GB2466527A - Antibacterial use of an extract from Morus australis Poir. and kuwanon H - Google Patents
Antibacterial use of an extract from Morus australis Poir. and kuwanon H Download PDFInfo
- Publication number
- GB2466527A GB2466527A GB0908520A GB0908520A GB2466527A GB 2466527 A GB2466527 A GB 2466527A GB 0908520 A GB0908520 A GB 0908520A GB 0908520 A GB0908520 A GB 0908520A GB 2466527 A GB2466527 A GB 2466527A
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- United Kingdom
- Prior art keywords
- use according
- bacteria
- extract
- eluent
- compound
- Prior art date
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- Granted
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- 239000000284 extract Substances 0.000 title claims abstract description 41
- 240000009253 Morus australis Species 0.000 title claims abstract description 15
- 235000006723 Morus australis Nutrition 0.000 title claims abstract description 15
- DKBPTKFKCCNXNH-YWUCGUBVSA-N Kuwanon H Natural products CC(C)=CCC1=C(O)C=CC(C(=O)[C@@H]2[C@@H](C=C(C)C[C@H]2C=2C(=CC(O)=CC=2)O)C=2C3=C(C(C(CC=C(C)C)=C(O3)C=3C(=CC(O)=CC=3)O)=O)C(O)=CC=2O)=C1O DKBPTKFKCCNXNH-YWUCGUBVSA-N 0.000 title abstract description 17
- DKBPTKFKCCNXNH-QXGWMLRCSA-N kuwanone H Chemical compound CC(C)=CCC1=C(O)C=CC(C(=O)[C@@H]2[C@H](C=C(C)C[C@H]2C=2C(=CC(O)=CC=2)O)C=2C3=C(C(C(CC=C(C)C)=C(O3)C=3C(=CC(O)=CC=3)O)=O)C(O)=CC=2O)=C1O DKBPTKFKCCNXNH-QXGWMLRCSA-N 0.000 title abstract description 15
- 230000000844 anti-bacterial effect Effects 0.000 title description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 241000894006 Bacteria Species 0.000 claims abstract description 22
- 239000003480 eluent Substances 0.000 claims abstract description 22
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 19
- 239000007864 aqueous solution Substances 0.000 claims abstract description 18
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 15
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 15
- 241000193998 Streptococcus pneumoniae Species 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 239000012141 concentrate Substances 0.000 claims abstract description 6
- 239000002798 polar solvent Substances 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims abstract description 5
- 241000192125 Firmicutes Species 0.000 claims abstract description 4
- 238000001704 evaporation Methods 0.000 claims abstract description 4
- 230000008020 evaporation Effects 0.000 claims abstract description 4
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims abstract description 4
- 238000010828 elution Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 37
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 14
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims description 13
- 229960003276 erythromycin Drugs 0.000 claims description 7
- 229960000723 ampicillin Drugs 0.000 claims description 6
- 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 claims description 6
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 229960003085 meticillin Drugs 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- ZXTQHAMOONDJDJ-YTAXAHCSSA-N (2s)-6-[(1s,5r,6s)-6-(2,4-dihydroxybenzoyl)-5-(2,4-dihydroxyphenyl)-3-(4-methylpent-3-enyl)cyclohex-2-en-1-yl]-2-(2,5-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydrochromen-4-one Chemical compound C1([C@H]2[C@@H]([C@H](C=C(C2)CCC=C(C)C)C=2C(=C3C(=O)C[C@H](OC3=CC=2O)C=2C(=CC=C(O)C=2)O)O)C(=O)C=2C(=CC(O)=CC=2)O)=CC=C(O)C=C1O ZXTQHAMOONDJDJ-YTAXAHCSSA-N 0.000 abstract description 6
- VYCKCQBOVSSJSK-ANWKEMATSA-N Sanggenon G Natural products O=C([C@H]1[C@H](c2c(O)c3C(=O)C[C@H](c4c(O)cc(O)cc4)Oc3cc2O)C=C(CC/C=C(\C)/C)C[C@@H]1c1c(O)cc(O)cc1)c1c(O)cc(O)cc1 VYCKCQBOVSSJSK-ANWKEMATSA-N 0.000 abstract description 6
- 206010035734 Pneumonia staphylococcal Diseases 0.000 abstract 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 abstract 1
- 239000003242 anti bacterial agent Substances 0.000 abstract 1
- 208000004048 staphylococcal pneumonia Diseases 0.000 abstract 1
- 208000011437 staphylococcus aureus pneumonia Diseases 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
