KR20220167294A - Antiviral composition containing placenta-derived material - Google Patents
Antiviral composition containing placenta-derived material Download PDFInfo
- Publication number
- KR20220167294A KR20220167294A KR1020227037509A KR20227037509A KR20220167294A KR 20220167294 A KR20220167294 A KR 20220167294A KR 1020227037509 A KR1020227037509 A KR 1020227037509A KR 20227037509 A KR20227037509 A KR 20227037509A KR 20220167294 A KR20220167294 A KR 20220167294A
- Authority
- KR
- South Korea
- Prior art keywords
- virus
- placenta
- antiviral composition
- coronavirus
- derived
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 76
- 210000002826 placenta Anatomy 0.000 title claims abstract description 61
- 230000000840 anti-viral effect Effects 0.000 title claims abstract description 46
- 239000000463 material Substances 0.000 title claims abstract description 12
- 241000700605 Viruses Species 0.000 claims abstract description 43
- 210000001808 exosome Anatomy 0.000 claims abstract description 42
- 230000009385 viral infection Effects 0.000 claims abstract description 34
- 210000004027 cell Anatomy 0.000 claims abstract description 30
- 208000036142 Viral infection Diseases 0.000 claims abstract description 29
- 239000002679 microRNA Substances 0.000 claims abstract description 17
- 239000011859 microparticle Substances 0.000 claims abstract description 12
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims abstract description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 29
- 241000711573 Coronaviridae Species 0.000 claims description 21
- 239000004480 active ingredient Substances 0.000 claims description 21
- 241000315672 SARS coronavirus Species 0.000 claims description 16
- 108700011259 MicroRNAs Proteins 0.000 claims description 14
- 230000036541 health Effects 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- 241001678559 COVID-19 virus Species 0.000 claims description 8
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims description 7
- 239000002537 cosmetic Substances 0.000 claims description 7
- 235000013376 functional food Nutrition 0.000 claims description 7
- 229960005486 vaccine Drugs 0.000 claims description 6
- 241000709661 Enterovirus Species 0.000 claims description 5
- 208000007514 Herpes zoster Diseases 0.000 claims description 5
- 206010022000 influenza Diseases 0.000 claims description 5
- 241000709687 Coxsackievirus Species 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 241000711443 Bovine coronavirus Species 0.000 claims description 3
- 241000991587 Enterovirus C Species 0.000 claims description 3
- 244000309467 Human Coronavirus Species 0.000 claims description 3
- 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 3
- 241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 3
- 241000711467 Human coronavirus 229E Species 0.000 claims description 3
- 241000282898 Sus scrofa Species 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 241000712461 unidentified influenza virus Species 0.000 claims description 3
- 241000711404 Avian avulavirus 1 Species 0.000 claims description 2
- 241000725619 Dengue virus Species 0.000 claims description 2
- 241001115402 Ebolavirus Species 0.000 claims description 2
- 241000125945 Protoparvovirus Species 0.000 claims description 2
- 241000700584 Simplexvirus Species 0.000 claims description 2
- 241000710886 West Nile virus Species 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 230000003053 immunization Effects 0.000 claims description 2
- 238000002649 immunization Methods 0.000 claims description 2
- 208000037798 influenza B Diseases 0.000 claims description 2
- 208000037799 influenza C Diseases 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 claims 1
- 108091070501 miRNA Proteins 0.000 abstract description 3
- 231100000673 dose–response relationship Toxicity 0.000 abstract description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 abstract 1
- 230000004083 survival effect Effects 0.000 abstract 1
- 238000011282 treatment Methods 0.000 description 20
- 230000000120 cytopathologic effect Effects 0.000 description 12
- 239000000284 extract Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 235000013361 beverage Nutrition 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 210000003501 vero cell Anatomy 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 108091027963 non-coding RNA Proteins 0.000 description 6
- 102000042567 non-coding RNA Human genes 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- -1 phosphate salts Chemical class 0.000 description 5
- 208000025721 COVID-19 Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 210000003754 fetus Anatomy 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 231100001083 no cytotoxicity Toxicity 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000001528 Coronaviridae Infections Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000009368 gene silencing by RNA Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 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 2
- 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 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
- 239000004471 Glycine Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 2
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 108020004417 Untranslated RNA Proteins 0.000 description 2
- 102000039634 Untranslated RNA Human genes 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000002155 anti-virotic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 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
- 230000031018 biological processes and functions Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000004209 hair Anatomy 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 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 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000005727 virus proliferation Effects 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-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
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000196324 Embryophyta 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000031448 Genomic Instability Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 101000895818 Homo sapiens Chorionic somatomammotropin hormone 1 Proteins 0.000 description 1
- 101000956228 Homo sapiens Chorionic somatomammotropin hormone 2 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 108050009363 Hyaluronidases Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 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
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108091007412 Piwi-interacting RNA Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 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
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000002583 cell-derived microparticle Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 239000012468 concentrated sample Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000013530 defoamer Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 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
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000008269 hand cream Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 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
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 244000052769 pathogen Species 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
- 229940111202 pepsin Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000005059 placental tissue Anatomy 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001230 polyarylate Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 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
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 235000009566 rice Nutrition 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
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 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
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
- A01N63/10—Animals; Substances produced thereby or obtained therefrom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
- A61K8/982—Reproductive organs; Embryos, Eggs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/204—Animal extracts
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Developmental Biology & Embryology (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Reproductive Health (AREA)
- Polymers & Plastics (AREA)
- Pregnancy & Childbirth (AREA)
- Birds (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Agronomy & Crop Science (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Environmental Sciences (AREA)
Abstract
본 발명은 태반 유래 세포, 중간엽 줄기세포, 세포외소포체, 엑소좀, 마이크로파티클, total RNA 및 miRNA로 구성된 군에서 선택되는 하나 이상의 태반 유래 물질을 포함하는 항바이러스 조성물에 관한 것이다. 본 발명의 태반 유래 세포, 중간엽 줄기세포, 세포외소포체, 엑소좀, 마이크로파티클, total RNA 또는 miRNA은 바이러스 감염된 세포에 투여하였을 때 바이러스의 생존을 용량 의존적으로 억제하였으므로 바이러스 감염의 예방 또는 치료에 유용하게 활용할 수 있다.The present invention relates to an antiviral composition comprising at least one placenta-derived material selected from the group consisting of placenta-derived cells, mesenchymal stem cells, extracellular vesicles, exosomes, microparticles, total RNA, and miRNA. Placenta-derived cells, mesenchymal stem cells, extracellular endoplasmic reticulum, exosomes, microparticles, total RNA or miRNA of the present invention inhibited the survival of viruses in a dose-dependent manner when administered to virus-infected cells, so they are useful for preventing or treating viral infections. can be put to good use.
Description
본 발명은 태반 유래의 세포, 중간엽줄기세포, 세포외소포체, 엑소좀, 마이크로파티클, total RNA 및 마이크로RNA(miRNA)로 구성된 군에서 선택된 하나 이상의 태반 유래 물질을 유효성분으로 포함하는 항바이러스 조성물에 관한 것이다.The present invention is an antiviral composition comprising at least one placenta-derived material selected from the group consisting of placenta-derived cells, mesenchymal stem cells, extracellular vesicles, exosomes, microparticles, total RNA, and microRNA (miRNA) as an active ingredient It is about.
인간 태반 추출물(Human placenta extract, HPE)은 다양한 성장인자, 사이토카인 및 기타 생리활성물질을 포함하며, 피로의 경감, 항산화 등의 용도로 널리 이용되고 있다(Lee KK, et al., Evid Based Complement Alternat. Med., vol. 2012,(2012) p.130875). 또한, 인간 태반 추출물은 동물을 이용한 연구에서 간 재생을 통해 간 기능 향상을 유도하고, TGF-β및 VEGF를 생산함으로써 상처 치료에 영향을 미친다고 알려져 있다. 그러나, 인간 태반 추출물에 대한 많은 관심에도 불구하고 인간 태반 추출물의 기능에 대해서는 아직 완전히 연구되지 않았으며, 특히 바이러스 감염이나 바이러스 감염에 의한 질환에 대한 연구는 진행된 바 없다. 또한 인간을 비롯하여 동물의 태반에는 여러 종류의 세포와 중간엽 줄기세포가 포함되어 있는 것으로 알려져 있어서 의학적 가치가 매우 높은 것이 특징이다.Human placenta extract (HPE) contains various growth factors, cytokines, and other physiologically active substances, and is widely used for fatigue relief and antioxidant purposes (Lee KK, et al., Evid Based Complement Alternat. Med., vol. 2012, (2012) p.130875). In addition, human placenta extract is known to induce liver function improvement through liver regeneration in studies using animals and affect wound healing by producing TGF-β and VEGF. However, despite much interest in human placenta extracts, the functions of human placenta extracts have not yet been fully studied, and in particular, studies on viral infections or diseases caused by viral infections have not been conducted. In addition, it is known that the placenta of humans and animals contains various types of cells and mesenchymal stem cells, so it is characterized by very high medical value.
