KR20220051628A - Pharmaceutical Composition for prevention or treatment of diseases of Coronavirus Infection - Google Patents
Pharmaceutical Composition for prevention or treatment of diseases of Coronavirus Infection Download PDFInfo
- Publication number
- KR20220051628A KR20220051628A KR1020200135248A KR20200135248A KR20220051628A KR 20220051628 A KR20220051628 A KR 20220051628A KR 1020200135248 A KR1020200135248 A KR 1020200135248A KR 20200135248 A KR20200135248 A KR 20200135248A KR 20220051628 A KR20220051628 A KR 20220051628A
- Authority
- KR
- South Korea
- Prior art keywords
- coronavirus
- justicidin
- cov
- composition
- sars
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 41
- 208000001528 Coronaviridae Infections Diseases 0.000 title claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 54
- 201000010099 disease Diseases 0.000 title claims description 44
- 230000002265 prevention Effects 0.000 title abstract description 15
- 238000011282 treatment Methods 0.000 title description 16
- RTDRYYULUYRTAN-UHFFFAOYSA-N Justicidin B Chemical compound C1=C2OCOC2=CC(C=2C=3C(=O)OCC=3C=C3C=C(C(=CC3=2)OC)OC)=C1 RTDRYYULUYRTAN-UHFFFAOYSA-N 0.000 claims abstract description 117
- ANFSXHKDCKWWDB-UHFFFAOYSA-N Justicidin A Chemical compound C1=C2OCOC2=CC(C=2C=3C(=O)OCC=3C(OC)=C3C=C(C(=CC3=2)OC)OC)=C1 ANFSXHKDCKWWDB-UHFFFAOYSA-N 0.000 claims abstract description 105
- 239000000203 mixture Substances 0.000 claims abstract description 67
- BBEFSDNXXNECSY-UHFFFAOYSA-N isojusticidin B Natural products C1=C2OCOC2=CC(C2=C3C(=O)OCC3=CC3=CC=C(C(=C32)OC)OC)=C1 BBEFSDNXXNECSY-UHFFFAOYSA-N 0.000 claims abstract description 61
- PQFYSRLXICNMSR-UHFFFAOYSA-N justicidine B Natural products COc1ccc(cc1OC)c2c3OCC(=O)c3cc4cc5OCOc5cc24 PQFYSRLXICNMSR-UHFFFAOYSA-N 0.000 claims abstract description 61
- VKNAGQVZXQTVMW-UHFFFAOYSA-N retrochinensinaphthol methyl ether Natural products C1=C(OC)C(OC)=CC=C1C(C1=C2)=C(OCC3=O)C3=C(OC)C1=CC1=C2OCO1 VKNAGQVZXQTVMW-UHFFFAOYSA-N 0.000 claims abstract description 51
- 239000000284 extract Substances 0.000 claims abstract description 39
- 239000004480 active ingredient Substances 0.000 claims abstract description 38
- 241000711573 Coronaviridae Species 0.000 claims abstract description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003960 organic solvent Substances 0.000 claims abstract description 20
- 208000015181 infectious disease Diseases 0.000 claims abstract description 19
- 235000013305 food Nutrition 0.000 claims abstract description 16
- 241001678559 COVID-19 virus Species 0.000 claims abstract description 13
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 9
- 244000308415 Justicia procumbens Species 0.000 claims abstract description 7
- 208000019202 Orthocoronavirinae infectious disease Diseases 0.000 claims abstract 2
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims description 29
- 241000315672 SARS coronavirus Species 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 208000024891 symptom Diseases 0.000 claims description 12
- -1 hydroxyl Justicidin-B Chemical compound 0.000 claims description 11
- 241000008904 Betacoronavirus Species 0.000 claims description 10
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 claims description 10
- 230000036541 health Effects 0.000 claims description 10
- 208000023504 respiratory system disease Diseases 0.000 claims description 10
- 208000025370 Middle East respiratory syndrome Diseases 0.000 claims description 8
- 235000013376 functional food Nutrition 0.000 claims description 7
- 206010011224 Cough Diseases 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 208000000059 Dyspnea Diseases 0.000 claims description 6
- 206010013975 Dyspnoeas Diseases 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 206010019233 Headaches Diseases 0.000 claims description 6
- 208000000616 Hemoptysis Diseases 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 206010028813 Nausea Diseases 0.000 claims description 6
- 206010068319 Oropharyngeal pain Diseases 0.000 claims description 6
- 201000007100 Pharyngitis Diseases 0.000 claims description 6
- 206010036790 Productive cough Diseases 0.000 claims description 6
- 206010037660 Pyrexia Diseases 0.000 claims description 6
- 231100000869 headache Toxicity 0.000 claims description 6
- 206010025482 malaise Diseases 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 230000008693 nausea Effects 0.000 claims description 6
- 208000024794 sputum Diseases 0.000 claims description 6
- 210000003802 sputum Anatomy 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 241001442129 Myosotis Species 0.000 claims 2
- 206010017964 Gastrointestinal infection Diseases 0.000 claims 1
- 206010023424 Kidney infection Diseases 0.000 claims 1
- 206010037596 Pyelonephritis Diseases 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 208000019836 digestive system infectious disease Diseases 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- NXDFXQJRGLAEKK-UHFFFAOYSA-N 4-(6-hydroxy-1,3-benzodioxol-5-yl)-6,7-dimethoxy-1h-benzo[f][2]benzofuran-3-one Chemical compound C=12C=C(OC)C(OC)=CC2=CC=2COC(=O)C=2C=1C(C(=C1)O)=CC2=C1OCO2 NXDFXQJRGLAEKK-UHFFFAOYSA-N 0.000 abstract description 49
- ZYUVOQCJYNAWNV-UHFFFAOYSA-N Chinensinaphthol Natural products C1=C(OC)C(OC)=CC=C1C(C1=C2)=C(C(=O)OC3)C3=C(O)C1=CC1=C2OCO1 ZYUVOQCJYNAWNV-UHFFFAOYSA-N 0.000 abstract description 48
- 239000000469 ethanolic extract Substances 0.000 abstract description 12
- 230000002401 inhibitory effect Effects 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 description 31
- 241000004176 Alphacoronavirus Species 0.000 description 26
- 239000003814 drug Substances 0.000 description 22
- 244000036975 Ambrosia artemisiifolia Species 0.000 description 19
- 235000003129 Ambrosia artemisiifolia var elatior Nutrition 0.000 description 19
- 235000003484 annual ragweed Nutrition 0.000 description 19
- 235000006263 bur ragweed Nutrition 0.000 description 19
- 235000003488 common ragweed Nutrition 0.000 description 19
- 235000009736 ragweed Nutrition 0.000 description 19
- 229940079593 drug Drugs 0.000 description 17
- 230000000840 anti-viral effect Effects 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000003833 cell viability Effects 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 210000003501 vero cell Anatomy 0.000 description 6
- 241000008920 Gammacoronavirus Species 0.000 description 5
- 238000011529 RT qPCR Methods 0.000 description 5
- 230000005540 biological transmission Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 241001461743 Deltacoronavirus Species 0.000 description 4
- 241000711467 Human coronavirus 229E Species 0.000 description 4
- 241000482741 Human coronavirus NL63 Species 0.000 description 4
- 241001428935 Human coronavirus OC43 Species 0.000 description 4
- 240000003705 Senecio vulgaris Species 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 229940033134 talc Drugs 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 3
- 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 3
- 241001061264 Astragalus Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241001109669 Human coronavirus HKU1 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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 229960003677 chloroquine Drugs 0.000 description 3
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229940041476 lactose 100 mg Drugs 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 229960003415 propylparaben Drugs 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000711506 Canine coronavirus Species 0.000 description 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-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
- 241000196324 Embryophyta Species 0.000 description 2
- 241000963676 Equine coronavirus Species 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 241000725579 Feline coronavirus Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000008906 Murine coronavirus Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 241001135549 Porcine epidemic diarrhea virus Species 0.000 description 2
- 241000156302 Porcine hemagglutinating encephalomyelitis virus Species 0.000 description 2
- 241000711484 Transmissible gastroenteritis virus Species 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 235000006533 astragalus Nutrition 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000000378 calcium silicate Substances 0.000 description 2
- 229910052918 calcium silicate Inorganic materials 0.000 description 2
- 235000012241 calcium silicate Nutrition 0.000 description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000020510 functional beverage Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- DFVZQTUMRRMHEL-UHFFFAOYSA-N isodiphyllin Natural products C=12C=C(OC)C(OC)=CC2=C(OC)C=2COC(=O)C=2C=1C(C(=C1)O)=CC2=C1OCO2 DFVZQTUMRRMHEL-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 239000000845 maltitol Substances 0.000 description 2
- 235000010449 maltitol Nutrition 0.000 description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 2
- 229940035436 maltitol Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 210000004233 talus Anatomy 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LHEJDBBHZGISGW-UHFFFAOYSA-N 5-fluoro-3-(3-oxo-1h-2-benzofuran-1-yl)-1h-pyrimidine-2,4-dione Chemical compound O=C1C(F)=CNC(=O)N1C1C2=CC=CC=C2C(=O)O1 LHEJDBBHZGISGW-UHFFFAOYSA-N 0.000 description 1
- MLRLQPQLTFPJMQ-UHFFFAOYSA-N 6,7-dimethoxy-4-[6-(methoxymethoxy)-1,3-benzodioxol-5-yl]-1H-benzo[f][2]benzofuran-3-one Chemical compound COCOC1=CC2=C(C=C1C3=C4C=C(C(=CC4=CC5=C3C(=O)OC5)OC)OC)OCO2 MLRLQPQLTFPJMQ-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 241000207965 Acanthaceae Species 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 102000053723 Angiotensin-converting enzyme 2 Human genes 0.000 description 1
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 1
- 206010003757 Atypical pneumonia Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000008921 Avian coronavirus Species 0.000 description 1
- 241000008922 Beluga Whale coronavirus SW1 Species 0.000 description 1
- 241000711443 Bovine coronavirus Species 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000223782 Ciliophora Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- YHJUKTOHEZLPJG-UHFFFAOYSA-N FC(S(=O)(=O)OC1=C2C=C(C(=CC2=CC=2COC(C21)=O)OC)OC)(F)F Chemical compound FC(S(=O)(=O)OC1=C2C=C(C(=CC2=CC=2COC(C21)=O)OC)OC)(F)F YHJUKTOHEZLPJG-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 244000309467 Human Coronavirus Species 0.000 description 1
- 241000207984 Justicia Species 0.000 description 1
- 240000004836 Justicia adhatoda Species 0.000 description 1
- 241001655940 Justicia anselliana Species 0.000 description 1
- 240000000084 Justicia gendarussa Species 0.000 description 1
- 241000366676 Justicia pectoralis Species 0.000 description 1
- 241000288904 Lemur Species 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 241000008902 Miniopterus bat coronavirus 1 Species 0.000 description 1
- 241000008903 Miniopterus bat coronavirus HKU8 Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001125039 Pipistrellus Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241001504477 Pycnonotidae Species 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 241000004178 Rhinolophus bat coronavirus HKU2 Species 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 241000289057 Rousettus Species 0.000 description 1
- 241001663342 Scotophilus Species 0.000 description 1
- 101710147732 Small envelope protein Proteins 0.000 description 1
- 241000947555 Thrush coronavirus HKU12 Species 0.000 description 1
- 241001418284 Tylonycteris Species 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940037769 calcium carbonate 100 mg Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- SFPLCCUNXOBTQY-UHFFFAOYSA-N chinensinaphthol methyl ester Natural products C1=C(OC)C(OC)=CC=C1C(C1=C2)=C(C(=O)OC3)C3=C(OC)C1=CC1=C2OCO1 SFPLCCUNXOBTQY-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 229940069647 citric acid 1000 mg Drugs 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229930190997 justicidin Natural products 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 208000026425 severe pneumonia Diseases 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/19—Acanthaceae (Acanthus family)
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
-
- 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
- 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
- A23V2250/30—Other Organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Food Science & Technology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Polymers & Plastics (AREA)
- Communicable Diseases (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
본 발명은 쥐꼬리망초(Justicia procumbens)의 유기용매 추출물 및 이의 활성 성분들을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 치료용 약학적 조성물 및 이의 용도에 관한 것이다. The present invention relates to a pharmaceutical composition for preventing or treating a coronavirus infection disease comprising an organic solvent extract of Justicia procumbens and its active ingredients as an active ingredient, and a use thereof.
