건조, 자외선 및 각종 공해 물질로부터 피부 건강을 유지할 수 있도록, 피부 조직의 수분 유지를 촉진하면서, 피부 조직의 수분의 손실을 방지하는 피부 장벽을 강화하도록 각질층을 형성할 수 있다. As described above, the strain according to one aspect can increase the expression of skin moisturizing and skin barrier-related hyaluronic acid synthase 3 (Hyaluronan synthase 3, HAS3, filagrin) and regenerate damaged cells. In addition, the strain can increase the expression of COL1A1 reduced by ultraviolet light, and decrease the increased expression of MMP-1. That is, the increase in markers such as HAS3 and filaggrin means that filaggrin, a precursor of NMF, and intercellular lipids are normalized in keratinocytes through the formation of a normal stratum corneum. Therefore, to prevent skin aging and maintain skin health from external environmental changes such as atmospheric drying, ultraviolet rays and various pollutants, to strengthen the skin barrier to prevent moisture loss in the skin tissue while promoting the maintenance of moisture in the skin tissue It can form a stratum corneum.
또한, 상기 균주는 손상된 섬유아세포 및 세포외기질의 증식을 촉진하여 피부를 재생시키고 상피층을 회복시키는 바, 피부 재생 또는 상처 회복에 유용하다. In addition, the strain promotes the proliferation of damaged fibroblasts and extracellular matrix to regenerate the skin and restore the epithelial layer, so it is useful for skin regeneration or wound healing.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 구강 조성물을 제공한다. 상기 균주의 구체적인 내용은 전술한 바와 같다. Another aspect provides an oral composition comprising the strain, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof as an active ingredient. Specific details of the strain are the same as described above.
일 실시예에서는 상기 균주가 구취 유발 미생물에 의해 발생하는 휘발성 유황화합물(Volatile Sulfur Compounds, VSC)인 황화수소, 메틸머캅탄 및 디메틸설파이드의 농도를 감소시키고, 구강 미생물의 양을 감소시키는 것을 확인하였다. 구체적으로, 상기 황화수소(Hydrogen sulfide, H2S)는 구강 내 오염 및 정신적, 생리적 원인과 관련된 질환에 의해 구취를 유발할 수 있다. 또한, 상기 메틸머캅탄(Methyl mercaptan, CH3SH)는 구강 내 질환(치주병)에 의해 구취를 유발할 수 있다. 또한, 디메틸설파이드(Dimethyl sulfide, (CH3)2S)는 음식물의 대사에 의한 일과성 구취를 유발할 수 있다. In one embodiment, the strain reduces the concentrations of volatile sulfur compounds (VSC), methyl mercaptan and dimethyl sulfide, which are volatile sulfur compounds (VSC) generated by bad breath-inducing microorganisms, and it was confirmed that the amount of oral microorganisms was reduced. Specifically, the hydrogen sulfide (Hydrogen sulfide, H 2 S) may cause bad breath due to oral contamination and diseases related to mental and physiological causes. In addition, the methyl mercaptan (Methyl mercaptan, CH 3 SH) may cause bad breath due to oral diseases (periodontal disease). In addition, dimethyl sulfide (Dimethyl sulfide, (CH 3 ) 2 S) may cause transient bad breath due to food metabolism.
본 명세서에서 용어, "구취"는 일상생활에서 겪는 문제로서 90%는 구강 내에서 치주염, 설태, 구강위생 불량, 부적적한 보철로부터 유래하며 나머지 10%는 위장관질환, 암종, 당뇨, 간부전, 신부전과 같은 전신질환에서 유래한다. 구강 내에는 600종 이상의 세균이 서식하는데 그 중에는 질병 유발 세균도 포함되어 있으며, 구강 세균, 플라그내와 혓바닥에 서식하는 세균이 불쾌한 냄새를 생성하여 구취를 유발할 수 있다. As used herein, the term "halitosis" is a problem experienced in daily life, and 90% of it is derived from periodontitis, tongue discoloration, poor oral hygiene, and inadequate prosthetics in the oral cavity, and the remaining 10% is gastrointestinal disease, carcinoma, diabetes, liver failure, renal failure and from the same systemic disease. More than 600 types of bacteria live in the oral cavity, including disease-causing bacteria.
따라서, 일 양상에 따른 균주는 구강 내 오염 및 각종 질환, 또는 음식물 대사에 의한 구취 개선, 치태 감소, 치석 감소, 구강 건조 감소, 또는 구강 세균 억제 효과를 가지는 것일 수 있다. Therefore, the strain according to an aspect may have an effect of improving oral contamination and various diseases, or bad breath caused by food metabolism, reducing plaque, reducing tartar, reducing dry mouth, or inhibiting oral bacteria.
일 구체예에 있어서, 상기 구강 조성물은 구강 청정제, 구강 세정제, 치약, 오랄 스프레이, 의치 세정제, 치약 미백제 등으로 제형화될 수 있다. In one embodiment, the oral composition may be formulated as a mouthwash, mouthwash, toothpaste, oral spray, denture cleaner, toothpaste whitening agent, and the like.
다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 구강 질환의 예방 또는 치료용 약학적 조성물을 제공한다. 또 다른 양상은 유효한 양의 상기 조성물을 그를 필요로 하는 개체에 투여하는 단계를 포함하는 구강 질환의 치료방법을 제공한다. 또 다른 양상은 상기 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 구강 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다. 상기 균주의 구체적인 내용은 전술한 바와 같다.Another aspect provides a pharmaceutical composition for preventing or treating oral diseases comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient. Another aspect provides a method of treating an oral disease comprising administering to a subject in need thereof an effective amount of the composition. Another aspect provides a health functional food composition for preventing or improving oral diseases comprising the strain, its lysate, culture medium, extract of the culture medium, or a mixture thereof as an active ingredient. Specific details of the strain are the same as described above.
상기 구강 질환은 예를 들어, 침습성치주염, 소아 치주염, 급성 또는 만성 치주염, 치조골 파괴, 만성 또는 난치성 치주염, 치은염, 궤양성 치은염, 급성 치관주위염, 급성 괴상성 치은염, 호르몬성 치주염, 복합 감염, 치근단 질환, 치주 농양, 치아우식, 치근단 농양, 치수염 등인 것일 수 있다. The oral disease is, for example, invasive periodontitis, juvenile periodontitis, acute or chronic periodontitis, alveolar bone destruction, chronic or intractable periodontitis, gingivitis, ulcerative gingivitis, acute paronychia, acute lumpy gingivitis, hormonal periodontitis, complex infection, apical It may be a disease, periodontal abscess, dental caries, apical abscess, pulpitis, and the like.
일 실시예에서는 상기 균주를 포함하는 조성물의 2주 사용 후 대표적인 구강 미생물인 타네렐라 포르시티아균(Tannerella forsythia), 후소박테리움 뉴클레아툼(Fusobacterium nucleatum), 프리보텔라 니그레센스균(Prevotella nigrescens), 스트렙토코서스 미티스균(Streptococcus mitis) 및 스트렙토코커스 무탄스균(Streptococcus mutans)의 사용 전과 비교하여 현저하게 감소하였으며, 장기 사용에 의한 이상 반응이 나타나지 않음을 확인하였다. In one embodiment, after 2 weeks of use of the composition containing the strain, representative oral microorganisms Tannerella forsythia , Fusobacterium nucleatum , Prevotella nigrescens ( Prevotella ) nigrescens ), Streptococcus mitis and Streptococcus mutans were significantly reduced compared to before use, and it was confirmed that no adverse reactions due to long-term use were observed.
따라서, 일 양상에 따른 균주는 구강 미생물 억제 효과가 우수할 뿐만 아니라 인체 구강에 대한 안정성이 우수하여 장기간 사용하더라도 구강 내 세균의 내성에 영향이 없으므로 치주염, 치은염, 치아 우식 등과 같은 구강 질환의 예방 또는 치료에 효과적이다. Therefore, the strain according to one aspect has excellent oral microbial inhibitory effect as well as excellent stability for the human oral cavity, so even if used for a long period of time, it does not affect the resistance of bacteria in the oral cavity. effective in treatment.
일 양상에 따른 바이셀라 시바이라 균주에 의하면, 피부 관련 상태의 예방, 개선 또는 치료에 유용하게 사용될 수 있다. 또한, 구취를 유발하는 유황 화합물의 감소 및 구강 미생물을 억제함으로써 구강 질환의 예방, 개선 또는 치료에 유용하게 사용될 수 있다.According to the Weissella sibaira strain according to an aspect, it can be usefully used for preventing, improving or treating skin-related conditions. In addition, it can be usefully used for the prevention, improvement or treatment of oral diseases by reducing the sulfur compounds causing bad breath and inhibiting oral microorganisms.