한편, 최근 세포 분비물(secretome)에 세포의 거동을 제어하는 다양한 생체활성인자가 포함되어 있다는 연구가 보고되고 있으며, 특히 세포 분비물 내에는 많은 기능을 가지는 '엑소좀(exosome)' 또는 '세포외 소포체(extracellular vesicle)'가 포함되어 있어 그 성분과 기능에 대한 연구가 활발히 진행 중에 있다. 세포는 세포외 환경에 다양한 막(membrane) 유형의 소포체를 방출하는데, 통상 이러한 방출 소포체들을 세포외 소포체(Extracellular vesicles, EV)라고 부르고 있다. 세포외 소포체는 세포막 유래 소포체, 엑토좀(ectosomes), 쉐딩 소포체(shedding vesicles), 마이크로파티클(microparticles), 엑소좀 등으로 불려지기도 하며, 경우에 따라서는 엑소좀과는 구별되어 사용되기도 한다.On the other hand, recently, studies have been reported that cell secretome contains various bioactive factors that control cell behavior. (extracellular vesicle)', so research on its components and functions is being actively conducted. Cells release vesicles of various membrane types into the extracellular environment, and these releasing vesicles are commonly referred to as extracellular vesicles (EVs). Extracellular vesicles are also referred to as cell membrane-derived vesicles, ectosomes, shedding vesicles, microparticles, exosomes, etc., and in some cases, they are used separately from exosomes.
엑소좀은 세포 내 엔도좀 트래피킹 과정을 통해 생성된 후기 엔도좀과 원형질막의 융합을 통해 생성된다. 엑소좀은 해당 세포에서 발현하고 있는 특정 단백질과 mRNA 전사체를 포함하고 있을 뿐만 아니라 중요하게도 RNA 자체로서 유전자의 발현을 조절하는 다양한 small non-coding RNA (microRNA, piRNA 등)들도 함유되어 있다. 따라서 엑소좀은 기원한 해당 세포의 유전적 특성을 반영하고 있다고 알려져 있다. Exosomes are produced through the fusion of late endosomes generated through the intracellular endosome trafficking process and the plasma membrane. Exosomes not only contain specific proteins and mRNA transcripts expressed in the cell, but also, importantly, various small non-coding RNAs (microRNA, piRNA, etc.) that regulate gene expression as RNA itself. Therefore, it is known that exosomes reflect the genetic characteristics of the cell of origin.
엑소좀 구성 물질 중 small non-coding RNA (ncRNA)는 매우 적은 양으로도 다양한 유전자 발현조절 효과를 보일 수 있으며, 또한 하나의 ncRNA가 매우 다양한 신호전달 경로에 관여할 수 있어 그 영향력이 매우 크다. ncRNA는 RNA 전사체의 일종으로 단백질로 번역 (translation)되지는 않지만 다양한 유전자의 안정성, 전사 및 번역을 조절하는 것으로 보고되었다. 인간 유전체로부터 전사되는 RNA들 가운데 97%는 단백질로 번역되지 않는 ncRNA다. 따라서 ncRNA는 생체 내 다양한 생물학적 과정과 밀접하게 연관되어 있어 이에 대한 연구는 생명과학분야의 핫이슈로 평가되고 있다. Among exosome components, small non-coding RNA (ncRNA) can show various gene expression regulating effects even in a very small amount, and one ncRNA can be involved in a wide variety of signal transduction pathways, so its influence is very large. ncRNA is a type of RNA transcript that is not translated into protein, but has been reported to regulate the stability, transcription, and translation of various genes. Of the RNAs transcribed from the human genome, 97% are ncRNAs that are not translated into proteins. Therefore, since ncRNA is closely related to various biological processes in vivo, research on it is evaluated as a hot issue in the field of life science.
특히 이러한 ncRNA 중 microRNA는 약 19~24 뉴클레오티드 (nucleotide)의 크기를 갖는 small RNA로 염기서열 상보적인 mRNA를 분해하거나 단백질로의 번역을 억제함으로써 유전자 발현을 조절하는 RNA 간섭현상을 유발한다. RNA 간섭은 생체의 발생 및 생리, 세포의 분화, 증식 및 사멸, 그리고 유전체의 안정성 등 거의 모든 생물학적 과정에 밀접하게 관련되어 있으며, 또한 바이러스에 대한 저항성 및 다양한 인간 질병과도 밀접하게 연관되어 있다. 이러한 RNA 간섭과 질병과의 연관성을 토대로 인간 질병 치료제의 개발을 위한 경쟁적 연구가 전 세계적으로 진행되고 있다.In particular, microRNA among these ncRNAs is a small RNA having a size of about 19 to 24 nucleotides, which induces RNA interference that regulates gene expression by degrading mRNAs complementary to nucleotide sequences or inhibiting translation into proteins. RNA interference is closely related to almost all biological processes, such as the development and physiology of living organisms, cell differentiation, proliferation and death, and genome stability, and is also closely related to virus resistance and various human diseases. Based on the relationship between RNA interference and disease, competitive research for the development of human disease treatments is being conducted worldwide.
한편, 코로나바이러스(Coronavirus)는 1937년 닭에서 처음 발견된 뒤 개, 돼지, 조류 등의 동물을 거쳐 1965년에는 사람에게서도 발견되었다. 코로나바이러스는 사람에게 감염될 때에는 감기, 상기도감염, 호흡기 질환, 어린이의 설사, 기타 장질환 등을 일으키는 것으로 알려졌다. 중증 급성 호흡기 증후군(severe acute respiratory syndrome: SARS)은 신종 또는 변종 코로나바이러스 관련 질환으로, 2002년 11월에서 2003년 6월 사이 중국에서 크게 유행하여 8,096명의 감염자가 발생하고 774명이 사망한 바 있다. 또한, 중동 호흡기 증후군(Middle East respiratory syndrome: MERS)은 2012년 사우디에서 처음 발견되었고, 요르단, 카타르, 아랍에미레이트 연합 및 쿠웨이트에서도 감염자가 확인되었는데, 세계보건기구에 따르면 2014년 5월 15일 기준 572명의 사람이 감염되었으며 그 중 173명이 사망한 것으로 보고되었다. 2019년에 발생하여 2020년도 초반에 WHO가 판데믹(Pandemic, 대유행)으로 지정한 신종 코로나바이러스(COVID-19 또는 Corona-19)에 대한 백신 개발이 속속 완료되고 있는 상황이고, 치료제들이 개발되고 있으나, 아직까지 확실한 효과를 내는 치료제는 없는 상황이다. On the other hand, coronavirus (Coronavirus) was first discovered in chickens in 1937, followed by animals such as dogs, pigs, and birds, and was also found in humans in 1965. When infecting humans, coronaviruses are known to cause colds, upper respiratory infections, respiratory diseases, diarrhea in children, and other intestinal diseases. Severe acute respiratory syndrome (SARS) is a new or variant coronavirus-related disease, which was highly prevalent in China between November 2002 and June 2003, resulting in 8,096 infections and 774 deaths. In addition, Middle East respiratory syndrome (MERS) was first discovered in Saudi Arabia in 2012, and infected persons were also confirmed in Jordan, Qatar, the United Arab Emirates and Kuwait. According to the World Health Organization, as of May 15, 2014, 572 100 people were infected, 173 of whom were reported dead. Vaccine development for the new coronavirus (COVID-19 or Corona-19), which occurred in 2019 and was designated as a pandemic by the WHO in early 2020, is being completed one after another, and treatments are being developed, but Until now, there is no cure that has a definite effect.
이에 따라 바이러스, 특히 신종 코로나바이러스 감염증 등에 대한 우수한 예방 및 치료 효능을 갖는 예방 및/또는 치료제에 대한 수요는 절실한 상황이며, 여전히 해결되어야 할 문제로 남아있다.Accordingly, there is an urgent need for preventive and/or therapeutic agents having excellent preventive and therapeutic effects against viruses, particularly new coronavirus infections, and the like, and still remains a problem to be solved.
