KR20170057474A - Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound - Google Patents
Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound Download PDFInfo
- Publication number
- KR20170057474A KR20170057474A KR1020150160103A KR20150160103A KR20170057474A KR 20170057474 A KR20170057474 A KR 20170057474A KR 1020150160103 A KR1020150160103 A KR 1020150160103A KR 20150160103 A KR20150160103 A KR 20150160103A KR 20170057474 A KR20170057474 A KR 20170057474A
- Authority
- KR
- South Korea
- Prior art keywords
- glioblastoma
- ppd
- ginsenoside
- cells
- metastasis
- Prior art date
Links
- 208000005017 glioblastoma Diseases 0.000 title claims abstract description 100
- 206010027476 Metastases Diseases 0.000 title claims abstract description 37
- 230000009401 metastasis Effects 0.000 title claims abstract description 37
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 30
- 150000001875 compounds Chemical class 0.000 title claims description 17
- PYXFVCFISTUSOO-HKUCOEKDSA-N (20S)-protopanaxadiol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@H]([C@@](C)(O)CCC=C(C)C)[C@H]4[C@H](O)C[C@@H]3[C@]21C PYXFVCFISTUSOO-HKUCOEKDSA-N 0.000 claims abstract description 85
- PYXFVCFISTUSOO-UHFFFAOYSA-N betulafolienetriol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC(C(C)(O)CCC=C(C)C)C4C(O)CC3C21C PYXFVCFISTUSOO-UHFFFAOYSA-N 0.000 claims abstract description 85
- SWQINCWATANGKN-UHFFFAOYSA-N protopanaxadiol Natural products CC(CCC=C(C)C)C1CCC2(C)C1C(O)CC1C3(C)CCC(O)C(C)(C)C3CCC21C SWQINCWATANGKN-UHFFFAOYSA-N 0.000 claims abstract description 85
- 238000011282 treatment Methods 0.000 claims abstract description 26
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 24
- 230000021164 cell adhesion Effects 0.000 claims description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 5
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 3
- 230000001394 metastastic effect Effects 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- FVIZARNDLVOMSU-IRFFNABBSA-N ginsenoside C-K Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FVIZARNDLVOMSU-IRFFNABBSA-N 0.000 abstract description 48
- 229930182494 ginsenoside Natural products 0.000 abstract description 31
- 229940089161 ginsenoside Drugs 0.000 abstract description 30
- 235000013305 food Nutrition 0.000 abstract description 16
- 230000025164 anoikis Effects 0.000 abstract description 10
- 230000003013 cytotoxicity Effects 0.000 abstract description 9
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 9
- 230000005764 inhibitory process Effects 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 91
- 206010028980 Neoplasm Diseases 0.000 description 23
- 201000011510 cancer Diseases 0.000 description 18
- 230000000694 effects Effects 0.000 description 15
- 206010018338 Glioma Diseases 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 208000032612 Glial tumor Diseases 0.000 description 9
- 230000022131 cell cycle Effects 0.000 description 9
- 102000006311 Cyclin D1 Human genes 0.000 description 7
- 108010058546 Cyclin D1 Proteins 0.000 description 7
- 230000003833 cell viability Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 241000208340 Araliaceae Species 0.000 description 6
- 208000003174 Brain Neoplasms Diseases 0.000 description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 6
- 235000003140 Panax quinquefolius Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 235000008434 ginseng Nutrition 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 5
- 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 235000009508 confectionery Nutrition 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229960004964 temozolomide Drugs 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- SWIROVJVGRGSPO-UHFFFAOYSA-N Ginsenoside F2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O SWIROVJVGRGSPO-UHFFFAOYSA-N 0.000 description 3
- AVTXSAWPGCSYFO-UHFFFAOYSA-N Ginsenoside Ia Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O AVTXSAWPGCSYFO-UHFFFAOYSA-N 0.000 description 3
- 235000002789 Panax ginseng Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000013376 functional food Nutrition 0.000 description 3
- SWIROVJVGRGSPO-JBVRGBGGSA-N ginsenoside F2 Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SWIROVJVGRGSPO-JBVRGBGGSA-N 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 235000012149 noodles Nutrition 0.000 description 3
- 235000015277 pork Nutrition 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 235000021067 refined food Nutrition 0.000 description 3
- 230000022983 regulation of cell cycle Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000036962 time dependent Effects 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 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 2
- 244000144730 Amygdalus persica Species 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-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
- 241000287828 Gallus gallus Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 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
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 235000006040 Prunus persica var persica Nutrition 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 235000015278 beef Nutrition 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- -1 olive oil Chemical compound 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 235000013324 preserved food Nutrition 0.000 description 2
- 238000000751 protein extraction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- 244000099147 Ananas comosus Species 0.000 description 1