도 1은 일 구체예에 따른 균주가 HAS3의 발현에 미치는 영향을 나타낸 그래프이다. 1 is a graph showing the effect of a strain according to an embodiment on the expression of HAS3.
도 2는 일 구체예에 따른 균주가 필라그린의 발현에 미치는 영향을 나타낸 그래프이다.2 is a graph showing the effect of a strain according to an embodiment on the expression of filaggrin.
도 3은 일 구체예에 따른 균주가 피부 재생 또는 상처 회복에 미치는 영향을 나타낸 그래프이다. 3 is a graph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
도 4는 일 구체예에 따른 균주가 피부 재생 또는 상처 회복에 미치는 영향을 나타낸 사진이다.4 is a photograph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
[규칙 제91조에 의한 정정 24.02.2022]
도 5는 일 구체예에 따른 균주가 COL1A1의 발현에 미치는 영향을 나타낸 그래프이다.[Correction by Rule 91 24.02.2022]
5 is a graph showing the effect of a strain according to an embodiment on the expression of COL1A1.
도 5는 일 구체예에 따른 균주가 COL1A1의 발현에 미치는 영향을 나타낸 그래프이다.[Correction by Rule 91 24.02.2022]
5 is a graph showing the effect of a strain according to an embodiment on the expression of COL1A1.
[규칙 제91조에 의한 정정 24.02.2022]
도 5는 일 구체예에 따른 균주가 MMP-1의 발현에 미치는 영향을 나타낸 그래프이다.[Correction by Rule 91 24.02.2022]
5 is a graph showing the effect of a strain according to an embodiment on the expression of MMP-1.
도 5는 일 구체예에 따른 균주가 MMP-1의 발현에 미치는 영향을 나타낸 그래프이다.[Correction by Rule 91 24.02.2022]
5 is a graph showing the effect of a strain according to an embodiment on the expression of MMP-1.
도 6a는 일 양상에 따른 조성물의 사용 전, 사용 직후 및 사용 2주 후의 황화수소의 농도 변화를 비교한 그래프이다. 6A is a graph comparing changes in the concentration of hydrogen sulfide before, immediately after, and after 2 weeks of use of the composition according to an aspect.
도 6b는 일 양상에 따른 조성물의 사용 전, 사용 직후 및 사용 2주 후의 메틸머캅탄의 농도 변화를 비교한 그래프이다. 6B is a graph comparing changes in the concentration of methyl mercaptan before, immediately after, and 2 weeks after use of the composition according to an aspect.
도 6c는 일 양상에 따른 조성물의 사용 전, 사용 직후 및 사용 2주 후의 디메틸설파이드의 농도 변화를 비교한 그래프이다.6c is a graph comparing changes in the concentration of dimethyl sulfide before, immediately after, and after 2 weeks of use of the composition according to an aspect.
도 7a는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 액티노마이세템코미탄스 균(Aa) 및 진지발리스균(Pg)의 양을 비교한 그래프이다. Figure 7a is a graph comparing the amounts of bacteria Actinomycetem comitans ( Aa ) and gingivalis ( Pg ) before and 2 weeks after use of the composition according to an aspect.
도 7b는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 포르시티아균(Tf) 및 덴티콜라균(Td)의 양을 비교한 그래프이다. Figure 7b is a graph comparing the amounts of bacteria forsythia ( Tf ) and bacteria denticola ( Td ) before and 2 weeks after use of the composition according to an aspect.
도 7c는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 뉴클레아툼균(Fn) 및 인터미디아균(Pi)의 양을 비교한 그래프이다. Figure 7c is a graph comparing the amounts of nucleatum bacteria ( Fn ) and intermediary bacteria ( Pi ) before and 2 weeks after use of the composition according to an aspect.
도 7d는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 니그레센스균(Pn) 및 미티스균(Smi)의 양을 비교한 그래프이다.Figure 7d is a graph comparing the amount of bacteria nigrescens ( Pn ) and Mytisbacterium ( Smi ) before and 2 weeks after use of the composition according to an aspect.
도 7e는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 무탄스균(Smu) 및 카제이균(Lc)의 양을 비교한 그래프이다.Figure 7e is a graph comparing the amounts of bacteria mutans ( Smu ) and casei bacteria ( Lc ) before and 2 weeks after use of the composition according to an aspect.
도 7f는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 총 미생물량을 비교한 그래프이다. 7f is a graph comparing the total amount of microorganisms before and 2 weeks after use of the composition according to an aspect.
도 8은 일 양상에 따른 조성물의 효능 및 사용성에 관한 설문 평가 결과를 분석한 그래프이다.8 is a graph analyzing the results of a questionnaire evaluation regarding the efficacy and usability of a composition according to an aspect.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred examples are presented to help the understanding of the present invention. However, the following examples are only provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples.
[실시예][Example]
실시예 1. 균주의 분리 및 동정Example 1. Isolation and identification of strains
사람의 구강 내 타액 및 김치로부터 채취한 시료를 MRS를 함유하는 액체 배지 또는 고체 배지(Becton Dickinson, Cockeysville, MD)에 접종하였다. 접종 후 28℃ 인큐베이터에서 48시간 동안 배양한 뒤 형성된 집락 100개를 순수 분리 배양하여, 28℃ 인큐베이터에서 48시간 동안 재배양 하였다. 배양이 완료된 집락은 16s rRNA 유전자 서열 동정을 실시하였다. 이때 사용된 프라이머는 박테리아에만 반응하여 증폭하도록 고안되었다(27F, 5'-AGAGTTTGATCCTGGCTCAG-3'; 1492R, 5'-GGTTACCTTGTTACGACTT-3). PCR 증폭은 95℃ 1분, 55℃ 1분, 75℃ 1분 30초씩 30 사이클로 실시 하였으며, 마지막으로 72℃에서 8분간 처리한 후 4℃에서 보관하였다. PCR 반응이 끝난 뒤 분리 배양된 종들의 DNA 서열은 ABI-3730XL(ABI, USA)를 이용하여 결정하였다. 분리 배양된 미생물 집락 중 결정된 16S rRNA부위의 염기서열을 미국 국립생물정보센터(NCBI, National Center for Biotechnology Information) 홈페이지에서 제공되는 BLAST 프로그램에 등록된 다른 균주들과 비교 분석 하여 상동성 97% 이하의 신규성 있는 종들만 선별하여 사용하였고, 그 중 상동성 97% 이하의 신규 미생물 바이셀라 시바리아(Weissella cibaria) 균주(이하 "CXO-1"이라 함)을 선별하였다. 선별된 CXO-1 균주를 2020년 12월 3일자로 한국 미생물 보존센터에 기탁하여 기탁번호 KCCM12889P를 부여 받았고, CXO-1 균주는 서열번호 1(complementary DNA)의 16s rRNA 서열을 갖는다.Samples collected from human oral saliva and kimchi were inoculated into a liquid or solid medium (Becton Dickinson, Cockeysville, MD) containing MRS. After inoculation, 100 colonies formed after culturing for 48 hours in an incubator at 28°C were purely separated and cultured, and cultured in an incubator at 28°C for 48 hours. The cultured colonies were subjected to 16s rRNA gene sequence identification. The primers used were designed to amplify in response to bacteria only (27F, 5'-AGAGTTTGATCCTGGCTCAG-3'; 1492R, 5'-GGTTACCTTGTTACGACTT-3). PCR amplification was carried out in 30 cycles of 95°C for 1 minute, 55°C for 1 minute, 75°C for 1 minute and 30 seconds, and finally, after treatment at 72°C for 8 minutes, it was stored at 4°C. After the PCR reaction, the DNA sequences of the isolated and cultured species were determined using ABI-3730XL (ABI, USA). The nucleotide sequence of the 16S rRNA region determined from the isolated and cultured microbial colonies was compared with other strains registered in the BLAST program provided on the website of the National Center for Biotechnology Information (NCBI), and the homology of 97% or less was found. Only novel species were selected and used, and among them, a novel microorganism with 97% homology or less Weissella cibaria strain (hereinafter referred to as "CXO-1") was selected. The selected CXO-1 strain was deposited with the Korea Microbial Conservation Center on December 3, 2020 and was given an accession number KCCM12889P, and the CXO-1 strain has a 16s rRNA sequence of SEQ ID NO: 1 (complementary DNA).