- 240000000249 Morus alba Species 0.000 description 11
- 235000008708 Morus alba Nutrition 0.000 description 11
- APPXYONGBIXGRO-UHFFFAOYSA-N kuwanon G Natural products OC1=CC(O)=C2C(=O)C(CC=C(C)C)=C(C=3C(=CC(O)=CC=3)O)OC2=C1C1C=C(C)CC(C=2C(=CC(O)=CC=2)O)C1C(=O)C1=CC=C(O)C=C1O APPXYONGBIXGRO-UHFFFAOYSA-N 0.000 description 11
- 239000000843 powder Substances 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- WCJPAQJEARHLGS-KEBDBYFISA-N 5-[7-[(2e)-3,7-dimethylocta-2,6-dienyl]-6-hydroxy-1-benzofuran-2-yl]-4-(3-methylbut-2-enyl)benzene-1,3-diol Chemical compound O1C=2C(C/C=C(C)/CCC=C(C)C)=C(O)C=CC=2C=C1C1=CC(O)=CC(O)=C1CC=C(C)C WCJPAQJEARHLGS-KEBDBYFISA-N 0.000 description 5
- 241000218213 Morus <angiosperm> Species 0.000 description 5
- WTGKDESIYCVAOP-NPPPIGHJSA-N Mulberrofuran C Natural products O=C([C@@H]1[C@@H](c2c(O)cc(-c3oc4c(c3)ccc(O)c4)cc2O)C=C(C)C[C@@H]1c1c(O)cc(O)cc1)c1c(O)cc(O)cc1 WTGKDESIYCVAOP-NPPPIGHJSA-N 0.000 description 5
- WCJPAQJEARHLGS-JMIUGGIZSA-N Mulberrofuran D Natural products Oc1c(C/C=C(\C)/C)c(-c2oc3c(C/C=C(\CC/C=C(\C)/C)/C)c(O)ccc3c2)cc(O)c1 WCJPAQJEARHLGS-JMIUGGIZSA-N 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- KEIIIPKLVSSAEI-UHFFFAOYSA-N Albanin A Chemical compound O1C2=CC(O)=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC=C(O)C=C1O KEIIIPKLVSSAEI-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 241000194017 Streptococcus Species 0.000 description 4
- 239000004599 antimicrobial Substances 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- APPXYONGBIXGRO-AIQWNVMPSA-N kuwanone G Chemical compound O=C([C@H]1[C@@H](CC(C)=C[C@@H]1C1=C2OC(=C(C(C2=C(O)C=C1O)=O)CC=C(C)C)C=1C(=CC(O)=CC=1)O)C=1C(=CC(O)=CC=1)O)C1=CC=C(O)C=C1O APPXYONGBIXGRO-AIQWNVMPSA-N 0.000 description 4
- WTGKDESIYCVAOP-UNTHUGQZSA-N mulberrofuran C Chemical compound C1([C@H]2[C@@H]([C@@H](C=C(C2)C)C=2C(=CC(=CC=2O)C=2OC3=CC(O)=CC=C3C=2)O)C(=O)C=2C(=CC(O)=CC=2)O)=CC=C(O)C=C1O WTGKDESIYCVAOP-UNTHUGQZSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 3
- MQQJRRDEGVHDBJ-UHFFFAOYSA-N Albanin F Natural products CC1CC(C(C(=O)c2ccc(O)cc2O)C(=C1)c3c(O)cc(O)c4C(=O)C(=C(Oc34)c5ccc(O)cc5O)CC=C(C)C)c6ccc(O)cc6O MQQJRRDEGVHDBJ-UHFFFAOYSA-N 0.000 description 3
- HDHRTQZSBFUBMJ-UHFFFAOYSA-N Artonin E Natural products O1C2=C3C=CC(C)(C)OC3=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC(O)=C(O)C=C1O HDHRTQZSBFUBMJ-UHFFFAOYSA-N 0.000 description 3
- 208000001953 Hypotension Diseases 0.000 description 3
- APPXYONGBIXGRO-FPQPQGOJSA-N Kuwanone G Natural products O=C([C@@H]1[C@H](c2c(O)cc(O)c3C(=O)C(C/C=C(\C)/C)=C(c4c(O)cc(O)cc4)Oc23)C=C(C)C[C@H]1c1c(O)cc(O)cc1)c1c(O)cc(O)cc1 APPXYONGBIXGRO-FPQPQGOJSA-N 0.000 description 3
- 208000021822 hypotensive Diseases 0.000 description 3
- 230000001077 hypotensive effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XFFOMNJIDRDDLQ-UHFFFAOYSA-N morusin Chemical compound O1C2=C3C=CC(C)(C)OC3=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC=C(O)C=C1O XFFOMNJIDRDDLQ-UHFFFAOYSA-N 0.000 description 3
- WUBUWBUVAKMGCO-UHFFFAOYSA-N morusin Natural products CC(=CCC1=C(Cc2c3C=CC(C)(C)Oc3cc(O)c2C1=O)c4ccc(O)cc4O)C WUBUWBUVAKMGCO-UHFFFAOYSA-N 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 102000003850 Dipeptidase 1 Human genes 0.000 description 2
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 244000293610 Morus bombycis Species 0.000 description 2
- 235000006721 Morus bombycis Nutrition 0.000 description 2
- 241000301120 Morus lhou Species 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000002815 broth microdilution Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000013101 initial test Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
- 230000017066 negative regulation of growth Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- -1 5, 7-dihydroxy -(3 -methyl-but2enyl)-chromen4one Chemical compound 0.000 description 1
- 229930192840 Albanin Natural products 0.000 description 1