- 235000007119 Ananas comosus Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241001149724 Cololabis adocetus Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241001137251 Corvidae Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 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
- FEWJPZIEWOKRBE-LWMBPPNESA-M D-tartrate(1-) Chemical compound OC(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-M 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 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
- 102100027270 Etoposide-induced protein 2.4 homolog Human genes 0.000 description 1
- 239000004606 Fillers/Extenders Substances 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
- 241000282412 Homo Species 0.000 description 1
- 101001057564 Homo sapiens Etoposide-induced protein 2.4 homolog Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 244000070406 Malus silvestris Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000269821 Scombridae Species 0.000 description 1
- 239000004288 Sodium dehydroacetate Substances 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 244000299461 Theobroma cacao 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
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 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
- 235000015895 biscuits Nutrition 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000008393 encapsulating agent Substances 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
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 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
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- 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 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000019990 fruit wine Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 208000029824 high grade glioma Diseases 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 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
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000020640 mackerel Nutrition 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000011614 malignant glioma Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 208000022084 motor paralysis Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000023578 negative regulation of cell adhesion Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 235000015108 pies Nutrition 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 229940050271 potassium alum Drugs 0.000 description 1
- GNHOJBNSNUXZQA-UHFFFAOYSA-J potassium aluminium sulfate dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GNHOJBNSNUXZQA-UHFFFAOYSA-J 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019992 sake Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020083 shōchū Nutrition 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- JBQYATWDVHIOAR-UHFFFAOYSA-N tellanylidenegermanium Chemical compound [Te]=[Ge] JBQYATWDVHIOAR-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000015041 whisky Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- 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
- A23V2250/60—Sugars, e.g. mono-, di-, tri-, tetra-saccharides
-
- 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
The present invention relates to a pharmaceutical composition for inhibiting a glioblastoma metastasis and a food composition for inhibiting a glioblastoma metastasis, which comprises PPD (protopanaxadiol) or Compound-K, which is a kind of paraxaxidol ginsenoside, as an active ingredient. The ginsenoside CK or PPD provided by the present invention inhibits the adherence of glioblastoma cells to induce anoikis, as well as exhibits cytotoxicity against glioblastoma cells, so that treatment of glioblastoma and inhibition of metastasis are simultaneously carried out And thus may be widely used to effectively treat patients with glioblastoma.
Description
The present invention relates to a pharmaceutical composition for inhibiting metastasis through treatment of a glioblastoma and a cell adhesion inhibitor comprising a panaxadius diol ginsenoside compound. More specifically, the present invention relates to a pharmaceutical composition for inhibiting metastasis by inhibiting PPD (protopanaxadiol) or Compound-K as an active ingredient, and a food composition for inhibiting the transplantation of a glioblastoma.
Cancer is one of the most common causes of death worldwide. Approximately 10 million new cases occur each year, accounting for approximately 12% of all deaths and the third leading cause of death. Among various types of cancer, brain cancer, especially in children, occurs more frequently than other cancers. Brain cancer is distinguished from primary brain tumors that develop in the brain tissue and brain membranes surrounding the brain and secondary brain tumors that migrate from the skull or other parts of the body to the brain. Symptoms include motor paralysis, perception, paralysis, , Equilibrium disorder, and cranial hypertensive symptoms. The brain cancer includes various types of cancer such as polymorphic glioblastoma, malignant glioma, lymphadenoma, blastomastoid, metastatic tumor and the like, unlike cancer that is developed in other tissues in which one or two kinds of cancer are tissue-specific Among them, glioma, especially glioblastoma, is the most malignant and aggressive disease with a very poor prognosis and a very fatal disease with an average survival of less than 1 year after diagnosis. It is known that it is almost impossible to completely remove the cancer tissue surgically since the boundary between the brain cell and the tumor cell is not clear in the patient with the above-mentioned glioblastoma. Thus, in order to develop a method for treating the glioblastoma, various studies have been conducted, and as a result, temozolomide (TMZ) has been developed.