코로나바이러스(Coronavirus, CoV)는 약 30kb 길이 유전체의 단일가닥 양성 RNA 바이러스로서 외피를 지닌 비교적 큰 바이러스에 속한다. 암호화된 유전자는 크게 뉴클레오캡시드 단백질, 매트릭스 단백질, 작은 외피 단백질 및 표면돌기 당단백질로 구성되어 있다. 다른 RNA 바이러스와 마찬가지로, 증식과정에서 돌연변이 및 유전자 재조합 현상이 빈번하게 발생하는 것으로 알려져 있다 표면돌기 단백질의 외관 상 왕관(crown) 혹은 태양광환(corona) 모양을 따서 '코로나바이러스'로 명명되었다. Coronavirus (CoV) is a single-stranded positive RNA virus with a genome of about 30 kb in length and belongs to a relatively large virus with an envelope. The encoded gene is largely composed of a nucleocapsid protein, a matrix protein, a small envelope protein, and a surface process glycoprotein. Like other RNA viruses, it is known that mutations and gene recombination occur frequently in the process of proliferation.
다양한 병인기전을 통해 동물, 사람 및 조류를 감염시켜 호흡기 혹은 위장관 질환을 유발하는 코로나바이러스는 일반적으로 사람에게 풍토병성(endemic) 감염 형태를 보여 지역사회 병원균으로 알려져 왔다. 코로나바이러스는 염기서열분석 및 항원성을 기반으로 알파-, 베타-, 감마- 및 델타-코로나바이러스 4개군으로 분류되며, 이중 알파-와 베타-코로나바이러스군은 사람을 감염시키는 사람코로나바이러스들이 속해 있다. Coronaviruses, which infect animals, humans, and birds through various etiological mechanisms, and cause respiratory or gastrointestinal diseases, have been known as community pathogens because they generally show an endemic form of infection in humans. Coronaviruses are classified into four groups of alpha-, beta-, gamma-, and delta-coronaviruses based on sequencing and antigenicity. there is.
대부분 호흡기 감염을 유발하는 사람코로나바이러스는 동물-사람 종간 감염을 일으키면서 인간에서 존재하지 않았던 신종 병원균의 출현을 야기할 수 있고, 이들 감염에 의해 심각한 증상과 병원성을 보여 큰 사회적 이슈를 일으킨 유행병성으로 나타나기도 한다. 특히, 베타-코로나바이러스에 속하는 중증급성호흡기증후군 코로나바이러스(severe acute respiratory syndrome-associated coronavirus, SARS-CoV)와 중동호흡기증후군 코로나바이러스(middle east respiratory syndrome coronavirus, MERS-CoV)의 출현이 이들의 사례이다. Human coronaviruses, which mostly cause respiratory infections, can cause the emergence of new pathogens that did not exist in humans while causing animal-human interspecies infections. may also appear as In particular, the appearance of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) belonging to beta-coronavirus and middle east respiratory syndrome coronavirus (MERS-CoV) is one of these cases. am.
2002년 중국 광동지역에서 발생하여 전세계적으로 심각한 중증 폐렴을 확산시킨 SARS-CoV의 출현은 그간 사람들에게 거의 관심을 받지 못했던 코로나바이러스가 동물-사람간 종(species) 방어벽을 넘나든 대유행의 위험성을 보여주는 사례가 되었다. 2003년 중반에 SARS 대유행이 종식되었지만 8000명 이상이 감염되었고, 약 10% 치사율인 744명의 사망자가 발생하였다. 아직까지도 정확한 전파 기전이 밝혀지지 않은 상황에서 재유행을 대비한 치료제 개발이 시급한 시점이다. The emergence of SARS-CoV, which occurred in Guangdong, China in 2002 and spread severe pneumonia worldwide, raised the risk of a pandemic, in which the coronavirus, which had received little attention, crossed the animal-human species barrier. became an example to show. Although the SARS pandemic ended in mid-2003, more than 8,000 people were infected and 744 deaths occurred, with a mortality rate of about 10%. In a situation where the exact mechanism of transmission is still unknown, it is urgent to develop a therapeutic agent in preparation for a resurgence.
MERS-CoV는 2012년 급성 호흡기 질환으로 사망한 중동지역환자로부터 동정된 새로운 고병원성 코로나바이러스로서 중간 숙주인 낙타를 통해 사람으로 전파된 것으로 추정되며, 이로 인해 코로나바이러스의 위험성이 다시 부각되었다. 단기간 전세계에 높은 전파력을 지닌 SARS-CoV와는 달리, MERS-CoV는 동물-사람 전파 특발성과 폭발적인 원내 전파력이 특징으로 나타났으며, SARS-CoV와는 유전적 차이가 크다. WHO는 MERS 유행은 사우디아라비아에서 주로 발생하였고, 약 2500명 감염과 37% 치사율이 있음을 보고했다. MERS-CoV is a novel highly pathogenic coronavirus identified from a patient in the Middle East who died of acute respiratory disease in 2012, and it is presumed that it was transmitted to humans via an intermediate host, camel, which re-emerges the risk of coronavirus. Unlike SARS-CoV, which has high transmission power worldwide in a short period of time, MERS-CoV is characterized by idiopathic animal-human transmission and explosive nosocomial transmission, and has a large genetic difference from SARS-CoV. The WHO reported that the MERS epidemic occurred mainly in Saudi Arabia, with about 2500 infections and a 37% fatality rate.
SARS와 MERS는 심각한 비전형 폐렴과 같은 임상증상을 보인다는 유사성이 있으나, 바이러스의 세포내 감염경로 차이에 의해 핵심적 임상 양상이 다르게 나타난다. 즉, SARS-CoV는 사람 하기도부 섬모세포에 분포된 ACE2 수용체를 통해 감염되어 하기도부 감염을 주로 보였고, MERS-CoV는 하기도부 포함 위장관, 신장에 분포된 비섬포세포내 DPP-4(혹은 CD26)와 결합함으로써 위장관 증상과 더불어 종종 급성신부전이 나타났다. SARS and MERS are similar in that they show clinical symptoms such as severe atypical pneumonia, but the core clinical features are different due to the difference in the intracellular infection route of the virus. That is, SARS-CoV was infected through the ACE2 receptor distributed in human lower respiratory tract ciliate cells and showed mainly lower respiratory tract infection, while MERS-CoV was DPP-4 (or CD26) in non-cylindrical cells distributed in the gastrointestinal tract, kidney, and lower respiratory tract. ) and often acute renal failure along with gastrointestinal symptoms.
아직까지 높은 전파력과 고위험성을 지닌 코로나바이러스 감염 질환을 치료하고 예방하는 확인된 약물 혹은 백신은 개발되어 있지는 않다. 따라서, 전세계적으로 큰 이슈가 되었던 SARS-CoV와 MERS-CoV 감염증의 재유행 혹은 신변종 코로나바이러스 감염에 의한 새로운 팬데믹 현상이 지속적으로 발생할 수 있다는 경험을 바탕으로, 코로나바이러스 감염에 의한 질환을 예방 및 치료할 수 있는 치료제 개발이 시급한 상황이다. 특히, 코로나바이러스의 유전적 차이나 감염경로 특이성에 제한적이지 않은 항코로나바이러스 약물의 개발은 다양한 코로나바이스 감염에 대응할 수 있는 방안이 될 것으로 보인다.No confirmed drug or vaccine has yet been developed to treat and prevent coronavirus-infected diseases with high transmission and high risk. Therefore, based on the experience that SARS-CoV and MERS-CoV infections, which have become big issues worldwide, or new pandemics caused by new coronavirus infection can continue to occur, diseases caused by coronavirus infection There is an urgent need to develop therapeutic agents that can prevent and treat the disease. In particular, the development of anti-coronavirus drugs that are not limited to the genetic differences or infection route specificity of the coronavirus is expected to be a way to respond to various coronavirus infections.
쥐꼬리망초과(Acanthaceae)의 쥐꼬리망초속(Justicia genus)은 약 600개의 종으로 이루어져 있다. 대표적인 쥐꼬리망초속 식물로는 Justicia procumbens, Justicia pectoralis, Justicia gendarussa, Justicia anselliana, 및 Justicia adhatoda 등이 있으며, 쥐꼬리망초 속 식물들은 항 바이러스 효과를 비롯한 여러 생리학적 활성이 있는 것으로 알려져 있으나 각각의 생리학적 활성을 나타내는 활성 성분에 대한 연구는 아직까지 많이 이루어지지 않았다. 이 중 쥐꼬리망초(Justicia procumbens)는 한해살이풀로서 한국, 일본, 중국, 인도 등에서 서식한다. 쥐꼬리망초의 약리학적 활성으로는 전초의 메탄올 추출물의 경우 토끼의 혈소판 응집 및 암세포의 증식을 억제시키는 작용이 알려져 있으며, 지상부(Aerial part) 메탄올 추출물 및 리그난(Lignan)계열의 주요 구성 성분들이 수포성 구내염 바이러스(vesicular stomatitis virus, VSV), 인간면역결핍 바이러스(HIV) 등에 억제효과가 있음이 알려져 있다(Asano, et al., 1996; XU Xin-Ya, et al., 2019). The genus Justicia genus of the family Acanthaceae consists of about 600 species. Representative plants of the genus Lemur are Justicia procumbens, Justicia pectoralis, Justicia gendarussa, Justicia anselliana, and Justicia adhatoda . There have not been many studies on active ingredients representing Among them, Justicia procumbens is an annual herb that lives in Korea, Japan, China, and India. As for the pharmacological activity of ragweed, the methanol extract of the outpost is known to inhibit platelet aggregation and the proliferation of cancer cells in rabbits. It is known that there is an inhibitory effect on stomatitis virus (vesicular stomatitis virus, VSV), human immunodeficiency virus (HIV), etc. (Asano, et al., 1996; XU Xin-Ya, et al., 2019).
하지만, SARS-CoV와 MERS-CoV 등의 코로나바이러스와 관련된 효과는 아직 알려진 것이 없다.However, effects related to coronaviruses such as SARS-CoV and MERS-CoV are not yet known.
본 발명의 목적은 쥐꼬리망초 유기용매 추출물을 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of coronavirus-infected diseases, comprising an organic solvent extract of ragweed as an active ingredient.
또한, 본 발명은 쥐꼬리망초 유기용매 추출물을 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.In addition, the present invention is to provide a food composition for the prevention or improvement of coronavirus-infected diseases, comprising an organic solvent extract of ragweed as an active ingredient.
또한, 본 발명은 쥐꼬리망초 유기용매 추출물을 유효성분으로 포함하는, 항코로나바이러스용 조성물을 제공하는 것이다.In addition, the present invention is to provide a composition for anti-coronavirus, comprising an organic solvent extract of ragweed as an active ingredient.