- MJJWBJFYYRAYKU-WPFUYSAKSA-N Albanol A Natural products Oc1c([C@@]23Oc4c(c(O)cc(-c5oc6c(c5)ccc(O)c6)c4)[C@H]4[C@H]2[C@@H](c2c(O3)cc(O)cc2)CC(C)=C4)ccc(O)c1 MJJWBJFYYRAYKU-WPFUYSAKSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- LTSRSDARASWSQF-UHFFFAOYSA-N Kuwanol A Natural products CC1=CC2C3C(C1)c4ccc(O)cc4OC3(Oc5cc(C=Cc6ccc(O)cc6O)ccc25)c7ccc(O)cc7O LTSRSDARASWSQF-UHFFFAOYSA-N 0.000 description 1
- HWGBHCRJGXAGEU-UHFFFAOYSA-N Methylthiouracil Chemical compound CC1=CC(=O)NC(=S)N1 HWGBHCRJGXAGEU-UHFFFAOYSA-N 0.000 description 1
- 241000218231 Moraceae Species 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 229930182734 Sanggenon Natural products 0.000 description 1
- 102100037667 TNFAIP3-interacting protein 1 Human genes 0.000 description 1
- 101710149776 TNFAIP3-interacting protein 1 Proteins 0.000 description 1
- WTGKDESIYCVAOP-CAHKVJEUSA-N [(1s,2s,6r)-2-[2,6-dihydroxy-4-(6-hydroxy-1-benzofuran-2-yl)phenyl]-6-(2,4-dihydroxyphenyl)-4-methylcyclohex-3-en-1-yl]-(2,4-dihydroxyphenyl)methanone Chemical compound C1([C@H]2[C@@H]([C@H](C=C(C2)C)C=2C(=CC(=CC=2O)C=2OC3=CC(O)=CC=C3C=2)O)C(=O)C=2C(=CC(O)=CC=2)O)=CC=C(O)C=C1O WTGKDESIYCVAOP-CAHKVJEUSA-N 0.000 description 1
- MJJWBJFYYRAYKU-OPKNDJPNSA-N albanol A Chemical compound C1([C@]23OC4=CC(O)=CC=C4[C@H]4[C@H]2[C@H](C2=C(O)C=C(C=C2O3)C=2OC3=CC(O)=CC=C3C=2)C=C(C4)C)=CC=C(O)C=C1O MJJWBJFYYRAYKU-OPKNDJPNSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 1
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 210000000003 hoof Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229930184898 kuwanon Natural products 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- LLROUPDIAXFXDY-UHFFFAOYSA-N moracenin B Natural products OC1=CC(O)=C2C(=O)C(CC=C(C)C)=C(C=3C(=CC(O)=CC=3)O)OC2=C1C1C=C(C)CC(C(=O)C=2C(=CC(O)=CC=2)O)C1C1=CC=C(O)C=C1O LLROUPDIAXFXDY-UHFFFAOYSA-N 0.000 description 1
- MJJWBJFYYRAYKU-UHFFFAOYSA-N mulberrofuran G Natural products C1C(C)=CC(C2=C(O)C=C(C=C2O2)C=3OC4=CC(O)=CC=C4C=3)C3C1C1=CC=C(O)C=C1OC32C1=CC=C(O)C=C1O MJJWBJFYYRAYKU-UHFFFAOYSA-N 0.000 description 1
- OPMAIQOGIRTPOM-UHFFFAOYSA-N mulberrofuran J Natural products CC1=CC(C(C(C1)c2ccc(O)cc2O)C(=O)c3ccc(O)cc3O)c4c(O)cc5oc(cc5c4O)c6cccc(O)c6 OPMAIQOGIRTPOM-UHFFFAOYSA-N 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N o-dihydroxy-benzene Natural products OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 1
- 229960001755 resorcinol Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K36/605—Morus (mulberry)
-
- 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
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Pyrane Compounds (AREA)
Abstract
An extract prepared from root bark of Morus australis Poir., for use as an antibacterial agent in treating a subject having a bacterial infection, wherein the extract is prepared by a process comprising the steps of (i) extracting root bark of Morus australis Poir. With a polar solvent (ii) concentrating the resulting extract solution (iii) introducing the resulting concentrate to a reverse phase chromatography column, and eluting the column with a first eluent and a second eluent in sequence, wherein the first eluent has a polarity of about 50 wt% of ethanol aqueous solution and the second eluent has a polarity of about 95 wt% of ethanol aqueous solution and (iv) collecting a second eluate from the elution of the column with the second eluent, and removing the second eluent from the second eluate by evaporation. The use of kuwanon H of formula (I) or a pharmaceutically acceptable salt thereof in treating a subject having a bacterial infection, wherein the bacteria are gram-positive bacteria such as staphylococcus aureus or streptococcus pneumonia is also provided. The extract obtained from Morus australis Poir. may comprise kuwanon H and sanggenon G of formula (II), wherein the kuwanon H and sanggenon G are subsequently separated from the extract.
Description
Anti-bacterial Use of Extract from Morus australis Poir. and Compound Kuwanon H
Field of the Invention
The present invention is related to a novel use of an extract prepared from root bark of Morus australis Poir. and a compound Kuwanon H separated from the extract in treating a bacterial infection.