발명의 요약Summary of Invention
상기와 같은 문제를 해결하기 위하여, 본 발명은 우수한 항 바이러스 활성을 갖는 신규 항바이러스 조성물을 제공하는 것을 목적으로 한다. In order to solve the above problems, an object of the present invention is to provide a novel antiviral composition having excellent antiviral activity.
본 발명의 다른 목적은 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염 예방용 백신 조성물을 제공하는 것이다.Another object of the present invention is to provide a vaccine composition for preventing viral infection containing the antiviral composition as an active ingredient.
본 발명의 또 다른 목적은 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증에 대한 예방 또는 개선용 건강기능성식품 조성물을 제공하는 것이다. Another object of the present invention is to provide a health functional food composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
본 발명의 또 다른 목적은 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증에 대한 예방 또는 개선용 화장료 조성물을 제공하는 것이다. Another object of the present invention is to provide a cosmetic composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
상기 과제를 해결하고자 바이러스 감염을 예방하거나 바이러스 감염 후 바이러스 증식을 억제할 수 있는 물질을 연구, 개발하기 위하여 노력하던 중, 태반 유래의 세포, 중간엽 줄기세포, 세포외소포체, 엑소좀, total RNA, miRNA 또는 마이크로 파티클이 우수한 항바이러스 활성을 나타내는 것을 확인하였고, 또한 인체에 안전하다는 것을 확인하고 본 발명을 완성하였다. In order to solve the above problems, while trying to research and develop substances that can prevent viral infection or inhibit viral proliferation after viral infection, placenta-derived cells, mesenchymal stem cells, extracellular vesicles, exosomes, and total RNA , It was confirmed that miRNA or microparticles exhibited excellent antiviral activity, and it was also confirmed that they were safe for the human body, and the present invention was completed.
이에 따라 본 발명은 태반 유래의 엑소좀, 마이크로파티클, total RNA, 마이크로RNA(miRNA), 세포외소포체, 태반유래 세포 및 중간엽 줄기세포로 구성된 군에서 선택되는 하나 이상의 태반유래 물질을 유효성분으로 포함하는 항바이러스 조성물을 제공한다. Accordingly, the present invention uses one or more placenta-derived materials selected from the group consisting of placenta-derived exosomes, microparticles, total RNA, microRNA (miRNA), extracellular vesicles, placenta-derived cells, and mesenchymal stem cells as an active ingredient. An antiviral composition comprising
본 발명은 또한, 상기 항바이러스 조성물을 유효성분으로 함유하는 백신 조성물을 제공한다. The present invention also provides a vaccine composition containing the antiviral composition as an active ingredient.
본 발명은 또한, 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증의 치료 또는 예방용 약학 조성물을 제공한다. The present invention also provides a pharmaceutical composition for treating or preventing a viral infection containing the antiviral composition as an active ingredient.
본 발명은 또한, 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증에 대한 예방 또는 개선용 건강기능성식품 조성물을 제공한다.The present invention also provides a health functional food composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
본 발명은 또한, 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증에 대한 예방 또는 개선용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
본 발명은 또한, 상기 항바이러스 조성물을 투여하는 단계를 포함하는 바이러스 감염증의 치료 또는 예방방법을 제공한다.The present invention also provides a method for treating or preventing a viral infection comprising administering the antiviral composition.
본 발명은 또한, 바이러스 감염증의 치료 또는 예방을 위한 상기 항 바이러스 조성물의 용도를 제공한다.The present invention also provides the use of the antiviral composition for the treatment or prevention of a viral infection.
본 발명은 또한, 바이러스 감염증의 치료 또는 예방용 약제 제조를 위한 상기 항바이러스 조성물의 사용을 제공한다.The present invention also provides the use of the antiviral composition for the preparation of a medicament for the treatment or prevention of a viral infection.
도 1은 NTA를 이용하여 태반 유래 엑소좀을 분석한 결과를 나타낸 것이다.
도 2는 ExoGlow-NTA를 이용하여 태반 유래 엑소좀을 분석한 결과를 나타낸 것이다.
도 3은 Vero 세포에서 태반 유래 total RNA의 세포독성을 확인한 MTT 어세이 결과를 나타낸 것이다.
도 4는 Vero 세포에서 태반 유래 엑소좀의 세포독성을 확인한 MTT 어세이 결과를 나타낸 것이다.
도 5는 태반 유래 엑소좀의 바이러스 억제효과 확인을 위한 바이러스 101TCID50 조건에서 CPE inhibition 어세이 결과를 나타낸 것이다.
도 6은 태반 유래 엑소좀의 바이러스 억제효과 확인을 위한 바이러스 102 TCID50 조건에서 CPE inhibition 어세이 결과를 나타낸 것이다.
도 7은 태반 유래 total RNA의 바이러스 억제효과 확인을 위한 바이러스 101TCID50 조건에서 CPE inhibition 어세이 결과를 나타낸 것이다.1 shows the results of analyzing placenta-derived exosomes using NTA.
2 shows the results of analyzing placenta-derived exosomes using ExoGlow-NTA.
Figure 3 shows the results of the MTT assay confirming the cytotoxicity of placenta-derived total RNA in Vero cells.
Figure 4 shows the results of MTT assay confirming the cytotoxicity of placenta-derived exosomes in Vero cells.
5 shows the results of CPE inhibition assay under the
6 shows the results of CPE inhibition assay under the
7 shows the results of CPE inhibition assay under the
발명의 상세한 설명 및 바람직한 구현예DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술분야에서 숙련된 전문가에 의해서 통상적으로 이해되는 것과 동일한 의미를 갖는다. 일반적으로 본 명세서에서 사용된 명명법은 본 기술분야에서 잘 알려져 있고 통상적으로 사용되는 것이다. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is one well known and commonly used in the art.
본 발명은 일 관점에서, 태반 유래의 엑소좀, 마이크로파티클, total RNA, 마이크로RNA(miRNA), 세포외소포체, 태반유래 세포 및 중간엽 줄기세포로 구성된 군에서 선택되는 태반 유래 물질을 유효성분으로 포함하는 항바이러스 조성물에 관한 것이다.In one aspect, the present invention provides a placenta-derived material selected from the group consisting of placenta-derived exosomes, microparticles, total RNA, microRNA (miRNA), extracellular vesicles, placenta-derived cells, and mesenchymal stem cells as an active ingredient. It relates to an antiviral composition comprising
“태반”은 임신과 함께 생성되는 장기로서, 모체에서 태아로 영양물과 효소의 공급, 태아에서 생기는 노폐물과 탄산가스 등을 모체로 배출, 생체에 있어서 이물질인 병원균이나 약물의 태아로의 이행저지 및 태아의 내분비조정 등의 기능을 한다.“Placenta” is an organ created during pregnancy, supplying nutrients and enzymes from the mother to the fetus, discharging waste products and carbon dioxide from the fetus to the mother, preventing the transfer of pathogens or drugs, which are foreign substances in the body, to the fetus, It has functions such as regulating the endocrine secretion of the fetus.
태반에는 아미노산류, 단백질류, 당류, 핵산류, 지질류, 무기물, 효소류, 호르몬류 등을 함유한다. 이때, 아미노산류는 아스파라긴산, 글루타민산, 루이신, 라이신, 글리신, 알라닌, 세린, 스레오닌, 페닐알라닌, 타이로신, 메치오닌, 히스티딘 등이 있다. 단백질 및 효소류는 알부민, 글로불린, 산성 및 알칼리성 포스파타제, 하알로니다제 등을 포함한다. 당류는 글루코스, 갈락토스, 리보스 등을 포함한다. 핵산류는 우라실, 크산틴, 히포크산틴 등을 포함하며, 지질류는 라우린산, 팔미틸산, 리놀레인산 등이 있다. 무기물은 Na, K, Ca, P, Fe, Cl 등을 포함하며, 호르몬류에는 고나도트롬빈, 락토겐, 스테로이드 호르몬 등이 있다.The placenta contains amino acids, proteins, sugars, nucleic acids, lipids, minerals, enzymes, hormones, and the like. At this time, amino acids include aspartic acid, glutamic acid, leucine, lysine, glycine, alanine, serine, threonine, phenylalanine, tyrosine, methionine, histidine, and the like. Proteins and enzymes include albumin, globulin, acidic and alkaline phosphatases, hyaluronidases, and the like. Sugars include glucose, galactose, ribose, and the like. Nucleic acids include uracil, xanthine, hypoxanthine, and the like, and lipids include lauric acid, palmitylic acid, and linoleic acid. Inorganic substances include Na, K, Ca, P, Fe, Cl, and the like, and hormones include gonadothrombin, lactogen, and steroid hormones.