또한, 본 발명은 저스티시딘-A(justicidin-A)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In addition, the present invention is to provide a pharmaceutical composition for preventing or treating a coronavirus infection disease, comprising justicidin-A (justicidin-A) as an active ingredient.
또한, 본 발명은 저스티시딘-A(justicidin-A)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.In addition, the present invention is to provide a food composition for the prevention or improvement of coronavirus infection disease, comprising justicidin-A (justicidin-A) as an active ingredient.
또한, 본 발명은 저스티시딘-A(justicidin-A)를 유효성분으로 포함하는, 항코로나바이러스용 조성물을 제공하는 것이다.In addition, the present invention is to provide a composition for anti-coronavirus, comprising justicidin-A (justicidin-A) as an active ingredient.
또한, 본 발명은 저스티시딘-B(justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In addition, the present invention is to provide a pharmaceutical composition for preventing or treating a coronavirus infection disease, comprising justicidin-B (justicidin-B) as an active ingredient.
또한, 본 발명은 저스티시딘-B(justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.In addition, the present invention is to provide a food composition for the prevention or improvement of coronavirus-infected diseases, comprising justicidin-B (justicidin-B) as an active ingredient.
또한, 본 발명은 저스티시딘-B(justicidin-B)를 유효성분으로 포함하는, 항코로나바이러스용 조성물을 제공하는 것이다.In addition, the present invention is to provide a composition for anti-coronavirus, comprising justicidin-B (justicidin-B) as an active ingredient.
또한, 본 발명은 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In addition, the present invention provides a pharmaceutical composition for preventing or treating coronavirus-infected diseases, comprising 6' hydroxy justicidin-B as an active ingredient.
또한, 본 발명은 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.In addition, the present invention is to provide a food composition for preventing or improving coronavirus-infected diseases, comprising 6' hydroxy justicidin-B as an active ingredient.
또한, 본 발명은 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 항코로나바이러스용 조성물을 제공하는 것이다.In addition, the present invention is to provide a composition for anti-coronavirus comprising 6' hydroxy justicidin-B (6' hydroxy justicidin-B) as an active ingredient.
상기 목적을 달성하기 위하여 본 발명은 쥐꼬리망초 추출물, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B), 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides an extract of Rathorn Cortex, justicidin-A, justicidin-B, or 6' hydroxy justicidin-B (6' hydroxyl justicidin). -B) as an active ingredient, it provides a pharmaceutical composition for preventing or treating coronavirus-infected diseases.
또한 본 발명은 쥐꼬리망초 추출물, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B), 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention is effective in the extract of Rathorn Cortex, justicidin-A (justicidin-A), justicidin-B (justicidin-B), or 6' hydroxy justicidin-B (6' hydroxy justicidin-B). It provides a food composition for the prevention or improvement of coronavirus-infected diseases, including as a component.
또한 본 발명은 쥐꼬리망초 추출물, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B), 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 코로나바이러스에 대한 항코로나바이러스용 조성물을 제공한다.In addition, the present invention is effective in the extract of Rathorn Cortex, justicidin-A (justicidin-A), justicidin-B (justicidin-B), or 6' hydroxy justicidin-B (6' hydroxy justicidin-B). It provides a composition for anti-coronavirus against coronavirus, including as a component.
또한 본 발명은 쥐꼬리망초 추출물, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B), 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)를 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 개선용 화장료 조성물을 제공한다.In addition, the present invention is effective in the extract of Rathorn Cortex, justicidin-A (justicidin-A), justicidin-B (justicidin-B), or 6' hydroxy justicidin-B (6' hydroxy justicidin-B). It provides a cosmetic composition for preventing or improving coronavirus-infected diseases, including as a component.
본 발명의 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B) 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)는 쥐꼬리망초에서 분리 정제한 것이나 합성한 것 모두를 포함한다. Justicidin-A, justicidin-B, or 6' hydroxy justicidin-B (6' hydroxy justicidin-B) of the present invention is isolated and purified from Astragalus Includes all composites.
본 발명의 쥐꼬리망초 추출물, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B), 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)는 코로나바이러스의 감염 및 증식을 억제 할 수 있으며, 이를 통해 코로나바이러스 감염에 의한 질환을 효과적으로 예방, 치료 또는 개선할 수 있다.The extract of Rathorn Cortex of the present invention, justicidin-A (justicidin-A), justicidin-B (justicidin-B), or 6' hydroxy justicidin-B (6' hydroxyl justicidin-B) is a coronavirus Infection and proliferation can be inhibited, and through this, diseases caused by coronavirus infection can be effectively prevented, treated, or ameliorated.
본 발명의 쥐꼬리망초 추출물은 유기용매 추출물일 수 있다. 상기 유기용매는 탄소수 1 이상 4 이하의 알코올일 수 있다.The extract of Rathorn Guinea extract of the present invention may be an organic solvent extract. The organic solvent may be an alcohol having 1 or more and 4 or less carbon atoms.
상기 유기용매는 메탄올, 에탄올, 이소프로판올, 부탄올, 헥산, 아세트산에틸, 디클로로메탄, 에테르, 클로로포름 및 아세톤 중에서 선택되는 어느 하나 이상일 수 있다. 상기 유기 용매는 예를 들어 무수에탄올일 수 있다.The organic solvent may be any one or more selected from methanol, ethanol, isopropanol, butanol, hexane, ethyl acetate, dichloromethane, ether, chloroform and acetone. The organic solvent may be, for example, absolute ethanol.
상기 코로나바이러스는 알파-코로나바이러스(Alphacoronavirus), 베타-코로나바이러스(Betacoronavirus), 감마-코로나바이러스(Gammacoronavirus) 또는 델타-코로나바이러스(Deltacoronavirus)를 포함할 수 있다.The coronavirus may include alpha- coronavirus , beta- coronavirus , gamma- coronavirus , or delta-coronavirus.
상기 알파-코로나바이러스는 인간 코로나바이러스 229E(Human coronavirus 229E), 인간 코로나바이러스 NL63(Human coronavirus NL63), 돼지 유행성 설사 바이러스(porcine epidemic diarrhea virus : PEDV), (돼지) 전염성 위장염 바이러스 (transmissible gastroenteritis virus : TGEV), 개코로나바이러스(canine coronavirus : CCoV), 고양이 코로나바이러스 (feline coronavirus : FCoV), Miniopterus bat(박쥐) coronavirus 1, Miniopterus bat(박쥐) coronavirus HKU8, Rhinolophus bat(박쥐) coronavirus HKU2, 및 Scotophilus bat(박쥐) coronavirus 512로 구성된 군에서 선택된 하나 이상일 수 있다.The alpha-coronavirus is human coronavirus 229E (Human coronavirus 229E), human coronavirus NL63 (Human coronavirus NL63), porcine epidemic diarrhea virus (PEDV), (porcine) transmissible gastroenteritis virus: TGEV), canine coronavirus (CCoV), feline coronavirus (FCoV), Miniopterus bat
보다 구체적으로 상기 알파-코로나바이러스는 인간 코로나바이러스 229E(Human coronavirus 229E) 또는 인간 코로나바이러스 NL63(Human coronavirus NL63)일 수 있다.More specifically, the alpha-coronavirus may be human coronavirus 229E (Human coronavirus 229E) or human coronavirus NL63 (Human coronavirus NL63).
상기 코로나바이러스는 베타-코로나바이러스(Betacoronavirus)일 수 있다.The coronavirus may be a beta-coronavirus ( Betacoronavirus ).
상기 베타-코로나바이러스는 인간 코로나바이러스 OC43(Human coronavirus OC43), 인간 코로나바이러스 HKU1(Human coronavirus HKU1), SARS-CoV, MERS-CoV, 돼지 혈구 응집성뇌척수염 바이러스(porcine hemagglutinating encephalomyelitis virus : PHEV), 우코로나바이러스(bovine coronavirus : BCoV), 말코로나바이러스 (equine coronavirus : EqCoV), 쥐코로나바이러스(murine coronavirus : MuCoV),Tylonycteris bat(박쥐) coronavirus HKU4, Pipistrellus bat(박쥐) coronavirus HKU5, 및 Rousettus bat(박쥐) coronavirus HKU9 로 구성된 군에서 선택된 하나 이상일 수 있다.The beta-coronavirus is human coronavirus OC43 (Human coronavirus OC43), human coronavirus HKU1 (HKU1), SARS-CoV, MERS-CoV, porcine hemagglutinating encephalomyelitis virus (PHEV), Wu Corona Virus (bovine coronavirus: BCoV), equine coronavirus (EqCoV), murine coronavirus (MuCoV), Tylonycteris bat (bat) coronavirus HKU4, Pipistrellus bat (bat) coronavirus HKU5, and Rousettus bat (bat) It may be one or more selected from the group consisting of coronavirus HKU9.
보다 구체적으로, 상기 베타-코로나바이러스는 인간 코로나바이러스 OC43(Human coronavirus OC43), 인간 코로나바이러스 HKU1(Human coronavirus HKU1), SARS-CoV(Severe acute respiratory syndrome coronavirus) 또는 MERS-CoV(Middle East respiratory syndrome coronavirus)를 포함할 수 있다. 더 구체적으로, 상기 베타-코로나바이러스는 SARS-CoV(Severe acute respiratory syndrome coronavirus) 또는 MERS-CoV(Middle East respiratory syndrome coronavirus)를 포함할 수 있다.More specifically, the beta-coronavirus is human coronavirus OC43 (Human coronavirus OC43), human coronavirus HKU1 (Human coronavirus HKU1), SARS-CoV (Severe acute respiratory syndrome coronavirus) or MERS-CoV (Middle East respiratory syndrome coronavirus) ) may be included. More specifically, the beta-coronavirus may include severe acute respiratory syndrome coronavirus (SARS-CoV) or Middle East respiratory syndrome coronavirus (MERS-CoV).
상기 코로나바이러스는 감마-코로나바이러스(Gammacoronavirus)를 포함할 수 있다. 상기 감마 코로나바이러스는 새코로나바이러스(Avian coronavirus) 및/또는 흰색 돌고래(Beluga whale)-코로나바이러스 SW1를 포함할 수 있다.The coronavirus may include gamma-coronavirus ( Gammacoronavirus ). The gamma coronavirus may include Avian coronavirus and/or Beluga whale-coronavirus SW1.
상기 코로나바이러스는 델타-코로나바이러스일 수 있다. 상기 델타-코로나바이러스는 제주직박구리(Bulbul)-코로나바이러스 HKU11, 개똥지빠귀(Thrush)-코로나바이러스 HKU12, 킨바라(Munia)-코로나바이러스 HKU13일 수 있다.The coronavirus may be a delta-coronavirus. The delta-coronavirus may be Jeju Jikbakguri (Bulbul)-coronavirus HKU11, thrush-coronavirus HKU12, Kinbara (Munia)-coronavirus HKU13.
상기 코로나바이러스 감염 질환은 급성 호흡기 증후군(Severe Acute Respiratory Syndrome, SARS) 일 수 있다. 상기 코로나바이러스 감염 질환은 중동 호흡기 증후군(Middle East Respiratory Syndrome, MERS) 일 수 있다. 상기 코로나바이러스 감염 질환은 호흡기 질환일 수 있다. 상기 호흡기 질환은 폐렴일 수 있다.The coronavirus-infected disease may be Severe Acute Respiratory Syndrome (SARS). The coronavirus-infected disease may be Middle East Respiratory Syndrome (MERS). The coronavirus-infected disease may be a respiratory disease. The respiratory disease may be pneumonia.
상기 코로나바이러스 감염 질환에서 SARA-CoV-2 감염 질환은 제외될 수도 있다.SARA-CoV-2 infectious diseases may be excluded from the above coronavirus-infected diseases.