[실험예][Experimental example]
피부 장벽 강화 및 피부 보습 활성 Skin barrier strengthening and skin moisturizing activity
상기 실시예 1에서 분리된 CXO-1 균주의 배양액이 피부장벽강화 및 피부 보습 활성에 미치는 영향을 분석하였다. 구체적으로, 인간 각질형성 세포주(human keratinocyte)인 HaCaT 세포를 10% 우혈청 (fetal bovine serum)을 포함한 DMEM 배지(Dulbecco'smodified Eagle's Medium, Gibco 1210-0038)에서 배양하였고, 배양은 모두 37℃ 5% CO2 배양기에서 수행하였다. 상기 배양된 세포주에 상기 CXO-1 균주의 배양액(1%, 10%(w/w))을 처리하고 24시간 동안 추가 배양하였다. The effect of the culture medium of the CXO-1 strain isolated in Example 1 on skin barrier strengthening and skin moisturizing activity was analyzed. Specifically, HaCaT cells, which are human keratinocytes, were cultured in DMEM medium (Dulbecco'smodified Eagle's Medium, Gibco 1210-0038) containing 10% fetal bovine serum, and all cultures were cultured at 37°C 5°C. % CO 2 in an incubator. The cultured cell line was treated with the culture solution of the CXO-1 strain (1%, 10% (w/w)) and further cultured for 24 hours.
양성 대조군으로 레티논산(Retionic acid) 1 μM을 사용하였다. 그 후 각 시료의 세포에서 트리졸(RNA iso, DAKARA, 일본)을 이용하여 RNA를 분리한 뒤 nanodrop으로 260㎚에서 RNA를 정량한 후, 각각 2㎍의 RNA를 사용하여 증폭기에서 cDNA를 합성하였다(C1000 Thermal Cycler, Bio-Rad, 미국). 합성된 cDNA를 주형으로 타겟 유전자인 피부 장벽 강화 및 보습과 관련된 인자인 HAS3(히알루론산 합성 효소), 및 필라그린에 대한 프라이머 및 cDNA와 함께 첨가하여 실시간(real-time) PCR 기계 (Step One Plus, Applied Biosystems, 미국)에서 실시간 중합효소 연쇄반응을 수행하였다. 유전자의 발현량은 β-actin 유전자에 대한 보정을 통해 최종적으로 분석하였고, 그 결과를 도 1 및 도 2에 나타내었다. As a positive control, 1 μM of retionic acid was used. After that, RNA was isolated from the cells of each sample using trizol (RNA iso, DAKARA, Japan), and RNA was quantified at 260 nm with nanodrops, and cDNA was synthesized in an amplifier using 2 μg of RNA each. (C1000 Thermal Cycler, Bio-Rad, USA). Using the synthesized cDNA as a template, the target gene, HAS3 (hyaluronic acid synthase), a factor related to skin barrier strengthening and moisturizing, and primers and cDNA for filaggrin were added together with a real-time PCR machine (Step One Plus, Real-time polymerase chain reaction was performed in Applied Biosystems, USA). The expression level of the gene was finally analyzed through correction for the β-actin gene, and the results are shown in FIGS. 1 and 2 .
도 1은 일 구체예에 따른 균주가 HAS3의 발현에 미치는 영향을 나타낸 그래프이다. 1 is a graph showing the effect of a strain according to an embodiment on the expression of HAS3.
도 2는 일 구체예에 따른 균주가 필라그린의 발현에 미치는 영향을 나타낸 그래프이다. 2 is a graph showing the effect of a strain according to an embodiment on the expression of filaggrin.
그 결과, 도 1 및 도 2에 나타낸 바와 같이, 일 구체예에 따른 균주는 농도 의존적으로 HAS3 및 필라그린의 발현을 유의적으로 증가시킴으로써 손상된 피부 장벽을 복원시키고 피부 장벽을 강화하여 피부 방어력을 높여줄 수 있다. 또한, 피부 보습에 탁월하여 보습 관련 질환의 예방 또는 치료에 효과적이다. As a result, as shown in FIGS. 1 and 2, the strain according to one embodiment restores the damaged skin barrier by significantly increasing the expression of HAS3 and filaggrin in a concentration-dependent manner, and strengthens the skin barrier to increase skin defense. can give In addition, it is excellent in moisturizing the skin and is effective in preventing or treating moisture-related diseases.
피부 재생 및 상처 회복 효능Skin regeneration and wound healing effect
상기 실시예 1에서 분리된 CXO-1 균주의 피부 재생 및 상처 회복 효능을 평가하기 위하여, 세포 이동성 검정(cell migration assay)을 수행하였다. 구체적으로, 96-웰 ImageLock쪠 플레이트(No. 4379; Essen BioScience)에 Hs68 인간 섬유아세포를 2Х104 세포/웰로 분주하였다. 실험은 90% cell confluent에서 진행하였다. 둘째 날, WoundMaker쪠(Essen BioScience, USA)를 70% 에탄올 용액 45 ㎖로 5분 동안 세척한 후, 증류수 45 ㎖로 5분 동안 세척하였다. 세척된 WoundMaker쪠를 사용하여 상기 플레이트 각 웰의 모든 세포층을 스크래치 하였다. 이후, 배지를 제거하고, PBS로 세척하였다. 무혈청배지를 채운 후, 각 시험 물질을 처리하였다. 셋째 날, IncuCyte ZOOM(Essen BioScience, USA) 프로그램을 사용하여 상처가 회복되는 정도를 2시간 간격으로 8시간 동안 측정하여 그래프화 하였다. 또한, 기기 내의 현미경으로 측정된 세포 사진을 확인하여 상처 회복 정도를 육안으로 확인하였다.In order to evaluate the skin regeneration and wound healing efficacy of the CXO-1 strain isolated in Example 1, a cell migration assay was performed. Specifically, Hs68 human fibroblasts were seeded in 96-well ImageLock plate (No. 4379; Essen BioScience) at 2Х10 4 cells/well. Experiments were conducted at 90% cell confluent. On the second day, WoundMaker (Essen BioScience, USA) was washed with 45 ml of 70% ethanol solution for 5 minutes, and then washed with 45 ml of distilled water for 5 minutes. All cell layers in each well of the plate were scratched using the washed WoundMaker™. Then, the medium was removed and washed with PBS. After filling the serum-free medium, each test substance was treated. On the third day, using the IncuCyte ZOOM (Essen BioScience, USA) program, the degree of wound recovery was measured and graphed at 2-hour intervals for 8 hours. In addition, the degree of wound recovery was visually confirmed by checking the photograph of the cell measured with a microscope in the device.
도 3은 일 구체예에 따른 균주가 피부 재생 또는 상처 회복에 미치는 영향을 나타낸 그래프이다. 3 is a graph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
도 4는 일 구체예에 따른 균주가 피부 재생 또는 상처 회복에 미치는 영향을 나타낸 사진이다. 4 is a photograph showing the effect of a strain according to an embodiment on skin regeneration or wound recovery.
그 결과, 도 3 및 도 4에 나타낸 바와 같이, 무처리 대조군과 비교하여 무혈청 배지 및 상기 실시예 1에서 분리된 CXO-1 균주의 배양액을 처리한 군에서 상처 회복 효과가 우수한 것을 확인할 수 있었다. 특히, CXO-1 균주의 배양액을 1% 농도로 처리한 군에서 8시간 후 약 60% 정도 회복되는 것을 확인할 수 있었다. As a result, as shown in FIGS. 3 and 4, it was confirmed that the wound healing effect was excellent in the group treated with the serum-free medium and the culture solution of the CXO-1 strain isolated in Example 1 compared to the untreated control group. . In particular, it was confirmed that about 60% recovery after 8 hours in the group treated with the culture solution of the CXO-1 strain at a concentration of 1%.
즉, 일 구체예에 따른 균주는 상처 부위의 세포를 활성화시켜 피부재생을 촉진하는 바, 피부 재생 또는 상처 회복 소재로 활용될 수 있다. That is, the strain according to one embodiment promotes skin regeneration by activating cells in the wound site, and thus can be used as a material for skin regeneration or wound healing.
항노화 활성 분석Anti-aging activity assay
상기 실시예 1에서 분리된 CXO-1 균주 배양액이 자외선(UV) 조사에 의한 노화피부 노화 및 주름 생성과 관련된 인자에 미치는 영향을 분석하였다. The effect of the CXO-1 strain culture medium isolated in Example 1 on factors related to aging skin aging and wrinkle generation by ultraviolet (UV) irradiation was analyzed.