본 발명에서 태반 유래 세포외 소포체, 엑소좀, miRNA 또는 마이크로 파티클 은 엑소좀 분리 장비나 기타 고전적인 초원심분리를 통해 얻을 수 있다.In the present invention, placenta-derived extracellular vesicles, exosomes, miRNA, or microparticles can be obtained through exosome separation equipment or other classical ultracentrifugation.
본 발명의 상기 항바이러스 조성물로 치료가능한 바이러스 감염증에 있어, 예방 및/또는 치료대상인 바이러스로는 뎅기바이러스, 급성호흡기 증후군 바이러스, 코로나바이러스(Coronavirus), 메르스 코로나 바이러스, 사스 코로나 바이러스, 웨스트 나일 바이러스, 에볼라바이러스, 소낭성 구내염 바이러스, 콕사키바이러스, 뉴캐슬병 바이러스, 파보바이러스, 헤르페스심플렉스바이러스(Herpes simplex virus), 헤르페스조스터바이러스(Herpes zoster virus), 코사키바이러스(Coxsackie virus), 엔테로바이러스(Enterovirus), 인플루엔자바이러스(Influenza), 폴리오바이러스, 인플루엔자 A형, 인플루엔자 B형, 인플루엔자 C형, 사람코로나바이러스(HCoV-229E), 돼지 코로나바이러스, 소코로나바이러스, 사스코로나바이러스(SARS-CoV), 헤르페스심플렉스 타입 1, 헤르페스심플렉스 타입 2 및 헤르페스조스터바이러스로 이루어진 그룹으로부터 선택하는 하나 이상의 바이러스가 예시될 수 있지만 이에 안정되는 것은 아니다.In the viral infections treatable by the antiviral composition of the present invention, viruses to be prevented and/or treated include dengue virus, acute respiratory syndrome virus, coronavirus, MERS coronavirus, SARS coronavirus, and West Nile virus , Ebola virus, follicular stomatitis virus, coxsackie virus, Newcastle disease virus, parvovirus, herpes simplex virus, herpes zoster virus, Coxsackie virus, enterovirus ( Enterovirus), influenza virus (Influenza), poliovirus, influenza type A, influenza type B, influenza type C, human coronavirus (HCoV-229E), swine coronavirus, bovine coronavirus, SARS-CoV, One or more viruses selected from the group consisting of Herpes simplex type 1,
엔테로바이러스에는 폴리오바이러스, 코사키바이러스, 엔테로바이러스 등이 포함되어 있으며 인플루엔자바이러스에는 인플루엔자 A형, B형, C형 바이러스가 포함되어 있으며 코로나바이러스에는 사람코로나바이러스(HCoV-229E), 돼지 코로나바이러스, 소코로나바이러스, 사스코로나바이러스(SARS-CoV) 등이 포함되어 있으며, 헤르페스바이러스는 헤르페스심플렉스 타입 1 및 타입 2 및 헤르페스조스터바이러스 등을 포함하고 있다.Enteroviruses include poliovirus, cossackievirus, and enterovirus; influenza viruses include influenza A, B, and C viruses; and coronaviruses include human coronavirus (HCoV-229E), swine coronavirus, It includes bovine coronavirus, SARS-CoV, and the like, and herpes viruses include herpes simplex type 1 and
특히 본 발명에 따른 항바이러스 조성물은 코로나바이러스의 예방 및/또는 치료용도로 사용될 수 있으며, 더욱 바람직하게는 SARS-CoV, SARS-CoV-1, SARS-CoV-2, 중동코로나바이러스(MERS-CoV) 및 COVID-19 바이러스로 구성된 군에서 선택된 하나 이상의 코로나바이러스 감염증의 예방 및/또는 치료용도로 사용될 수 있다. In particular, the antiviral composition according to the present invention can be used for prevention and / or treatment of coronaviruses, more preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV ) and COVID-19 virus.
또한, 본 발명에 따른 항바이러스 조성물은 엔데믹(endemic), 프리-판데믹(prepandemic) 또는 판데믹(pandemic, 전세계 대유행) 바이러스 감염에 대한 면역조치용으로 사용될 수 있다. In addition, the antiviral composition according to the present invention can be used for immunization against endemic, pre-pandemic or pandemic (pandemic) virus infections.
본 발명에서 용어, "항바이러스[anti-virus] 활성" 또는 "항바이러스 (효)능”이란 상기 예시된 바이러스의 다양한 아형과 변이형 바이러스 입자가 숙주세포에 감염되는 것을 억제하는 능력, 즉 숙주세포의 세포막에 바이러스 입자가 달라붙어 세포 내로 유입되는 것을 억제하는 능력을 의미한다. 이러한 결과로 바이러스는 숙주세포를 이용하여 바이러스 입자를 복제 또는 증식하는 데에 필요한 기작을 방해하게 되며 이를 통해 항바이러스 활성을 가진다.In the present invention, the term "anti-virus [anti-virus] activity" or "anti-viral (efficacy) ability" means the ability to inhibit infection of host cells by various subtypes and mutant virus particles of the above-exemplified viruses, that is, the host It refers to the ability of viral particles to stick to the cell membrane and inhibit entry into the cell.As a result, the virus interferes with the mechanism necessary for replicating or multiplying viral particles using the host cell, thereby preventing the virus from entering the cell. have an active
본 발명의 일 양태에서는 In vitro에서 태반 유래 엑소좀과 태반 유래 total RNA가 corona-19 바이러스에 대해 항바이러스 효능이 있는지 확인하기 위하여, Vero 세포에 corona-19 바이러스와 태반 유래 엑소좀과 태반 유래 total RNA를 각각 처리한 결과, 태반 유래 엑소좀 5ug 처리군에서 101TCID50과 102TCID50 두 가지 바이러스 감염조건에서 바이러스 증식이 억제되는 것을 확인하였다. 아울러, 태반 유래 total RNA 100ng 처리군에서 101TCID50 바이러스 조건에서 바이러스 증식이 억제되는 것을 확인하였다. In one aspect of the present invention, in order to determine whether placenta-derived exosomes and placenta-derived total RNA have antiviral efficacy against corona-19 virus in vitro , corona-19 virus, placenta-derived exosomes, and placenta-derived total RNA were injected into Vero cells. As a result of RNA treatment, it was confirmed that virus proliferation was inhibited under two virus infection conditions, 10 1 TCID 50 and 10 2 TCID 50 in the placenta-derived exosome 5ug treatment group. In addition, it was confirmed that virus growth was inhibited in the 10 1 TCID 50 virus condition in the placenta-derived total RNA treatment group of 100 ng.
다른 관점에서, 본 발명은 상기 항바이러스 조성물을 유효성분으로 함유하는 백신조성물에 관한 것이다.In another aspect, the present invention relates to a vaccine composition containing the antiviral composition as an active ingredient.
또 다른 관점에서, 본 발명은 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증, 바람직하게는 SARS-CoV, SARS-CoV-1, SARS-CoV-2, 중동코로나바이러스(MERS-CoV) 및 COVID-19 바이러스로 구성된 군에서 선택된 하나 이상의 바이러스 감염증 치료 또는 예방용 약학 조성물에 관한 것이다. In another aspect, the present invention relates to viral infections containing the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle Eastern coronavirus (MERS-CoV) and COVID-19. It relates to a pharmaceutical composition for treating or preventing one or more viral infections selected from the group consisting of -19 viruses.
본 발명의 태반 추출물을 포함하는 항바이러스 조성물 또는 백신 조성물 약제학적으로 허용 가능한 담체를 포함할 수 있다.An antiviral composition or vaccine composition containing the placenta extract of the present invention may include a pharmaceutically acceptable carrier.