상기 코로나바이러스 감염 질환의 증상은 발열, 권태감, 기침, 호흡곤란, 가래, 인후통, 두통, 객혈, 오심, 위장관 증상, 신장질환, 호흡기 질환 및 설사 중 적어도 하나일 수 있다.The symptoms of the coronavirus-infected disease may be at least one of fever, malaise, cough, shortness of breath, sputum, sore throat, headache, hemoptysis, nausea, gastrointestinal symptoms, kidney disease, respiratory disease, and diarrhea.
상기 SARS-CoV(Severe acute respiratory syndrome coronavirus) 감염 질환의 증상은 발열, 권태감, 기침, 호흡곤란, 가래, 인후통, 두통, 객혈, 오심, 호흡기 질환 및 설사 중 적어도 하나일 수 있다.Symptoms of the SARS-CoV (Severe acute respiratory syndrome coronavirus) infectious disease may be at least one of fever, malaise, cough, dyspnea, sputum, sore throat, headache, hemoptysis, nausea, respiratory disease, and diarrhea.
상기 MERS-CoV(Middle East respiratory syndrome coronavirus) 감염 질환의 증상은 발열, 권태감, 기침, 호흡곤란, 가래, 인후통, 두통, 객혈, 오심, 위장관 증상, 신장질환, 호흡기 질환 및 설사 중 적어도 하나일 수 있다.The symptoms of the MERS-CoV (Middle East Respiratory Syndrome Coronavirus) infectious disease may be at least one of fever, malaise, cough, dyspnea, sputum, sore throat, headache, hemoptysis, nausea, gastrointestinal symptoms, kidney disease, respiratory disease and diarrhea. there is.
예를 들어, 상기 항코로나바이러스용 조성물은 항알파-코로나바이러스에 대한 항코로나바이러스용 조성물일 수 있고, 항베타-코로나바이러스에 대한 항코로나바이러스용 조성물일 수 있고, 항감마-코로나바이러스에 대한 항코로나바이러스용 조성물일 수 있고, 또는 항델타-코로나바이러스에 대한 항코로나바이러스용 조성물일 수 있다. 보다 구체적으로 상기 항코로나바이러스용 조성물은 항베타-코로나바이러스에 대한 항코로나바이러스용 조성물일 수 있다. 보다 구체적으로 상기 항코로나바이러스용 조성물은 SARS-CoV(Severe acute respiratory syndrome coronavirus)에 대한 항바이러스용 조성물 또는 MERS-CoV(Middle East respiratory syndrome coronavirus)에 대한 항바이러스용 조성물일 수 있다.For example, the anti-coronavirus composition may be an anti-coronavirus composition for anti-alpha-coronavirus, anti-beta-coronavirus anti-coronavirus composition, and anti-gamma-coronavirus It may be a composition for anti-coronavirus, or an anti-delta-coronavirus composition for anti-coronavirus. More specifically, the anti-coronavirus composition may be an anti-beta-coronavirus anti-coronavirus composition. More specifically, the anti-coronavirus composition may be an antiviral composition for SARS-CoV (Severe acute respiratory syndrome coronavirus) or an antiviral composition for MERS-CoV (Middle East respiratory syndrome coronavirus).
상기 항코로나바이러스용 조성물의 항바이러스 대상이 되는 코로나바이러스에서 SARS-CoV-2는 제외될 수도 있다.SARS-CoV-2 may be excluded from the coronavirus, which is the antiviral target of the anti-coronavirus composition.
본 발명의 약학적 조성물은 코로나바이러스 감염 질환을 예방하고 치료하기 위한 통상의 방법에 따라 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 에어로졸, 주사용액 등의 형태로 제형화하여 사용될 수 있다. 예를 들어, 본 발명의 약학적 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.The pharmaceutical composition of the present invention is in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, aerosols, injection solutions, etc. It can be formulated and used as For example, carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 복합 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제도 사용될 수 있다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 포함되며, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제, 감미제, 방향제, 보존제 등이 사용될 수 있다. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the complex composition, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be prepared by mixing. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. in addition to commonly used simple diluents such as water and liquid paraffin. can be used
비경구투여를 위한 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제 등을 포함할 수 있다. 비수성용제와 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일 등과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Vegetable oils such as propylene glycol, polyethylene glycol, and olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions.
또한, 본 발명의 약학적 조성물은 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 담체, 부형제 또는 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오즈, 메틸 셀룰로오즈, 하이드록시 프로필 메틸 셀룰로오즈, 미정질 셀룰로오즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 이산화규소 등의 광물 등이 사용될 수 있다. In addition, the pharmaceutical composition of the present invention may further include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxypropyl Minerals such as methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, silicon dioxide, and the like can be used.
본 발명에 따른 약학적 조성물의 투여량은 약학적으로 유효한 양이어야 한다. “약학적으로 유효한 양”은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 예방 또는 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 제제화 방법, 환자의 상태 및 체중, 환자의 성별, 연령, 질환의 정도, 약물형태, 투여경로 및 기간, 배설 속도, 반응 감응성 등과 같은 요인들에 따라 당업자에 의해 다양하게 선택될 수 있다. 유효량은 당업자에게 인식되어 있듯이 처리의 경로, 부형제의 사용 및 다른 약제와 함께 사용할 수 있는 가능성에 따라 변할 수 있다.The dosage of the pharmaceutical composition according to the present invention should be a pharmaceutically effective amount. “Pharmaceutically effective amount” means an amount sufficient to prevent or treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level includes the formulation method, the patient's condition and weight, and the patient's sex and age. , can be variously selected by those skilled in the art according to factors such as the degree of disease, drug form, administration route and duration, excretion rate, reaction sensitivity, and the like. An effective amount will vary depending on the route of treatment, the use of excipients, and the potential for use with other agents, as will be appreciated by those skilled in the art.
본 발명에 따른 쥐꼬리망초의 유기용매 추출물의 투여량 또는 복용량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하나, 성인 기준으로 0.001 mg/kg 내지 1000 mg/kg을 1회 내지 수회에 나누어 복용하는 것이 바람직하다.The dosage or dosage of the organic solvent extract of ragweed according to the present invention varies depending on the weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of the disease of the patient, It is preferable to take 0.001 mg/kg to 1000 mg/kg once to several times as a standard.
본 발명의 약제학적 조성물은 마우스, 가축, 인간 등의 포유동물에 다양한 경로를 통해 투여될 수 있다. 투여의 모든 방식은 예상될 수 있으며, 예를 들어 경구, 비경구, 정맥내, 진피내, 및 피하 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention may be administered to mammals such as mice, livestock, and humans through various routes. All modes of administration can be contemplated and can be administered, for example, by oral, parenteral, intravenous, intradermal, and subcutaneous injection.
또한 다른 하나의 양태로서, 본 발명은 쥐꼬리망초 유기용매 추출물을 포함하는 약학적 조성물을 이를 필요로 하는 대상체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공한다.As another aspect, the present invention provides a method for preventing or treating a coronavirus-infected disease, comprising administering to a subject in need thereof a pharmaceutical composition comprising an organic solvent extract of Rathorn Cortex.
본 발명은 또한 저스티시딘-A(justicidin-A)를 포함하는 약학적 조성물을 이를 필요로 하는 대상체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공한다.The present invention also provides a method for preventing or treating a coronavirus-infected disease, comprising administering a pharmaceutical composition comprising justicidin-A to a subject in need thereof.
본 발명은 또한 저스티시딘-B(justicidin-B)를 포함하는 약학적 조성물을 이를 필요로 하는 대상체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공한다.The present invention also provides a method for preventing or treating a coronavirus-infected disease, comprising administering a pharmaceutical composition comprising justicidin-B to a subject in need thereof.
본 발명은 또한 6' 하이드록시 저스티시딘-B(justicidin-B)를 포함하는 약학적 조성물을 이를 필요로 하는 대상체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공한다.The present invention also provides a method for preventing or treating a coronavirus-infected disease, comprising administering a pharmaceutical composition comprising 6' hydroxy justicidin-B to a subject in need thereof.
본 발명에서 상기 대상체는 동물을 말하며, 전형적으로 본 발명의 추출물을 이용한 치료로 유익한 효과를 나타낼 수 있는 포유 동물이다. 이러한 대상체의 바람직한 예에는 인간과 같은 영장류가 포함된다. 또한 이와 같은 대상체들에는 코로나바이러스 감염 질환의 증상(예를 들어, 발열, 권태감, 기침, 호흡곤란, 폐렴, 가래, 인후통, 두통, 객혈, 오심, 위장관 증상, 신장질환 또는 설사)을 갖거나 이와 같은 증상을 가질 위험이 있는 대상체들이 모두 포함된다. 코로나바이러스 감염 질환을 예방 또는 치료하는데 유효한 양은 단일 또는 다중 용량으로, 단독 또는 하나 또는 그 이상의 다른 조성물들(예를 들어, 다른 호흡기 질환 치료제 등)과 조합으로, 대상체에서 원하는 성과 또는 객관적이거나 또는 주관적인 이점을 제공하는 양을 의미한다. In the present invention, the subject refers to an animal, and is typically a mammal that can exhibit beneficial effects by treatment using the extract of the present invention. Preferred examples of such subjects include primates such as humans. In addition, such subjects have or have symptoms of a coronavirus-infected disease (eg, fever, malaise, cough, dyspnea, pneumonia, sputum, sore throat, headache, hemoptysis, nausea, gastrointestinal symptoms, kidney disease or diarrhea) All subjects at risk of having the same symptoms are included. An amount effective to prevent or treat a coronavirus-infected disease, in single or multiple doses, alone or in combination with one or more other compositions (eg, other therapeutic agents for respiratory diseases, etc.), results in a desired outcome or objective or subjective outcome in a subject. amount that provides an advantage.
이상 본 명세서에 기재된 수치값은 달리 명시되어 있지 않은 한 균등범위까지 포함하는 것으로 해석되어야 한다.Numerical values described in the present specification above should be interpreted as including equivalent ranges unless otherwise specified.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 쥐꼬리망초 유기용매 추출물을 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising an organic solvent extract of Rathorn ragweed as an active ingredient for the prevention or treatment of coronavirus-infected diseases.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 쥐꼬리망초 저스티시딘-A(justicidin-A)를 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising Rathornworm justicidin-A (justicidin-A) as an active ingredient for the prevention or treatment of coronavirus-infected diseases.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 쥐꼬리망초 저스티시딘-B(justicidin-B)를 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising Rathorn ragweed justicidin-B (justicidin-B) as an active ingredient for the prevention or treatment of coronavirus-infected diseases.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 6' 하이드록시 저스티시딘-B(justicidin-B)를 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising 6' hydroxy justicidin-B (justicidin-B) as an active ingredient for the prevention or treatment of coronavirus-infected diseases.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 약학적 제제를 제조하기 위한 쥐꼬리망초 유기용매 추출물을 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising an organic solvent extract of Rathorn fern as an active ingredient for preparing a pharmaceutical formulation for the prevention or treatment of coronavirus-infected diseases.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 약학적 제제를 제조하기 위한 저스티시딘-A(justicidin-A)를 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising justicidin-A as an active ingredient for preparing a pharmaceutical formulation for the prevention or treatment of a coronavirus-infected disease.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 약학적 제제를 제조하기 위한 저스티시딘-B(justicidin-B)를 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising justicidin-B as an active ingredient for preparing a pharmaceutical formulation for the prevention or treatment of a coronavirus-infected disease.
