KR20220123183A - A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract - Google Patents
A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract Download PDFInfo
- Publication number
- KR20220123183A KR20220123183A KR1020220102711A KR20220102711A KR20220123183A KR 20220123183 A KR20220123183 A KR 20220123183A KR 1020220102711 A KR1020220102711 A KR 1020220102711A KR 20220102711 A KR20220102711 A KR 20220102711A KR 20220123183 A KR20220123183 A KR 20220123183A
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- hepatitis
- formula
- present
- hcv
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 72
- 239000000203 mixture Substances 0.000 title claims abstract description 54
- 208000010710 hepatitis C virus infection Diseases 0.000 title claims abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 19
- 238000011282 treatment Methods 0.000 title claims description 14
- 230000002265 prevention Effects 0.000 title claims description 5
- 239000000284 extract Substances 0.000 title abstract description 91
- 241001278836 Agrimonia pilosa Species 0.000 title abstract description 27
- 235000000641 Agrimonia pilosa Nutrition 0.000 title abstract description 27
- 244000144994 Galla Rhois Species 0.000 title description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 101800001014 Non-structural protein 5A Proteins 0.000 claims abstract description 16
- 108700039791 Hepatitis C virus nucleocapsid Proteins 0.000 claims abstract description 14
- 230000036541 health Effects 0.000 claims description 35
- 235000013376 functional food Nutrition 0.000 claims description 29
- JBFOLLJCGUCDQP-ZFORQUDYSA-N Apigenin 7-glucuronide Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC1=CC(O)=C2C(=O)C=C(C=3C=CC(O)=CC=3)OC2=C1 JBFOLLJCGUCDQP-ZFORQUDYSA-N 0.000 claims description 20
- GTDSSCNJWWPJHR-UHFFFAOYSA-N apigenin 7-O-beta-D-glucuronide Natural products OC1C(Oc2ccc3C(=O)C=C(Oc3c2O)c4ccc(O)cc4)OC(C(O)C1O)C(=O)O GTDSSCNJWWPJHR-UHFFFAOYSA-N 0.000 claims description 19
- JBFOLLJCGUCDQP-UHFFFAOYSA-N scutellarin A Natural products O1C(C(O)=O)C(O)C(O)C(O)C1OC1=CC(O)=C2C(=O)C=C(C=3C=CC(O)=CC=3)OC2=C1 JBFOLLJCGUCDQP-UHFFFAOYSA-N 0.000 claims description 19
- JBFOLLJCGUCDQP-UNJWAJPSSA-N apigenin-7-O-alpha-D-glucuronide Natural products O[C@H]1[C@@H](Oc2cc(O)c3c(c2)oc(cc3=O)-c2ccc(O)cc2)O[C@@H]([C@@H](O)[C@@H]1O)C(O)=O JBFOLLJCGUCDQP-UNJWAJPSSA-N 0.000 claims description 18
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 15
- 229960000329 ribavirin Drugs 0.000 claims description 15
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 15
- 239000004480 active ingredient Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 238000011260 co-administration Methods 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 11
- 208000019423 liver disease Diseases 0.000 abstract description 10
- 235000013305 food Nutrition 0.000 abstract description 7
- 240000003152 Rhus chinensis Species 0.000 abstract 2
- 235000014220 Rhus chinensis Nutrition 0.000 abstract 2
- 235000010889 Rhus javanica Nutrition 0.000 abstract 2
- 241000711549 Hepacivirus C Species 0.000 description 35
- 238000002360 preparation method Methods 0.000 description 22
- 235000013402 health food Nutrition 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- CXQWRCVTCMQVQX-LSDHHAIUSA-N (+)-taxifolin Chemical compound C1([C@@H]2[C@H](C(C3=C(O)C=C(O)C=C3O2)=O)O)=CC=C(O)C(O)=C1 CXQWRCVTCMQVQX-LSDHHAIUSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- XFZJEEAOWLFHDH-NFJBMHMQSA-N procyanidin B2 Chemical compound C1([C@@H]2[C@H](O)[C@H](C3=C(O)C=C(O)C=C3O2)C=2C(O)=CC(O)=C3C[C@H]([C@H](OC3=2)C=2C=C(O)C(O)=CC=2)O)=CC=C(O)C(O)=C1 XFZJEEAOWLFHDH-NFJBMHMQSA-N 0.000 description 15
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 14
- 239000000126 substance Substances 0.000 description 12
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- RTATXGUCZHCSNG-QHWHWDPRSA-N Nicotiflorin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-QHWHWDPRSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 10
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 10
- 235000009498 luteolin Nutrition 0.000 description 10
- DVGGLGXQSFURLP-VWMSDXGPSA-N tribuloside Chemical compound C([C@@H]1[C@H]([C@@H]([C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1)O)O)OC(=O)\C=C\C1=CC=C(O)C=C1 DVGGLGXQSFURLP-VWMSDXGPSA-N 0.000 description 10
- SOSLMHZOJATCCP-AEIZVZFYSA-N afzelin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O SOSLMHZOJATCCP-AEIZVZFYSA-N 0.000 description 9
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 9
- 235000008714 apigenin Nutrition 0.000 description 9
- 229940117893 apigenin Drugs 0.000 description 9
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- JPUKWEQWGBDDQB-QSOFNFLRSA-N kaempferol 3-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O JPUKWEQWGBDDQB-QSOFNFLRSA-N 0.000 description 9
- DVGGLGXQSFURLP-FIZCXTQCSA-N potengriffioside A Natural products O[C@@H]1[C@@H](COC(=O)C=Cc2ccc(O)cc2)O[C@@H](Oc2c(oc3cc(O)cc(O)c3c2=O)-c2ccc(O)cc2)[C@H](O)[C@H]1O DVGGLGXQSFURLP-FIZCXTQCSA-N 0.000 description 9
- LTRRTGCXRIMDTF-UHFFFAOYSA-N tiliroside Natural products OC1C(COC(=O)C=Cc2ccc(O)cc2)OC(OC3=C(Oc4cc(O)cc(O)c4C3)c5ccc(O)c(O)c5)C(O)C1O LTRRTGCXRIMDTF-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- MQVRGDZCYDEQML-UHFFFAOYSA-N Astragalin Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(CO)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 MQVRGDZCYDEQML-UHFFFAOYSA-N 0.000 description 8
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 description 8
- SOSLMHZOJATCCP-PADPQNGGSA-N afzelin Natural products O([C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1)C1=C(c2ccc(O)cc2)Oc2c(c(O)cc(O)c2)C1=O SOSLMHZOJATCCP-PADPQNGGSA-N 0.000 description 8
- 229960003321 baicalin Drugs 0.000 description 8
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- RTATXGUCZHCSNG-ZFDPGQBLSA-N nicotiflorin Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC2=C(c3ccc(O)cc3)Oc3c(c(O)cc(O)c3)C2=O)O1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 RTATXGUCZHCSNG-ZFDPGQBLSA-N 0.000 description 8
- RTATXGUCZHCSNG-UHFFFAOYSA-N nicotiflorine Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-UHFFFAOYSA-N 0.000 description 8
- OVSQVDMCBVZWGM-DTGCRPNFSA-N quercetin 3-O-beta-D-galactopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-DTGCRPNFSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XFZJEEAOWLFHDH-UHFFFAOYSA-N (2R,2'R,3R,3'R,4R)-3,3',4',5,7-Pentahydroxyflavan(48)-3,3',4',5,7-pentahydroxyflavan Natural products C=12OC(C=3C=C(O)C(O)=CC=3)C(O)CC2=C(O)C=C(O)C=1C(C1=C(O)C=C(O)C=C1O1)C(O)C1C1=CC=C(O)C(O)=C1 XFZJEEAOWLFHDH-UHFFFAOYSA-N 0.000 description 7
- 208000005176 Hepatitis C Diseases 0.000 description 7
- OVSQVDMCBVZWGM-SJWGPRHPSA-N Hyperin Natural products O[C@H]1[C@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-SJWGPRHPSA-N 0.000 description 7
- FVQOMEDMFUMIMO-UHFFFAOYSA-N Hyperosid Natural products OC1C(O)C(O)C(CO)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 FVQOMEDMFUMIMO-UHFFFAOYSA-N 0.000 description 7
- 102000008070 Interferon-gamma Human genes 0.000 description 7
- 108010074328 Interferon-gamma Proteins 0.000 description 7
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 7
- 229920002350 Procyanidin B2 Polymers 0.000 description 7
- KQNGHARGJDXHKF-UHFFFAOYSA-N dihydrotamarixetin Natural products C1=C(O)C(OC)=CC=C1C1C(O)C(=O)C2=C(O)C=C(O)C=C2O1 KQNGHARGJDXHKF-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229960003130 interferon gamma Drugs 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- BBFYUPYFXSSMNV-UHFFFAOYSA-N quercetin-7-o-galactoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C2C(=O)C(O)=C(C=3C=C(O)C(O)=CC=3)OC2=C1 BBFYUPYFXSSMNV-UHFFFAOYSA-N 0.000 description 7
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 6
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 235000005875 quercetin Nutrition 0.000 description 6
- 229960001285 quercetin Drugs 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 102000014150 Interferons Human genes 0.000 description 5
- 108010050904 Interferons Proteins 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 208000019425 cirrhosis of liver Diseases 0.000 description 5
- 235000001671 coumarin Nutrition 0.000 description 5
- 229960000956 coumarin Drugs 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 208000006454 hepatitis Diseases 0.000 description 5
- 229940079322 interferon Drugs 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 240000005979 Hordeum vulgare Species 0.000 description 4
- 235000007340 Hordeum vulgare Nutrition 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- -1 patients Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 238000003809 water extraction Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 3
- 206010008909 Chronic Hepatitis Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002250 absorbent Substances 0.000 description 3
- 230000002745 absorbent Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 3
- 235000005493 rutin Nutrition 0.000 description 3
- 229960004555 rutoside Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 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
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 235000004347 Perilla Nutrition 0.000 description 2
- 244000124853 Perilla frutescens Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 235000007215 black sesame Nutrition 0.000 description 2