The above-mentioned temozolomide is a type of alkylating agent that damages DNA of a glioblastoma cell and exhibits an anticancer effect. Recently, a method of using a surgical operation and a treatment with temozolomide has been used to treat glioblastoma. However, since the glioblastoma includes various genetic mutations, the median survival rate of the glioblastoma patients is remarkably low even now, and the development of a new therapeutic agent is required. Research on the development of a new glioblastoma therapeutic agent is actively pursuing this need. For example, International Patent Publication No. 2012-061120 discloses a method of treating glioblastoma using purified glioblastoma GBM6-AD stem cells, and International Patent Publication No. 2012-104822 discloses a method of treating glioblastoma A method of treating a glioblastoma is disclosed.
On the other hand, the glioblastoma is known to have a high incidence of metastasis. Because cancer metastasis is multiple, systemic and difficult to determine whether it is present, treatment efficacy is not satisfactory with current cancer treatment methods. However, cancer metastasis is an inefficient process in which only a small fraction of the cancer cells that make up the primary tumor successfully complete several stages of the metastatic process and become metastatic cancer. Therefore, it is possible to develop a useful treatment method that can effectively control death by cancer metastasis by understanding the transition process, developing a clinically and biologically useful therapeutic target, and effectively inhibiting it. For example, Korean Patent Registration No. 1213033 discloses a method for diagnosing cancer metastasis by measuring EI24 protein levels, Korean Patent Publication No. 2009-0084149 discloses a pharmaceutical composition comprising caffeine and / A method for inhibiting the invasion, metastasis and proliferation of brain cancer using the same. However, a method for inhibiting the progression of glioblastoma has not yet been reported.
Under these circumstances, the present inventors have made extensive efforts to develop a method for inhibiting the progression of glioblastoma. As a result, PPD or a compound-K (CK), a kind of PPD (protopanaxadiol) To inhibit metastasis, thus completing the present invention.
It is an object of the present invention to provide a pharmaceutical composition for inhibiting metastasis through treatment of glioblastoma and inhibition of cell adhesion comprising a PPD-type ginsenoside as an active ingredient.
Another object of the present invention is to provide a food composition for inhibiting the transplantation of glioblastoma which comprises a PPD-type ginsenoside compound as an active ingredient.
The present inventors paid attention to anoikis while carrying out various studies to develop a method for inhibiting the progression of glioblastoma. Normally, when cancer cells of solid cancer do not contact the surrounding tissues and cells, apoptosis is induced. This phenomenon is known as Anoikis. However, when the cancer cells are transferred, resistance to anoikis is acquired. Therefore, an agent that induces anoikis against the cancer cells can exhibit an effect of inhibiting cancer cell metastasis. While searching for an agent capable of inducing anoikis in glioblastomas, attention was paid to PPD (protopanaxadiol) -ginsenoside compounds. The PPD-type ginsenoside compound is a kind of ginsenoside compound contained in ginseng or red ginseng, and it was examined whether the PPD-type ginsenoside compound can induce anoikis in glioblastoma. As a result, since ginsenoside CK or PPD not only inhibits cell adhesion but also exhibits cytotoxicity upon culturing glioma cells corresponding to solid tumors, the ginsenoside CK or PPD not only treats glioblastoma, It can be used as an agent for inhibiting the metastasis of glioblastoma by inducing kissing.
Therefore, the ginsenoside PPD or CK can be used as an active ingredient of a pharmaceutical composition capable of simultaneously exhibiting a therapeutic effect and a transplantation-inhibiting effect of a glioblastoma, and PPD or CK capable of simultaneously treating the glioblastoma and inhibiting the metastasis Has not been known at all and has been first identified by the present inventors.
In order to achieve the above object, the present invention provides, as one embodiment, a pharmaceutical composition for treating a glioblastoma and inhibiting metastasis, which comprises PPD (protopanaxadiol), Compound-K or a combination thereof as an active ingredient.