본 발명은 또한, 코로나바이러스 감염 질환의 예방 또는 치료를 위한 약학적 제제를 제조하기 위한 6' 하이드록시 저스티시딘-B를 유효성분으로 포함하는 약학적 조성물의 용도를 제공한다.The present invention also provides the use of a pharmaceutical composition comprising 6' hydroxy justicidin-B as an active ingredient for preparing a pharmaceutical formulation for the prevention or treatment of a coronavirus-infected disease.
본 발명에 따른 약학적 조성물, 식품 조성물, 항바이러스용 조성물, 상기 조성물들의 용도 및 상기 조성물들을 투여하는 단계를 포함하는 예방 또는 치료 방법에 대해서는, 모순되지 않는 한 상기 조성물들, 용도 또는 방법에 적용된 설명이 각각의 조성물들, 용도 또는 방법에 대해서도 동일하게 적용될 수 있다.Regarding the pharmaceutical composition, food composition, antiviral composition, use of the composition, and the method of prophylaxis or treatment comprising administering the composition according to the present invention, unless contradictory, the composition, use or method applied The description is equally applicable for each composition, use, or method.
본 발명에 따른 조성물은 코로나바이러스의 세포내 감염 및 증식의 억제 효과가 우수한 쥐꼬리망초 유기용매 추출물, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B) 또는 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B) 를 포함하므로, 궁극적으로 코로나바이러스 감염 질환의 예방 또는 치료제, 개선제 또는 항바이러스제로 널리 활용될 수 있다.The composition according to the present invention is an organic solvent extract of Rathorn Cortex, which has excellent inhibitory effect on intracellular infection and proliferation of coronavirus, justicidin-A, justicidin-B, or 6' hydride Because it contains 6' hydroxyl justicidin-B, it can ultimately be widely used as a preventive or therapeutic agent, ameliorating agent, or antiviral agent for coronavirus-infected diseases.
도 1은 본 발명에 따른 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B) 및 6' 하이드록시 저스티시딘-B(6' hydroxyl Justicidin-B)의 화학식을 나타낸 도면이다.
도 2는 본 발명에 따른 쥐꼬리망초 무수 에탄올 추출물의 HPLC 결과를 나타낸 그래프로, 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B) 및 6' 하이드록시 저스티시딘-B(6' hydroxy Justicidin B)를 나타내는 피크를 표시한 도면이다.
도 3은 본 발명에 따른 쥐꼬리망초 무수 에탄올 추출물, 저스티시딘-B(justicidin-B), 6' 하이드록시 저스티시딘-B(6' hydroxy Justicidin B)의 SARS-CoV에 대한 항바이러스 효과 및 세포 생존율을 나타낸 도면이다.
도 4는 본 발명에 따른 쥐꼬리망초 무수 에탄올 추출물, 저스티시딘-B(justicidin-B), 6' 하이드록시 저스티시딘-B(6' hydroxy Justicidin B)의 MERS-CoV에 대한 항바이러스 효과 및 세포 생존율을 나타낸 도면이다.1 shows the chemical formulas of justicidin-A, justicidin-B, and 6' hydroxy Justicidin-B according to the present invention; It is a drawing.
Figure 2 is a graph showing the HPLC results of the anhydrous ethanol extract of Rathorn Cortex according to the present invention, justicidin-A (justicidin-A), justicidin-B (justicidin-B) and 6' hydroxy justicidin- B (6' hydroxy Justicidin B) is a diagram showing the peak.
3 is an antiviral effect on SARS-CoV of anhydrous ethanol extract of Rathorn ragwort according to the present invention, justicidin-B (justicidin-B), and 6' hydroxy Justicidin-B (6' hydroxy Justicidin B); A diagram showing the cell viability.
4 is an antiviral effect on MERS-CoV of MERS-CoV, justicidin-B, 6' hydroxy Justicidin B, and A diagram showing the cell viability.
이하, 본 발명의 이해를 돕기 위하여 바람직한 제조예, 실시예 및 제제예를 제시한다. 그러나 하기의 제조예, 실시예 및 제제예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 제조예, 실시예 및 제제예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred preparation examples, examples and preparation examples are presented to help the understanding of the present invention. However, the following Preparation Examples, Examples and Formulation Examples are only provided for easier understanding of the present invention, and the content of the present invention is not limited by the Preparation Examples, Examples and Formulation Examples.
제조예 1: 쥐꼬리망초 무수에탄올 추출물의 제조Preparation Example 1: Preparation of anhydrous ethanolic extract
실험에 사용한 쥐꼬리망초 무수에탄올 추출물은 충북 제천에서 재배하여 채취 후 국립생물자원관 (National Institute of Biological Resources, Ministry of Environment, Korea)으로부터 식물의 기원을 동정 받은 쥐꼬리망초(확증표본번호: NIBRVP0000642884, 2017년)을 이용하여 제조하였다. The anhydrous ethanol extract of Lespidoptera used in the experiment was grown and collected in Jecheon, North Chungcheong Province, and the plant's origin was identified by the National Institute of Biological Resources, Ministry of Environment, Korea (confirmed sample number: NIBRVP0000642884, 2017) ) was prepared using
건조한 쥐꼬리망초를 일정하게 절단한 뒤 10배액에 해당하는 무수 에탄올(anhydrous ethanol)을 가하여 24시간 상온에서 침지 추출한 후 여과하여 1차 추출물을 제조한 뒤 감압농축한다. 여기에 다시 8배액의 무수 에탄올을 가하여 24시간 상온에서 다시 침지 추출한 후 여과하여 2차 추출물을 제조한 뒤 감압농축한다. 상기 농축물을 합하여 최종 고형분 함량이 약 10%인 쥐꼬리망초 무수에탄올 추출물을 제조한 뒤 추출물 고형분 대비 1:1이 되게 콜로이드성이산화규소를 균일하게 혼합한다. 이 혼합물을 60℃도에서 감압 건조한 뒤 일정하게 분쇄하여 파우더 형태의 최종 쥐꼬리망초 무수 에탄올 추출물을 제조하였다.After constant cutting of dried ragweed, anhydrous ethanol corresponding to a 10-fold solution is added, followed by immersion extraction at room temperature for 24 hours, followed by filtration to prepare a primary extract, and then concentrated under reduced pressure. Again, 8-fold of absolute ethanol was added thereto, followed by immersion extraction again at room temperature for 24 hours, followed by filtration to prepare a secondary extract, and then concentrated under reduced pressure. The concentrates are combined to prepare anhydrous ethanol extract of Rathorn ragwort having a final solid content of about 10%, and then colloidal silicon dioxide is uniformly mixed so as to be 1:1 with respect to the solid content of the extract. The mixture was dried under reduced pressure at 60° C. and then ground to a constant level to prepare a final absolute ethanol extract of Astragalus spp.
제조예 2: 유기 합성법을 통한 저스티시딘-A(justicidin-A)의 제조Preparation Example 2: Preparation of justicidin-A through organic synthesis
저스티시딘-A(9-벤조[1,3]디옥솔-5-일-4,6,7-트리메톡시-3H-나프토[2,3-c]퓨란-1-온)은 이전에 공지된 방법(Gunaganti Naresh, et al., 2015)을 통해 제조하였으며 아래와 같이 동정하였다. Justicidin-A (9-benzo[1,3]dioxol-5-yl-4,6,7-trimethoxy-3H-naphtho[2,3-c]furan-1-one) was previously It was prepared through a known method (Gunaganti Naresh, et al., 2015) and identified as follows.
1H-NMR (CDCl3, 500 MHz) δ 7.54(s, 1H), 7.06(s, 1H), 6.95(d, 1H, J = 7.9Hz), 6.82(d, 1H, J = 1.5Hz), 6.79(dd, 1H, J = 1.6, 7.875Hz), 6.04, 6.08(dd, 2H, J = 1.45, 22.775Hz), 5.54(s, 2H), 4.13(s, 3H), 4.07(s, 3H), 3.80(s, 3H). 13C-NMR (CDCl3, 125 MHz) δ 169.6, 151.7, 150.4, 147.9, 147.6, 147.5, 134.5, 130.7, 128.6, 126.1, 124.6, 123.7, 119.4, 110.9, 108.3, 106.2, 101.3, 100.7, 66.7, 59.7, 56.2, 55.9. 저스티시딘-A 순도는 99.52% 이었다. 1 H-NMR (CDCl 3 , 500 MHz) δ 7.54 (s, 1H), 7.06 (s, 1H), 6.95 (d, 1H, J = 7.9 Hz), 6.82 (d, 1H, J = 1.5 Hz), 6.79 (dd, 1H, J = 1.6, 7.875 Hz), 6.04, 6.08 (dd, 2H, J = 1.45, 22.775 Hz), 5.54 (s, 2H), 4.13 (s, 3H), 4.07 (s, 3H) , 3.80(s, 3H). 13 C-NMR (CDCl 3 , 125 MHz) δ 169.6, 151.7, 150.4, 147.9, 147.6, 147.5, 134.5, 130.7, 128.6, 126.1, 124.6, 123.7, 119.4, 110.9, 108.3, 106.2, 101.3, 100.7, 66.7, 59.7, 56.2, 55.9. Justicidin-A purity was 99.52%.
제조예 3: 유기 합성법을 통한 저스티시딘-B(justicidin-B)의 제조Preparation Example 3: Preparation of justicidin-B through organic synthesis
저스티시딘-B(9-벤조[1,3]디옥솔-5-일-6,7-디메톡시-3H-나프토[2,3-c]퓨란-1-온)는 이전에 공지된 방법(David C. Harrowven, et al., 2001)을 통해 제조하였으며 아래와 같이 동정하였다. Justicidin-B (9-benzo[1,3]dioxol-5-yl-6,7-dimethoxy-3H-naphtho[2,3-c]furan-1-one) is a previously known Method (David C. Harrowven, et al., 2001) was prepared and identified as follows.
1H-NMR (CDCl3, 500 MHz) δ 7.70(s, 1H), 7.18(s, 1H), 7.11(s, 1H), 6.97(d, 1H, J = 7.7Hz), 6.86(d, 1H, J = 1.45Hz), 6.83(dd, 1H, J = 1.7, 8.025Hz), 6.07(d, 2H, J = 22.6Hz), 5.37(s, 2H), 4.05(s, 3H), 3.81(s, 3H). 13C-NMR (CDCl3, 125 MHz) δ 170.0, 151.9, 150.2, 147.7, 147.6, 139.7, 139.6, 133.3, 128.9, 128.5, 123.6, 118.6, 118.4, 110.7, 108.3, 106.1, 105.9, 101.3, 68.1, 56.2, 55.9. 저스티시딘-B의 순도는 98.55% 이었다. 1 H-NMR (CDCl 3 , 500 MHz) δ 7.70(s, 1H), 7.18(s, 1H), 7.11(s, 1H), 6.97(d, 1H, J = 7.7Hz), 6.86(d, 1H) , J = 1.45 Hz), 6.83 (dd, 1H, J = 1.7, 8.025 Hz), 6.07 (d, 2H, J = 22.6 Hz), 5.37 (s, 2H), 4.05 (s, 3H), 3.81 (s) , 3H). 13 C-NMR (CDCl 3 , 125 MHz) δ 170.0, 151.9, 150.2, 147.7, 147.6, 139.7, 139.6, 133.3, 128.9, 128.5, 123.6, 118.6, 118.4, 110.7, 108.3, 106.1, 105.9, 101.3, 68.1, 56.2, 55.9. The purity of Justicidin-B was 98.55%.
제조예 4: 유기 합성법을 통한 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)의 제조Preparation Example 4: Preparation of 6' hydroxy justicidin-B through organic synthesis
6' 하이드록시 저스티시딘-B는 아래의 공정을 통해 합성하였다.6' hydroxy justicidin-B was synthesized through the following process.