- 235000021329 brown rice Nutrition 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000011049 filling 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
- 235000019253 formic acid Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940041476 lactose 100 mg Drugs 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
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 229910052754 neon Inorganic materials 0.000 description 2
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000002137 ultrasound extraction Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241001107116 Castanospermum australe Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 208000037041 Community-Acquired Infections Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 240000008397 Ganoderma lucidum Species 0.000 description 1
- 235000001637 Ganoderma lucidum Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108010086093 Mung Bean Nuclease Proteins 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
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 244000088415 Raphanus sativus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 241000405414 Rehmannia Species 0.000 description 1
- 208000035415 Reinfection Diseases 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
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 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
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- XUOUCKWEYQFUMB-UHFFFAOYSA-N afzelin C Natural products CC(=CCOC1=C(Oc2cc3OC(C)(C)C=Cc3c(O)c2C1=O)c4ccc(OCC=C(C)C)cc4)C XUOUCKWEYQFUMB-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 150000001471 apigenin Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229910002056 binary alloy Inorganic materials 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
- 235000021279 black bean Nutrition 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 235000001046 cacaotero Nutrition 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
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- OACTWOBLPKAISB-UHFFFAOYSA-N chromen-2-one Chemical compound C1=CC=C2OC(=O)C=CC2=C1.C1=CC=C2OC(=O)C=CC2=C1 OACTWOBLPKAISB-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- XCGZWJIXHMSSQC-UHFFFAOYSA-N dihydroquercetin Natural products OC1=CC2OC(=C(O)C(=O)C2C(O)=C1)c1ccc(O)c(O)c1 XCGZWJIXHMSSQC-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000003134 dye exclusion method Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 208000010706 fatty liver disease Diseases 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
- 239000012467 final product 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
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000020510 functional beverage Nutrition 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
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- JGBUYEVOKHLFID-UHFFFAOYSA-N gelred Chemical compound [I-].[I-].C=1C(N)=CC=C(C2=CC=C(N)C=C2[N+]=2CCCCCC(=O)NCCCOCCOCCOCCCNC(=O)CCCCC[N+]=3C4=CC(N)=CC=C4C4=CC=C(N)C=C4C=3C=3C=CC=CC=3)C=1C=2C1=CC=CC=C1 JGBUYEVOKHLFID-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 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
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 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
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000021251 pulses Nutrition 0.000 description 1
- 235000019203 rebaudioside A Nutrition 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
- 235000009566 rice Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- CXQWRCVTCMQVQX-UHFFFAOYSA-N taxifolin Chemical compound O1C2=CC(O)=CC(O)=C2C(=O)C(O)C1C1=CC=C(O)C(O)=C1 CXQWRCVTCMQVQX-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- 230000009466 transformation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000003612 virological effect Effects 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
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
Description
본 발명은 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 포함하는 C형 간염 바이러스 감염 질환의 예방 또는 약학적 조성물에 관한 것이다.The present invention relates to a hepatitis C virus infection prevention or pharmaceutical composition comprising a compound isolated from an extract of Seonhakcho ( Agrimonia pilosa ) and an extract of Galla rhois .
C형 간염 바이러스 (Hepatitis C virus, HCV: 이하 "HCV"라 함)는 주로 수혈 및 지역 특이적 감염 (communityacquired)에 의해 일어난다. HCV에 감염되면, 그 징후가 나타나는 경우 약 20%는 급성 간염으로 진행되고 약 80% 정도가 만성 간염으로 진행되고 이 중 약 30%가 간경화 및 간암으로 진행된다. 최근의 보고에 의하면, 전세계적으로 약 2억명 이상이 HCV에 감염되어 있으며 미국 내에서는 4백 50만 명 이상으로 추정되며 (최대 천오백만 명까지 될 것으로 추정됨) 유럽에서도 5백만 명 이상이 C형 간염 환자인 것으로 알려져 있다.Hepatitis C virus (HCV: hereinafter referred to as "HCV") is mainly caused by blood transfusion and community-acquired infection. When infected with HCV, when the symptoms appear, about 20% progress to acute hepatitis, about 80% to chronic hepatitis, and about 30% of them progress to cirrhosis and liver cancer. According to recent reports, more than 200 million people worldwide are infected with HCV, and it is estimated that there are more than 4.5 million people in the United States (up to 15 million people) and more than 5 million people in Europe. He is known to be a hepatitis patient.
현재까지 C형 간염에 대한 탁월한 백신이나 효과적인 치료제는 존재하지 않기 때문에 세계의 많은 제약회사와 연구소에서 C형 간염 치료제를 개발하고 있다. C형 간염은 B형 간염과 비교하여 전 세계적으로 고른 분포를 보이고 있으며, 간경화와 간암으로 전이되는 비율이 B형 간염보다 월등히 높다. 그리고 만성 간염으로의 진행 비율이 훨씬 높은데 이러한 진행 기전에 대한 연구는 아직도 진행 중이다. 또한, C형 간염은 수혈을 통할 뿐만 아니라 정맥주사를 통한 약물 사용이나 문신을 하는 것에 의해서도 감염이 가능하지만 주로 직접적인 혈액 접촉에 의해서 감염된다. C형 간염 바이러스에 감염이 되면 대부분의 환자가 만성으로 진행되며 다시 간경화와 간암으로 진행되게 된다. 따라서 효과적인 백신과 치료제의 개발이 절실한 상태이다. HCV는 바이러스주(strain) 간에 그 유전형(genotype)이 다양하고 돌연변이(mutation)가 일어나는 경우가 많은데, HCV에 의한 만성간염이 된 경우 유전적 변이형(genetic variants)에 의해 재감염(reinfection), 동시감염(coinfection) 등이 일어나기도 한다. 이 때문에 C형 간염의 효과적인 백신 개발은 성공하기가 매우 어렵다.Since there is no effective vaccine or effective treatment for hepatitis C so far, many pharmaceutical companies and research institutes around the world are developing hepatitis C treatments. Compared to hepatitis B, hepatitis C has an even distribution worldwide, and the rate of liver cirrhosis and metastasis to liver cancer is significantly higher than that of hepatitis B. And the rate of progression to chronic hepatitis is much higher, and research on the mechanism of this progression is still ongoing. In addition, hepatitis C can be transmitted not only through blood transfusion but also through intravenous drug use or tattooing, but is mainly transmitted through direct blood contact. When infected with hepatitis C virus, most patients progress to chronic liver cirrhosis and liver cancer again. Therefore, there is an urgent need to develop effective vaccines and therapeutics. HCV has various genotypes between strains and mutations often occur. In the case of chronic hepatitis caused by HCV, reinfection and simultaneous Infection may also occur. For this reason, it is very difficult to succeed in developing an effective vaccine for hepatitis C.
현재 C형 간염의 치료방법으로는 인터페론-알파(interferon-α)와 리바비린(Ribavirin)을 병용 사용하는 치료법이 시행되고 있으나 그 치료율이 낮고 부작용이 매우 심한 편이다. 인터페론 요법의 경우 전혀 반응을 보이지 않는 경우가 약 25%이고, 일시적으로 반응하다가 재발하는 경우가 약 25% 정도이다. 나머지 약 50%의 환자에서는 치료 종료 후까지 에이엘티(ALT)치가 정상으로 유지되고 HCV RNA가 음성이 되는데 그 중에서 50% 정도는 치료 종료 후 3-6개월 내에 재발하므로 결국 25% 정도에서만 6개월 이상 치료효과가 유지되는 지속적 바이러스 반응(sustained viral response)을 보이는 셈이다. 또한, C형 간염 바이러스에는 6가지 유전자형(genotype)이 존재하는데 우리나라에 가장 많은 1b형은 2, 3형에 비해 인터페론 치료에 좋은 반응을 보이지 않는다. 이러한 이유로 리바비린과 병용요법을 사용하는데 이 경우 치료 효과가 2배 정도 높아지는 것으로 나타났으나, 리바비린만을 단독으로 사용하는 경우에는 효과가 거의 없고 적혈구가 파괴되어 빈혈 등의 부작용이 나타나므로, 주로 인터페론 치료에 반응이 없거나 재발한 경우에만 처방하는 것으로 알려져 있다. 현재까지는 HCV에 특이적으로 작용하여 증식을 억제함으로써 C형 간염을 효과적으로 치료하는 항바이러스제는 개발되지 못한 상태이다. 인터페론 치료는 HCV NS5A의 치료제인 리바비린을 병용했을 때 HCV Core 1b에 대한 민감성을 높여주므로 치료효과가 나타나는 것인 반면, 리바비린 단독으로는 HCV core 1b에 대한 억제 효과가 전혀 없으므로, HCV CORE 1b 자체를 억제하면서 동시에 HCV NS5A를 억제하는 매우 효과적인 C형 간염 바이러스 질환을 치료할 수 있는 치료제를 개발하고자 하였다.Currently, as a treatment method for hepatitis C, interferon-alpha and ribavirin are used in combination, but the treatment rate is low and side effects are very severe. In the case of interferon therapy, about 25% of cases do not respond at all, and about 25% of cases that respond temporarily and then recur. In the remaining 50% of patients, the ALT level remains normal until the end of treatment and the HCV RNA becomes negative. In other words, it shows a sustained viral response in which the abnormal therapeutic effect is maintained. In addition, there are six genotypes of the hepatitis C virus, and
이에 본 발명자들은 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물이 HCV Core 1b 및 HCV NS5A의 발현을 억제함에 따라 C형 간염 바이러스 감염 질환을 효과적으로 예방 또는 치료할 수 있는 것을 확인하고 본 발명을 완성하였다.Accordingly, the present inventors confirmed that the hepatitis C virus infection disease can be effectively prevented or treated by inhibiting the expression of
본 발명의 목적은 C형 간염 바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating hepatitis C virus infection disease.
본 발명의 다른 목적은 C형 간염 바이러스 감염 질환의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for preventing or improving hepatitis C virus infection disease.
본 발명의 또 다른 목적은 C형 간염 바이러스 감염 질환의 예방 또는 개선용 건강식품 조성물을 제공하는 것이다. Another object of the present invention is to provide a health food composition for preventing or improving hepatitis C virus infection disease.