Background of the Invention
JP1O-007555 discloses five compounds separated from an extract of tree bark of a mulberry tree such as Morus bomb ycis Koidz, Morus alba L., and Morus Lhou Koidz, which are mulberrofuran C, D, and G, kuwanol A and sanggenone G, and the anti-bacterial use of the five compounds against such as Staphylococcus aureus and Methicillin resistant Staphylococcus aureus (MRSA).
JP56-123979 discloses two compounds, kuwanon G and H, and their use in reducing the blood pressure of a hypertensive patient, which are separated from an extract prepared from root bark of a mulberry tree such as Morus bomb ycis Koidz, Morus alba L., and Morus Lhou Koidz.
Summary of the Invention
An objective of the present invention is to provide an anti-bacterial use of Kuwanon H, a compound having the following formula (I):
HOOH
HO/\ I (I) or a pharmaceutically acceptable salt thereof.
The above-mentioned anti-bacterial use of the present invention includes a pharmaceutical composition for treating a bacterial infection comprising, as a potent component, Kuwanon H, or a pharmaceutically acceptable salt thereof use of Kuwanon H, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treatment of bacterial infection in a patient; and a method of treating a subject having a bacterial infection, which comprises administering to said subject a therapeutically effective amount of kuwanon H, or a pharmaceutically acceptable salt thereof.
Another objective of the present invention is to provide an anti-bacterial use of an extract prepared from root bark of Morus australis Poir.
The anti-bacterial use of the extract according to the present invention includes a pharmaceutical composition for treating a bacterial infection comprising, as a potent component, the extract of the present invention; use of the extract of the present invention in the manufacture of a medicament for treatment of bacterial infection in a subject; and a method of treating a subject having a bacterial infection, which comprises administering to said subject a therapeutically effective amount of the extract of the present invention.
The "treating a bacterial infection" in the present invention extensively means treating any disorder caused by bacterial infection, or strictly means inhibiting growth of bacteria.
Detailed Description of the Invention
"Sang-Bai-Pi" is a traditional Chinese herb, a dried root bark of Morus alba L., for anti-inflammation, releasing coughing and diuresis. The plant of Morus alba L. is rare in Taiwan; however, Morus australis Poir. can be easily found. These motivate the inventors of the present invention to prepare extracts from Morus australis Poir. and isolate compounds from the extract with industrially useful potential.
The present invention provides a method of treating a subject having a bacterial infection, which comprises administering to said subject a therapeutically effective amount of a compound having formula (I): HOOf
HO IJ
T HOOH
H H00 OH: or a pharmaceutically acceptable salt thereof.
The present invention provides a method of treating a subject having a bacterial infection, which comprises administering to said subject a therapeutically effective amount of an extract prepared from root bark of Morus australis Poir., wherein the extract is prepared by a process comprising the following steps: a) extracting root bark of Morus australis Poir. with a polar solvent; b) concentrating the resulting extract solution from step a); c) introducing the resulting concentrate from step b) to a reverse phase chromatography column, and eluting the column with a first eluent and a second eluent in sequence, said first eluent having a polarity of about 50 wt% of ethanol aqueous solution and said second eluent having a polarity of about 95 wt% of ethanol aqueous solution; and d) collecting a second eluate from the elution of the column with the second eluent, and removing the second eluent from the second eluate by evaporation.
Preferably, the bacteria are Gram-positive bacteria.
Preferably, the bacteria are Staphylococcus aureus (Smith) or Streptococcus pneumoniae. More preferably the bacteria are Staphylococcus aureus (Smith). Most preferably, the bacteria are Staphylococcus aureus, Methicil un Resistant (MRSA). More preferably, the bacteria are Streptococcus pneurnoniae. Most preferably, the bacteria are Streptococcus pneuinoniae, Erythromycin and Ampidilhin Resistant.
Preferably, the extract of the present invention comprises the compound of the formula (I) and a compound, Sanggenon G, having the following formula (II): HO OH (II).
Preferably, the extract comprises 1-5% of the compound (I) and 1-5% of the compound (II), based on the weight of the extract. More preferably, the extract comprises about 3.7% of the compound (I) and 2.3% of the compound (II), based on the weight of the extract Preferably, the first eluent is a 50 wt% ethanol aqueous solution and the second eluent is a 95 wt% ethanol aqueous solution.
Preferably, the polar solvent in step a) is water or 95 wt% ethanol aqueous solution, wherein 95 wt% ethanol aqueous solution is more preferable.
The present invention will be better understood through the following examples which are merely illustrative, not for limiting the scope of the present invention.
Percentages and other amounts referred to in this specification are by weight unless indicated otherwise. Percentages are selected from any ranges used to total 100%.
Example 1: Preparation of an Extract, EX-1 Sliced dried root barks of Morus australis Poir. (Moraceae) were pulverized and screen with a sieve. 100 g of the resulting powder was mixed with 95 wt% ethanol aqueous solution 1000 ml (10: 1 (v/w)) in a round-bottom flask, and the resulting mixture was boiled under refluxing for one hour and filtered with a sieve of mesh number 350 and #2 filter paper to obtain a filtrate and a residue. The residue was subjected to the extraction under refluxing and the filtration under the conditions same as the above.