본 발명의 조성물에 사용된 담체는 약제학적으로 허용되는 담체, 보조제 및 비히클을 포함하며 총괄적으로 “약제학적으로 허용되는 담체”라고 한다. 본 발명의 조성물에 사용될 수 있는 약제학적으로 허용되는 담체로는 이들로 한정되는 것은 아니지만 이온 교환, 알루미나, 알루미늄 스테아레이트, 레시틴, 혈청 단백질(예, 사람 혈청 알부민), 완충 물질(예, 여러 인산염, 글리신, 소르브산, 칼륨 소르베이트, 포화 식물성 지방산의 부분적인 글리세라이드 혼합물), 물, 염 또는 전해질(예, 프로타민 설페이트, 인산수소이나트륨, 인산수소칼륨, 염화나트륨 및 아연 염), 교질성 실리카, 마그네슘 트리실리케이트, 폴리비닐 피롤리돈, 셀룰로즈-계 기질, 폴리에틸렌 글리콜, 나트륨 카르복시메틸셀룰로스, 폴리아릴레이트, 왁스, 폴리에틸렌-폴리옥시프로필렌-차단 중합체, 폴리에틸렌 글리콜 및 양모지 등이 포함된다.Carriers used in the composition of the present invention include pharmaceutically acceptable carriers, adjuvants and vehicles, collectively referred to as "pharmaceutically acceptable carriers". Pharmaceutically acceptable carriers that may be used in the compositions of the present invention include, but are not limited to, ion exchange, alumina, aluminum stearate, lecithin, serum proteins (eg, human serum albumin), buffer substances (eg, various phosphate salts). , glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids), water, salts or electrolytes (eg protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride and zinc salts), colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substrates, polyethylene glycols, sodium carboxymethylcellulose, polyarylates, waxes, polyethylene-polyoxypropylene-blocked polymers, polyethylene glycols and woolen wool; and the like.
본 발명에 따른 조성물은 경구 투여 또는 비경구 투여될 수 있으며, 비경구 투여는 비내, 비강내, 구강, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 피내, 복강내, 장관, 국소, 설하 또는 직장 투여 형태로 투여될 수 있지만, 이에 한정되는 것은 아니다. The composition according to the present invention may be administered orally or parenterally, and parenteral administration is intranasal, intranasal, buccal, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intradermal. , intraperitoneal, enteral, topical, sublingual or rectal administration forms, but are not limited thereto.
바람직하게는 경구 투여되거나, 비내 또는 비강내 투여될 수 있으며, 특히 비내 또는 비경구 투여시에는 스프레이(spray) 또는 에어로솔(aerosol) 형태로의 투여, 또는 흡입(inhalation) 투여되는 것이 더욱 바람직하지만 이에 한정되는 것은 아니다. 상기 비내 또는 비강내 투여용 조성물은 약제의 분야에 잘 알려진 기술에 따라 제조하며 벤질 알코올 또는 다른 적합한 보존제, 생체이용율을 증강시키기 위한 흡수 촉진제, 플루오로카본 및/또는 기타 본 분야에 알려진 가용화제 또는 분산제를 사용하여 염수중의 용액으로서 제조할 수 있다.Preferably, it can be administered orally, intranasally or intranasally, and in particular, in the case of intranasal or parenteral administration, administration in the form of a spray or aerosol, or administration by inhalation is more preferred. It is not limited. The composition for intranasal or intranasal administration is prepared according to techniques well known in the field of medicine, and includes benzyl alcohol or other suitable preservatives, absorption promoters for enhancing bioavailability, fluorocarbons and/or other solubilizers known in the art, or It can be prepared as a solution in saline using a dispersing agent.
또 다른 형태로서, 본 발명에 따른 태반 추출물을 포함하는 조성물은 멸균 주사용 수성 또는 유성 현탁액으로서 멸균 주사용 제제의 형태일 수 있다. 이 현탁액은 적합한 분산제 또는 습윤제(예, 트윈 80) 및 현탁화제를 사용하여 본 분야에 공지된 기술에 따라 제형될 수 있다. 멸균 주사용 제제는 또한 무독성의 비경구적으로 허용되는 희석제 또는 용매중의 멸균 주사용액 또는 현탁액(예, 1,3-부탄디올중의 용액)일 수 있다. 허용적으로 사용될 수 있는 비히클 및 용매로는 만니톨, 물, 링겔 용액 및 등장성 염화나트륨 용액이 있다. 또한, 멸균 불휘발성 오일이 통상적으로 용매 또는 현탁화 매질로서 사용된다. 이러한 목적을 위해, 합성 모노 또는 디글리세라이드를 포함하여 자극성이 적은 어떠한 불휘발성 오일도 사용할 수 있다. 올레산 및 이의 글리세라이드 유도체와 같은 지방산이 약제학적으로 허용되는 천연 오일(예, 올리브유 또는 피마자유), 특히 이들의 폴리옥시에틸화된 것과 마찬가지로 주사 제제에 유용하다.In another form, the composition comprising the placenta extract according to the present invention may be in the form of a sterile injectable preparation as a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to techniques known in the art using suitable dispersing or wetting agents (eg, Tween 80) and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent (eg, as a solution in 1,3-butanediol). Vehicles and solvents that may be employed that are acceptable include mannitol, water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile fixed oils are usually employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or diglycerides. Fatty acids such as oleic acid and its glyceride derivatives are useful in injectable preparations as are pharmaceutically acceptable natural oils (eg olive oil or castor oil), especially polyoxyethylated ones thereof.
본 발명의 조성물은 이들로 한정되는 것은 아니지만 캡슐, 정제 및 수성 현탁액 및 용액을 포함하여 경구적으로 허용되는 어떠한 용량형으로도 경구 투여될 수 있다. 경구용 정제의 경우, 흔히 사용되는 담체로는 락토스 및 옥수수 전분이 포함된다. 마그네슘 스테아레이트와 같은 윤활제가 또한 전형적으로 첨가된다. 캡슐형으로 경구 투여하는 경우 유용한 희석제로는 락토스 및 건조된 옥수수 전분이 포함된다. 수성 현탁액이 경구 투여될 때 활성 성분은 유화제 및 현탁화제와 배합된다. 필요한 경우, 감미제 및/또는 풍미제 및/또는 착색제가 첨가될 수 있다.The compositions of the present invention may be administered orally in any orally acceptable dosage form including, but not limited to, capsules, tablets, and aqueous suspensions and solutions. For oral tablets, carriers commonly used include lactose and corn starch. A lubricant such as magnesium stearate is also typically added. For oral administration in capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are administered orally, the active ingredient is combined with emulsifying and suspending agents. If desired, sweetening and/or flavoring and/or coloring agents may be added.
본 발명의 조성물은 또한 직장 투여를 위한 좌제의 형태로 투여될 수 있다. 이들 조성물은 본 발명의 화합물을 실온에서 고형이지만 직장 온도에서는 액상인 적합한 비자극성 부형제와 혼합하여 제조할 수 있다. 이러한 물질로는 이들로 한정되는 것은 아니지만 코코아 버터, 밀랍 및 폴리에틸렌 글리콜이 포함된다.Compositions of the present invention may also be administered in the form of suppositories for rectal administration. These compositions can be prepared by mixing a compound of the present invention with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature. Such materials include, but are not limited to, cocoa butter, beeswax, and polyethylene glycol.
본 발명에 따른 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형될 수 있다.The composition according to the present invention may be formulated as a pill, dragee, capsule, liquid, gel, syrup, slurry, or suspension.
바람직한 양태로서, 구강내 투여를 위한 의약 조성물은 고체상의 부형제와 함께 활성 성분을 혼합함으로써 제조할 수 있으며 정제 또는 당의정 형태로 제조하기 위해 과립형태로 제조할 수 있다. 적합한 부형제로는 락토스, 수크로스, 만니톨 및 소비톨과 같은 슈가 형태 또는 옥수수, 밀가루, 쌀, 감자 또는 다른 식물로부터 전분, 메틸 셀룰로스, 하이드로시프로필메틸-셀룰로스 또는 나트륨 카복시메틸셀룰로스와 같은 셀룰로스, 아라빅 검, 타가칸쓰 검을 포함하는 검류와 같은 카보하이드레이트 또는 젤라틴, 콜라겐과 같은 단백질 필러를 사용할 수 있다. 필요한 경우에는, 교차결합된 폴리비닐피롤리돈, 아가 및 알긴산 또는 나트륨 알긴산과 같은 각각의 염 형태의 붕해제 또는 용해제를 첨가할 수 있다.In a preferred embodiment, a pharmaceutical composition for oral administration can be prepared by mixing the active ingredient together with a solid excipient and can be prepared in the form of granules for preparation in the form of tablets or dragees. Suitable excipients include sugar forms such as lactose, sucrose, mannitol and sorbitol, or starch from corn, flour, rice, potato or other plants, cellulose such as methyl cellulose, hydroxypropylmethyl-cellulose or sodium carboxymethylcellulose, ara. Carbohydrates such as gums including Big Gum and Tagacanth Gum, or protein fillers such as gelatin and collagen may be used. If necessary, disintegrants or solubilizers in the form of cross-linked polyvinylpyrrolidone, agar and their respective salts such as alginic acid or sodium alginate may be added.