본 발명의 다른 목적은 간질환 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating liver disease.
본 발명의 또 다른 목적은 간질환 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다. Another object of the present invention is to provide a health functional food composition for preventing or improving liver disease.
본 발명의 다른 목적은 간질환 예방 또는 개선용 건강식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health food composition for preventing or improving liver disease.
본 발명은 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide)를 유효성분으로 포함하는, C형 간염 바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating hepatitis C virus infection disease, comprising apigenin-7-glucuronide as an active ingredient.
본 발명에 있어서, 상기 화합물은, 바람직하게는 HCV Core 1b, NS5A 또는 HCV 214의 발현을 억제하는 것이 좋다.In the present invention, the compound preferably inhibits the expression of
또한, 본 발명은 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide)를 유효성분으로 포함하는, 리바비린과 병용 투여를 통한 C형 간염 바이러스 감염 질환의 치료 효과 증강용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for enhancing the therapeutic effect of hepatitis C virus infection through co-administration with ribavirin, comprising apigenin-7-glucuronide as an active ingredient. .
본 발명에 있어서, 상기 화합물은, 바람직하게는 HCV Core 1b, NS5A 또는 HCV 214의 발현을 억제하는 것이 좋다.In the present invention, the compound preferably inhibits the expression of
또한, 본 발명은 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide)를 유효성분으로 포함하는, C형 간염 바이러스 감염 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving hepatitis C virus infection disease, comprising apigenin-7-glucuronide as an active ingredient.
또한, 본 발명은 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide)를 유효성분으로 포함하는, 리바비린과 병용 투여를 통한 C형 간염 바이러스 감염 질환의 치료 효과 증강용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for enhancing the therapeutic effect of hepatitis C virus infection disease through co-administration with ribavirin, comprising apigenin-7-glucuronide as an active ingredient do.
본 발명에 따른 선학초 추출물 및 오배자 추출물에서 분리한 화합물은 HCV Core 1b 및 HCV NS5A의 발현을 억제함에 따라 C형 간염 바이러스 감염 질환 및 간질환을 효과적으로 예방 또는 치료할 수 있는 약학적 조성물 및 식품 조성물로 유용할 수 있다.The compound isolated from the Seonhakcho extract and the baeja extract according to the present invention is useful as a pharmaceutical composition and food composition that can effectively prevent or treat hepatitis C virus infection and liver disease by inhibiting the expression of
도 1은 선학초 추출물(AP), 오배자 추출물(RG) 및 선학초 추출물 및 오배자 추출물의 혼합물(APRG64)의 HCV 단백질 발현 억제를 확인한 결과이다.
도 2는 선학초 추출물 및 오배자 추출물의 혼합물(APRG64)의 총 이온 크로마토그램(Total ion chromatograms; TIC)을 나타낸 것이다.
도 3은 본 발명의 선학초 추출물 및 오배자 추출물의 혼합물(APRG64)에서 분리한 화합물 14종의 세포독성을 확인한 결과이다.
도 4는 본 발명의 선학초 추출물 및 오배자 추출물의 혼합물(APRG64)에서 분리한 화합물 14종의 HCV Core 1b의 발현을 확인한 결과이다.
도 5는 본 발명의 선학초 추출물 및 오배자 추출물의 혼합물(APRG64)에서 분리한 화합물 14종의 NS5A의 발현을 확인한 결과이다.
도 6은 본 발명의 선학초 추출물 및 오배자 추출물의 혼합물(APRG64)에서 분리한 화합물 14종의 인터페론 감마 치료제와 병용 처리 시 HCV 억제 활성을 확인한 결과이다.1 is a result confirming the suppression of HCV protein expression of a Seonhakcho extract (AP), a baeja extract (RG), and a mixture of seonhakcho extract and baeja extract (APRG64).
Figure 2 shows the total ion chromatograms (TIC) of the mixture (APRG64) of the extract of Seonhakcho and baeja extract.
3 is a result of confirming the cytotoxicity of 14 compounds isolated from a mixture (APRG64) of a Seonhakcho extract and an extract of the present invention.
4 is a result confirming the expression of
5 is a result confirming the expression of NS5A of 14 kinds of compounds isolated from a mixture (APRG64) of a Seonhakcho extract and a baeja extract of the present invention.
6 is a result confirming HCV inhibitory activity when treated in combination with interferon-gamma therapeutics of 14 types of compounds isolated from a mixture (APRG64) of Seonhakcho extract and baeja extract of the present invention.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
C형 간염 바이러스 감염 질환의 예방 또는 치료용 약학적 조성물Pharmaceutical composition for preventing or treating hepatitis C virus infection disease
본 발명은 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물을 포함하는 C형 간염 바이러스 감염 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating hepatitis C virus infection disease comprising a compound represented by the following Chemical Formula 1 or Chemical Formula 2 isolated from an Agrimonia pilosa extract and an extract of Galla rhois .
[화학식 1][Formula 1]
(상기 화학식 1에서,(In
R1 내지 R6 및 R8 내지 R11은 독립적으로 -H, -OH, C1-5의 직쇄 또는 측쇄 알콕시, . , , , 또는 이고;R 1 to R 6 and R 8 to R 11 are independently -H, -OH, C 1-5 straight-chain or branched alkoxy; . , , , or ego;
R7은 독립적으로 수소 또는 옥소기(=O)이다).R 7 is independently hydrogen or an oxo group (=O).
[화학식 2][Formula 2]
. .
본 발명의 약학적 조성물에 있어서, 상기 R1 내지 R6 및 R8 내지 R11은 독립적으로 -H, -OH, C1-3의 직쇄 또는 측쇄 알콕시, . , , , 또는 이고;In the pharmaceutical composition of the present invention, the R 1 to R 6 and R 8 to R 11 are independently -H, -OH, C 1-3 linear or branched alkoxy; . , , , or ego;
R7은 독립적으로 수소 또는 옥소기(=O)일 수 있다.R 7 may be independently hydrogen or an oxo group (=O).
본 발명의 약학적 조성물에 있어서, 상기 화학식 1로 표시되는 화합물의 바람직한 일례로는 하기 화합물을 들 수 있다.In the pharmaceutical composition of the present invention, a preferred example of the compound represented by Formula 1 may include the following compound.
(1) 프로시아니딘 B2(procyanidin B2);(1) procyanidin B2;
(2) 탁시폴린(taxifolin);(2) taxifolin;
(4) 루틴(rutin);(4) routines;
(5) 히페린(hyperin);(5) hyperin;
(6) 루테올린(luteolin);(6) luteolin;
(7) 아스트라갈린(astragalin);(7) astragalin;
(8) 퀘르세틴(quercetin);(8) quercetin;
(9) 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide);(9) apigenin-7-glucuronide;
(10) 바이칼린(baicalin);(10) baicalin;
(11) 아프젤린(afzelin);(11) afzelin;
(12) 니코티플로린(nicotiflorin);(12) nicotiflorin;
(13) 틸리로시드(tiliroside); 및 (13) tiliroside; and
(14) 아피게닌(apigenin).(14) apigenin.
보다 바람직하게는 more preferably
(2) 탁시폴린 (Taxifolin);(2) Taxifolin;
(9) 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide);(9) apigenin-7-glucuronide;
(10) 바이칼린 (baicalin);(10) baicalin;
(11) 아프젤린 (afzelin);(11) afzelin;
(12) 니코티플로린(nicotiflorin); 및(12) nicotiflorin; and
(13) 틸리로시드(tiliroside)일 수 있다. (13) tiliroside.
본 발명의 약학적 조성물에 있어서, 상기 화학식 2로 표시되는 화합물은 (3) 쿠마린(coumarin)일 수 있다.In the pharmaceutical composition of the present invention, the compound represented by
본 발명의 약학적 조성물에 있어서, 상기 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물은 탄소수 1 내지 탄소수 4의 알코올 또는 이들의 혼합용매로 추출하여 추출물을 제조할 수 있으며, 바람직하게는 50% 에탄올 수용액을 이용하여 추출할 수 있다.In the pharmaceutical composition of the present invention, the seonhakcho ( Agrimonia pilosa ) extract and the Galla rhois extract may be extracted with an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof to prepare an extract, preferably 50 % It can be extracted using an aqueous ethanol solution.
본 발명에서 사용되는 용어 "추출물(extract)"은 추출 대상을 적절한 침출액으로 짜내고 침출액을 증발시켜 농축한 제제를 의미하는 것으로, 이에 제한되지는 않으나, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 이들의 조정제물 또는 정제물일 수 있다. 상기 선학초 추출물 및 오배자 추출물은 통상의 기술분야에 공지된 일반적인 추출방법, 분리 및 정제방법을 이용하여 제조할 수 있다. 상기 추출방법으로는, 이에 제한되지는 않으나, 바람직하게 열탕 추출, 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 방법을 사용할 수 있다.As used herein, the term “extract” refers to a preparation concentrated by squeezing an extraction target with an appropriate leachate and evaporating the leachate. , may be a dried product obtained by drying the extract, a crude product or a purified product thereof. The Seonhakcho extract and baeja extract can be prepared using general extraction methods, separation and purification methods known in the art. The extraction method is not limited thereto, but preferably, methods such as hot water extraction, hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction may be used.
본 발명의 약학적 조성물에 있어서, 상기 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물은 5 : 5 내지 8 : 2의 중량비로 혼합하여 사용할 수 있고, 바람직하게는 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물은 6 : 4의 중량비로 혼합하여 사용할 수 있다.In the pharmaceutical composition of the present invention, the Seonhakcho ( Agrimonia pilosa ) extract and the Galla rhois extract may be used by mixing in a weight ratio of 5: 5 to 8: 2, preferably, the Seonhakcho ( Agrimonia pilosa ) extract and Five baeja ( Galla rhois ) extract can be used by mixing in a weight ratio of 6: 4.