공정 1: 6,7-디메톡시-3-옥소-1,3-디히드로나프토[2,3-c]퓨란-4-일 트리플루오로메탄설포네이트 (3.0g, 7.65mmol)을 디옥산(90ml)용매에 녹인 후, 5-메톡시메톡시-6-(4,4,5,5,-테트라메틸-[1,3,2]다이옥사보로란-2-일)-벤조[1,3]디옥솔 (2.83g, 9.18mmol), [1,1'-비스(디 페닐 포스피노) 페로센]디클로로 팔라듐(II) (1.12g, 1.53mmol), 수산화리튬 1수화물(642mg, 15.3mmol) 질소대기하에서 순차적으로 부가하였다. 온도를 60℃까지 올린 뒤 4시간을 반응시켰다. 상온으로 냉각 후에 물을 가하여 반응을 종결시키고 디클로로메탄으로 추출하였다. 유기층을 무수 Na2SO4로 건조시키고, 여과 및 농축시켰다. 잔사를 실리카겔 컬럼 크로마토그래피로 정제하여 표제화합물 6,7-디메톡시-9-(6-메톡시메톡시-벤조[1,3]디옥솔-5-일)-3H-나프토[2,3-c]퓨란-1-온 (9g, 21.2mmol)을 얻었다.Step 1: 6,7-dimethoxy-3-oxo-1,3-dihydronaphtho [2,3-c] furan-4-yl trifluoromethanesulfonate (3.0 g, 7.65 mmol) was mixed with dioxane (90ml) After dissolving in a solvent, 5-methoxymethoxy-6-(4,4,5,5,-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1 ,3]dioxol (2.83g, 9.18mmol), [1,1'-bis(diphenyl phosphino)ferrocene]dichloropalladium(II) (1.12g, 1.53mmol), lithium hydroxide monohydrate (642mg, 15.3mmol) ) were sequentially added under a nitrogen atmosphere. After raising the temperature to 60 °C, the reaction was carried out for 4 hours. After cooling to room temperature, water was added to terminate the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel column chromatography, and the title compound 6,7-dimethoxy-9-(6-methoxymethoxy-benzo[1,3]dioxol-5-yl)-3H-naphtho[2,3] -c] furan-1-one (9 g, 21.2 mmol) was obtained.
1H NMR: (DMSO-d 6, 400 MHz) δ 7.92 (s, 1H), 7.48 (s, 1H), 6.95 (s, 1H), 6.87 (s, 1H), 6.73 (s, 1H), 6.08 (d, 2H, J = 2.8 Hz), 5.38 - 5.49 (m, 2H), 4.90 (d, 1H, J = 6.8 Hz), 4.81 (d, 1H, J = 6.8Hz), 3.93 (s, 3H), 3.65 (s, 3H), 2.93 (s, 3H). 1 H NMR: (DMSO- d 6 , 400 MHz) δ 7.92 (s, 1H), 7.48 (s, 1H), 6.95 (s, 1H), 6.87 (s, 1H), 6.73 (s, 1H), 6.08 (d, 2H, J = 2.8 Hz), 5.38 - 5.49 (m, 2H), 4.90 (d, 1H, J = 6.8 Hz), 4.81 (d, 1H, J = 6.8 Hz), 3.93 (s, 3H) , 3.65 (s, 3H), 2.93 (s, 3H).
공정 2: 6,7-디메톡시-9-(6-메톡시메톡시-벤조[1,3]디옥솔-5-일)-3H-나프토[2,3-c]퓨란-1-온 (8g, 18.9mmol)을 에탄올(80ml)에 녹이고, 12M HCl 44ml를 적가하여 50℃에서 12시간 반응시켰다. 반응이 종결된 후에 물100ml를 가하고, 디클로로메탄(200ml, 100ml, 50ml)으로 추출하였다. 얻어진 유기층을 물(150ml), brine(100ml)를 사용하여 씻어주고, 무수 Na2SO4로 건조시킨 후에 여과하여 농축시켰다. 잔사를 실리카겔 컬럼 크로마토그래피로 정제하여 표제화합물 9-(6-하이드록시-벤조[1,3]다이옥솔-5-일)-6,7-디메톡시-3H-나프토[2,3-c]퓨란-1-온 (6'-HJB, 5.20g, 13.7mmol, 72.5%)을 얻었다.Step 2: 6,7-dimethoxy-9-(6-methoxymethoxy-benzo[1,3]dioxol-5-yl)-3H-naphtho[2,3-c]furan-1-one (8g, 18.9mmol) was dissolved in ethanol (80ml), and 44ml of 12M HCl was added dropwise, followed by reaction at 50°C for 12 hours. After completion of the reaction, 100 ml of water was added, and the mixture was extracted with dichloromethane (200 ml, 100 ml, 50 ml). The obtained organic layer was washed with water (150ml) and brine (100ml), dried over anhydrous Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel column chromatography, and the title compound 9-(6-hydroxy-benzo[1,3]dioxol-5-yl)-6,7-dimethoxy-3H-naphtho[2,3-c ] furan-1-one (6'-HJB, 5.20 g, 13.7 mmol, 72.5%) was obtained.
1H NMR: (DMSO-d 6, 400 MHz) δ 9.01 (s, 1H), 7.88 (s, 1H), 7.46 (s, 1H), 6.95 (s, 1H), 6.63 (s, 1H), 6.57 (s, 1H), 6.00 (d, 2H, J = 2.00 Hz), 5.41 (s, 2H), 3.93 (s, 3H), 3.66 (s, 3H). 6' 하이드록시 저스티시딘-B의 순도는 98.76%이었다. 1 H NMR: (DMSO- d 6 , 400 MHz) δ 9.01 (s, 1H), 7.88 (s, 1H), 7.46 (s, 1H), 6.95 (s, 1H), 6.63 (s, 1H), 6.57 (s, 1H), 6.00 (d, 2H, J = 2.00 Hz), 5.41 (s, 2H), 3.93 (s, 3H), 3.66 (s, 3H). The purity of 6' hydroxy justicidin-B was 98.76%.
저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B의 구조는 도 1에 표시하였다.The structures of justicidin-A, justicidin-B and 6' hydroxy justicidin-B are shown in FIG. 1 .
실시예 1: 쥐꼬리망초 추출물의 고속액체크로마토그래피(HPLC) 패턴 및 저스티시딘-A(justicidin-A), 저스티시딘-B(justicidin-B), 6' 하이드록시 저스티시딘-B(6' hydroxyl justicidin-B)의 동정Example 1: High performance liquid chromatography (HPLC) pattern and justicidin-A, justicidin-B, 6' hydroxy justicidin-B (6 ' Identification of hydroxyl justicidin-B)
상기 제조예 1의 제조방법으로 제조한 쥐꼬리망초 무수에탄올 추출물 중 포함된 활성성분을 확인하기 위하여 고속액체크로마토그래피(HPLC, Agilent 1260, USA)를 하기 표 1와 같은 조건으로 수행하였고, 그 결과를 도 2에 나타내었다.High-performance liquid chromatography (HPLC, Agilent 1260, USA) was performed under the conditions shown in Table 1 below to confirm the active ingredients contained in the anhydrous ethanol extract of Rathorn Seedlings prepared by the manufacturing method of Preparation Example 1, and the results were 2 is shown.
HPLC 시험결과, 쥐꼬리망초 무수 에탄올 추출물에서 저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B가 검출되었다. 구체적으로 쥐꼬리망초 무수 에탄올 추출물 중 저스티시딘 A의 피크는 RT(Retention Time) 약 52분, 저스티시틴 B의 피크는 RT 약 48분, 6' 하이드록시 저스티시딘-B의 피크는 RT 약 38분에서 검출되었다. As a result of the HPLC test, justicidin-A, justicidin-B and 6' hydroxy justicidin-B were detected in the anhydrous ethanol extract of Rathorn serrata. Specifically, in the anhydrous ethanol extract of Rathorn ragwort, the peak of justicidin A is about 52 minutes RT (Retention Time), the peak of justicitin B is about 48 minutes, and the peak of 6' hydroxy justicidin-B is about RT. detected at 38 min.
실시예 2. SARS-CoV가 감염된 Vero 세포주에서 항바이러스 효과 실험Example 2. Antiviral effect experiment in Vero cell line infected with SARS-CoV
쥐꼬리망초 무수 에탄올 침지 추출물 및 이의 주요 물질인 저스티시딘-A, 저스티시딘-B, 6’ 하이드록시 저스티시딘-B의 SARS-CoV에 대한 항바이러스 효과를 확인하기 위하여, real-time RT-PCR(qRT-PCR) 기법을 사용하였다. Real-time RT to confirm the antiviral effect on SARS-CoV of anhydrous ethanol immersion extract of Rathorn ragwort and its main substances, justicidin-A, justicidin-B, and 6' hydroxy justicidin-B, -PCR (qRT-PCR) technique was used.
qRT-PCR은 약물이 바이러스의 유전자 복제를 얼마나 억제하는지 세포배양액 내 존재하는 바이러스 입자안의 RNA level을 분석하여 약물의 항바이러스 효능을 평가하는 것이다 이를 위해 96-well plate에 well당 2x104 개의 Vero cell을 배양한 후, MOI 0.1(2x103 PFU/100uL)의 SARS-CoV를 접종하여 37ºC에서 1시간 동안 감염시켰다. 감염시킨 세포를 PBS로 씻겨 낸 후, 제조예 1 내지 4에서 제조한 시험 약물이 들어있는 세포배양액을 세포에 넣어 주었다. 이 후 48시간째 배양액을 수득하여 SARS-CoV 바이러스 입자내에 존재하는 RNA level을 qRT-PCR로 측정하여 대조군 (약물 미처리 바이러스 감염군)과 비교 분석하였다. 약물의 IC50 산출을 위해 처리 농도는 50uM로 시작하여 4단계씩 연속 희석하여 0.012uM, 0.048uM, 0.19uM, 0.78uM, 3.12uM, 12.5uM, 50uM와 같이 7개 농도로 사용하였다. 또한 양성대조 약물로서 클로로퀸(chloroquine)도 동일한 농도로 처리하였다. qRT-PCR is to evaluate the antiviral efficacy of a drug by analyzing the level of RNA in virus particles in cell culture to see how much the drug inhibits viral gene replication. For this purpose, 2x10 4 Vero cells per well in a 96-well plate After culturing, SARS-CoV at an MOI of 0.1 (2x10 3 PFU/100uL) was inoculated and inoculated at 37 ºC for 1 hour. After washing the infected cells with PBS, the cell culture solution containing the test drug prepared in Preparation Examples 1 to 4 was put into the cells. After that, the culture medium was obtained at 48 hours, and the RNA level present in the SARS-CoV virus particles was measured by qRT-PCR and analyzed in comparison with the control group (drug-untreated virus-infected group). In order to calculate the IC 50 of the drug, the treatment concentration was started with 50 uM and serially diluted in 4 steps to use 7 concentrations such as 0.012 uM, 0.048 uM, 0.19 uM, 0.78 uM, 3.12 uM, 12.5 uM, and 50 uM. In addition, as a positive control drug, chloroquine was treated at the same concentration.
동시에, 시험물질이 세포독성을 유발하는지 확인하게 위하여 96 well plate에 well 당 2x104 개 Vero cell을 배양 후, 약물을 처리하고 48시간째 약물에 의한 세포독성 여부를 WST-1 assay로 확인하였다. 이때 처리약물 및 약물의 농도는 상기 항바이러스 효능시험과 동일하게 수행하였고, 세포 생존율은 대조군(약물 미처리군)과 비교하여 50% 세포 생존율(CC50 value)로 나타내었다. At the same time, in order to check whether the test substance induces cytotoxicity, 2x10 4 Vero cells per well were cultured in a 96-well plate, the drug was treated, and the cytotoxicity of the drug was checked by WST-1 assay at 48 hours. At this time, the concentration of the treated drug and the drug was performed in the same manner as in the antiviral efficacy test, and the cell viability was expressed as 50% cell viability (CC 50 value) compared to the control group (drug untreated group).