또 다른 관점에서, 본 발명은 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스 감염증, 바람직하게는 SARS-CoV, SARS-CoV-1, SARS-CoV-2, 중동코로나바이러스(MERS-CoV) 및 COVID-19 바이러스로 구성된 군에서 선택된 하나 이상의 바이러스 감염증에 대한 예방 또는 개선용 건강기능성식품 조성물에 관한 것이다. In another aspect, the present invention relates to viral infections containing the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle Eastern coronavirus (MERS-CoV) and COVID-19. It relates to a health functional food composition for preventing or improving one or more viral infections selected from the group consisting of -19 viruses.
본 발명의 기능성 식품은 산화 예방을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 기능성 식품은, 예를 들어, 각종 식품류, 캔디, 초콜릿, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The functional food of the present invention can be used in various ways such as pharmaceuticals, foods, and beverages for preventing oxidation. Functional foods of the present invention include, for example, various foods, candy, chocolate, beverages, gum, tea, vitamin complexes, health supplements, etc., and can be used in the form of powders, granules, tablets, capsules or beverages.
본 발명의 상기 항바이러스 조성물은 바이러스 감염증의 예방 또는 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 추출물의 양은 일반적으로 본 발명의 건강 기능 식품 조성물은 전체 식품 중량의 0.01 내지 50 중량%, 바람직하게는 0.1 내지 20 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있지만 이에 한정되는 것은 아니다. The antiviral composition of the present invention may be added to food or beverages for the purpose of preventing or improving viral infections. At this time, the amount of the extract in the food or beverage is generally 0.01 to 50% by weight, preferably 0.1 to 20% by weight of the total food weight of the health functional food composition of the present invention, and the health drink composition is 100 ml Based on 0.02 to 10 g, preferably may be added at a rate of 0.3 to 1 g, but is not limited thereto.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에는 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.The health drink composition of the present invention has no particular limitations on the liquid component except for containing the extract as an essential component in the indicated ratio, and may contain various flavors or natural carbohydrates as additional components like conventional beverages. Examples of the aforementioned natural carbohydrates include monosaccharides, such as disaccharides such as glucose and fructose, polysaccharides such as maltose and sucrose, such as common sugars such as dextrins and cyclodextrins. and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
본 발명의 조성물은 여러가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.The composition of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids , a protective colloidal thickener, a pH adjusting agent, a stabilizer, a preservative, glycerin, alcohol, a carbonating agent used in carbonated beverages, and the like. In addition, the compositions of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
또 다른 관점에서, 본 발명은 상기 항바이러스 조성물을 유효성분으로 함유하는 바이러스, 바람직하게는 SARS-CoV, SARS-CoV-1, SARS-CoV-2, 중동코로나바이러스(MERS-CoV) 및 COVID-19 바이러스로 구성된 군에서 선택된 하나 이상의 바이러스 감염증에 대한 예방 또는 개선용 화장료 조성물에 관한 것이다. In another aspect, the present invention is a virus containing the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) and COVID-19. It relates to a cosmetic composition for preventing or improving one or more viral infections selected from the group consisting of 19 viruses.
본 발명의 항바이러스 조성물은 화장용으로 유용한 물질과 함께 화장품 조성물을 형성한다. 화장용으로 유용한 물질에는 항산화제, 결합제, 벌크화제(bulking agent), 킬레이트제, 색소, 연화제, 에멀션 안정제, 막형성제, 충전재, 방향 성분, 젤화제, 두발 조절제, 헤어 고정제, 습윤제, 가소제, 보존제, 피부 조절제, 용매, 햇빛차단제, 계면활성제, 자외선 흡수제, 점도조절제, 왁스 등이 포함되나 이에 한정되지 않는다. 여러 가지 화장용으로 유용한 물질은 CTFS Cosmetic Ingredient Handbook, J.M. Nikitakis, Ed., 1st Edition, p.51-101 (1988)에서 찾을 수 있으며, 여기에 공개된 것들은 모두 본 명세서에 참고자료로서 포함되어 있다.The antiviral composition of the present invention forms a cosmetic composition together with cosmetically useful substances. Cosmetically useful substances include antioxidants, binders, bulking agents, chelating agents, pigments, emollients, emulsion stabilizers, film formers, fillers, fragrance ingredients, gelling agents, hair conditioning agents, hair fixatives, humectants, and plasticizers. , preservatives, skin conditioners, solvents, sunscreens, surfactants, ultraviolet absorbers, viscosity modifiers, waxes, and the like, but are not limited thereto. A number of cosmetically useful substances are described in CTFS Cosmetic Ingredient Handbook, J.M. Nikitakis, Ed., 1st Edition, p.51-101 (1988), all disclosures of which are incorporated herein by reference.
기능에 따라, 본 발명의 화장품 조성물은 용액(로션형 조성물), 농축 용액, 젤, 연고, 에멀션(크림, 유제), 소포 분산, 파우더, 조밀 파우더(dense powder), 페이스트 또는 고형제 등의 다양한 형태로 제공될 수 있다. 더 자세히 설명하자면, 본 발명의 화장품 조성물은 볼연지, 크림(안면 크림, 핸드 크림, 보습 크림, 햇빛 차단 크림), 크림 파우더, 아이 라이너, 아이 셰도우, 아이브로우 펜슬, 파운데이션, 로션, 마스카라, 마이크로에멀션, 연고, 포마드 및 루즈 등의 다양한 형태 내에서 분산될 수 있으나 이에 한정되지 않는다. 이들은 거품 또는 스프레이의 형태로 적용할 수 있는 추진제를 포함한 압착 팩으로 포장될 수 있다.Depending on the function, the cosmetic composition of the present invention can be used in various forms such as solutions (lotion-type compositions), concentrated solutions, gels, ointments, emulsions (creams, emulsions), vesicle dispersions, powders, dense powders, pastes or solids. can be provided in the form More specifically, the cosmetic composition of the present invention is a cheek rouge, cream (facial cream, hand cream, moisturizing cream, sun protection cream), cream powder, eye liner, eye shadow, eyebrow pencil, foundation, lotion, mascara, micro It can be dispersed in various forms such as, but not limited to, emulsions, ointments, pomades and rouges. They can be packaged in compression packs containing propellants that can be applied in the form of foam or spray.
또 다른 관점에서, 본 발명은 상기 항바이러스 조성물을 투여하는 단계를 포함하는 바이러스 감염증의 치료 또는 예방방법에 관한 것이다.In another aspect, the present invention relates to a method for treating or preventing a viral infection comprising administering the antiviral composition.
또 다른 관점에서, 본 발명은 바이러스 감염증의 치료 또는 예방을 위한 상기 항 바이러스 조성물의 용도에 관한 것이다. In another aspect, the present invention relates to the use of the above antiviral composition for the treatment or prevention of a viral infection.
또 다른 관점에서, 본 발명은 바이러스 감염증의 치료 또는 예방용 약제 제조를 위한 상기 항바이러스 조성물의 사용에 관한 것이다. In another aspect, the present invention relates to the use of the antiviral composition for the preparation of a medicament for the treatment or prevention of a viral infection.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시 예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들 실시 예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
실시예 1. 태반 유래 세포외소포체, 엑소좀, total RNA 및 마이크로 파티클의 제조Example 1. Preparation of placenta-derived extracellular vesicles, exosomes, total RNA and microparticles
1.1 태반 유래 물질의 제조1.1 Preparation of placenta-derived material
인간 또는 동물의 태반을 NaCl과 증류수 등으로 세척하고 아세톤 처리하여 탈지 및 건조시켜 건조 태반을 얻었다. 불완전 가수분해물이 생성되지 않도록 건조 태반에 펩신 또는 염산 처리로 충분히 가수분해 과정을 거치고 적절한 효소 처리와 멸균 과정을 통해 태반 조직 유래 세포외소포체를 얻는다. 엑소좀, miRNA 또는 마이크로 파티클을 얻는 과정은 엑소좀 분리 장비를 이용하거나 전통적인 초원심분리 방법으로도 얻을 수 있다. A human or animal placenta was washed with NaCl and distilled water, treated with acetone, degreased, and dried to obtain a dry placenta. To prevent incomplete hydrolyzate from being produced, the dried placenta is sufficiently hydrolyzed by pepsin or hydrochloric acid treatment, and placental tissue-derived extracellular vesicles are obtained through appropriate enzyme treatment and sterilization. The process of obtaining exosomes, miRNAs or microparticles can be obtained using exosome separation equipment or by traditional ultracentrifugation.