[규칙 제91조에 의한 정정 24.02.2022]
구체적으로, 인간 섬유아세포 세포주(Human dermal fibroblast, Hs68)를 6 웰 플레이트에 3.5x105 세포/웰로 분주한 후, 37℃, 5% CO2 조건의 배양기에서 24시간 동안 배양하였다. 이후 배지를 제거하고 DPBS를 넣은 후 20 mJ/㎠의 UVB를 조사하거나 조사하지 않았다. UVB 조사 직후 DPBS를 제거하고 FBS가 없는 배지로 갈아 준 후, 상기 CXO-1 균주의 배양액을 농도별(1%(w/w), 10%(w/w))로 처리하고 24시간 동안 추가 배양하였다. 음성 대조군으로 자외선 처리 및 균주 배양액 비처리군을 사용하였다. 그 후 각 시료의 세포에서 트리졸(RNA iso, DAKARA, 일본)을 이용하여 RNA를 분리한 뒤 nanodrop으로 260 ㎚에서 RNA를 정량한 후, 각각 2㎍의 RNA를 사용하여 증폭기에서 cDNA를 합성하였다(C1000 Thermal Cycler, Bio-Rad, 미국). 합성된 cDNA를 주형으로 타겟 유전자인 COL1A1, 및 MMP-1에 대하여 사이버그린 (SYBR Green supermix, Applied Biosystems, USA)을 프라이머 및 cDNA와 함께 첨가하여 실시간(real-time) PCR 기계 (Step One Plus, Applied Biosystems, 미국)에서 실시간 중합효소 연쇄반응을 수행하였다. 유전자의 발현량은 β-actin 유전자에 대한 보정을 통해 최종적으로 분석하였고, 그 결과를 도 5에 나타내었다.[Correction by Rule 91 24.02.2022]
Specifically, a human dermal fibroblast (Hs68) cell line was seeded in a 6-well plate at 3.5x10 5 cells/well, and then cultured in an incubator at 37° C. and 5% CO 2 condition for 24 hours. After removing the medium and adding DPBS, 20 mJ/cm2 of UVB was irradiated or not. Immediately after UVB irradiation, after removing DPBS and replacing it with a medium without FBS, the culture solution of the CXO-1 strain was treated by concentration (1% (w/w), 10% (w/w)) and added for 24 hours cultured. As a negative control group, UV-treated and strain culture untreated groups were used. After that, RNA was isolated from the cells of each sample using trizol (RNA iso, DAKARA, Japan), and RNA was quantified at 260 nm using nanodrops, and cDNA was synthesized in an amplifier using 2 μg of each RNA. (C1000 Thermal Cycler, Bio-Rad, USA). Using the synthesized cDNA as a template, a real-time PCR machine (Step One Plus, Step One Plus, Real-time polymerase chain reaction was performed in Applied Biosystems, USA). The expression level of the gene was finally analyzed through correction for the β-actin gene, and the results are shown in FIG. 5 .
구체적으로, 인간 섬유아세포 세포주(Human dermal fibroblast, Hs68)를 6 웰 플레이트에 3.5x105 세포/웰로 분주한 후, 37℃, 5% CO2 조건의 배양기에서 24시간 동안 배양하였다. 이후 배지를 제거하고 DPBS를 넣은 후 20 mJ/㎠의 UVB를 조사하거나 조사하지 않았다. UVB 조사 직후 DPBS를 제거하고 FBS가 없는 배지로 갈아 준 후, 상기 CXO-1 균주의 배양액을 농도별(1%(w/w), 10%(w/w))로 처리하고 24시간 동안 추가 배양하였다. 음성 대조군으로 자외선 처리 및 균주 배양액 비처리군을 사용하였다. 그 후 각 시료의 세포에서 트리졸(RNA iso, DAKARA, 일본)을 이용하여 RNA를 분리한 뒤 nanodrop으로 260 ㎚에서 RNA를 정량한 후, 각각 2㎍의 RNA를 사용하여 증폭기에서 cDNA를 합성하였다(C1000 Thermal Cycler, Bio-Rad, 미국). 합성된 cDNA를 주형으로 타겟 유전자인 COL1A1, 및 MMP-1에 대하여 사이버그린 (SYBR Green supermix, Applied Biosystems, USA)을 프라이머 및 cDNA와 함께 첨가하여 실시간(real-time) PCR 기계 (Step One Plus, Applied Biosystems, 미국)에서 실시간 중합효소 연쇄반응을 수행하였다. 유전자의 발현량은 β-actin 유전자에 대한 보정을 통해 최종적으로 분석하였고, 그 결과를 도 5에 나타내었다.[Correction by Rule 91 24.02.2022]
Specifically, a human dermal fibroblast (Hs68) cell line was seeded in a 6-well plate at 3.5x10 5 cells/well, and then cultured in an incubator at 37° C. and 5% CO 2 condition for 24 hours. After removing the medium and adding DPBS, 20 mJ/cm2 of UVB was irradiated or not. Immediately after UVB irradiation, after removing DPBS and replacing it with a medium without FBS, the culture solution of the CXO-1 strain was treated by concentration (1% (w/w), 10% (w/w)) and added for 24 hours cultured. As a negative control group, UV-treated and strain culture untreated groups were used. After that, RNA was isolated from the cells of each sample using trizol (RNA iso, DAKARA, Japan), and RNA was quantified at 260 nm using nanodrops, and cDNA was synthesized in an amplifier using 2 μg of each RNA. (C1000 Thermal Cycler, Bio-Rad, USA). Using the synthesized cDNA as a template, a real-time PCR machine (Step One Plus, Step One Plus, Real-time polymerase chain reaction was performed in Applied Biosystems, USA). The expression level of the gene was finally analyzed through correction for the β-actin gene, and the results are shown in FIG. 5 .
[규칙 제91조에 의한 정정 24.02.2022]
도 5는 일 구체예에 따른 균주가 COL1A1의 발현에 미치는 영향을 나타낸 그래프이고, 도 5b는 일 구체예에 따른 균주가 MMP-1의 발현에 미치는 영향을 나타낸 그래프이다.[Correction by Rule 91 24.02.2022]
Figure 5 is a graph showing the effect of the strain according to one embodiment on the expression of COL1A1, Figure 5b is a graph showing the effect of the strain according to one embodiment on the expression of MMP-1.
도 5는 일 구체예에 따른 균주가 COL1A1의 발현에 미치는 영향을 나타낸 그래프이고, 도 5b는 일 구체예에 따른 균주가 MMP-1의 발현에 미치는 영향을 나타낸 그래프이다.[Correction by Rule 91 24.02.2022]
Figure 5 is a graph showing the effect of the strain according to one embodiment on the expression of COL1A1, Figure 5b is a graph showing the effect of the strain according to one embodiment on the expression of MMP-1.
[규칙 제91조에 의한 정정 24.02.2022]
그 결과, 도 5에 나타낸 바와 같이, 무처리 대조군과 비교하여 무혈청 배지 및 상기 실시예 1에서 분리된 CXO-1 균주의 배양액을 처리한 군에서 자외선에 의해 감소된 COL1A1의 발현을 농도 의존적으로 증가시키는 것을 확인할 수 있었다. 특히, CXO-1 균주 배양액을 10%의 농도로 처리한 군은 동일한 농도의 무혈청 배지와 비교하여 COL1A 발현이 유의적으로 높은 것을 확인할 수 있었다. 또한, 도 5b에 나타낸 바와 같이, 무처리 대조군과 비교하여 무혈청 배지 및 상기 실시예 1에서 분리된 CXO-1 균주의 배양액을 처리한 군에서 자외선에 의해 증가된 MMP-1의 발현을 농도 의존적으로 감소시키는 것을 확인할 수 있었다. 특히, CXO-1 균주 배양액을 10%의 농도로 처리한 군은 동일한 농도의 무혈청 배지와 비교하여 MMP-1의 발현이 현저하게 감소한 것을 확인할 수 있었다.[Correction by Rule 91 24.02.2022]
As a result, as shown in Figure 5, compared to the untreated control group, the expression of COL1A1 reduced by ultraviolet rays in the group treated with the serum-free medium and the culture solution of the CXO-1 strain isolated in Example 1 was concentration-dependently increase could be observed. In particular, it was confirmed that the group treated with the CXO-1 strain culture solution at a concentration of 10% had significantly higher COL1A expression compared to the serum-free medium at the same concentration. In addition, as shown in FIG. 5b, the expression of MMP-1 increased by UV in the group treated with the serum-free medium and the culture solution of the CXO-1 strain isolated in Example 1 was concentration-dependent as compared to the untreated control group. was found to decrease. In particular, it was confirmed that the group treated with the CXO-1 strain culture solution at a concentration of 10% significantly reduced the expression of MMP-1 compared to the serum-free medium at the same concentration.