The term "PPD (protopanaxadiol) " of the present invention means a compound represented by the formula C 30 H 52 O 3 , having a molecular weight of about 460 Da and having a structure of the following formula (1) separated from ginseng.
In the present invention, the PPD can be used as an active ingredient of a pharmaceutical composition for inhibiting glioma-type metastasis which induces aniosis of a glioblastoma. The concentration at which the PPD can be used as an active ingredient of a pharmaceutical composition for inhibiting metastatic tumor metastasis is As long as it is capable of inhibiting cell adhesion of the glioblastoma, for example, it may be a treatment concentration of 10 to 50 μg / ml, and as another example, it may be a treatment concentration of 20 to 40 μg / ml And, as another example, a treatment concentration of 40 μg / ml.
The term "compound-K (CK)" of the present invention means that saponins such as ginsenosides Rb1, Rb2, Rc and Rd present in ginseng or red ginseng are not present in ginseng itself A ginsenoside compound represented by the formula C 36 H 62 O 8 and having a molecular weight of about 622 Da and having a structure represented by the following formula 2: ≪ / RTI >
In the present invention, the CK can be used as an effective component of a pharmaceutical composition for inhibiting glioma-type metastasis which induces aniosis of a glioblastoma. The concentration at which CK can be used as an active ingredient of a pharmaceutical composition for inhibiting metastatic tumor metastasis is As long as it is capable of inhibiting cell adhesion of the glioblastoma, for example, it may be a treatment concentration of 10 to 50 μg / ml, and as another example, it may be a treatment concentration of 20 to 40 μg / ml And, as another example, a treatment concentration of 30 μg / ml.
The term "PPD (protopanaxadiol) ginsenoside compound" of the present invention means a ginsenoside compound having a chemical structure similar to PPD.
In the present invention, the PPD-type ginsenoside compound can be interpreted as a compound that inhibits the cell adhesion of glioblastoma by inducing anoikis of the glioblastoma, thereby inhibiting the metastasis of the glioblastoma. The PPD of Formula 1, the CK of Formula 2, and the like. The PPD-derived ginsenoside compounds may be those extracted from ginseng, red ginseng or the like, or chemically synthesized ones.
According to one embodiment of the present invention, gliosinocyte CK or PPD is treated on a glioblastoma cell that forms a cell aggregate upon culturing, and the phenomenon caused thereby is analyzed. As a result, the cell aggregate is disassembled and decomposed into individual cells (Fig. 1), the expression levels of N-carderine, integrin [beta] l, phosphorylated FAK and FAK involved in cell adhesion decreased (Fig. 2) and the number of cell cycles stopped in the G0 / G1 state was significantly increased (FIG. 3a), and the expression level of cyclin D1, which converts the G1 state to the S state in the cell cycle, is decreased (FIG. 3b).
As such, since ginsenoside CK or PPD exhibits an effect of inhibiting cell adhesion upon culturing glioma cells corresponding to solid tumors, the ginsenoside CK or PPD induces anoikis to inhibit the progression of glioblastoma It could be used as a preparation.
According to another embodiment of the present invention, the cultured human glioblastoma cell line U251 was treated with various concentrations of ginsenoside CK, PPD or F2 and the cell viability was evaluated. As a result, the concentration of ginsenoside CK or PPD Dependent (Fig. 4a) and time-dependent (Fig. 4b) cytotoxicity.
As such, since ginsenoside CK or PPD exhibits concentration-dependent and time-dependent cytotoxicity against glioblastoma cells corresponding to solid tumors, it can be seen that the ginsenoside CK or PPD can be used as a preparation for treating glioblastoma I could.
Taken together, the above-mentioned ginsenoside CK or PPD can not only inhibit the metastasis of the glioblastoma but also exhibit the effect of treating the glioblastoma, so that the ginsenoside CK or PPD can be used as a preparation for treating a glioblastoma patient comprehensively And it was found.
The composition of the present invention may be prepared in the form of a pharmaceutical composition for the inhibition of glioblastoma metastasis further comprising an appropriate carrier, excipient or diluent conventionally used in the production of a pharmaceutical composition, non-naturally occuring carrier. Specifically, the pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method . In the present invention, the carrier, excipient and diluent which may be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate , Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension, liquid solutions, emulsions and syrups have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
The content of the PPD or CK contained in the pharmaceutical composition of the present invention is not particularly limited, but may be included in an amount of 0.0001 to 50% by weight, and as another example, 0.01 to 10% by weight based on the total weight of the final composition have.