The resulting two filtrates were combined, and a small portion thereof was dried by evaporation to calculate a dry power weight of the combined filtrate, which is 10.21 g, i.e. 10.21 wt% yield of crude extract. The combined filtrate was concentrated to 1/10 of its original weight, and to the resulting concentrate an equal weight of water was added. The resulting mixture was introduced to a reverse phase chromatography column packed with polystyrene adsorption resin (Diaion� HP2O, Mitsubishi, Japan) in an amount of 30 times by dry weight of the concentrate of the combined filtrate, which was then eluted with 2 bed volumes (bed volume = 600 ml) of 50 wt% ethanol aqueous solution (1200 ml), and then 2 bed volumes of 95 wt% ethanol aqueous solution (1200 ml) in sequence. The eluate from 95 wt% ethanol aqueous solution was collected and concentrated in vacuo to dry.
2.73 g of diy extract with a code name of EX-1 was thus obtained with a yield of 26.7%, based on the dry weight of the concentrate of the combined filtrate, and 2.73%, based on the weight of the dried root barks.
Example 2: Separation of Extract EX-l To a homogenous solution of 2 g EX-l in 10 ml methanol 10 ml pure water was added, and the resulting mixture was then vigorously shaken to facilitate precipitating therein, followed by centrifugation at 10000 rpm for minutes. The solid resulting from the centrifugation was subjected to the dissolution, precipitating and centrifugation steps. Total six cycles were carried out.
The six liquids obtained from the six centrifugations were combined and was concentrated in vacuo to dry (weight 1.3 g). The resulting dry powder was introduced to a silica gel column (3.2 cm x 48.5 cm) packed with Silica Gel 60 in an amount of 30 times by weight of the dry powder, which was then eluted with 15 bed volumes (bed volume = 250) of a mixed mobile phase of toluene: ethyl acetate = 7: 3 (3750 ml). The eluate was collected in a pre-determined number of bottles in sequence. The liquid in each bottle was concentrated in vacuo to dry, and a small amount of methanol was added back tO dissolve the resulting dry powder, which was then introduced into a dextran gel column (1.5 cm x 40 cm) packed with Sephadex LH-20 resin in an amount of 100 times by weight of the dry powder. The column was eluted with one bed volume of methanol (30 ml), and fractions of compounds P2-i, P2-2, P3.-i and P3-2 were obtained.
Each fraction was concentrated in vacuo to dry, and then subjected to purification with preparative HPLC. Compounds P2-i, P2-2, P3-i and P3-2 were obtained. Yield of compound P3-I is 2.3% (46 mg), based on the weight of EX-1, and yield of compound P3-2 is 3.65% (73 mg), based on the weight of EX-1.
The residue after the six centrifugation was dissolved in methanol and the resulting solution was concentrated in vacuo to dry. The resulting dry powder was introduced to a silica gel column (3.2 cm x 48.5 cm) packed with Silica Gel 60 in an amount of 30 times by weight of the dry powder, which was then eluted with two bed volumes (bed volume = 250) of a mixed mobile phase of toluene: ethyl acetate = 9: 1 (500 ml). The eluate was collected in a pre-determined number of bottles in sequence. The liquid in each bottle was concentrated in vacuo to dry, and a small amount of methanol was added back to dissolve the resulting dry powder, which was then introduced into a dextran gel column (1.5 cm x 40 cm) packed with Sephadex LH-20 resin in an amount of 100 times by weight of the dry powder. The column was eluted with one bed volume of methanol (30 ml), and compounds P3-3 and P3-4 were obtained.
Structuie Analysis of Compounds P2-i, P2-2, P3-i, P3-2, P3-3 and P3-4 P2-I Mulberrofuran C P2-2 Kuwanon G (Albanin F) C34H2809 MW=58059 C40H36011 MW= 692.72 2[26dihydroXy4(6hyd {ó(24dihydroxybenzoy1)5 -(2 4-dihydroXY benzoran2y1)phenJ]6(24 phenyl)-3 -methyIcyc1ohex2fllJ2(2,4 Pheny1)4methy1cycJOh3 -enyl]-(2,4 dihydroxypheflyj)S 7-dihydroxy-3 (3 dih)Tdroxypheflyj)th methyJbut2efly1)c4
OH HOOH
HO
HOOH OH H8)
OH OH OH 0
P3-I Sanggeno11 G P3-2 Kuwanon H (Albanin A) C40H38011 MW=694 74 C45J-j4411 MW=76084 I6(24-dihydroxy benzoyl)5(24djhydr 8{6[2,4dihydroxy3 -(3 -methyl-but-2-eflYl) phenyl)-3 -(4-methylpeflt3eflyl)1 benzoylj5(2,4djh)Tdroxyphefll)3 -methyl-enYlJ2(2,4dihydroxyphel)5 7-cYclohex2eflyJj2(24d.hdhflyj) 5, 7-dihydroxy -(3 -methyl-but2enyl)-chromen4one
HO OH
HO OH
HO0 I OHHO 0 HO/\ I OH
HO 0 I 1 1
HO OH OH 0 P3-3 Morusin P3-4 Mulberrofuran D C25H2406 M\V=420.46 C29H3404 MW=446. 59 2-(2,4-dihydroxy-phenyl)-5-hydroxy-8,8-3,7-dimethyl-octa-2,6-dienyl) -6-hydroxy- dimethyl-3 -(3 -inethyl-but-2-enyl)-8H-benzofuran-2-yl] -4-(3 -methyl-but-2-enyl)-pyrano[2,3-J]chromen-4-one benzene-1,3-diol H HOu10 H P2-i: ESI-MS: mlz 603.3 ([M+NaJ) and mlz 579.2 ([M-Hfl. The NMR analysis were also carried out. The ESI-MS and NMR data indicate the formula of P2-i is C34H2809. The NMR data were compared with the study of Fukai, T.; Hano, Y; Hirakura, K.; Nomura, T.; Uzawa, J.; Fukushima, K., Structure of mulberrofuran J, a 2-arylbenzofuran derivative from the cultivated mulberry tree (Morus i/iou Koidz.), Heterocycles 1984, 22, 1007-10 11, and compound P2-i is confirmed to be mulberrofuran C reported in said study. Mulberrofuran C is also disclosed in Japanese patent publication JP57-144223.