본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물은 임상 투여시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있으며, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제조된다.The compound represented by the following
경구투여를 위한 고형 제제에는 정제, 환자, 산제, 과립제, 캡슐제, 트로키제 등이 포함되며, 이러한 고형 제제는 하나 이상의 본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스(sucrose), 락토오스(lactose) 또는 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, and the like, and these solid preparations are one or more of Agrimonia pilosa extracts and Galla rhois extracts of the present invention. It is prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, or gelatin, with the compound represented by
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁용제, 유제, 동결건조제제, 좌제 등이 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤, 젤라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, lyophilized formulations, suppositories, and the like. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, etc. may be used.
본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물의 인체에 대한 효과적인 투여량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 및 질환 정도에 따라 달라질 수 있으며, 일반적으로 약 0.01-1000 mg/kg/일이며, 바람직하게는 0.1-500 mg/kg/일 수 있고, 의사 또는 약사의 판단에 따라 일정시간 간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다.The effective dosage for the human body of the compound represented by the following
C형 간염 바이러스 감염 질환의 예방 또는 개선용 건강기능식품 또는 건강식품 조성물Health functional food or health food composition for prevention or improvement of hepatitis C virus infection disease
본 발명은 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물을 포함하는 C형 간염 바이러스 감염 질환의 예방 또는 개선용 건강기능식품 또는 건강식품 조성물을 제공한다.The present invention provides a health functional food or health food composition for preventing or improving hepatitis C virus infection disease comprising a compound represented by the following
[화학식 1] [Formula 1]
(상기 화학식 1에서,(In
R1 내지 R11은 제1항에서 정의한 바와 같다).R 1 to R 11 are as defined in claim 1).
[화학식 2][Formula 2]
. .
본 발명의 조성물에 있어서, 상기 화학식 1로 표시되는 화합물의 바람직한 일례로는 하기 화합물을 들 수 있다.In the composition of the present invention, preferred examples of the compound represented by
(1) 프로시아니딘 B2(procyanidin B2);(1) procyanidin B2;
(2) 탁시폴린(taxifolin);(2) taxifolin;
(4) 루틴(rutin);(4) routines;
(5) 히페린(hyperin);(5) hyperin;
(6) 루테올린(luteolin);(6) luteolin;
(7) 아스트라갈린(astragalin);(7) astragalin;
(8) 퀘르세틴(quercetin);(8) quercetin;
(9) 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide);(9) apigenin-7-glucuronide;
(10) 바이칼린(baicalin);(10) baicalin;
(11) 아프젤린(afzelin);(11) afzelin;
(12) 니코티플로린(nicotiflorin);(12) nicotiflorin;
(13) 틸리로시드(tiliroside); 및 (13) tiliroside; and
(14) 아피게닌(apigenin).(14) apigenin.
보다 바람직하게는 more preferably
(2) 탁시폴린 (Taxifolin);(2) Taxifolin;
(9) 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide);(9) apigenin-7-glucuronide;
(10) 바이칼린 (baicalin);(10) baicalin;
(11) 아프젤린 (afzelin);(11) afzelin;
(12) 니코티플로린(nicotiflorin); 및(12) nicotiflorin; and
(13) 틸리로시드(tiliroside)일 수 있다. (13) tiliroside.
본 발명의 조성물에 있어서, 상기 화학식 2로 표시되는 화합물은 (3) 쿠마린(coumarin)일 수 있다.In the composition of the present invention, the compound represented by
본 발명의 조성물에 있어서, 상기 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물은 탄소수 1 내지 탄소수 4의 알코올 또는 이들의 혼합용매로 추출하여 추출물을 제조할 수 있으며, 바람직하게는 50% 에탄올 수용액을 이용하여 추출할 수 있다.In the composition of the present invention, the seonhakcho ( Agrimonia pilosa ) extract and the Galla rhois extract may be extracted with an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof to prepare an extract, preferably 50% ethanol It can be extracted using an aqueous solution.
본 발명에서 사용되는 용어 "추출물(extract)"은 추출 대상을 적절한 침출액으로 짜내고 침출액을 증발시켜 농축한 제제를 의미하는 것으로, 이에 제한되지는 않으나, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 이들의 조정제물 또는 정제물일 수 있다. 상기 선학초 추출물 및 오배자 추출물은 통상의 기술분야에 공지된 일반적인 추출방법, 분리 및 정제방법을 이용하여 제조할 수 있다. 상기 추출방법으로는, 이에 제한되지는 않으나, 바람직하게 열탕 추출, 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 방법을 사용할 수 있다.As used herein, the term “extract” refers to a preparation concentrated by squeezing an extraction target with an appropriate leachate and evaporating the leachate. , may be a dried product obtained by drying the extract, a crude product or a purified product thereof. The Seonhakcho extract and baeja extract can be prepared using general extraction methods, separation and purification methods known in the art. The extraction method is not limited thereto, but preferably, methods such as hot water extraction, hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction may be used.
본 발명의 조성물에 있어서, 상기 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물은 5 : 5 내지 8 : 2의 중량비로 혼합하여 사용할 수 있고, 바람직하게는 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물은 6 : 4의 중량비로 혼합하여 사용할 수 있다.In the composition of the present invention, the seonhakcho ( Agrimonia pilosa ) extract and the Galla rhois extract may be mixed and used in a weight ratio of 5: 5 to 8: 2, preferably, the seonhakcho ( Agrimonia pilosa ) extract and pentagram ( Galla rhois ) extract can be used by mixing in a weight ratio of 6: 4.
본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 건강기능식품 및 건강식품 조성물로 사용하는 경우, 식품의 종류에는 특별한 제한은 없다. 본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 첨가할 수 있는 건강기능식품의 예로는 정제, 캡슐제, 환제 또는 액제 형태일 수 있으며, 건강식품의 예로는 각종 드링크제, 육류, 소세지, 빵, 캔디류, 스넥류, 면류, 아이스크림, 유제품, 스프, 이온음료, 음료수, 알코올 음료, 껌, 차 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능식품 및 건강식품 조성물을 모두 포함한다.When the compound isolated from the extract of Seonhakcho ( Agrimonia pilosa ) and the Galla rhois extract of the present invention is used as a health functional food and health food composition, the type of food is not particularly limited. Examples of health functional foods to which the compound isolated from the Agrimonia pilosa extract and the Galla rhois extract of the present invention can be added may be in the form of tablets, capsules, pills or liquids, and examples of health foods include various There are drinks, meat, sausages, bread, candy, snacks, noodles, ice cream, dairy products, soups, ionic drinks, beverages, alcoholic beverages, gum, tea and vitamin complexes, and health functional food and health food composition in the usual sense. includes all
본 발명에 따른 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 함유하는 건강기능식품 및 건강식품 조성물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강기능식품 및 건강식품 조성물 중의 상기 조성물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 유지를 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물은 상기 범위 이상의 양으로도 사용될 수 있다.The health functional food and health food composition containing the compound isolated from the Seonhakcho ( Agrimonia pilosa ) extract and the Galla rhois extract according to the present invention can be added directly to food or used together with other food or food ingredients, It can be used appropriately depending on the method. Seonhakcho ( Agrimonia pilosa ) extract and baeja ( Galla rhois ) The mixing amount of the compound isolated from the extract may be suitably determined depending on the purpose of its use (for prevention or improvement). In general, the amount of the composition in the health functional food and health food composition may be added in an amount of 0.1 to 90 parts by weight based on the total weight of the food. However, in the case of long-term intake for the purpose of maintaining health or for health control, the amount may be less than the above range, and since there is no problem in terms of safety, it is derived from Agrimonia pilosa extract and Galla rhois extract. The isolated compound may be used in an amount greater than or equal to the above range.
본 발명의 건강기능식품 및 건강식품 조성물은 지시된 비율로 필수 성분으로서 본 발명 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 함유하는 것 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트라이톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강기능식품 및 건강식품 조성물 100 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional food and health food composition of the present invention is not particularly limited in other ingredients except for containing the compound isolated from the present invention Agrimonia pilosa extract and Galla rhois extract as an essential ingredient in the indicated ratio. It may contain various flavoring agents or natural carbohydrates as additional ingredients, such as beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 health functional food and health food composition of the present invention.
상기 외에 본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 함유하는 건강기능식품 및 건강식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강기능식품 및 건강식품 조성물은 천연 과일쥬스 및 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition to the above, the health functional food and health food composition containing the compound isolated from the Agrimonia pilosa extract and the Galla rhois extract of the present invention are various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors. Flavoring agents such as agents, colorants and thickeners (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonated beverages It may contain a carbonation agent used and the like. In addition, the health functional food and health food composition of the present invention may contain natural fruit juice, fruit juice, and fruit for the production of a vegetable drink.
이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 화합물을 함유하는 건강기능식품 및 건강식품 조성물 100 중량부 당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.These components may be used independently or in combination. The proportion of these additives is not so important, but in the range of 0.1 to about 20 parts by weight per 100 parts by weight of a health functional food and health food composition containing a compound isolated from an Agrimonia pilosa extract and a Galla rhois extract of the present invention. It is usually selected from
간질환 예방 또는 치료용 약학적 조성물Pharmaceutical composition for preventing or treating liver disease
본 발명은 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물을 포함하는 간질환 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating liver disease, comprising a compound represented by the following
[화학식 1][Formula 1]
(상기 화학식 1에서,(In
R1 내지 R11은 제1항에서 정의한 바와 같다).R 1 to R 11 are as defined in claim 1).
[화학식 2][Formula 2]
. .
본 발명의 약학적 조성물에 있어서, 상기 간질환의 예로는 지방간, 간섬유증, 간경변증 또는 간암일 수 있다.In the pharmaceutical composition of the present invention, examples of the liver disease may be fatty liver, liver fibrosis, cirrhosis or liver cancer.
간질환 예방 또는 개선용 건강기능식품 또는 건강식품 조성물Health functional food or health food composition for preventing or improving liver disease
본 발명은 선학초(Agrimonia pilosa) 추출물 및 오배자(Galla rhois) 추출물로부터 분리한 하기 화학식 1 또는 화학식 2로 표시되는 화합물을 포함하는 간질환 예방 또는 개선용 건강기능식품 또는 건강식품 조성물을 제공한다.The present invention provides a health functional food or health food composition for preventing or improving liver disease comprising a compound represented by the following
[화학식 1][Formula 1]
(상기 화학식 1에서,(In
R1 내지 R11은 제1항에서 정의한 바와 같다).R 1 to R 11 are as defined in claim 1).