The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount " of the present invention means a therapeutic or prophylactic treatment of a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention And the effective dose level refers to the level of the disease to be treated, the severity of the disease, the activity of the drug, the age, body weight, health, sex, sensitivity of the patient to the drug, Duration, duration of administration, factors involved in combination with or contemporaneously with the composition of the present invention, and other factors well known in the medical arts. The pharmaceutical composition of the present invention may be administered alone or in combination with a known agent for inhibiting cancer metastasis. It is important to take into account all of the above factors and administer an amount that will achieve the maximum effect in the least amount without side effects.
The dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction to the disease, the age, body weight, sex, history, or kind of the substance used as the active ingredient. For example, the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 100 mg / kg, preferably 1 ng to about 10 mg / kg, per adult, and the frequency of administration of the composition of the present invention is particularly It is not limited, but it can be administered once a day or divided into several doses. The dose is not intended to limit the scope of the invention in any way.
In another aspect, the present invention provides a method for treating and inhibiting the progression of glioblastoma comprising administering the pharmaceutical composition to a subject suffering from a glioblastoma in a pharmaceutically effective amount.
The term "individual" of the present invention can include, without limitation, mammals, including fish, rats, livestock, humans, and the like, which are capable of developing a glioblastoma or have an onset.
The administration route of the pharmaceutical composition for inhibiting the transbronchial metastasis of the present invention can be administered through any common route as long as it can reach the target tissue. The pharmaceutical composition of the present invention is not particularly limited, but may be administered by intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, rectal administration and the like ≪ / RTI > However, since the PPD or C-K may be denatured by gastric acid upon oral administration, the oral composition may be formulated so as to coat the active agent or protect it from decomposition at the top. In addition, the composition may be administered by any device capable of transferring the active agent to the target cell.
The present invention provides, in yet another aspect, a food composition for improving glioblastoma and inhibiting metastasis comprising PPD or C-K.
Since PPD or CK, which is an active ingredient of the pharmaceutical composition for inhibiting the glioblastoma metastasis, is derived from a natural herb that has been heretofore used as a medicinal herb such as medicinal natural product ginseng and has proven its safety, the PPD or CK is a common, Can be prepared and ingested in the form of a food which can be improved and metastasis inhibited.
At this time, the content of the PPD or C-K contained in the food is not particularly limited, but may be in the range of 0.001 to 50% by weight, more preferably 0.1 to 10% by weight based on the total weight of the food composition. When the food is a beverage, it may be contained in a proportion of 1 to 10 g, preferably 2 to 7 g based on 100 ml. In addition, the composition may contain additional ingredients which are commonly used in food compositions and which can improve odor, taste, vision and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid and the like. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn) and copper (Cu) It may also include amino acids such as lysine, tryptophan, cysteine, valine, and the like. In addition, it is also possible to use antiseptics (such as potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate), disinfectants (such as bleaching powder and highly bleached white powder, sodium hypochlorite), antioxidants (butylhydroxyanilide (BHA), butylhydroxytoluene BHT), etc.), coloring agents (such as tar pigments), coloring agents (such as sodium nitrite and sodium acetic acid), bleaching agents (sodium sulfite), seasoning (such as MSG sodium glutamate), sweeteners (such as hypoglycemia, , Food additives such as flavorings (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen D-tartrate), emulsifiers, emulsifiers, thickeners, encapsulating agents, gum bases, foam inhibitors, ) Can be added. The additives are selected according to the type of food and used in an appropriate amount.
On the other hand, a health functional food for improving glioblastoma and inhibiting metastasis can be prepared using the PPD or C-K-containing glycombastoma improving and transfer inhibiting food composition.