표 2 및 도 3에 각 시험물질에 대한 SARS-CoV의 50% 억제능 (IC50 값)과 50% 세포 생존율(CC50)을 도출하여 그 결과를 정리하였다. 이후 약물과 세포독성 사이의 비율인 SI(selectivity index = CC50/IC50)를 구하였다. In Table 2 and Figure 3, 50% inhibitory ability (IC 50 value) and 50% cell viability (CC 50 ) of SARS-CoV for each test substance were derived and the results were summarized. Then, the ratio between the drug and cytotoxicity, SI (selectivity index = CC 50 /IC 50 ) was calculated.
표 2 및 도 3에서 확인할 수 있는 바와 같이, 쥐꼬리망초 무수에탄올 추출물 및 이들의 활성 성분들인 저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B 의 SARS-CoV 억제 능력은 50% 억제농도(IC50) 수치로 비교 시 양성대조군인 클로로퀸(Chloroquine)보다 약 1.3배 내지 약 17배 더 우수함을 확인하였다. 이들 시험군들은 시험한 최고농도까지 특별한 세포독성을 보이지 않았으며, SI 값도 양성대조군에 비해 월등히 우수하였다.As can be seen in Table 2 and Figure 3, the SARS-CoV inhibitory ability of the anhydrous ethanol extract of Astragalus and their active ingredients, justicidin-A, justicidin-B and 6' hydroxy justicidin-B was confirmed to be about 1.3 times to about 17 times superior to that of the positive control, chloroquine, when compared with the 50% inhibitory concentration (IC 50 ) value. These test groups did not show any particular cytotoxicity up to the highest concentration tested, and the SI value was also significantly superior to that of the positive control group.
위 실시예 2의 결과로부터 쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B 각각은 SARS-CoV와 같은 코로나바이러스가 감염된 세포내에서의 우수한 항바이러스 활성이 확인된다. 따라서, 쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B 각각의 SARS-CoV와 같은 코로나바이러스 감염 질환의 예방 또는 치료 효과가 확인된다.From the results of Example 2 above, it can be seen from the results of Example 2, that each of the extract, justicidin-A, justicidin-B, and 6' hydroxy justicidin-B is excellent antiviral in cells infected with a coronavirus such as SARS-CoV. activity is confirmed. Therefore, the preventive or therapeutic effect of each of the ragweed extract, justicidin-A, justicidin-B, and 6' hydroxy justicidin-B, SARS-CoV, on coronavirus-infected diseases is confirmed.
실시예 3. MERS-CoV가 감염된 Vero 세포주에서 항바이러스 효과 실험Example 3. Antiviral effect experiment in Vero cell line infected with MERS-CoV
쥐꼬리망초 무수 에탄올 침지 추출물 및 이의 주요 물질인 저스티시딘-A, 저스티시딘-B 및 6’ 하이드록시 저스티시딘-B의 MERS-CoV 치료 효과를 확인하기 위하여, 상기 실시예 2와 동일한 방법으로 VERO 세포주 이용 qRT-PCR 기법으로 항바이러스 효과를 측정하였고, 세포독성시험도 WST-1 assay로 확인하였다.In order to confirm the MERS-CoV treatment effect of the MERS-CoV extract and its main substances, justicidin-A, justicidin-B, and 6' hydroxy justicidin-B, the same method as in Example 2 The antiviral effect was measured using the qRT-PCR technique using the VERO cell line, and the cytotoxicity test was also confirmed by the WST-1 assay.
좀 더 상세하게, Vero cell을 배양한 후(2x104cell/well), MOI 0.2의 MERS-CoV 바이러스를 접종하여 37°C incubator에서 1시간 동안 감염시켰다. 감염시킨 세포를 PBS로 washing 하였고, 제조예 1 ~ 4를 통해 제조한 약물을 실시예 2와 동일 농도별로 세포에 넣어 주었다. 그 후 48시간째 배양액을 수득하여 MERS-CoV 바이러스 입자내에 존재하는 RNA level을 qRT-PCR로 측정하여 대조군과 비교분석 하였다. 이때의 세포 생존률은 WST-1 assay로 확인하였다.In more detail, after culturing Vero cells (2x10 4 cells/well), MERS-CoV virus at MOI 0.2 was inoculated and inoculated at 37°C in an incubator for 1 hour. The infected cells were washed with PBS, and the drugs prepared in Preparation Examples 1 to 4 were put into the cells at the same concentration as in Example 2. After that, the culture medium was obtained at 48 hours, and the RNA level present in the MERS-CoV virus particles was measured by qRT-PCR and compared with the control group. The cell viability at this time was confirmed by WST-1 assay.
표 3과 도 4에 각 시험물질에 대한 MERS-CoV의 50% 억제능 (IC50 값)과 50% 세포 생존율(CC50)을 도출하여 그 결과를 정리하였다. 이후 약물과 세포독성 사이의 비율인 SI(selectivity index = CC50/IC50)를 구하였다In Table 3 and FIG. 4, 50% inhibitory capacity (IC 50 value) and 50% cell viability (CC 50 ) of MERS-CoV for each test substance were derived and the results were summarized. Then, the ratio between drug and cytotoxicity, SI (selectivity index = CC 50 /IC 50 ) was calculated.
위 표 3 내지 도 4에서 확인할 수 있듯이, 쥐꼬리망초 무수에탄올 추출물 및 이들의 활성 성분들 저스티시딘-B, 6' 하이드록시 저스티시딘-B 의 MERS-CoV 억제 능력은 50% 억제농도(IC50) 수치로 비교 시 양성대조군인 클로로퀸(Chloroquine)보다 약 5배 내지 약 40배 더 우수함을 확인하였다. 이들 시험군들은 시험한 최고농도까지 특별한 세포독성을 보이지 않았으며, SI 값도 양성대조군에 비해 월등히 높은 수치를 통해 안전한 약물 임을 확인하였다.As can be seen in Tables 3 to 4 above, the MERS-CoV inhibitory ability of MERS-CoV inhibitory ability of MERS-CoV anhydrous ethanol extract and their active ingredients Justicidin-B and 6' Hydroxyjusticidin-B is 50% inhibitory concentration (IC 50 ), it was confirmed that it was about 5 to about 40 times superior to that of the positive control, chloroquine, when compared numerically. These test groups did not show any particular cytotoxicity up to the highest concentration tested, and the SI value was also significantly higher than that of the positive control group, confirming that it was a safe drug.
위 실시예 3의 결과로부터 쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B 각각은 MERS-CoV 와 같은 코로나바이러스가 감염된 세포내에서의 우수한 항바이러스 활성이 확인된다. 따라서, 쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B 및 6' 하이드록시 저스티시딘-B 각각의 MERS-CoV와 같은 코로나바이러스의 감염 질환의 예방 또는 치료 효과가 확인된다.From the results of Example 3 above, it was found that each of the extracts of ragweed, justicidin-A, justicidin-B and 6' hydroxy justicidin-B was excellent antiviral in cells infected with coronavirus such as MERS-CoV. activity is confirmed. Therefore, the preventive or therapeutic effect of the MERS-CoV infection disease of the coronavirus is confirmed, respectively.
제제예 1: 의약품의 제조Formulation Example 1: Preparation of pharmaceuticals
1-1: 산제의 제조1-1: Preparation of powder
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B or 6' hydroxy justicidin-B
유당 100mgLactose 100mg
탈크 10mgtalc 10mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight bag to prepare a powder.
1-2 정제의 제조Preparation of 1-2 tablets
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B or 6' hydroxy justicidin-B
옥수수전분 100mgCorn Starch 100mg
유당 100mgLactose 100mg
스테아린산 마그네슘 2mg2mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional manufacturing method of tablets.
1-3 캡슐제의 제조1-3 Preparation of capsules
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B, 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B, or 6' hydroxy justicidin-B
옥수수전분 100mgCorn Starch 100mg
유당 100mgLactose 100mg
스테아린산 마그네슘 2mg2mg magnesium stearate
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 정제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled in a gelatin capsule to prepare a tablet.
1-4 주사제의 제조1-4 Preparation of injections
쥐꼬리망초 추출물 또는 저스티시딘-B, 저스티시딘-A, 6' 하이드록시 저스티시딘-B 100mg100mg of ragweed extract or justicidin-B, justicidin-A, 6' hydroxy justicidin-B
주사용 멸균 증류수 적량Appropriate amount of sterile distilled water for injection
pH 조절제 적량Appropriate amount of pH adjuster
통상의 주사제의 제조방법에 따라 1 앰플당(2ml) 상기의 성분 함량으로 제조한다.According to a conventional method for preparing injections, the content of the above ingredients per 1 ampoule (2 ml) is prepared.
1-5 액제의 제조1-5 Preparation of liquid formulations
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B, 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B, or 6' hydroxy justicidin-B
설탕 20g20 g sugar
이성화당 20gIsomerized sugar 20g
레몬향 적량Lemon flavored amount
정제수를 가하여 전체 1,00 ml로 맞춘다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조한다.Add purified water to make the total volume of 100 ml. After mixing the above ingredients according to a conventional liquid preparation method, it is filled in a brown bottle and sterilized to prepare a liquid preparation.
1-6 흡입제의 제조1-6 Preparation of inhalants
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B, 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B, or 6' hydroxy justicidin-B
1,1,1,2-테트라플루오르에탄 15g15 g of 1,1,1,2-tetrafluoroethane
무수에탄올 1.5g1.5 g of absolute ethanol
구연산(무수물) 0.05mgCitric acid (anhydrous) 0.05 mg
폴리에틸렌글리콜 500mgPolyethylene glycol 500mg
통상의 흡입제의 제조방법에 따라, 상기의 성분을 혼합하여 용기에 충전한다.According to a conventional method for preparing inhalants, the above ingredients are mixed and filled in a container.
제제예 2: 식품의 제조Formulation Example 2: Preparation of food
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B, 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B, or 6' hydroxy justicidin-B
비타민 혼합물 적량appropriate amount of vitamin mixture
비타민 A 아세테이트 70 ㎍70 μg vitamin A acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 ㎎
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 ㎎Nicotinamide 1.7 mg
엽산 50 ㎍50 μg of folic acid
판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture appropriate amount
황산제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄제1인산칼륨 15 ㎎Potassium tandiphosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎
탄산칼슘 100 ㎎
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 건강기능식품에 적합한 성분을 바람직한 실시예로서 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합한 다음, 통상의 방법에 따라 건강기능식품 조성물 제조(예, 영양캔디 등)에 사용할 수 있다.The composition ratio of the above vitamin and mineral mixture is mixed composition with ingredients suitable for health functional food as a preferred embodiment, but the mixing ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method. Next, according to a conventional method, it can be used for manufacturing a health functional food composition (eg, nutritional candy, etc.).
제제예 3: 음료의 제조Formulation Example 3: Preparation of beverage
쥐꼬리망초 추출물, 저스티시딘-A, 저스티시딘-B, 또는 6' 하이드록시 저스티시딘-B 100mg100 mg of ragweed extract, justicidin-A, justicidin-B, or 6' hydroxy justicidin-B
구연산 1000 ㎎citric acid 1000 mg
올리고당 100 g100 g of oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 ㎖Total 900 ml by adding purified water
통상의 건강기능성 음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강기능성 음료 조성물 제조에 사용한다. After mixing the above ingredients according to the usual health functional beverage manufacturing method, after stirring and heating at 85° C. for about 1 hour, the resulting solution is filtered and acquired in a sterilized 2ℓ container, sealed and sterilized, then refrigerated. It is used to prepare the health functional beverage composition of the present invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용 용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the blending ratio may be arbitrarily modified according to regional and national preferences such as demand class, demanding country, and use purpose.