P2-2: ESI-MS: m/z 715.3 ([M+Na]) and nilz 691.3([M-H]-). The NMR analysis were also carried out. The ESI-MS and NMR data indicate the formula of P2-2 C40H36011. The NMR data were compared with the study of Nomura, T.; Fukai, T.; Narita, T., Hypotensive constituent, kuwanon H, a new flavone derivative from the root bark of the cultivated mulberry tree (Morus alba L.), Heterocycles 1980, 14, 1943-195 1, and compound P2-2 is confirmed to be albanin F (Kuwanon G) reported in said article.
Albanin F (Kuwanon G) is also disclosed in Korean patent publication KR20020087225.
P3-i: ESI-MS: rnlz 695.4 ([M+H]') and rn/z 693.7 ({M-Hf). The NMR analysis were also carried out. The ESI-MS and NMR data indicate the foririula of P3-i is C40H38011. The NMR data were compared with the study of Fukai, T.; Hano, Y.; Fujimoto, T.; Nomura, T., Structure of sanggenon G, a new Diels-Alder adduct from the Chinese crude drug "Sang-Bai-Pi" (Morus root barks), 1-Jeterocycles 1983, 20, 6 11-615, and compound P3-i is confirmed to be Sanggenon G. Sanggenon G is also disclosed in Japanese patent publication JP1O-007555.
P3-2: ESI-MS: m/z 761 ({M+H]), 783 ([M+Naf1) and 759 ([M-Hfl.
The molecular weight of P3-2 was calculated as 760. The NMIR analysis were also carried out. The ESI-MS and NMR data indicate the formula of P3-2 is C45H44011. The NMR data were compared with the studies of Noinura, T.; Fukai, T.; Narita, T.; Terada, S.; Uzawa, J.; litaka, Y.; Takasugi, M.; Ishikawa, S. I.; Nagao, S.; Masarnune, T., Confirmation of the structures of kuwanons G and H (albanins F and G) by partial synthesis, Tetrahedron Letters 1981, 22, 2i95-2198; Oshima, Y.; Konno, C.; Hikino, H., Structure of moracenin A, a hypotensive principle of Morus root barks, Hetero cycles 1980, 14, 1287-i290; and Oshima, Y.; Konno, C.; Hikino, H.; Matsushita, K., Structure of moracenin B, a hypotensive principle of Morus root barks, Tetrahedron Letters 1980, 2], 338 1-3384, and compound P3-2 is confirmed to be Kuwanon H (also called Albanin A or Moracenin A. Japanese patent publication JP56-123979 discloses Kuwanon H is potent in reducing the blood pressure of a hypertensive patient.
P3-3: ESI-MS: m/z 421 ([M+H]). The NMR analysis were also carried out. The ESI-MS and NMR data indicate the formula of P3-3 is C25H2406. The NIMR data were compared with the study of Nomura, T.; -10 -Fukai, T.; Yamada, S.; Katayanagi, M., Phenolic constituents of the cultivated mulberry tree (Morus a/ba L.), Chem. Pharm. Bull. 1976, 24, 2898-2900, and compound P3-3 is confirmed to Morusin. Morusin is also disclosed in US patent publication US2008/0286213.
P3-4: ESI-MS: m/z 447.0 ([M+H]). The NMR analysis were also carried out. The ESI-MS and NMR data indicate the formula of P3-4 is C29H3404. The NMR data were compared with the study of Nomura, T.; Fukai, T.; Shimada, T.; Chen, 1.-S. Mulberrofuran D, a new 2-arylbenzofuran from the root barks of the mulberry tree (Morus australis Poir.), Heterocycles, 1982, 19, 185 5-1860, and compound P3-4 is confirmed to be Mulberrofuran D. Mulberrofuran D is also disclosed in Japanese patent publication JP1O-007555.