As a specific example, the food composition can be used to produce a processed food which can improve the glioblastoma and inhibit metastasis. Examples of the processed food include confectionery, beverage, liquor, fermented food, canned food, Can be manufactured as a health functional food in the form of processed noodles. The sweets include biscuits, pies, cakes, breads, candies, jellies, gums, cereals (including dinner utensils such as cereal flakes). Drinks include drinking water, carbonated beverages, functional ionic beverages, juices (such as apples, pears, grapes, aloes, citrus fruits, peaches, carrots, tomato juices, etc.) and sikhye. The mainstream includes sake, whiskey, shochu, beer, liquor, and fruit wine. Fermented foods include soy sauce, miso, and kochujang. Canned products include canned goods (eg, tuna, mackerel, saury, canned fish, etc.), canned products (beef, pork, chicken, turkey canned food, etc.) and canned products (corn, peach and canned pineapple). Milk processed foods include cheese, butter, yogurt and the like. Meat-processed foods include pork cutlet, beef cutlet, chicken cutlet, sausage. Sweet and sour pork, nuggets, and nubani. And noodles such as sealed packaging raw noodles. In addition, the composition may be used in retort food, soup and the like.
The term "functional food " of the present invention refers to a food for special health use (FoSHU) The food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, and circles to obtain a beneficial effect on improvement of glioblastoma and inhibition of metastasis.
The ginsenoside CK or PPD provided by the present invention inhibits the adherence of glioblastoma cells to induce anoikis, as well as exhibits cytotoxicity against glioblastoma cells, so that treatment of glioblastoma and inhibition of metastasis are simultaneously carried out And thus may be widely used to effectively treat patients with glioblastoma.
1 is a photomicrograph showing the effect of ginsenoside affecting the culture of glioma cells.
Fig. 2 is a graph showing the results of analysis of four proteins involved in cell adhesion according to the treatment time of ginsenoside in ginsenoside CK treated with 30 μg / ml of ginsenoside CK or 40 μg / ml of ginsenoside PPD Western blot analysis image showing the result of analysis of the expression level change.
FIG. 3A is a graph showing the results of classification according to cell cycle in gingenocide CK, PPD or F2-treated glioblastoma cells at 30 占 퐂 / ml.
FIG. 3B shows the expression of cyclin D1 involved in the cell cycle regulation of the ginsenoside-treated glioblastoma cells treated with 30 μg / ml of ginsenoside CK or 40 μg / ml of ginsenoside PPD This is a western blot analysis showing the result of analyzing the level change.
4A is a graph showing changes in cell survival rate of glioblastoma cells according to treatment concentrations of ginsenoside CK, PPD or F2.
4B is a graph showing changes in cell viability of glioblastoma cells with the treatment time of ginsenoside CK, PPD or F2.
Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
Example 1: for adhesion of glioblastoma cells Gin Senocide C-K or PPD Effect of
Human glioblastoma cell line U251 was inoculated into a 12-well plate containing DMEM medium containing 10% FBS and 1% penicillin / streptomycin at a concentration of 150,000 cells / well, cultured at 5% CO 2 and 37 ° C, Glioblastoma cells were obtained. The U251 glioblastoma cells obtained above were cultured for 24 hours using a medium containing 30 or 40 ㎍ / ml of ginsenoside CK or PPD. Next, the cultured conditions of each of the cultured glioma cells under a microscope were compared with the culture conditions of the U251 glioblastoma cells of the control group in which the ginsenosides were not treated (Fig. 1). At this time, the control group used cultured glioblastoma cells treated with DMSO (Fig. 1).
1 is a photomicrograph showing the effect of ginsenoside affecting the culture of glioma cells. As shown in FIG. 1, the glioblastoma cells of the control group formed cell aggregates due to strong binding between cells as is commonly known, but when the cells were treated with ginsenoside C-K or PPD, cell aggregates were disassembled. Particularly, when the ginsenoside C-K of 30 占 퐂 / ml or the ginsenoside PPD of 40 占 퐂 / ml was treated, the cell aggregates were completely disassembled and individual cells were maintained.
Therefore, it was found that the ginsenoside C-K or PPD had an effect of inhibiting the adhesion of the glioma cell line.
Example 2: Effect of ginsenoside C-K or PPD on the expression level of cell adhesion protein
From the results of Example 1, it was confirmed that ginsenoside CK or PPD inhibits the adhesion of glioblastoma cells. Therefore, it was confirmed that the ginsenoside CK or PPD is a kind of protein involved in cell adhesion, β1 and FAK (Focal Adhesion Kinase) expression level of the cells.