그 결과, 도 5에 나타낸 바와 같이, 무처리 대조군과 비교하여 무혈청 배지 및 상기 실시예 1에서 분리된 CXO-1 균주의 배양액을 처리한 군에서 자외선에 의해 감소된 COL1A1의 발현을 농도 의존적으로 증가시키는 것을 확인할 수 있었다. 특히, CXO-1 균주 배양액을 10%의 농도로 처리한 군은 동일한 농도의 무혈청 배지와 비교하여 COL1A 발현이 유의적으로 높은 것을 확인할 수 있었다. 또한, 도 5b에 나타낸 바와 같이, 무처리 대조군과 비교하여 무혈청 배지 및 상기 실시예 1에서 분리된 CXO-1 균주의 배양액을 처리한 군에서 자외선에 의해 증가된 MMP-1의 발현을 농도 의존적으로 감소시키는 것을 확인할 수 있었다. 특히, CXO-1 균주 배양액을 10%의 농도로 처리한 군은 동일한 농도의 무혈청 배지와 비교하여 MMP-1의 발현이 현저하게 감소한 것을 확인할 수 있었다.[Correction by Rule 91 24.02.2022]
As a result, as shown in Figure 5, compared to the untreated control group, the expression of COL1A1 reduced by ultraviolet rays in the group treated with the serum-free medium and the culture solution of the CXO-1 strain isolated in Example 1 was concentration-dependently increase could be observed. In particular, it was confirmed that the group treated with the CXO-1 strain culture solution at a concentration of 10% had significantly higher COL1A expression compared to the serum-free medium at the same concentration. In addition, as shown in FIG. 5b, the expression of MMP-1 increased by UV in the group treated with the serum-free medium and the culture solution of the CXO-1 strain isolated in Example 1 was concentration-dependent as compared to the untreated control group. was found to decrease. In particular, it was confirmed that the group treated with the CXO-1 strain culture solution at a concentration of 10% significantly reduced the expression of MMP-1 compared to the serum-free medium at the same concentration.
즉, 일 양상에 따른 균주는 자외선에 의해 자외선에 의해 파괴된 콜라겐을 회복시키고, 자외선에 의해 증가된 MMP-1의 생성을 억제함으로써 탄력 감소, 주름 생성 억제 등과 같은 피부 노화 방지에 탁월한 효과가 있다. That is, the strain according to one aspect has an excellent effect in preventing skin aging, such as reducing elasticity and inhibiting wrinkle production, by restoring collagen destroyed by ultraviolet rays by ultraviolet rays, and inhibiting the production of MMP-1 increased by ultraviolet rays .
구취 분석bad breath analysis
[규칙 제91조에 의한 정정 24.02.2022]
자신의 구취를 자각하고 있으며, 구취 측정기인 Oral ChromaTM(FIS Inc. Inc., J apan)로 측정한 결과, 구취인지 파라미터인 황화수소 112 ppb, 메틸머캅탄(methyl mercaptan) 26 ppb 및 디메틸설파이드(dimethyl sulfide) 8 ppb 농도 이상인 20~60세의 지원자 20명을 대상으로 상기 실시예 1의 균주 배양액을 포함하는 조성물을 1일 2회(아침, 저녁)씩 적당량(10 ㎖)을 입안에 머금고 약 30초 동안 가글 후 뱉어내게 하였다. 사용 전, 사용 직후 및 사용 2주 후 시점에서 1 ㎖ syringe(TOP Corp., Taiwan)를 이용하여 지원자의 구강 내 구취인지 파라미터인 휘발성 유황화합물(Volatile Sulfur Compound, VSC)을 채취한 후 성분별 농도를 측정하여 표 1 및 도 6a 내지 6c에 나타내었다.[Correction by Rule 91 24.02.2022]
He is aware of his own bad breath, and as a result of measuring with Oral Chroma TM (FIS Inc. Inc., J apan), which is a bad breath measuring instrument, the parameters for detecting bad breath are 112 ppb of hydrogen sulfide, 26 ppb of methyl mercaptan and dimethyl sulfide ( For 20 volunteers aged 20 to 60 years with a concentration of dimethyl sulfide) of 8 ppb or higher, take an appropriate amount (10 ml) of the composition containing the culture solution of Example 1 twice a day (morning and evening) twice a day. Gargle for about 30 seconds and then spit out. Volatile Sulfur Compound (VSC), a parameter for detecting bad breath in the applicant's oral cavity, was collected before, immediately after, and 2 weeks after use using a 1 ㎖ syringe (TOP Corp., Taiwan), and then the concentration of each component was measured and shown in Table 1 and FIGS. 6A to 6C.
자신의 구취를 자각하고 있으며, 구취 측정기인 Oral ChromaTM(FIS Inc. Inc., J apan)로 측정한 결과, 구취인지 파라미터인 황화수소 112 ppb, 메틸머캅탄(methyl mercaptan) 26 ppb 및 디메틸설파이드(dimethyl sulfide) 8 ppb 농도 이상인 20~60세의 지원자 20명을 대상으로 상기 실시예 1의 균주 배양액을 포함하는 조성물을 1일 2회(아침, 저녁)씩 적당량(10 ㎖)을 입안에 머금고 약 30초 동안 가글 후 뱉어내게 하였다. 사용 전, 사용 직후 및 사용 2주 후 시점에서 1 ㎖ syringe(TOP Corp., Taiwan)를 이용하여 지원자의 구강 내 구취인지 파라미터인 휘발성 유황화합물(Volatile Sulfur Compound, VSC)을 채취한 후 성분별 농도를 측정하여 표 1 및 도 6a 내지 6c에 나타내었다.[Correction by Rule 91 24.02.2022]
He is aware of his own bad breath, and as a result of measuring with Oral Chroma TM (FIS Inc. Inc., J apan), which is a bad breath measuring instrument, the parameters for detecting bad breath are 112 ppb of hydrogen sulfide, 26 ppb of methyl mercaptan and dimethyl sulfide ( For 20 volunteers aged 20 to 60 years with a concentration of dimethyl sulfide) of 8 ppb or higher, take an appropriate amount (10 ml) of the composition containing the culture solution of Example 1 twice a day (morning and evening) twice a day. Gargle for about 30 seconds and then spit out. Volatile Sulfur Compound (VSC), a parameter for detecting bad breath in the applicant's oral cavity, was collected before, immediately after, and 2 weeks after use using a 1 ㎖ syringe (TOP Corp., Taiwan), and then the concentration of each component was measured and shown in Table 1 and FIGS. 6A to 6C.
분석항목Analysis items | 평가시점evaluation time | 평균(ppb)Average (ppb) | 표준편차(SD)standard deviation (SD) |
유의확률 (p-value)Significance Probability (p-value) |
변화율(%)rate of change (%) |
황화수소 (H2S)hydrogen sulfide (H 2 S) |
사용 전before use | 461.85461.85 | 268.04268.04 | -- | -- |
사용 직후immediately after use | 48.9048.90 | 82.6582.65 | 0.000* 0.000 * | - 89.41- 89.41 | |
사용 2주 후2 weeks after use | 56.3556.35 | 95.2095.20 | 0.000* 0.000 * | - 87.80- 87.80 | |
메틸머캅탄 (CH3SH)methyl mercaptan (CH 3 SH) |
사용 전before use | 179.15179.15 | 140.34140.34 | -- | -- |
사용 직후immediately after use | 56.5056.50 | 39.3939.39 | 0.000*W 0.000 *W | - 68.46- 68.46 | |
사용 2주 후2 weeks after use | 32.1532.15 | 32.5632.56 | 0.000*W 0.000 *W | - 82.05- 82.05 | |
디메틸설파이드 ((CH3)2S)dimethyl sulfide ((CH 3 ) 2 S) |
사용 전before use | 85.2085.20 | 92.4892.48 | -- | -- |
사용 직후immediately after use | 1.61.6 | 2.642.64 | 0.000*W 0.000 *W | - 98.12- 98.12 | |
사용 2주 후2 weeks after use | 8.158.15 | 30.8430.84 | 0.000*W 0.000 *W | - 90.43- 90.43 |
* 휘발성 유황화합물(Volatile Sulfur Compounds) * Volatile Sulfur Compounds
P<0.05 이면, 사용전과 비교하여 유의차(significant difference)가 있음If P<0.05, there is a significant difference compared to before use
W Wilcoxon signed ranks test, Post-Hoc test (Bonferroni correction) W Wilcoxon signed ranks test, Post-Hoc test (Bonferroni correction)
도 6a 내지 도 6c는 일 양상에 따른 조성물의 사용 전, 사용 직후 및 사용 2주 후의 휘발성 유황화합물(황화수소, 메틸머캅탄 및 디메틸설파이드)의 농도 변화를 비교한 그래프이다. 6A to 6C are graphs comparing changes in the concentration of volatile sulfur compounds (hydrogen sulfide, methyl mercaptan and dimethyl sulfide) before, immediately after, and after 2 weeks of use of the composition according to an aspect.