[화학식 2][Formula 2]
. .
하기의 실시예를 통하여 본 발명을 보다 상세하게 설명한다. 그러나 하기 실시예는 본 발명의 내용을 구체화하기 위한 것일 뿐 이에 의해 본 발명이 한정되는 것은 아니다.The present invention will be described in more detail through the following examples. However, the following examples are only intended to embody the contents of the present invention, and the present invention is not limited thereto.
<실시예 1> 추출물의 제조 및 화합물 분리<Example 1> Preparation of extract and separation of compounds
<1-1> 추출물의 제조<1-1> Preparation of extract
선학초(Agrimonia Pilosa)와 오배자(Galla rhois)의 잎은 서울의 BioKorea Co., LTd(Seoul)에서 구입하고, 바우처 표본 (BMRI-AP-1601, BMRI-RG-1602)은 한국 용인 경희대학교 바이오메디컬연구센터에 기탁하였다. 건조된 샘플(20kg)을 80 ± 2℃에서 6시간 동안 50% 에탄올로 추출한 다음 여과하였다. 그 후, 회전 증발기를 사용하여 농축시키고 동결건조하였다. 최종 생성물 수율은 선학초 1.57kg 및 오배자 11.59kg이었다. 선학초와 오배자의 혼합물은 각각 6:4의 비율로 혼합하여 사용하였으며, APRG64로 약칭하였다. 모든 샘플은 사용전까지 4 ℃에서 보관하였다.The leaves of Agrimonia Pilosa and Galla rhois were purchased from BioKorea Co., LTd (Seoul) in Seoul, and voucher specimens (BMRI-AP-1601, BMRI-RG-1602) were obtained from Kyunghee University Biomedical, Yongin, Korea. It was deposited with the Research Center. The dried sample (20 kg) was extracted with 50% ethanol at 80 ± 2 °C for 6 hours and then filtered. Then, it was concentrated using a rotary evaporator and lyophilized. The final product yield was 1.57 kg of Seonhakcho and 11.59 kg of Obaeja. A mixture of seonhakcho and baeja was used in a ratio of 6:4, respectively, and abbreviated as APRG64. All samples were stored at 4°C until use.
<1-2> 화합물 분리<1-2> Compound separation
상기 선학초 및 오배자 추출물의 혼합물(APRG64)에서 화합물을 분리하기 위해 tiMate™3000 Rapid Separation Binary System (Thermo fisher scientific Inc., Waltham, MA, USA) 및 Kinetex F5 C18 column (2.6 μm, 2.1 × 100 mm)을 사용하여 HPLC를 수행하였다. 컬럼 오븐을 25℃로 유지하고, 이동상에는 용매 A(0.1% 포름산 수용액(v/v) 및 용매 B(아세토니트릴(v/v)에 0.1% 포름산 용해)가 포함되었다. 용리 기울기는 다음과 같다 0-2 min, B 5%; 2-8 min, B 5-20%; 8-16 min, B 20%; 16-28 min, B 20-35%; 28-32 min, B 35-100%; and 32-35 min, B 100%.tiMate™3000 Rapid Separation Binary System (Thermo fisher scientific Inc., Waltham, MA, USA) and Kinetex F5 C18 column (2.6 μm, 2.1 × 100 mm) to separate compounds from the mixture (APRG64) of the Seonhak plant and P. baeja extract HPLC was performed using The column oven was maintained at 25° C., and the mobile phase contained solvent A (0.1% aqueous formic acid solution (v/v) and solvent B (0.1% formic acid dissolved in acetonitrile (v/v)). The elution gradient was as follows. 0-2 min,
유속은 250㎕/분이고, 주입 부피는 각 실행에 대해 5㎕였다. 양이온 모드에서 작동하는 SCIEX Triple TOF 5600 (SCIEX, Framingham, MA, USA)을 사용하여 MS 분석을 수행하였다. 질량분석기는 MSE acquisition mode라고 알려진 고에너지 및 저에너지 스캔을 교대로 수행했다. 동작 파라미터는 다음과 같이 설정되었다: 콘 전압(cone voltage) 40 V; 캐필러리(capillary) 3.0 kV; 소스 온도(source temperature) 500℃콘 가스 유속(cone gas flow) 30 L/h; 및 800 L/h에서 탈용매화 가스 유속(desolvation gas flow). 데이터는 100 내지 1000 m/z에서 수집되었다.The flow rate was 250 μl/min and the injection volume was 5 μl for each run. MS analysis was performed using a SCIEX Triple TOF 5600 (SCIEX, Framingham, MA, USA) operating in positive ion mode. The mass spectrometer performed alternating high-energy and low-energy scans, known as the MSE acquisition mode. The operating parameters were set as follows: cone voltage 40 V; capillary 3.0 kV; source temperature 500° C. cone gas flow 30 L/h; and a desolvation gas flow at 800 L/h. Data were collected from 100 to 1000 m/z.
실시예 1 APRG64의 총 이온 크로마토그램(Total ion chromatograms; TIC)을 도 1에 나타내었다. 하기 표 1에 총 14개의 화합물의 이름, 분자식, 머무른 시간(retention time), 질량값 및 질량 정확도에 대한 정보가 도시되었다. 피크는 Analyst library에서 0.95보다 높은 값을 갖는 공유 특성 및 40ppm보다 작은 각 피크의 질량 정확도에 기초하여 선택하였다.Example 1 Total ion chromatograms (TIC) of APRG64 are shown in FIG. 1 . In Table 1 below, the names, molecular formulas, retention times, mass values, and information on mass accuracy of a total of 14 compounds are shown. Peaks were selected based on the covalent properties with values higher than 0.95 in the Analyst library and the mass accuracy of each peak less than 40 ppm.
FormulaMolecular
Formula
도 2 및 상기 표 1의 결과를 바탕으로 선학초 및 오배자 추출물에서 분리한 화합물의 구조식을 하기 표 2에 나타내었다.Structural formulas of compounds isolated from Seonhakcho and Obaeja extracts based on the results of FIG. 2 and Table 1 are shown in Table 2 below.
(taxifolin)Taxifolin
(taxifolin)
(coumarin)coumarin
(coumarin)
(rutin)Routine
(rutin)
(hyperin)Hyperin
(hyperin)
(luteolin)luteolin
(luteolin)
(astragalin)astragalin
(astragalin)
(quercetin)quercetin
(quercetin)
(Apigenin 7-glucuronide)Apigenin-7-glucuronide
(Apigenin 7-glucuronide)
(baicalin)baicalin
(baicalin)
(afzelin)apzelin
(afzelin)
(nicotiflorin)Nicotiflorin
(nicotiflorin)
(tiliroside)tiliroside
(tiliroside)
(apigenin)apigenin
(apigenin)
<준비예 1> 세포배양<Preparation Example 1> Cell culture
Huh 7.5 세포는 10% 소태아혈청(FBS, GE Healthcare Life Sciences) 및 1% 페니실린-스트렙토마이신(PS, WELGENE, Daegu, Korea)이 보충된 DMEM(Dulbecco's Modified Eagle's Medium, WELGENE, Daegu, Korea)에서 배양하였다. 세포는 5% CO2가 포함된 습한 대기하에서 37℃로 유지되었다.Huh 7.5 cells were cultured in DMEM (Dulbecco's Modified Eagle's Medium, WELGENE, Daegu, Korea) supplemented with 10% fetal bovine serum (FBS, GE Healthcare Life Sciences) and 1% penicillin-streptomycin (PS, WELGENE, Daegu, Korea). cultured. Cells were maintained at 37° C. under a humid atmosphere containing 5% CO 2 .
<준비예 2> HCV(Hepatitis C virus) RNA 준비<Preparation Example 2> HCV (Hepatitis C virus) RNA preparation
<2-1> 형질전환<2-1> Transformation
제조업자의 지시(ECOS 101, Yeastern Biotech Co., Ltd, Taipei, Taiwan)에 따라 세포를 형질전환 하였다. 간략하게, 1㎕의 플라스미드 DNA를 50㎕의 세포와 혼합한 다음 얼음에서 5분간 배양하였다. 배양된 세포를 암피실린(ampicillin)이 함유된 한천 플레이트에 적용하고 박테리아 콜로니가 나타날 때까지 37℃배양기에서 배양하였다.Cells were transformed according to the manufacturer's instructions (ECOS 101, Yeastern Biotech Co., Ltd, Taipei, Taiwan). Briefly, 1 μl of plasmid DNA was mixed with 50 μl of cells and then incubated on ice for 5 minutes. The cultured cells were applied to an agar plate containing ampicillin and cultured in an incubator at 37° C. until bacterial colonies appeared.
<2-2> 미디프렙(Midiprep)<2-2> Midiprep
미디프렙은 PureLink™HiPure Plasmid DNA Purification Kits (Invitrogen, CA, USA)을 사용하여 수행하였다. 플라스미드 DNA를 Multiskan Sky Microplate Spectrophotometer (Thermo Fisher, Waltham MA, USA)를 사용하여 적절한 부피의 TE 완충액에 용해시켜 농도 및 순도를 측정하였다. 수득된 DNA 1μg은 Mupid-2 Plus 전기 영동 시스템(ADVANCE)에서 GelRed®Nucleic Acid Gel Stain (Biotium, CA, USA)을 함유하는 아가로오스겔에 적용하였다.Midiprep was performed using PureLink™ HiPure Plasmid DNA Purification Kits (Invitrogen, CA, USA). Plasmid DNA was dissolved in an appropriate volume of TE buffer using a Multiskan Sky Microplate Spectrophotometer (Thermo Fisher, Waltham MA, USA) to determine the concentration and purity. 1 μg of the obtained DNA was applied to an agarose gel containing GelRed®Nucleic Acid Gel Stain (Biotium, CA, USA) in a Mupid-2 Plus electrophoresis system (ADVANCE).