1.2 본 발명의 태반 유래 엑소좀의 확인1.2 Identification of placenta-derived exosomes of the present invention
소프트웨어 NTA (Nanoparticle Tracking Analysis; Version 2.3 Build 2.3.5.0033.7-Beta7)를 이용하여 태반 유래 엑소좀을 분석한 결과를 도 1에 나타내었다.The results of analyzing the placenta-derived exosomes using the software NTA (Nanoparticle Tracking Analysis; Version 2.3 Build 2.3.5.0033.7-Beta7) are shown in FIG. 1 .
엑소좀 입자의 Size distribution은 148 nm ± 1.4 nm이었고, Total concentration은 7.99 x 1010 particles/ml이다. 본 실험에 사용한 장비는 Malvern NanoSight이다.The size distribution of exosome particles was 148 nm ± 1.4 nm, and the total concentration was 7.99 x 10 10 particles/ml. The equipment used in this experiment is Malvern NanoSight.
소프트웨어 ExoGlow-NTA를 이용한 엑소좀 분석 결과를 도 2에 나타내었다. 태반 유래 엑소좀 입자의 Size distribution은 239 nm ± 12.3 nm이었고, Total concentration은 2.2 x 1010 particles/ml이었다. ExoGlow-NTA Fluorescent Labeling Kit 를 이용하면 세포외소포제의 정량 정확도가 높은 것으로 알려져 있다. Malvern NanoSight (488 nm laser)를 사용하였고, NTA Version 2.3 Build 2.3.5.0033.7-Beta7 소프트웨어를 사용하였다.The results of exosome analysis using the software ExoGlow-NTA are shown in FIG. 2 . The size distribution of placenta-derived exosome particles was 239 nm ± 12.3 nm, and the total concentration was 2.2 x 1010 particles/ml. ExoGlow-NTA Fluorescent Labeling Kit is known to have high quantitative accuracy of extracellular defoamer. A Malvern NanoSight (488 nm laser) was used, and NTA Version 2.3 Build 2.3.5.0033.7-Beta7 software was used.
본 발명에서 2회 반복하여 얻어진 세포외소포체의 양은 다음과 같다.The amount of extracellular vesicles obtained by repeating twice in the present invention is as follows.
본 발명에서 5회 반복으로 얻어진 total RNA의 양은 다음과 같다.The amount of total RNA obtained by repeating 5 times in the present invention is as follows.
No.1과 No.2의 시료는 No.3~5의 2배 농축 시료에 해당하며, 본 발명에서는 5회 얻어진 total RNA를 모두 pooling하여 사용하였다.Samples No.1 and No.2 correspond to the twice-concentrated samples of No.3 to 5, and in the present invention, total RNA obtained 5 times was pooled and used.
실시예 2. 세포독성 분석Example 2. Cytotoxicity assay
MTT assay 방법이란 in vitro 상에서 세포 생존을 확인하는 시험이다. 연속희석(serial dilution)한 시료를 처리한 세포를 일정 시간 배양한 뒤 세포 내 기관인 미토콘드리아(mitochondria)가 가지고 있는 탈수소효소와 반응하는 시약인 MTT를 이용하여 색 변화 정도를 측정하여 세포 생존율을 알아보는 방법이다. 시험 결과를 나타내는 단위는 cell viability(%)로 표현한다.The MTT assay method is a test to confirm cell viability in vitro. Cells treated with serial dilution samples are cultured for a certain period of time, and then the degree of color change is measured using MTT, a reagent that reacts with dehydrogenase in mitochondria, an intracellular organ, to determine cell viability. way. The unit representing the test result is expressed as cell viability (%).
실험을 위해 적정량의 PBS, Vero cell (아프리카 녹색원숭이 신장세포), DMSO, 96 well plate (flat bottom)을 준비하고, MTT 용액은 MTT를 2 ~ 5mg/ml로 PBS에 녹인 후, 여과하여 tube에 담아 빛 차단 후 4℃에 보관하였다.For the experiment, an appropriate amount of PBS, Vero cells (African green monkey kidney cells), DMSO, and 96 well plate (flat bottom) were prepared. For the MTT solution, MTT was dissolved in PBS at 2 ~ 5 mg/ml, filtered, and put into a tube. After blocking the light, it was stored at 4℃.
실험은 다음과 같은 순서로 진행하였으며, 모든 시험은 3회 반복하여 실시하였다.The experiment was conducted in the following order, and all tests were repeated three times.
96 well plate에 각 well 당 1 Х 104 cell의 Vero 세포를 분주하였다. (37℃ 5% CO2, 24h 배양) 측정하고자 하는 태반 유래 엑소좀 및 Total RNA를 각각 농도 별로 2-fold serial dilution하여 각 well에 첨가한다. 시험물질이 충분히 노출될 수 있도록 각각 24시간 동안 37℃ 5% CO2 인큐베이터에서 배양하였다. 상층액을 제거하고 각 웰에 2 ~ 5mg/ml MTT 용액을 첨가하였다. 이 때, MTT 용액은 빛에 민감하므로 빛의 노출은 최소화시키도록 주의한다. 37℃ 5% CO2 인큐베이터에서 4시간 정치하였다. MTT 용액을 제거 또는 제거하지 않은 채로 DMSO를 분주하고, 빛을 차단한 상태에서 플레이트롤 10 ~ 30분 동안 충분히 흔들어주었다. 플레이트 리더기를 이용하여 500nm ~ 600nm 파장에서 각 웰의 흡광도를 측정하였다. 본 실험 결과, 다음과 같이 각 시료에서 세포독성이 나타나지 않았음을 확인하였다.1
그 결과, 도 3에 나타난 바와 같이, Total RNA 처리군 모두 세포독성이 관찰되지 않았다.As a result, as shown in FIG. 3, no cytotoxicity was observed in all of the Total RNA treatment groups.
아울러, 도 4에 나타난 바와 같이, 태반 유래 엑소좀 처리군에서도 모두 세포 독성이 관찰되지 않았으며, 최대희석배수 (MNTD: maximum non-toxic dose)를 확인한 결과, 엑소좀과 Total RNA 모두 최고 용량에서도 세포독성이 없음을 확인하였다.In addition, as shown in FIG. 4, no cytotoxicity was observed in the placenta-derived exosome-treated group, and as a result of checking the maximum non-toxic dose (MNTD), both exosomes and total RNA were found at the highest dose. It was confirmed that there was no cytotoxicity.
실시예 3. 세포에서의 항바이러스 효능평가Example 3. Evaluation of antiviral efficacy in cells
실험을 위해 적정량의 PBS, corona-19 바이러스, Vero 세포, 태반 유래 엑소좀, 태반 가수분해물 유래 total RNA, 96 well plate (flat bottom), Crystal violet 염료, 10% Formalin을 준비하였다.For the experiment, an appropriate amount of PBS, corona-19 virus, Vero cells, placenta-derived exosomes, placental hydrolysate-derived total RNA, 96 well plate (flat bottom), Crystal violet dye, and 10% Formalin were prepared.
96 well plate에 각 well 당 1 Х 104으로 Vero 세포를 분주하였다(37℃ 5% CO2, 24h 배양). 1 단계 시험에서 결정된 MNTD 농도와 한 단계 이후 희석 배수 농도로 각 시료가 함유된 접종용 배양액 각 50 μL, corona-19 바이러스 50 μL 를 세포에 접종하였다. 정상세포 및 바이러스만 접종한 세포를 대조군으로 하였다. 1 시간 후, 상층액을 제거한 다음 새 배양액으로 갈아주었다. 72시간 동안 37℃ 5% CO2 인큐베이터에서 배양하였다. 상층액 제거 후, PBS로 세포를 세척하고 10% 포르말린으로 세포를 고정하였다. PBS로 세포를 세척한 다음 1% crystal violet으로 세포를 염색하였다. CPE(세포병리효과, Cytopathic effect)를 확인하여, 태반 유래 엑소좀, 태반 유래 Total RNA에 의한 CPE 억제효과를 비교 관찰하여 Positive well수 / total well수로 산정하여 판정하였다. Vero cells were dispensed in a 96-well plate at 1 Х 10 4 per well (37°C, 5% CO 2 , 24 h culture). Cells were inoculated with 50 μL of each sample-containing culture medium for inoculation and 50 μL of corona-19 virus at the MNTD concentration determined in the first stage test and the dilution factor concentration after the first stage. Normal cells and cells inoculated only with virus were used as controls. After 1 hour, the supernatant was removed and replaced with fresh culture medium. For 72 hours, it was cultured in a 37°C 5% CO 2 incubator. After removing the supernatant, the cells were washed with PBS and the cells were fixed with 10% formalin. After washing the cells with PBS, the cells were stained with 1% crystal violet. CPE (Cytopathic effect) was confirmed, and the CPE inhibition effect by placenta-derived exosomes and placenta-derived total RNA was compared and observed, and the number of positive wells / total number of wells was calculated and judged.