Anti-microbial Test Staphylococcus aureus (Smith), and Staphylococcus aureus, Methicillin Resistant (ATCC 33591), In Vitro Bacteria Minimum inhibitory concentration (MIC) of sample on Staphylococcus aureus (Smith) and Staphylococcus aureus, Methicill in Resistant (ATCC 33591) was determined by the broth dilution method [Edwards J.R. et al. In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I. Antimicrobial Agents Chemotherapy. 33: pp. 215-222, 1989]. The test substance was dissolved (generally 100% DMSO) and serially diluted in solvent to desired stock concentrations. For each concentration tested, a 0.01 ml aliquot (1% DMSO final concentration) was added to a 48-well plate after which 0.99 ml of Mueller-Hinton Broth (DIFCO, USA.) with 1-5 x i05 CFU/ml of Staphylococcus aureus (Smith) or Staphylococcus aureus, Methicillin Resistant (ATCC 33591) was added. Thus, final maximal concentration of DMSO was 1% and the initial test substance concentration was 100 jig/mi or jiM. The plates were incubated at 37°C for 20 hours and then visually examined and scored positive (+) for inhibition of growth or turbidity or negative (-) for no effect upon growth or turbidity. Vehicle-control and active reference agents were used as blank and positive controls, respectively. Each concentration was evaluated in duplicate. The results are shown in Table 1.
Streptococcus pneumoniae (ATCC 6301) and Streptococcus pneumoniae (Erythromycin and Ampicillin Res. Clin. Isol.), In Vitro Bacteria Minimum inhibitory concentration (MIC) of sample on Streptococcus pneumoniae and Streptococcus pneurnoniae (Erythromycin and Amp ici 11 in Res. Clin. Isol.) was determined by the broth dilution method [Edwards J.R.
et al. In vitro antibacterial activity of SM-7338, a carbapenern antibiotic with stability to dehydropeptidase I. Antimicrobial Agents Chemotherapy. 33: pp. 215-222, 1989.]. The test substance was dissolved (generally 100% DMSO) and serially diluted in solvent to desired stock concentrations. For each concentration tested, a 0.Olml aliquot (1% DMSO final concentration) was added to a 48-well plate after which 0.99 ml of Tryptic Soy Broth (DIFCO, U. S. A.) containing 7% fetal bovine serum with 1-5 x i05 CFU/ml of Streptococcus pneurnoniae (ATCC 6301) or Streptococcus pneumoniae (Erythromycin and Ampicillin Res. Clin. Isol.) was added. Thus, final maximal concentration of DMSO was 1% and the initial test substance concentration was 100 jig/ml or 30 jiM. The plates were incubated at 37°C for 20 hours and then visually examined and scored positive (+) for inhibition of growth or turbidity or negative (-) for no effect upon growth or turbidity. Vehicle-control and active reference agents were used as blank -12-and positive controls, respectively. Each concentration was evaluated in duplicate. The results are shown in Table 1.
Table 1 Minimum inhibitory concentration (MIC) of Extract EX-l and single compound in anti-microbial test MIC (ig/m1) Sample SA (Smith) MRSA SF SF (EM & AM Res.) EX-1 0.3 1 30 30 P2-i >100 100 30 P2-2 > 100 30 30 P3-i 1 3 30 10 P3-2 0.3 0.3 10 10 P3-3 10 100 100 30 P3-4 3 100 30 10 Gentamicin 0.1 1 100 100 Ampicillin 0.1 30 0.01 3 SA (Smith): Stapkvlococcus aureus (Smith); MRSA: Staphylococcus aureus, Methicillin Resistant; SP: Streptococcus pneumoniae; SP (EM & AM Res.): Streptococcus pneumoniae, Erythromycin and Ampicillin resistant, clinical isolates.
It can be seen from Table 1 that compound P3-2 is very potent in inhibiting growth of SA (smith) and MRSA with MIC of both 0.3 pg/ml.
In contrast, MIC of Gentamicin on MRSA is 10 times to that on SA (Smith).
Compound P3-i shows potency in inhibiting growth on SA (Smith) and MRSA with MIC of 1 and 3pg/ml, respectively. Compound P3-i is -13 -relatively less potent in in inhibiting growth on SP and SP (EM & AM Res.) with MIC of 30 and 10 pg/m1, respectively.
Surprisingly, the Extract EX-1 of the present invention shows very strong inhibition on growth of SA and MRSA with MIC of 0.3 and 1 pg/ml, S respectively, in view of the contents of P3-2 and P3-i being respectively 3.65 wt% and 2.3 wt% therein. It is apparent that components contained in the extract EX-1 create a synergistic effect on inhibiting the growth of SA and MRSA, so that the extract EX-1 has very low MIC values on SA and MRSA.
Although the present invention has been described with reference to specific details of certain embodiments thereof, it is not intended that such details should be regarded as limitations upon the scope of the invention except as and to the extent that they are included in the accompanying claims. Many modifications and variations are possible in light of the
above disclosure. 14-4
Claims (20)
- Claims 1. Use of a compound having formula (I), or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating a subject having a bacterial infection:HO OH HO/\OH OH:T (I).
- 2. The use according to claim 1, wherein the bacteria are Gram-positive bacteria.
- 3. The use according to claim 1, wherein the bacteria are Staphylococcus aureus (Smith) or Streptococcus pneumoniae.
- 4. The use according to claim 3, wherein the bacteria are Staphylococcus aureus (Smith).
- 5. The use according to claim 4, wherein the bacteria are Staphylococcus aureus, Methicillin Resistant.