본 발명의 일 실시예에 따른 조성물은 쥐꼬리망초 유기용매 추출물, 저스티시딘-A, 저스티시딘-B, 6' 하이드록시 저스티시딘-B를 포함한다. 따라서, 일 실시예에 따른 조성물은 우수한 항코로나바이러스 효과를 나타내며, 코로나바이러스 감염 질환의 예방, 치료 또는 개선에 우수한 효과를 나타낸다.The composition according to an embodiment of the present invention includes an organic solvent extract of ragweed, justicidin-A, justicidin-B, and 6' hydroxy justicidin-B. Therefore, the composition according to an embodiment exhibits an excellent anti-coronavirus effect, and exhibits an excellent effect in preventing, treating or improving coronavirus-infected diseases.
Claims (26)
Forget-me-not ( Justicia procumbens L. ) A pharmaceutical composition for preventing or treating a coronavirus (SARS-CoV-2 is excluded from the coronavirus) infection disease comprising an organic solvent extract as an active ingredient.
상기 유기용매는 메탄올, 에탄올, 이소프로판올, 부탄올, 헥산, 아세트산에틸, 디클로로메탄, 에테르, 클로로포름 및 아세톤으로 이루어진 군에서 선택되는 어느 하나 이상인 약학적 조성물.
According to claim 1,
The organic solvent is at least one selected from the group consisting of methanol, ethanol, isopropanol, butanol, hexane, ethyl acetate, dichloromethane, ether, chloroform and acetone.
상기 유기용매는 무수에탄올인 약학적 조성물.
According to claim 1,
The organic solvent is anhydrous ethanol pharmaceutical composition.
상기 코로나바이러스는 베타-코로나바이러스(Betacoronavirus)인 약학적 조성물.
According to claim 1,
The coronavirus is a beta-coronavirus ( Betacoronavirus ) A pharmaceutical composition.
상기 코로나바이러스는 SARS-CoV 또는 MERS-CoV인 약학적 조성물.
According to claim 1,
The coronavirus is SARS-CoV or MERS-CoV pharmaceutical composition.
상기 코로나바이러스 감염 질환은 급성 호흡기 증후군(Severe Acute Respiratory Syndrome, SARS)인 약학적 조성물.
6. The method of claim 5,
The coronavirus-infected disease is a pharmaceutical composition of Severe Acute Respiratory Syndrome (SARS).
상기 코로나바이러스 감염 질환은 중동 호흡기 증후군(Middle East Respiratory Syndrome, MERS)인 약학적 조성물.
6. The method of claim 5,
The coronavirus-infected disease is Middle East Respiratory Syndrome (MERS), a pharmaceutical composition.
상기 코로나바이러스 감염 질환의 증상은 발열, 권태감, 기침, 호흡곤란, 폐렴, 가래, 인후통, 두통, 객혈, 오심, 위장관 장애, 신장 질환, 호흡기 질환 및 설사 중 적어도 하나인 약학적 조성물.
According to claim 1,
The symptoms of the coronavirus-infected disease are fever, malaise, cough, dyspnea, pneumonia, sputum, sore throat, headache, hemoptysis, nausea, gastrointestinal disorder, kidney disease, respiratory disease, and diarrhea at least one pharmaceutical composition.
상기 코로나바이러스 감염 질환은 상기 코로나바이러스의 호흡기 감염, 위장관 감염, 또는 신장 감염 질환인 약학적 조성물.
According to claim 1,
The coronavirus infectious disease is a respiratory infection, gastrointestinal infection, or kidney infection disease of the coronavirus pharmaceutical composition.
A composition for anti-coronavirus against a coronavirus (SARS- CoV -2 is excluded from the coronavirus) comprising an organic solvent extract as an active ingredient.
Forget-me-not ( Justicia procumbens L. ) A food composition for preventing or improving coronavirus (SARS-CoV-2 is excluded from the coronavirus) infectious disease comprising an organic solvent extract as an active ingredient.
상기 식품은 건강기능식품 또는 음료 중 어느 하나 이상인 조성물.
12. The method of claim 11,
The food is a health functional food or drink any one or more composition.
A pharmaceutical composition for preventing or treating a coronavirus (SARS-CoV-2 is excluded from the coronavirus) infectious disease comprising Justicidin-A as an active ingredient.
A food composition for preventing or improving coronavirus (SARS-CoV-2 is excluded from the coronavirus) infection disease comprising Justicidin-A as an active ingredient.
상기 식품은 건강기능식품 또는 음료 중 어느 하나 이상인 조성물.
15. The method of claim 14,
The food is a health functional food or drink any one or more composition.
A pharmaceutical composition for preventing or treating a coronavirus (SARS-CoV-2 is excluded from the coronavirus) infectious disease comprising Justicidin-B as an active ingredient.
A food composition for preventing or improving coronavirus (SARS-CoV-2 is excluded from the coronavirus) infectious disease comprising Justicidin-B as an active ingredient.
상기 식품은 건강기능식품 또는 음료 중 어느 하나 이상인 조성물.
18. The method of claim 17,
The food is a health functional food or drink any one or more composition.
A pharmaceutical composition for preventing or treating a coronavirus (SARS-CoV-2 is excluded from the coronavirus) infection disease comprising 6' hydroxyl Justicidin-B as an active ingredient.
A food composition for preventing or improving coronavirus (SARS-CoV-2 is excluded from the coronavirus) infection disease comprising 6' hydroxyl Justicidin-B as an active ingredient.
상기 식품은 건강기능식품 또는 음료 중 어느 하나 이상인 조성물.
21. The method of claim 20,
The food is a health functional food or drink any one or more composition.
상기 코로나바이러스는 SARS-CoV 또는 MERS-CoV인 조성물.
22. The method according to any one of claims 13 to 21,
The coronavirus is SARS-CoV or MERS-CoV composition.
상기 코로나바이러스 감염 질환은 급성 호흡기 증후군(Severe Acute Respiratory Syndrome, SARS)인 조성물.
22. The method according to any one of claims 13 to 21,
The coronavirus-infected disease is acute respiratory syndrome (Severe Acute Respiratory Syndrome, SARS) composition.
상기 코로나바이러스 감염 질환은 중동 호흡기 증후군(Middle East Respiratory Syndrome, MERS)인 조성물.
22. The method according to any one of claims 13 to 21,
The coronavirus-infected disease is Middle East Respiratory Syndrome (MERS).
상기 코로나바이러스 감염 질환의 증상은 발열, 권태감, 기침, 호흡곤란, 폐렴, 가래, 인후통, 두통, 객혈, 오심, 위장관 장애, 신장 질환, 호흡기 질환 및 설사 중 적어도 하나인 조성물.
22. The method according to any one of claims 13 to 21,
The symptoms of the coronavirus-infected disease are fever, malaise, cough, dyspnea, pneumonia, sputum, sore throat, headache, hemoptysis, nausea, gastrointestinal disorders, kidney disease, respiratory disease, and diarrhea at least one composition.
At least one or more of the group consisting of Justicidin-A, Justicidin-B, and 6' hydroxyl Justicidin-B as an active ingredient A composition for anti-coronavirus against coronavirus (SARS-CoV-2 is excluded from the coronavirus), comprising:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020200135248A KR20220051628A (en) | 2020-10-19 | 2020-10-19 | Pharmaceutical Composition for prevention or treatment of diseases of Coronavirus Infection |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020200135248A KR20220051628A (en) | 2020-10-19 | 2020-10-19 | Pharmaceutical Composition for prevention or treatment of diseases of Coronavirus Infection |
Publications (1)
Publication Number | Publication Date |
---|---|
KR20220051628A true KR20220051628A (en) | 2022-04-26 |
Family
ID=81391336
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020200135248A KR20220051628A (en) | 2020-10-19 | 2020-10-19 | Pharmaceutical Composition for prevention or treatment of diseases of Coronavirus Infection |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR20220051628A (en) |
-
2020
- 2020-10-19 KR KR1020200135248A patent/KR20220051628A/en unknown
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102174934B1 (en) | Pharmaceutical Composition for prevention or treatment of diseases caused by SARS-CoV-2 | |
KR101317318B1 (en) | A composition comprising the extract of Galla Rhois or the compounds isolated therefrom showing inhibiting activity of novel influenza, avian influenza, or SARS syndrome | |
KR102456294B1 (en) | Composition for preventing or treating coronavirus infection | |
KR102204299B1 (en) | Therapeutic agent for coronavirus comprising Elaeocarpus sylvestris extract as effective component | |
KR101782532B1 (en) | A composition comprising extract of Angelica dahurica or furanocoumarins isolated therefrom for preventing or treating Avian influenza, Swine influenza or Corona virus | |
US8470378B2 (en) | Anti-influenza viral composition containing bark or stem extract of Alnus japonica | |
CA2746437C (en) | Composition for the prevention and treatment of viral infections | |
KR101189823B1 (en) | Composition for prevention and treatment of influenza virus and composition for inhibiting the activity of neuraminidase comprising polyphenol compounds | |
KR20220051628A (en) | Pharmaceutical Composition for prevention or treatment of diseases of Coronavirus Infection | |
KR102551499B1 (en) | Composition for the prevention or treatment of SARS-CoV-2 infection, comprising the extract of Agrimonia pilosa as an active ingredient | |
KR101427096B1 (en) | Composition comprising extract of Dryopteris crassirhizoma or phloroglucinol derivatives isolated therefrom for treating or preventing Corona virus related disease | |
WO2011160684A1 (en) | Use of uleine for the prevention and/or the treatment of infectious diseases | |
JP2011079817A (en) | Compositions for preventing and/or treating viral infectious diseases, comprising plant extract, agent for preventing and/or treating viral infectious disease, having them as active ingredients, and inhibitor for adsorption onto viral cell | |
KR102583001B1 (en) | Composition for preventing or treating severe acute respiratory syndrome- corona virus infection comprising Chlorella sp. extract or pheophytinized fraction or pyphyrins or carotenones isolated therefrom as active ingredients | |
KR102665503B1 (en) | Composition for the prevention or treatment of SARS-CoV-2 infection, comprising the extract of Galla rhois as an active ingredient | |
WO2022085806A1 (en) | Pharmaceutical composition for prevention or treatment of coronavirus infectious diseases | |
KR101624707B1 (en) | Composition for Preventing and Treating Tuberculosis Comprising Flavan Family Compounds | |
EP4151226A1 (en) | Coronavirus therapeutic agent comprising zanthoxylum piperitum leaf extract as active ingredient | |
JP2018118959A (en) | Antimicrobial composition having lindera umbellate as source material | |
KR101563219B1 (en) | Composition comprising carnosic acid having anti-Respiratory syncytial virus activity | |
KR101189822B1 (en) | Composition for inhibiting the activity of neuraminidase and composition for prevention and treatment of influenza viral diseases comprising coumarin compounds | |
CN106692127B (en) | Application of luteolin in preparation of medicine for preventing and treating dengue fever virus infection | |
CN106265659B (en) | The purposes of plan food | |
US20220175868A1 (en) | INHIBITION OF SARS-CoV-2 VIRUS BY ARUM PALAESTINUM | |
KR20230028651A (en) | Composition for prevention or treatment of COVID-19 comprising sesquiterpenoid compounds isolated from extract of leaves of Psidium guajava or fraction therefrom as active ingredients |