<2-3> DNA 선형화<2-3> DNA linearization
JFH-1 플라스미드는 Takaji Wakita 박사 (National Institute of Infectious Diseases, Japan)로부터 제공받았다. 플라스미드를 37℃에서 밤새 Xba Ⅰ(New England Biolabs, NEB, MA, USA)로 소화시킨 후, Mungbean nuclease (New England Biolabs, NEB, MA, USA)와 함께 12분간 배양하였다. 선형화된 플라스미드 DNA를 페놀:클로로포름:이소아밀알코올로 2회 추출하고 pH 5.2 아세트산나트륨 및 100% 에탄올로 침전시켰다. 70% 에탄올로 1회 세척한 후, 분광광도계를 사용하여 농도 및 순도를 측정하였다. The JFH-1 plasmid was provided by Dr. Takaji Wakita (National Institute of Infectious Diseases, Japan). Plasmids were digested with Xba I (New England Biolabs, NEB, MA, USA) overnight at 37°C and then incubated with Mungbean nuclease (New England Biolabs, NEB, MA, USA) for 12 min. The linearized plasmid DNA was extracted twice with phenol:chloroform:isoamyl alcohol and precipitated with pH 5.2 sodium acetate and 100% ethanol. After washing once with 70% ethanol, the concentration and purity were measured using a spectrophotometer.
<준비예 3> 시험관내 전사(Transcription)<Preparation Example 3> In vitro transcription (Transcription)
시험관내 전사는 제조사의 지시에 따라 MEGAscript®kit (Life Technology, CA, USA)를 사용하여 수행하였다. 전사 후, 추출된 RNA를 동일한 부피의 이소프로판올로 침전시켰다. 침전된 RNA 펠릿을 RNase 비함유 물로 충분히 용해시킨 후, 분광광도계를 사용하여 농도 및 순도를 확인하였다.In vitro transcription was performed using the MEGAscript®kit (Life Technology, CA, USA) according to the manufacturer's instructions. After transcription, the extracted RNA was precipitated with an equal volume of isopropanol. After the precipitated RNA pellet was sufficiently dissolved in RNase-free water, the concentration and purity were checked using a spectrophotometer.
<준비예 4> 형질감염<Preparation Example 4> Transfection
전기청공법(electroporation)은 Neon®transfection system (Invitrogen, CA, USA)을 사용하였다. 간단히, Huh 7.5 세포를 100㎕ R 완충액으로 재현탁시키고 추출된 RNA를 첨가하였다. 100㎕ Neon® 팁에 세포혼합물을 첨가한 후, 충격(1400 V·20 ms-1 pulse)을 가하였다. 충격을 받은 세포를 항생제가 없는 배지로 재현탁시키고, 5% CO2가 포함된 습한 대기하에서 37℃로 배양하였다. Electroporation was performed using the Neon® transfection system (Invitrogen, CA, USA). Briefly, Huh 7.5 cells were resuspended with 100 μl R buffer and extracted RNA was added. After adding the cell mixture to 100 μl Neon® tip, shock (1400 V·20 ms -1 pulse) was applied. Shocked cells were resuspended in antibiotic-free medium and incubated at 37° C. in a humid atmosphere containing 5% CO 2 .
<실험예 1> 추출물의 항 HCV 활성<Experimental Example 1> Anti-HCV activity of the extract
상기 실시예 1-1의 선학초 및 오배자 추출물(APRG64)이 항-HCV 활성을 나타내는지 여부를 확인하기 위해, Huh 7.5 세포를 pJFH-1 플라스미드로부터 전사된 full length HCV RNAs로 형질감염시켰다. 이틀 후, Huh 7.5 세포를 2일간 각 추출물로 처리하였다. HCV Core 1b 및 NS5A의 발현 수준은 HCV의 복제를 나타내므로, 이들 단백질의 발현 수준을 웨스턴 블롯팅으로 분석하였다. To determine whether the extract of Seonhak root and baeja baeja (APRG64) of Example 1-1 showed anti-HCV activity, Huh 7.5 cells were transfected with full-length HCV RNAs transcribed from the pJFH-1 plasmid. After two days, Huh 7.5 cells were treated with each extract for two days. Since the expression levels of
그 결과, 도 1에 나타낸 바와 같이 선학초 추출물(AP) 및 오배자 추출물(RG)는 HCV Core 1b 및 NS5A의 발현을 억제하였으며, 선학초 추출물 및 오배자 추출물의 혼합물(APRG64) 또한 HCV 단백질의 발현을 강력하게 억제하였다. As a result, as shown in FIG. 1 , the Seonhakcho extract (AP) and the baeja extract (RG) inhibited the expression of
<실험예 2> 세포독성 <Experimental Example 2> Cytotoxicity
먼저 Huh 7.5 세포를 다양한 농도로 상기 실시예 1-2에서 분리한 화합물 14개를 각각 24시간 처리하고, 트리판 블루가 살아있는 세포에는 염색되지 않는 점을 이용한 색소 배제법으로 세포독성을 분석하였다. First, Huh 7.5 cells were treated with 14 compounds isolated in Example 1-2 at various concentrations for 24 hours, respectively, and cytotoxicity was analyzed by a dye exclusion method using the point that trypan blue does not stain live cells.
그 결과, 도 3에 나타낸 바와 같이, 상기 실시예 1-2에서 분리한 화합물 14종의 최적 처리 농도는 각각 프로시아니딘 B2(Procyanidin B2) (1, 5 μg/mL), 탁시폴린(taxifolin) (2, 5 μg/mL), 쿠마린(Coumarin) (3, 50 μg/mL), 루틴(Rutin) (4, 5 μg/mL), 히페린(hyperin) (5, 5 μg/mL), 루테올린(luteolin) (6, 2.5 μg/mL), 아스트라갈린(astragalin) (7, 50 μg/mL), 퀘르세틴(Quercetin) (8, 2.5 μg/mL), 아피게닌-7-글루쿠로니드(Apigenin 7-glucuronide) (9, 50 μg/mL), 바이칼린(Baicalin) (10, 50 μg/mL), 아프젤린(afzelin) (11, 50 μg/mL), 니코티플로린(Nicotiflorin) (12, 50 μg/mL), 틸리로시드(Tiliroside) (13, 50 μg/mL), 및 아피게닌(apigenin) (14, 5 μg/mL)이었으며, 상기 확인한 농도를 후속 실험에 사용하였다.As a result, as shown in FIG. 3 , the optimal treatment concentrations of 14 compounds isolated in Example 1-2 were procyanidin B2 (Procyanidin B2) (1, 5 μg/mL), taxifolin (2), respectively. , 5 μg/mL), Coumarin (3, 50 μg/mL), Rutin (4, 5 μg/mL), hyperin (5, 5 μg/mL), luteolin ( luteolin) (6, 2.5 μg/mL), astragalin (7, 50 μg/mL), quercetin (8, 2.5 μg/mL), apigenin-7-glucuronide (Apigenin 7) -glucuronide) (9, 50 μg/mL), Baicalin (10, 50 μg/mL), afzelin (11, 50 μg/mL), Nicotiflorin (12, 50) μg/mL), Tiliroside (13, 50 μg/mL), and apigenin (14, 5 μg/mL), and the concentrations identified above were used in subsequent experiments.
<실험예 3> HCV 억제 활성<Experimental Example 3> HCV inhibitory activity
상기 실시예 1-2에서 분리한 화합물 14종의 항 HCV 활성을 확인하기 위해, 형질감염되지 않은(Mock) Huh 7.5 세포 또는 HCV RNA로 형질감염된 Huh 7.5 세포에 상기 실시예 1-2의 화합물 14종을 각각 48시간 동안 처리하고, 세포 용해물을 제조하여, HCV Core 1b 및 NS5A의 발현을 웨스턴블롯으로 분석하였다. GAPDH를 대조군으로 사용하였다. 단백질의 밴드 강도를 이미지 J 소프트웨어에 의해 정량하고 GAPDH에 대한 상대적인 표현을 나타내었다(*, p ≤ 0.05).In order to confirm the anti-HCV activity of 14 compounds isolated in Example 1-2, the
그 결과, 도 4에 나타낸 바와 같이, 모든 화합물은 미처리 대조군과 비교할 때 HCV Core 1b 단백질의 발현을 억제하였다. 히페린(hyperin), 루테올린(luteolin), 아스트라갈린(astragalin), 아프젤린(afzelin), 아피게닌(apigenin)은 다른 화합물에 비해 상대적으로 강한 억제 활성을 나타냈다.As a result, as shown in FIG. 4 , all compounds inhibited the expression of
또한, 도 5에 나타낸 바와 같이, NS5A의 발현 또한 현저하게 억제하였다. 특히, 14종의 화합물 중에서 루테올린(luteolin) 및 틸리로시드(tiliroside)는 HCV NS5A 발현에 대해 비교적 강한 억제 활성을 나타냈다.In addition, as shown in Fig. 5, the expression of NS5A was also remarkably suppressed. In particular, among the 14 compounds, luteolin and tiliroside showed relatively strong inhibitory activity against HCV NS5A expression.
<실험예 4> 인터페론 감마 치료제와 병용 처리 시 HCV 억제<Experimental Example 4> HCV inhibition in combination treatment with interferon gamma treatment
상기 실시예 1-2에서 분리한 화합물 14종의 인터페론 치료제와 병용 처리시 항 HCV 활성을 확인하기 위해, HCV RNA로 형질 감염된 Huh 7.5 세포에 상기 실시예 1-2의 화합물 14종 각각 상기 실시예 1-2의 화합물 14종과 인터페론 감마 치료제(리바비린)를 병용처리(CO-Treat)하여 48시간 동안 처리하고, 세포로부터 RNA 추출 및 cDNA합성을 진행 한 후 HCV 214의 발현을 qRT-PCR로 분석하였다. Beta-actin을 대조군으로 사용하였다.In order to confirm the anti-HCV activity when combined with the interferon therapeutics of 14 types of compounds isolated in Example 1-2, Huh 7.5 cells transfected with HCV RNA were subjected to 14 types of compounds of Example 1-2, respectively. 14 kinds of compounds of 1-2 and interferon gamma treatment (ribavirin) were co-treated (CO-Treat) for 48 hours, RNA extraction from cells and cDNA synthesis were performed, and then the expression of HCV 214 was analyzed by qRT-PCR did. Beta-actin was used as a control.