- 6. The use according to claim 3, wherein the bacteria are Streptococcus pneumoniae. -15-
- 7. The use according to claim 6, wherein the bacteria are Streptococcus pneumoniae, Erythromycin and Ampicillin Resistant.
- 8. Use of an extract prepared from root bark of Morus australis Poir. in the preparation of a medicament for treating a subject having a bacterial infection, wherein the extract is prepared by a process comprising the following steps: a) extracting root bark of Morus australis Poir. with a polar solvent; b) concentrating the resulting extract solution from step a); c) introducing the resulting concentrate from step b) to a reverse phase chromatography column, and eluting the column with a first eluent and a second eluent in sequence, said first eluent having a polarity of about 50 wt% of ethanol aqueous solution and said second eluent having a polarity of about 95 wt% of ethanol aqueous solution; and d) collecting a second eluate from the elution of the column with the second eluent, and removing the second eluent from the second eluate by evaporation.
- 9. The use according to claim 8, wherein the extract comprises the compound having the formula (I) as set forth in claim 1 and a compound having the following formula (II): HO OH (II). -16-
- 10. The use according to claim 9, wherein the extract comprises 1-5% of the compound (I) and 1-5% of the compound (II), based on the weight of the extract.
- 11. The use according to claim 10, wherein the extract comprises about 3.7% of the compound (I) and 2.3% of the compound (II), based on the weight of the extract
- 12. The use according to claim 8, wherein the first eluent is a 50 wt% ethanol aqueous solution and the second eluent is a 95 wt% ethanol aqueous solution.
- 13. The use according to claim 8, wherein the polar solvent in step a) is water or 95 wt% ethanol aqueous solution.
- 14. The use according to claim 13, wherein the polar solvent is 95 wt% ethanol aqueous solution.
- 15. The use according to claim 8, wherein the bacteria are Gram-positive bacteria.
- 16. The use according to claim 8, wherein the bacteria are Staphylococcus aureus (Smith) or Streptococcus pneumoniae.
- 17. The use according to claim 16, wherein the bacteria are Staphylococcus aureus (Smith).
- 18. The use according to claim 17, wherein the bacteria are Staphylococcus aureus, Methici ilin Resistant.
- 19. The use according to claim 16, wherein the bacteria are Streptococcus pneumoniae.
- 20. The use according to claim 19, wherein the bacteria are Streptococcus pneumoniae, Erythromycin and Ampicillin Resistant. -18-
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| JPS5843990A (en) * | 1981-09-09 | 1983-03-14 | Zenyaku Kogyo Kk | Kuwanon compound |
| JPS58150584A (en) * | 1982-03-03 | 1983-09-07 | Zenyaku Kogyo Kk | Kuwanon compound |
| JPS58150538A (en) * | 1982-03-03 | 1983-09-07 | Zenyaku Kogyo Kk | Kuwanon compound |
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| JPS5615297A (en) * | 1979-07-13 | 1981-02-14 | Takeda Chem Ind Ltd | Moracenin compound and its preparation |
| JPS56123979A (en) | 1980-03-04 | 1981-09-29 | Zenyaku Kogyo Kk | Novel 8-substituted cyclohexenylflavone derivative obtained from plant of genus morus |
| JPS57144223A (en) | 1981-03-04 | 1982-09-06 | Zenyaku Kogyo Kk | Mulberrofuran |
| JPH0523185A (en) * | 1991-07-16 | 1993-02-02 | Ichimaru Pharcos Co Ltd | Tyrosinase activity inhibitor |
| JPH107555A (en) * | 1996-06-17 | 1998-01-13 | Oji Paper Co Ltd | Antimicrobial agent |
| JP4143139B2 (en) * | 1996-10-04 | 2008-09-03 | 利博 山瀬 | Anti-PRSP drug |
| KR20020087225A (en) | 2001-05-14 | 2002-11-22 | (주)바이오케어 | Antibacterial agent for oral pathogens |
| JP2007022957A (en) * | 2005-07-15 | 2007-02-01 | Tsumura & Co | TGF-beta RECEPTOR ANTAGONIST |
| CN101148451A (en) | 2007-05-16 | 2008-03-26 | 好维股份有限公司 | Oral cavity medicament and oral cavity nursing article |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5843990A (en) * | 1981-09-09 | 1983-03-14 | Zenyaku Kogyo Kk | Kuwanon compound |
| JPS58150584A (en) * | 1982-03-03 | 1983-09-07 | Zenyaku Kogyo Kk | Kuwanon compound |
| JPS58150538A (en) * | 1982-03-03 | 1983-09-07 | Zenyaku Kogyo Kk | Kuwanon compound |
Non-Patent Citations (3)
| Title |
|---|
| Journal of Ethnopharmacology, vol 27, 1989, pages 285-295 * |
| Journal of Medicinal Plant Research, vol. 49, 1983, pages 90-94 * |
| Shoyakugaku-Zasshi, vol. 41(3), 1987, pages 215-225 * |
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| TWI378798B (en) | 2012-12-11 |
| FR2940614A1 (en) | 2010-07-02 |
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| GB2466527B (en) | 2011-03-23 |
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