그 결과, 도 6a 내지 도 6c에 나타낸 바와 같이 사용 전과 비교하여 사용 직후 및 사용 2주 후 시점에서 구취인지 파라미터인 휘발성 유황화합물의 농도가 유의하게 감소하는 것을 확인할 수 있었다(p<0.05). 구체적으로, 표 1에 나타낸 바와 같이, 휘발성 유황화합물의 변화율은 황화수소가 각각 89.41%, 및 87.80%이고, 메틸머캅탄은 68.46%, 및 82.05%이며, 디메틸설파이드는 98.12%, 및 90.43%로 사용 2주 후 각각의 농도가 80% 이상 감소하는 것을 확인할 수 있었다. As a result, as shown in FIGS. 6a to 6c , it was confirmed that the concentration of volatile sulfur compounds, which is a parameter for bad breath, significantly decreased immediately after use and 2 weeks after use compared to before use (p<0.05). Specifically, as shown in Table 1, the rate of change of volatile sulfur compounds is 89.41% and 87.80% for hydrogen sulfide, 68.46%, and 82.05% for methyl mercaptan, and 98.12% and 90.43% for dimethyl sulfide. After 2 weeks, it was confirmed that each concentration decreased by 80% or more.
즉, 일 양상에 따른 조성물은 휘발성 유황화합물의 농도를 유의적으로 감소시킴으로써 구취 개선에 효과적이다. That is, the composition according to an aspect is effective in improving bad breath by significantly reducing the concentration of volatile sulfur compounds.
구강 세균 분석Oral Bacterial Analysis
상기와 동일한 대상에게 실시예 1의 균주 배양액을 포함하는 조성물을 동일한 방법으로 사용하게 한 후, 사용 전, 사용 2주 후 시점에서 구강병원성 미생물 검사 의뢰기관(DENOMICS, Korea)으로부터 검체 용기를 제공받아 지원자의 타액 샘플을 채취한 뒤, OBD(Oral Bacteria Dignosis) 분석 서비스를 이용하여 하기 표 2의 구강 미생물 및 총 미생물 양의 변화를 분석하고 그 결과를 하기 표 3에 나타내었다. After having the same subject as above use the composition containing the strain culture medium of Example 1 in the same way, before use and 2 weeks after use, the sample container was provided from the oral pathogenic microorganism test requesting institution (DENOMICS, Korea). After collecting a volunteer's saliva sample, changes in oral microorganisms and total amount of microorganisms in Table 2 below were analyzed using Oral Bacteria Dignosis (OBD) analysis service, and the results are shown in Table 3 below.
분석 균종Analytical strains | 균주의 특징Characteristics of the strain | |
1One | Aggregatibacter actinomycetemcomitans[Aa] Aggregatibacter actinomycetemcomitans [ Aa ] |
침습성치주염, 소아치주염 유도Invasive periodontitis, induction of |
22 | Porphyromonas gingivalis [Pg] Porphyromonas gingivalis [ Pg ] | 급성/만성 치주염 유도, 치조골 파괴Induction of acute/chronic periodontitis, destruction of alveolar bone |
33 | Tannerella forsythia [Tf] Tannerella forsythia [ Tf ] |
만성, 난치성치주염, 치은염유도Chronic, intractable periodontitis, |
44 | Treponema denticola [Td] Treponema denticola [ Td ] | 궤양성치은염, 급성 치관주위염 유도Induction of ulcerative gingivitis, acute paronychia |
55 | Fusobacterium nucleatum [Fn] Fusobacterium nucleatum [ Fn ] |
급성 괴상성 치은염, 치석 형성 유도Acute massive gingivitis, induction of |
66 | Prevotella intermedia [Pi] Prevotella intermedia [ Pi ] | 호르몬 성치주염, 복합감염 유도Hormonal periodontitis, combined infection induction |
77 | Prevotella nigrescens [Pn] Prevotella nigrescens [ Pn ] |
치근단 질환, 치주 농양 유도Periodontal disease, |
88 | Streptococcus mitis[Smi] Streptococcus mitis [ Smi ] | 치아우식, 치근단 농양 유도Induction of dental caries, apical abscess |
99 | Streptococcus mutans[Smu] Streptococcus mutans [ Smu ] |
치수염, 치아우식 유도Induction of pulpitis, |
1010 | Lactobacillus casei [Lc] Lactobacillus casei [ Lc ] | 치아우식 유도Induction of dental caries |
분석 균종Analytical strains | 평가시점evaluation time |
평균 (copy/㎖ X 103)Average (copy/ml X 10 3 ) |
표준편차 (X 103)Standard Deviation (X 10 3 ) |
유의확률 (P-value)Significance Probability (P-value) |
변화율(%)rate of change (%) |
AaAa | 사용 전before use | 175.00175.00 | 558.07558.07 | -- | -- |
사용 2주 후 2 weeks after use | 62.5062.50 | 119.68119.68 | 0.465 W 0.465 W | -64.29-64.29 | |
PgPg | 사용 전before use | 1,139.161,139.16 | 1,954.581,954.58 | -- | -- |
사용 2주 후2 weeks after use | 240.15240.15 | 428.12428.12 | 0.0590.059 | -78.92-78.92 | |
TfTf | 사용 전before use | 5,563.705,563.70 | 12,098.0412,098.04 | -- | -- |
사용 2주 후2 weeks after use | 1,312.301,312.30 | 1,628.221,628.22 | 0.014*W 0.014 *W | -76.41-76.41 | |
TdTd | 사용 전before use | 360.43360.43 | 908.33908.33 | -- | -- |
사용 2주 후2 weeks after use | 65.4665.46 | 102.87102.87 | 0.421 W 0.421 W | -81.84-81.84 | |
FnFn | 사용 전before use | 519,635.00519,635.00 | 1,781,383.151,781,383.15 | -- | -- |
사용 2주 후2 weeks after use | 2,290.502,290.50 | 1,502.251,502.25 | 0.000*W 0.000 *W | -99.56-99.56 | |
PiPi | 사용 전before use | 2,138.452,138.45 | 4,308.094,308.09 | -- | -- |
사용 2주 후2 weeks after use | 1,091.101,091.10 | 2,739.602,739.60 | 0.3580.358 | -49.06-49.06 | |
PnPn | 사용 전before use | 132,565.00132,565.00 | 510,358.53510,358.53 | -- | -- |
사용 2주 후2 weeks after use | 5,610.455,610.45 | 5,056.615,056.61 | 0.002*W 0.002 *W | -95.77-95.77 | |
SmiSmi | 사용 전before use | 184,240.90184,240.90 | 144,154.23144,154.23 | -- | -- |
사용 2주 후2 weeks after use | 43,640.5543,640.55 | 145,637.20145,637.20 | 0.002* 0.002 * | -76.31-76.31 | |
SmuSmu | 사용 전before use | 7,319.007,319.00 | 6,205.666,205.66 | -- | -- |
사용 2주 후2 weeks after use | 891.55891.55 | 1,333.291,333.29 | 0.000* 0.000 * | -87.82-87.82 | |
LcLc | 사용 전before use | 0.060.06 | 0.180.18 | -- | -- |
사용 2주 후2 weeks after use | 0.080.08 | 0.360.36 | 1.000W 1.000 W | +33.33+33.33 |
도 7a 내지 7e는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 상기 표 2에 기재된 미생물 양을 비교한 그래프이다. 7A to 7E are graphs comparing the amount of microorganisms described in Table 2 before and after 2 weeks of use of a composition according to an aspect.
도 7f는 일 양상에 따른 조성물의 사용 전 및 사용 2주 후의 총 미생물 양을 비교한 그래프이다. 7f is a graph comparing the total amount of microorganisms before and 2 weeks after use of the composition according to an aspect.
그 결과, 표 3 및 도 7a 내지 7e에 나타낸 바와 같이, 실시예 1의 균주 배양액을 포함하는 조성물을 사용하기 전과 비교하여 사용 2주 후 10종의 구강 세균 중 총 5개의 균종(Tf, Fn, Pn, Smi 및 Smu)이 유의하게 감소한 것을 확인할 수 있었다. 구체적으로, 상기 5개의 균종은 사용 전과 비교하여 사용 2주 후 각각 76.41%, 99.56%, 95.77%, 76.31%, 87.82% 및 84.28%로 유의하게 감소한 것을 확인할 수 있었다. As a result, as shown in Table 3 and FIGS. 7a to 7e, a total of 5 bacterial species ( Tf, Fn, Pn, Smi and Smu ) were confirmed to be significantly reduced. Specifically, it was confirmed that the five strains significantly decreased to 76.41%, 99.56%, 95.77%, 76.31%, 87.82%, and 84.28%, respectively, after 2 weeks of use compared to before use.