그 결과, 도 6에 나타낸 바와 같이, 화합물 단독으로 처리한 군과 화합물과 인터페론 감마 치료제(리바비린)를 병용처리(co-treat)하여 처리한 군을 비교하였을 때, 루테올린(luteolin), 아스트라갈린 (astragalin), 아피게닌-7-글루쿠로니드 (Apigenin 7-glucuronide) 및 아피게닌(apigenin) 화합물의 경우 Core1B를 억제하므로, 인터페론 감마 치료제(리바비린)와 병용처리시, 상승효과가 없는 것을 확인하였으며, 단독으로 처리하였을 때 HCV 214의 발현이 현저하게 억제되는 것을 확인하였다. As a result, as shown in FIG. 6 , when comparing the group treated with the compound alone and the group treated with the compound and the interferon gamma therapeutic agent (ribavirin) co-treated, luteolin, astragalin (astragalin), apigenin-7-glucuronide (Apigenin 7-glucuronide) and apigenin (apigenin) compounds inhibit Core1B, so it was confirmed that there is no synergistic effect when combined with interferon gamma treatment (ribavirin) and it was confirmed that the expression of HCV 214 was significantly inhibited when treated alone.
또한, 쿠마린 (coumarin), 아프젤린 (afzelin) 및 니코티플로린 (nicotiflorin) 화합물의 경우 NS5A와 Core1B를 모두 억제하므로, 단독으로 처리하였을 때는 HCV 214의 발현이 미비하게 억제되었으나 인터페론 감마 치료제(리바비린)를 병용 처리하였을 때 HCV 214의 발현이 우수하게 억제된 것을 확인하였다. In addition, since the coumarin, afzelin and nicotiflorin compounds inhibit both NS5A and Core1B, the expression of HCV 214 was slightly inhibited when treated alone, but interferon gamma therapeutic agent (ribavirin) It was confirmed that the expression of HCV 214 was excellently inhibited when treated in combination.
따라서, 상기 실험결과로 인해 선학초와 오배자 추출물로부터 분리된 상기 실시예 1-2의 화합물은 인터페론 감마 치료제(리바비린)와 병용 처리할 수도 있고, 단독으로 처리하더라도 HCV 억제 활성을 나타내는 것을 확인하였다.Therefore, it was confirmed that the compound of Example 1-2, which was isolated from the extract of Seonhakcho and P. baeja due to the above experimental results, may be treated in combination with an interferon gamma therapeutic agent (ribavirin) or exhibited HCV inhibitory activity even when treated alone.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허 청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far, with respect to the present invention, the preferred embodiments have been looked at. Those of ordinary skill in the art to which the present invention pertains will understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments are to be considered in an illustrative rather than a restrictive sense. The scope of the present invention is indicated in the claims rather than in the foregoing description, and all differences within the scope equivalent thereto should be construed as being included in the present invention.
약제의 제조예Preparation example of drug
본 발명에 따른 상기 화학식 1 또는 화학식 2로 표시되는 화합물은 목적에 따라 여러 형태로 제제화가 가능하다. 하기는 본 발명에 따른 상기 화학식 1 또는 화학식 2로 표시되는 화합물을 활성성분으로 함유시킨 몇몇 제제화 방법을 예시한 것으로 본 발명이 이에 한정되는 것은 아니다.The compound represented by
<약제 제조예 1> 산제의 제조<Pharmaceutical Preparation Example 1> Preparation of powder
화학식 1 또는 화학식 2의 화합물
2 gA compound of
유당 1 glactose 1 g
상기의 성분을 혼합한 후, 기밀포에 충진하여 산제를 제조하였다.After mixing the above ingredients, the powder was prepared by filling in an airtight cloth.
<약제 제조예 2> 정제의 제조<Pharmaceutical Preparation Example 2> Preparation of tablets
화학식 1 또는 화학식 2의 화합물
100 ㎎A compound of
옥수수전분 100 ㎎corn starch 100 mg
유 당 100 ㎎lactose 100 mg
스테아린산 마그네슘
2 ㎎
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above ingredients, tablets were prepared by tableting according to a conventional method for manufacturing tablets.
<약제 제조예 3> 캡슐제의 제조<Pharmaceutical Preparation Example 3> Preparation of capsules
화학식 1 또는 화학식 2의 화합물
100 ㎎A compound of
옥수수전분 100 ㎎corn starch 100 mg
유 당 100 ㎎lactose 100 mg
스테아린산 마그네슘
2 ㎎
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above ingredients, the capsules were prepared by filling in gelatin capsules according to a conventional manufacturing method of capsules.
<약제 제조예 4> 주사제의 제조<Pharmaceutical Preparation Example 4> Preparation of injection
화학식 1 또는 화학식 2의 화합물
10 ㎍/㎖A compound of
묽은 염산 BP pH 3.5로 될 때까지dilute hydrochloric acid BP until pH 3.5
주사용 염화나트륨 BP 최대 1 ㎖Sodium Chloride BP for Injection up to 1 ml
적당한 용적의 주사용 염화나트륨 BP 중에 본 발명에 따른 화학식 1 또는 화학식 2의 화합물을 용해시키고, 생성된 용액의 pH를 묽은 염산 BP를 사용하여 pH 3.5로 조절하고, 주사용 염화나트륨 BP를 사용하여 용적을 조절하고 충분히 혼합하였다. 용액을 투명 유리로 된 5 ㎖ 타입 I 앰플 중에 충전시키고, 유리를 용해시킴으로써 공기의 상부 격자하에 봉입시키고, 120 ℃에서 15 분 이상 오토클래이브시켜 살균하여 주사액제를 제조하였다.Dissolve the compound of formula (1) or formula (2) according to the present invention in an appropriate volume of sodium chloride BP for injection, adjust the pH of the resulting solution to pH 3.5 with dilute hydrochloric acid BP, and adjust the volume with sodium chloride BP for injection Adjust and mix thoroughly. The solution was filled in a 5 ml type I ampoule made of clear glass, sealed under an upper grid of air by dissolving the glass, and sterilized by autoclaving at 120° C. for 15 minutes or more to prepare an injection solution.
<약제 제조예 5> 경비흡수제 (Nasal spray)의 제조<Pharmaceutical Preparation Example 5> Preparation of nasal absorbent (Nasal spray)
화학식 1 또는 화학식 2의 화합물
1.0 gA compound of
아세트산나트륨 0.3 gsodium acetate 0.3 g
메틸파라벤 0.1 gmethylparaben 0.1 g
프로필파라벤 0.02 gPropylparaben 0.02 g
염화나트륨 적량sodium chloride appropriate amount
HCl 또는 NaOH pH 조정 적량HCl or NaOH pH adjustment appropriate amount
정제수 적량Purified water appropriate amount
통상의 경비흡수제의 제조방법에 따라, 염수 (0.9% NaCl, w/v, 용매는 정제수) 1 mL당 화학식 1 또는 화학식 2의 화합물 3 mg이 포함되도록 제조하고, 이를 불투명한 스프레이 용기에 충진하고 멸균시켜 경비흡수제를 제조하였다.According to a conventional method for preparing a nasal absorbent, 3 mg of a compound of
<약제 제조예 6> 액제의 제조<Pharmaceutical Preparation Example 6> Preparation of liquid preparation
화학식 1 또는 화학식 2의 화합물
100 mgA compound of
이성화당 10 gLee Seonghwadang 10 g
만니톨 5 gmannitol 5 g
정제수 적량Purified water appropriate amount
통상의 액제의 제조방법에 따라, 정제수에 각각의 성분을 가하여 용해시키고 레몬 향을 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체 100 mL로 조절한 후 갈색 병에 충진하고 멸균시켜 액제를 제조하였다.According to a conventional method for preparing a liquid, add each component to purified water to dissolve, add lemon flavor, mix the above components, add purified water to adjust the total to 100 mL, fill in a brown bottle, and sterilize to prepare a liquid did.
건강식품의 제조예Manufacturing example of health food
본 발명에 따른 상기 화학식 1 또는 화학식 2의 화합물은 목적에 따라 여러 형태의 건강식품으로 제조 가능하다. 하기는 본 발명에 따른 화학식 1 또는 화학식 2의 화합물을 활성성분으로 함유시킨 몇몇 건강식품의 제조방법을 예시한 것으로 본 발명이 이에 한정되는 것은 아니다.The compound of
<건강식품 제조예 1> 유제품(dairy products)의 제조<Health food production example 1> Production of dairy products
본 발명의 화학식 1 또는 화학식 2의 화합물 0.01-1 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.0.01-1 parts by weight of the compound of
<건강식품 제조예 2> 선식의 제조<Health food production example 2> Preparation of wire food
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 본 발명의 화학식 1 또는 화학식 2의 화합물을 진공 농축기에서 감압농축하고 건조분말을 얻었다. 상기에서 제조한 곡물류, 종실류 및 화학식 1 또는 화학식 2의 화합물의 건조분말을 다음의 비율로 배합하여 제조하였다.Brown rice, barley, glutinous rice, and barley radish were pregelatinized by a known method and dried, and then roasted and prepared as a powder having a particle size of 60 mesh with a grinder. Black soybeans, black sesame, and perilla were also steamed and dried by a known method, and then roasted and prepared into powder having a particle size of 60 mesh with a grinder. The compound of
곡물류(현미 34 중량부, 율무 19 중량부, 보리 20 중량부),Grains (34 parts by weight of brown rice, 19 parts by weight of barley, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame),
화학식 1 또는 화학식 2의 화합물 (2 중량부),A compound of
영지(1.5 중량부), 및Reishi (1.5 parts by weight), and
지황(1.5 중량부).Rehmannia (1.5 parts by weight).