다음과 같이 세포 염색 방법으로 TCID50 값을 확인하여 바이러스 억제효과를 측정하였다.The virus inhibitory effect was measured by checking the TCID 50 value by the cell staining method as follows.
3.1 바이러스 역가 101TCID50 조건3.1
엑소좀은 5μg 처리군 (3/3), 2.5μg 처리군 (3/3), 1.25μg 처리군 (2/3)에서 CPE가 관찰되지 않았다(도 5). 나머지 처리군에서는 모두 CPE가 관찰되었다. (Positive well 수/ total well 수)CPE was not observed in exosomes in the 5 μg treated group (3/3), the 2.5 μg treated group (3/3), and the 1.25 μg treated group (2/3) ( FIG. 5 ). CPE was observed in all other treatment groups. (Number of positive wells/ total number of wells)
3.2 바이러스 역가 102TCID50 조건3.2
엑소좀은 5μg 처리군 (2/3), 2.5μg 처리군 (1/3)에서 CPE가 관찰되지 않았고, 나머지 처리군에서는 모두 CPE가 관찰되었다(도 6).CPE was not observed in the 5 μg treated group (2/3) and the 2.5 μg treated group (1/3), and CPE was observed in all other treated groups (FIG. 6).
3.3 태반유래 total RNA의 바이러스 101TCID50 결과3.3
바이러스 역가가 101TCID50 조건일 경우, 100ng RNA 처리군 (2/3)에서만 바이러스에 의한 CPE가 보이지 않는 것을 관찰하였고, 나머지 RNA 처리군에서는 모두 CPE를 관찰하였다(도 7).When the virus titer was 10 1 TCID 50 , only the 100ng RNA-treated group (2/3) did not show CPE caused by the virus, and CPE was observed in all other RNA-treated groups (FIG. 7).
In vitro에서 태반 유래 엑소좀 및 태반 유래 total RNA가 각각 COVID-19 바이러스에 대해 항바이러스 효능이 있는지 확인한 결과, 태반 유래 엑소좀의 경우, 바이러스 역가 101TCID50 에서 5μg 처리군, 2.5μg 처리군에서 바이러스 감염 세포가 100% 생존하는 결과를 관찰하였으며, 12.5μg 처리군 66% 세포 생존율을 관찰하였다. 102TCID50 바이러스 감염 조건에서 5μg 처리군 66%, 2.5μg 처리군에서 33% 정도 세포 생존을 관찰하였다(data not shown). 따라서, 엑소좀 5ug 처리군이 101TCID50과 102TCID50 두 가지 바이러스 감염조건에서 바이러스 증식을 억제하는 것을 알 수 있다. As a result of confirming the antiviral efficacy of placenta-derived exosomes and placenta-derived total RNA against the COVID-19 virus in vitro , in the case of placenta-derived exosomes, 5μg treatment group and 2.5μg treatment group at a virus titer of 10 1 TCID 50 100% viability of virus-infected cells was observed, and 66% cell viability was observed in the 12.5μg treatment group. Under the 10 2 TCID 50 virus infection condition, cell viability was observed at 66% in the 5μg-treated group and 33% in the 2.5μg-treated group (data not shown). Therefore, it can be seen that the exosome 5ug treatment group inhibits virus growth under two virus infection conditions: 10 1 TCID 50 and 10 2 TCID 50 .
태반 유래 total RNA의 경우, 바이러스 감염세포에 처리한 결과, 바이러스 역가 101TCID50 조건에서 100ng 처리군에서 세포가 66% 생존한 결과를 관찰하였으므로, 태반 유래 total RNA 100ng 처리군이 101TCID50 바이러스 조건에서 바이러스 증식을 억제하는 효과를 확인할 수 있었다. In the case of placenta-derived total RNA, as a result of treatment with virus-infected cells, 66% of cells survived in the 100ng treatment group under the condition of virus titer 10 1 TCID 50 . The effect of inhibiting viral growth under viral conditions was confirmed.
본 발명에 따른 태반 유래의 엑소좀, 마이크로파티클, total RNA, 마이크로RNA(miRNA), 세포외소포체, 태반유래 세포 및 중간엽 줄기세포로 구성된 군에서 선택되는 하나 이상의 태반유래 물질을 포함하는 조성물은 코로나바이러스에 감염시킨 세포에서 용량 의존적으로 코로나바이러스의 증식을 억제하는 효과를 가지므로 코로나바이러스를 비롯하여 RNA 바이러스 또는 다른 바이러스 감염 예방 및 바이러스 감염 후 치료에 유용하게 활용될 수 있다.The composition comprising at least one placenta-derived material selected from the group consisting of placenta-derived exosomes, microparticles, total RNA, microRNA (miRNA), extracellular vesicles, placenta-derived cells and mesenchymal stem cells according to the present invention Since it has the effect of inhibiting the proliferation of coronavirus in a dose-dependent manner in cells infected with coronavirus, it can be usefully used for prevention of infection with coronavirus, RNA virus or other viruses, and treatment after viral infection.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적 기술은 단지 바람직한 실시 양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.Having described specific parts of the present invention in detail above, it will be clear to those skilled in the art that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. will be. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (12)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063009640P | 2020-04-14 | 2020-04-14 | |
US63/009,640 | 2020-04-14 | ||
KR1020200066577 | 2020-06-02 | ||
KR20200066577 | 2020-06-02 | ||
PCT/KR2021/004465 WO2021210852A1 (en) | 2020-04-14 | 2021-04-09 | Anti-viral composition comprising placenta-derived material |
Publications (1)
Publication Number | Publication Date |
---|---|
KR20220167294A true KR20220167294A (en) | 2022-12-20 |
Family
ID=78083842
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020227037509A KR20220167294A (en) | 2020-04-14 | 2021-04-09 | Antiviral composition containing placenta-derived material |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR20220167294A (en) |
WO (1) | WO2021210852A1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101919081B1 (en) | 2017-05-11 | 2018-11-16 | (주)녹십자웰빙 | Composition for prevention or treatment of muscular atrophy or sarcopenia and improvement of muscular functions comprising human placenta extract |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2015330855A1 (en) * | 2014-10-09 | 2017-04-27 | Celularity Inc. | Placenta-derived adherent cell exosomes and uses thereof |
CN108143750B (en) * | 2017-12-26 | 2020-09-15 | 湖北未来家园高科技农业股份有限公司 | Preparation method and application of deer placenta exosome |
WO2020051362A1 (en) * | 2018-09-05 | 2020-03-12 | Children's Medical Center Corporation | Use of mesenchymal stromal cell exosomes in antenatal therapy |
-
2021
- 2021-04-09 KR KR1020227037509A patent/KR20220167294A/en unknown
- 2021-04-09 WO PCT/KR2021/004465 patent/WO2021210852A1/en active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101919081B1 (en) | 2017-05-11 | 2018-11-16 | (주)녹십자웰빙 | Composition for prevention or treatment of muscular atrophy or sarcopenia and improvement of muscular functions comprising human placenta extract |
Non-Patent Citations (1)
Title |
---|
한국보건사회연구원 발행 '보건복지 Issue & Focus' 제373호(2020-04) 발행일 2020.03.05. ISSN 2092-7117 |
Also Published As
Publication number | Publication date |
---|---|
WO2021210852A1 (en) | 2021-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TW546143B (en) | Comprising vitamin p and a processed product of Pfaffia extract | |
JP4731321B2 (en) | Composition for preventing or treating viral infection | |
CN107073057B (en) | Composition for preventing and treating viral diseases containing Epimedium koreanum extract as active ingredient | |
TW200826954A (en) | Herbal extract with anti-influenza virus activity and preparation of same | |
KR102524071B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102521871B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
TW201221133A (en) | A medical compositions for inhibition of influenza Hemagglutinin and process for the preparation thereof | |
KR20220167294A (en) | Antiviral composition containing placenta-derived material | |
KR20220161415A (en) | Antiviral composition containing placenta extract | |
KR102526308B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102516639B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102506856B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102546110B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102527527B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102508942B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102533344B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102512522B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102526488B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102540814B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102524088B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102497912B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR102499066B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component | |
KR101665016B1 (en) | Composition for the prevention and treatment of antiviral comprising extracts of crude drug complex | |
KR20210049698A (en) | Composition for prevention or treatment of Porcine epidemic diarrhea virus infection including a complex comprising a curcuminoid compound, and licorice extract or a fraction thereof | |
KR102529571B1 (en) | Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component |