또한, 도 7f에 나타낸 바와 같이, 실시예 1의 균주 배양액을 포함하는 조성물을 사용하기 전과 비교하여 사용 2주 후 총 미생물 양이 84.28% 현저하게 감소한 것을 확인할 수 있었다. In addition, as shown in FIG. 7f , it was confirmed that the total amount of microorganisms was significantly reduced by 84.28% after 2 weeks of use compared to before using the composition containing the strain culture solution of Example 1.
즉, 일 양상에 따른 조성물은 구강 미생물을 유의적으로 감소시킴으로써 치주염, 치은염, 치근단 질환, 치아우식, 치수염 등과 같은 구강 질환을 예방 또는 치료할 뿐만 아니라 치석 형성을 방지할 수 있다. That is, the composition according to one aspect can prevent or treat oral diseases such as periodontitis, gingivitis, apical disease, dental caries, pulpitis, and the like, as well as prevent tartar formation by significantly reducing oral microorganisms.
관능 평가sensory evaluation
상기 20명의 지원자들에게 실시예 1의 균주 배양액을 포함하는 조성물을 2주 동안 사용하게 한 후, 하기 표 4의 평가기준 1에 따라 구취 개선, 치태 감소, 구강건조 감소 효능을 평가하여 그 결과를 하기 표 5에 나타내었다. 또한, 하기 표 4의 평가기준 2에 따라 사용할 때 느끼는 상쾌함, 자극 여부, 향 및 맛 등과 같은 사용성을 평가하여 그 결과를 하기 표 6에 나타내었다. After allowing the 20 volunteers to use the composition containing the culture medium of Example 1 for 2 weeks, the efficacy of improving bad breath, reducing plaque, and reducing dry mouth was evaluated according to the evaluation criteria 1 of Table 4 below, and the results were obtained. It is shown in Table 5 below. In addition, according to the evaluation criteria 2 of Table 4 below, usability such as freshness, stimulation, flavor and taste were evaluated, and the results are shown in Table 6 below.
점수 | 평가기준 1Evaluation Criteria 1 |
평가기준 2 |
|
1One | 전혀 그렇지 않다.Not at all. | 매우 좋지 않다. Not very good. | |
22 | 그렇지 않다. Not like that. | 좋지 않다. Not good. | |
33 | 그렇지 않은 것 같다. I don't think so. | 좋지 않은 것 같다. It doesn't look good. | |
44 | 그런 것 같다. It seem to be like that. | 좋은 편이다. It's good. | |
55 | 그렇다. Yes. | 좋다. good night. | |
66 | 매우 그렇다 it really is | 매우 좋다. very good. |
항목Item | 수(n)number (n) | 응답률(%)Response rate (%) |
구취 개선bad breath improvement | 1919 | 95.0095.00 |
치태 감소plaque reduction | 1616 | 80.0080.00 |
구강건조 감소Reduce dry mouth | 1717 | 85.0085.00 |
항목Item | 수(n)number (n) | 응답률(%)Response rate (%) |
상쾌함refreshing | 1616 | 80.0080.00 |
자극 없음no irritation | 1919 | 95.0095.00 |
향 |
88 | 40.0040.00 |
맛taste | 99 | 45.0045.00 |
수(n): 4점, 5점 및 6점을 선택한 지원자 수 Number (n): Number of applicants who selected 4, 5 and 6 points
도 8은 일 양상에 따른 조성물의 효능 및 사용성에 관한 설문 평가 결과를 분석한 그래프이다. 8 is a graph analyzing the results of a questionnaire evaluation regarding the efficacy and usability of a composition according to an aspect.
그 결과, 도 8 및 표 3에 나타낸 바와 같이, 실시예 1의 균주 배양액을 포함하는 조성물은 구취 개선, 치태 감소 및 구강건조 감소 효과가 우수하다는 평가를 받았다. 또한, 표 4에 나타낸 바와 같이, 상기 조성물은 상쾌하고 자극이 없어 사용감이 전반적으로 우수하다는 평가를 받았다. As a result, as shown in FIG. 8 and Table 3, the composition containing the strain culture solution of Example 1 was evaluated to have excellent effects of improving bad breath, reducing plaque, and reducing dry mouth. In addition, as shown in Table 4, the composition was evaluated as being refreshing and having no irritation, so that the feeling of use was excellent overall.
따라서, 일 양상에 따른 조성물은 구취 개선, 치태 감소 및 구강건조 감소와 같은 기능성을 가질 뿐만 아니라 사용감이 우수한 구강 케어 제품을 제공할 수 있다. Accordingly, the composition according to an aspect may provide an oral care product having excellent feeling of use as well as functionalities such as improving bad breath, reducing plaque, and reducing dry mouth.
구강 안정성 평가Oral Stability Assessment
구강 안정성을 평가하기 위하여 상기 20명의 지원자들에게 실시예 1의 균주 배양액을 포함하는 조성물을 2주 동안 사용하게 한 후, 지원자의 시험부위를 관찰하였다. 이후, 질의 응답을 통해 시험 부위 상태를 확인하여 기록, 평가하였다. 이상반응 발생 시 이상 반응 보고서를 작성하도록 하였으며, 이상 반응과 상기 조성물의 관련성은 전문가가 판단하도록 하였다. In order to evaluate oral stability, the 20 volunteers were allowed to use the composition containing the culture medium of Example 1 for 2 weeks, and then the test site of the volunteers was observed. Thereafter, the state of the test site was checked, recorded, and evaluated through Q&A. In the event of an adverse reaction, an adverse reaction report was prepared, and an expert judged the relationship between the adverse reaction and the composition.
그 결과, 시험 기간 동안 모든 지원자들에게서 구상 이상반응은 관찰되지 않았다. As a result, no adverse events were observed in all volunteers during the trial period.
즉, 일 양상에 따른 조성물은 구강 미생물 억제 효과가 우수할 뿐만 아니라 인체 구강에 대한 안정성이 우수하여 장기간 사용하더라도 구강 내 세균의 내성에 영향이 없는 이점이 있다. That is, the composition according to one aspect has an advantage in that it has excellent oral microbial inhibitory effect as well as excellent stability to the human oral cavity, so that even when used for a long period of time, it does not affect the resistance of bacteria in the oral cavity.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The description of the present invention described above is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.
Claims (13)
- 기탁번호 KCCM12889P로 기탁된, 바이셀라 속(Weissella sp.)에 속하는 바이셀라 시바이라(Weissella cibaria) CXO-1 균주.Deposited with accession number KCCM12889P, Weissella sp. belonging to Weissella cibaria ( Weissella cibaria ) CXO-1 strain.
- 청구항 1의 균주의 파쇄액, 또는 배양액.The lysate of the strain of claim 1, or a culture solution.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 화장료 조성물. A cosmetic composition comprising the strain of claim 1, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof.
- 청구항 3에 있어서, 피부 상태 개선, 또는 보습용 화장료 조성물.The cosmetic composition for improving skin condition or moisturizing according to claim 3 .
- 청구항 4에 있어서, 상기 피부 상태는 피부 노화, 피부 장벽 강화, 피부 주름, 피부 탄력, 피부 재생 또는 상처 개선인 것인 화장료 조성물. The cosmetic composition of claim 4, wherein the skin condition is skin aging, skin barrier strengthening, skin wrinkles, skin elasticity, skin regeneration or wound improvement.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 함유하는 상처 치료용 약학적 조성물.A pharmaceutical composition for treating wounds comprising the strain of claim 1, a lysate thereof, a culture medium, an extract of the culture medium, or a mixture thereof as an active ingredient.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 구강 조성물.An oral composition comprising the strain of claim 1, a lysate thereof, a culture solution, an extract of the culture solution, or a mixture thereof as an active ingredient.
- 청구항 7에 있어서, 구취 개선, 치태 감소, 치석 감소, 구강 건조 감소, 또는 구강 세균 억제용 구강 조성물. The oral composition according to claim 7, wherein the oral composition is for improving bad breath, reducing plaque, reducing tartar, reducing dry mouth, or inhibiting oral bacteria.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 구강 질환의 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for the prevention or treatment of oral diseases comprising the strain of claim 1, a lysate thereof, a culture medium, an extract of the culture medium, or a mixture thereof as an active ingredient.