건강기능식품의 제조예Manufacturing example of health functional food
본 발명에 따른 화학식 1 또는 화학식 2의 화합물은 목적에 따라 여러 형태의 건강기능식품으로 제조 가능하다. 하기는 본 발명에 따른 화학식 1 또는 화학식 2의 화합물을 활성성분으로 함유시킨 몇몇 건강기능식품의 제조방법을 예시한 것으로 본 발명이 이에 한정되는 것은 아니다.The compound of
<건강기능식품 제조예 1> 건강기능식품의 제조<Health functional food manufacturing example 1> Manufacture of health functional food
화학식 1 또는 화학식 2의 화합물
100 mgA compound of
비타민 혼합물 적량vitamin mixture appropriate amount
비타민 A 아세테이트 70 μgvitamin A acetate 70 μg
비타민 E 1.0 mgvitamin E 1.0 mg
비타민 B1 0.13 mgvitamin B1 0.13 mg
비타민 B2 0.15 mgvitamin B2 0.15 mg
비타민 B6 0.5 mgvitamin B6 0.5 mg
비타민 B12 0.2 μgvitamin B12 0.2 μg
비타민 C
10 mg
비오틴
10 μg
니코틴산아미드 1.7 mgnicotinic acid amide 1.7 mg
엽산 50 μgfolic acid 50 μg
판토텐산 칼슘 0.5 mgCalcium Pantothenate 0.5 mg
무기질 혼합물 적량mineral mixture appropriate amount
황산제1철 1.75 mgferrous sulfate 1.75 mg
산화아연 0.82 mgzinc oxide 0.82 mg
탄산마그네슘 25.3 mgmagnesium carbonate 25.3 mg
제1인산칼륨
15 mg
제2인산칼슘 55 mgdicalcium phosphate 55 mg
구연산칼륨 90 mgPotassium Citrate 90 mg
탄산칼슘 100 mgcalcium carbonate 100 mg
염화마그네슘 24.8 mgmagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능성 식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능성 식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능성 식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the vitamin and mineral mixture is relatively suitable for health functional food in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method. Then, the granules can be prepared and used in the preparation of a health functional food composition according to a conventional method.
<건강기능식품 제조예 2> 건강 기능 음료의 제조<Health functional food production example 2> Preparation of health functional beverage
화학식 1 또는 화학식 2의 화합물
100 mgCompounds of
구연산 100 mgcitric acid 100 mg
올리고당 100 mgoligosaccharide 100 mg
매실농축액
2 mg
타우린 100 mgTaurine 100 mg
정제수를 가하여 전체 500 mLPurified water is added to 500 mL
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 1 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. 상기 조성비는 비교적 기호 음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용 용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.After mixing the above ingredients according to a conventional health drink manufacturing method, stirring and heating at 85° C. for about 1 hour, the resulting solution is filtered and obtained in one sterilized container, sealed and sterilized, and then refrigerated. used in the manufacture of health beverage compositions of Although the composition ratio is mixed composition with ingredients suitable for relatively favorite beverages in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and national preferences such as demand class, demand country, and use purpose.
Claims (6)
상기 화합물은,
HCV Core 1b, NS5A 또는 HCV 214의 발현을 억제하는 것을 특징으로 하는, C형 간염 바이러스 감염 질환의 예방 또는 치료용 약학적 조성물.According to claim 1,
The compound is
A pharmaceutical composition for preventing or treating hepatitis C virus infection disease, characterized in that it inhibits the expression of HCV Core 1b, NS5A or HCV 214.
상기 화합물은,
HCV Core 1b, NS5A 또는 HCV 214의 발현을 억제하는 것을 특징으로 하는, 리바비린과 병용 투여를 통한 C형 간염 바이러스 감염 질환의 치료 효과 증강용 약학적 조성물.4. The method of claim 3,
The compound is
A pharmaceutical composition for enhancing the therapeutic effect of hepatitis C virus infection through co-administration with ribavirin, characterized in that it inhibits the expression of HCV Core 1b, NS5A or HCV 214.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190054463 | 2019-05-09 | ||
KR20190054463 | 2019-05-09 | ||
KR1020200054862A KR102449933B1 (en) | 2019-05-09 | 2020-05-08 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020200054862A Division KR102449933B1 (en) | 2019-05-09 | 2020-05-08 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
Publications (1)
Publication Number | Publication Date |
---|---|
KR20220123183A true KR20220123183A (en) | 2022-09-06 |
Family
ID=73697978
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020200054862A KR102449933B1 (en) | 2019-05-09 | 2020-05-08 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
KR1020220102711A KR20220123183A (en) | 2019-05-09 | 2022-08-17 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
KR1020220102712A KR102615399B1 (en) | 2019-05-09 | 2022-08-17 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020200054862A KR102449933B1 (en) | 2019-05-09 | 2020-05-08 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020220102712A KR102615399B1 (en) | 2019-05-09 | 2022-08-17 | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract |
Country Status (1)
Country | Link |
---|---|
KR (3) | KR102449933B1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023038480A1 (en) * | 2021-09-08 | 2023-03-16 | 에이피알지 주식회사 | Composition, for preventing, treating or relieving influenza virus infection, comprising mixture of agrimonia pilosa extract and galla rhois extract as active ingredient |
KR102475104B1 (en) * | 2021-11-05 | 2022-12-07 | 에이피알지 주식회사 | Vaccine Adjuvant Composition comprising Agrimonia pilosa Extract and Galla rhois Extract |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100901761B1 (en) | 2007-06-28 | 2009-06-11 | (주)리즈바이오텍 | The pharmaceutical composition and functional food containing extracts and fractions of Genus Hovenia for prevention and treatment of hepatitis B |
-
2020
- 2020-05-08 KR KR1020200054862A patent/KR102449933B1/en active IP Right Grant
-
2022
- 2022-08-17 KR KR1020220102711A patent/KR20220123183A/en not_active IP Right Cessation
- 2022-08-17 KR KR1020220102712A patent/KR102615399B1/en active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100901761B1 (en) | 2007-06-28 | 2009-06-11 | (주)리즈바이오텍 | The pharmaceutical composition and functional food containing extracts and fractions of Genus Hovenia for prevention and treatment of hepatitis B |
Also Published As
Publication number | Publication date |
---|---|
KR102449933B1 (en) | 2022-10-04 |
KR20200130177A (en) | 2020-11-18 |
KR102615399B1 (en) | 2023-12-19 |
KR20220122939A (en) | 2022-09-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102615399B1 (en) | A composition for the prevention or treatment of hepatitis C virus infection disease comprising a compound isolated from Agrimonia pilosa extract and Galla rhois extract | |
US7645465B2 (en) | Method of preparing a pharmaceutical composition comprising fermented ginseng | |
KR101577111B1 (en) | Pharmaceutical compositions for anti-inflammation or anti-oxidation containing ginsenoside rh4-enriched extraction | |
KR20170121866A (en) | Extract of cordyceps militaris, manufacturing method of the same, and composition comprising cordycepin isolated thereform for the prevent or treatment of lung cancer | |
KR102187951B1 (en) | Pharmaceutical composition for the treatment of Epstein-Barr virus-positive gastric cancer, comprising an extract of Ganoderma lucidum and quercetin as an active ingredient | |
Kaewkod et al. | Combinations of traditional kombucha tea with medicinal plant extracts for enhancement of beneficial substances and activation of apoptosis signaling pathways in colorectal cancer cells | |
KR102485608B1 (en) | Composition comprising nodakenin and nodakenetin for suppressing influenza virus | |
KR102032034B1 (en) | Pharmaceutical composition comprising ishige okamurae extracts for prevention and treatment of neurodegenerative disorders as an active ingredient | |
KR101722567B1 (en) | Pharmaceutical composition containing isolated compounds from Saururus chinensis extract and fractions thereof for anti-virus | |
KR20200104749A (en) | Composition for preventing or treating muscular disease containing Salvia officinalis extract | |
KR101691032B1 (en) | Pharmaceutical composition containing Saururus chinensis extract or fractions thereof for anti-virus | |
KR102246349B1 (en) | Composition for Preventing or Treating Muscular disease containing Rhodiola rosea extract | |
KR101816601B1 (en) | Pharmaceutical composition for blood vessel disease prevention or treatment comprising substance extracted from the fruits of acanthopanax sessiliflorus and method for manufacturing thereof | |
KR20110000323A (en) | Pharmaceutical and health food composition for preventing and treating diabetes mellitus comprising fruit extracts of chaenomeles sinensis as effective component | |
KR20220077317A (en) | Composition for preventing and improving viral diseases | |
KR20140065184A (en) | Composition for preventing or treating liver cancer comprising ethyl acetate fraction from orostachys japonicus | |
KR102194345B1 (en) | Composition for Preventing or Treating Muscular disease containing Angelica gigas Nakai extract | |
KR20040004764A (en) | Composition comprising the extract of Acanthopanax senticosus or buthyl alcol soluble fraction or syringin or (-)-syringaresinol-di-O-β-D-glucopyranoside derivatives therefrom having anti-oxidant and hepato-protective activity | |
KR102311887B1 (en) | Composition comprising Sargassum Horner extract for preventing or treating liver disease | |
KR101373173B1 (en) | Composition comprising an extract of combined crude drug for preventing and treating inflammatory disease or allergic disease | |
KR102142854B1 (en) | Agent for improvement of Catechin absorptance on the intestinal epithelium | |
WO2022060168A1 (en) | Composition comprising hemp stem extract as active ingredient for prevention, alleviation, or treatment of fatty liver disease | |
KR20210028618A (en) | Composition for Preventing or Treating Muscular disease containing Artemisia dracunculus L. extract | |
KR20200139114A (en) | Composition for Preventing or Treating Muscular disease containing Artemisia dracunculus L. extract | |
KR20160103547A (en) | Antioxidant composition containing purified bee venom |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A107 | Divisional application of patent | ||
E902 | Notification of reason for refusal | ||
AMND | Amendment | ||
E601 | Decision to refuse application | ||
X091 | Application refused [patent] | ||
AMND | Amendment | ||
X601 | Decision of rejection after re-examination |