- 청구항 9에 있어서, 상기 구강 질환은 침습성치주염, 소아 치주염, 급성 또는 만성 치주염, 치조골 파괴, 만성 또는 난치성 치주염, 치은염, 궤양성 치은염, 급성 치관주위염, 급성 괴상성 치은염, 호르몬성 치주염, 복합 감염, 치근단 질환, 치주 농양, 치아우식, 치근단 농양, 및 치수염으로 구성된 군에서 선택되는 어느 하나 이상인 것인 구강 질환의 예방 또는 치료용 약학적 조성물.The method according to claim 9, wherein the oral disease is invasive periodontitis, juvenile periodontitis, acute or chronic periodontitis, alveolar bone destruction, chronic or intractable periodontitis, gingivitis, ulcerative gingivitis, acute paronychia, acute gingivitis gangrene, hormonal periodontitis, complex infection, A pharmaceutical composition for the prevention or treatment of oral diseases that is at least one selected from the group consisting of apical disease, periodontal abscess, dental caries, apical abscess, and pulpitis.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는 상처를 치료하는 방법. A method of treating a wound comprising administering to an individual a composition comprising the strain of claim 1, a lysate thereof, a culture medium, an extract of the culture medium, or a mixture thereof as an active ingredient.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는 구강 질환을 치료하는 방법.The method of treating an oral disease comprising administering to an individual a composition comprising the strain of claim 1, a lysate thereof, a culture medium, an extract of the culture medium, or a mixture thereof as an active ingredient.
- 청구항 1의 균주, 그의 파쇄액, 배양액, 배양액의 추출물 또는 이들의 혼합물을 포함하는 조성물의 상처 치료, 구강 질환의 예방 또는 치료 용도.The use of a composition comprising the strain of claim 1, a lysate thereof, a culture medium, an extract of the culture medium, or a mixture thereof for wound treatment, prevention or treatment of oral diseases.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2020-0185220 | 2020-12-28 | ||
KR1020200185220A KR102529325B1 (en) | 2020-12-28 | 2020-12-28 | Weissella cibaria strain and uses thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2022145960A1 true WO2022145960A1 (en) | 2022-07-07 |
WO2022145960A9 WO2022145960A9 (en) | 2023-03-16 |
Family
ID=82260615
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2021/020031 WO2022145960A1 (en) | 2020-12-28 | 2021-12-28 | Weissella cibaria strain and use thereof |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR102529325B1 (en) |
WO (1) | WO2022145960A1 (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060056996A (en) * | 2004-08-25 | 2006-05-25 | 전남대학교산학협력단 | Lactic acid bacteria inhibiting halitosis |
KR20150031922A (en) * | 2013-09-17 | 2015-03-25 | 충북대학교 산학협력단 | Novel Weissella cibaria JW15 strain and use the same |
KR20160035219A (en) * | 2014-09-23 | 2016-03-31 | 한국 한의학 연구원 | Composition for moisturizing skin and anti-wrinkle comprising tyndalized lactic acid bacteria as effective component |
KR101667496B1 (en) * | 2015-10-15 | 2016-10-18 | 한국식품연구원 | Pharmaceutical composition for prevention or treatment of atopic dermatitis comprising Weissella cibaria WIKIM28 as active ingredient |
KR20180059728A (en) * | 2018-04-06 | 2018-06-05 | (주)앰틱스바이오 | A novel Weissella cibaria strain and the use thereof |
KR20200070989A (en) * | 2018-12-10 | 2020-06-18 | 주식회사 엠디헬스케어 | Nanovesicles derived from Weissella bacteria and Use thereof |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015525800A (en) * | 2012-08-07 | 2015-09-07 | トップジェニックス, インコーポレーテッドTopgenix, Inc. | Topical composition containing transformed bacteria expressing compound of interest (target compound) |
JP6438668B2 (en) * | 2014-03-28 | 2018-12-19 | 株式会社ロッテ | Weisella lactic acid bacteria |
KR101873393B1 (en) * | 2016-12-21 | 2018-07-02 | 창원대학교 산학협력단 | Novel Weissella cibaria BCNU 3003 strain |
EP3428286A1 (en) * | 2017-07-13 | 2019-01-16 | Université de Bordeaux | Predictive test of anti-tnf alpha response in patients with an inflammatory disease |
KR102404383B1 (en) * | 2020-05-27 | 2022-06-07 | 주식회사 피토메카 | Cosmetic composition for skin anti-aging or anti-wrinkle containing Weissella cibaria cell lysates |
-
2020
- 2020-12-28 KR KR1020200185220A patent/KR102529325B1/en active IP Right Grant
-
2021
- 2021-12-28 WO PCT/KR2021/020031 patent/WO2022145960A1/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060056996A (en) * | 2004-08-25 | 2006-05-25 | 전남대학교산학협력단 | Lactic acid bacteria inhibiting halitosis |
KR20150031922A (en) * | 2013-09-17 | 2015-03-25 | 충북대학교 산학협력단 | Novel Weissella cibaria JW15 strain and use the same |
KR20160035219A (en) * | 2014-09-23 | 2016-03-31 | 한국 한의학 연구원 | Composition for moisturizing skin and anti-wrinkle comprising tyndalized lactic acid bacteria as effective component |
KR101667496B1 (en) * | 2015-10-15 | 2016-10-18 | 한국식품연구원 | Pharmaceutical composition for prevention or treatment of atopic dermatitis comprising Weissella cibaria WIKIM28 as active ingredient |
KR20180059728A (en) * | 2018-04-06 | 2018-06-05 | (주)앰틱스바이오 | A novel Weissella cibaria strain and the use thereof |
KR20200070989A (en) * | 2018-12-10 | 2020-06-18 | 주식회사 엠디헬스케어 | Nanovesicles derived from Weissella bacteria and Use thereof |
Also Published As
Publication number | Publication date |
---|---|
KR20220093990A (en) | 2022-07-05 |
KR102529325B1 (en) | 2023-05-08 |
WO2022145960A9 (en) | 2023-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102273232B1 (en) | Micrococcus lylae strain and skin condition improving uses of thereof | |
KR102273950B1 (en) | Cutibacterium acnes subsp. acnes strain and skin condition improving uses of thereof | |
WO2021060659A1 (en) | Staphylococcus capitis st-1 strain, and use thereof for improving skin condition | |
WO2021060656A1 (en) | Staphylococcus gallinarum st-4 strain, and use thereof for improving skin condition | |
WO2021060654A1 (en) | Staphylococcus epidermidis strain st-6 and use thereof for improving condition of skin | |
WO2022145960A1 (en) | Weissella cibaria strain and use thereof | |
WO2021060652A1 (en) | Staphylococcus haemolyticus strain st-8 and use thereof for improving condition of skin | |
WO2021060658A1 (en) | Staphylococcus lentus st-2 strain and use thereof for skin condition improvement | |
KR102321536B1 (en) | Corynebacterium amycolatum strain and skin condition improving uses of thereof | |
KR102334454B1 (en) | Corynebacterium tuberculostearicum strain and skin condition improving uses of thereof | |
KR102334455B1 (en) | Corynebacterium macginleyi strain and skin condition improving uses of thereof | |
WO2024005443A1 (en) | Micrococcus flavus strain and use thereof for improving skin condition | |
WO2023018077A1 (en) | Microccocus cohnii strain, and use thereof for improving condition of skin | |
WO2023243924A1 (en) | Micrococcus terreus strain and use thereof for improving skin condition | |
WO2023018078A1 (en) | Micrococcus antarcticus strain and skin condition improving use thereof | |
WO2022114783A1 (en) | Composition containing fermented product of cactus honey and use thereof for improving skin condition | |
KR102334457B1 (en) | Microbacterium oleivorans strain and skin condition improving uses of thereof | |
KR102394429B1 (en) | Composition comprising fermented snowberry and its use for improving skin condition | |
KR102336747B1 (en) | Pantoea ananatis strain and skin condition improving uses of thereof | |
WO2022114784A1 (en) | Composition comprising fermentation product of cactus oil and use thereof for improving skin condition | |
KR102286080B1 (en) | Rothia kristinae strain and skin condition improving uses of thereof | |
WO2021060648A1 (en) | Staphylococcus warneri strain st-12, and use thereof for improving skin condition | |
WO2021060650A1 (en) | Staphylococcus xylosus st-10 strain, and use thereof for improving skin condition | |
WO2021060653A1 (en) | Staphylococcus sciuri st-7 strain, and use thereof for improving skin condition | |
WO2021060655A1 (en) | Staphylococcus saprophyticus st-5 strain and use thereof for improving skin condition |
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: 21915758 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21915758 Country of ref document: EP Kind code of ref document: A1 |