That is, according to the method of Example 1, cultured human glioblastoma cell line U251 was treated with 30 μg / ml of ginsenoside CK or 40 μg / ml of ginsenoside PPD, and cultured for 6, 12 and 24 hours And each cell was obtained. The obtained cells were treated with an M-PER mammalian protein extraction reagent containing a 10% protease inhibitor and a 2% dephosphorylase inhibitor to obtain respective cell lysates, and each cell lysate thus obtained was subjected to western blot analysis Respectively. At this time, the expression levels of the four proteins involved in cell adhesion were evaluated by using anti-N-carderine antibody, anti-integrin? 1 antibody, anti-phosphorylated FAK antibody or anti-FAK antibody as primary antibodies The effect of senoside CK or PPD was confirmed (Fig. 2). At this time, GAPDH was used as an internal control group.
Fig. 2 is a graph showing the results of analysis of four proteins involved in cell adhesion according to the treatment time of ginsenoside in ginsenoside CK treated with 30 μg / ml of ginsenoside CK or 40 μg / ml of ginsenoside PPD Western blot analysis image showing the result of analysis of the expression level change. As shown in FIG. 2, it was confirmed that the expression levels of all four proteins involved in cell adhesion expressed in glioblastoma cells were reduced by treatment with ginsenoside C-K or PPD.
Example 3: Effect of ginsenoside C-K or PPD on cell cycle
Generally, when cell aggregates are formed upon cell culture, it is known that when cell aggregation is inhibited, the cell cycle is terminated. Therefore, according to the results obtained in Example 1, ginsenoside CK or PPD is formed into glioblastoma cells To stop the cell cycle of the cells.
That is, according to the method of Example 1, cultured human glioblastoma cell line U251 was treated with 30 μg / ml of ginsenoside C-K, PPD or F2, and cultured for 18 hours to obtain respective cultures. The obtained culture was treated with trypsin to separate each cell, and the separated cells were washed with PBS, and each cell was recovered. Then, the recovered cells were treated with 70% ethanol at 4 DEG C for 30 minutes to fix the recovered cells. The fixed cells were centrifuged at 1200 RPM for 5 minutes to obtain the precipitated length, and the obtained cells were washed with PBS. 50 μl of 100 μg / ml RNAse A solution was added to each of the washed cells, and 200 μl of a 50 μg / ml PI solution was added to each of the cells to stain the cells. The stained cells were flowed at a flow rate of 400 events / sec and analyzed by flow cytometry. At this time, as a control group, glioblastoma cells cultured without treatment with ginsenoside were used.
FIG. 3A is a graph showing the results of classification according to cell cycle in gingenoside C-K, PPD or F2-treated glioblastoma cells at 30 占 퐂 / ml. As shown in FIG. 3A, when ginsenoside F2 was treated, there was no significant difference from the control group. However, when ginsenoside CK or PPD was treated, the number of cells suspended in G0 / G1 state was significantly Respectively.
Thus, it was found that ginsenoside CK or PPD induced cell cycle arrest in G0 / G1 state in glioblastoma cells.
On the other hand, it is known that cyclin D1 promotes the conversion of the G1 state to the S state in the cell cycle, so that the effect of the ginsenoside C-K or PPD on the expression of cyclin D1 was examined.
That is, according to the method of Example 1, cultured human glioblastoma cell line U251 was treated with 30 μg / ml of ginsenoside CK or 40 μg / ml of ginsenoside PPD, and cultured for 6, 12 and 24 hours And each cell was obtained. The obtained cells were treated with an M-PER mammalian protein extraction reagent containing a 10% protease inhibitor and a 2% dephosphorylase inhibitor to obtain respective cell lysates, and each cell lysate thus obtained was subjected to western blot analysis Respectively. At this time, anti-cyclin D1 antibody was used as a primary antibody, and the effect of ginsenoside C-K or PPD on the expression level of cyclin D1 protein involved in the regulation of the cell cycle was confirmed (FIG. 3B). At this time, GAPDH was used as an internal control group.
FIG. 3B shows the expression of cyclin D1 involved in the cell cycle regulation of the ginsenoside-treated glioblastoma cells treated with 30 μg / ml of ginsenoside CK or 40 μg / ml of ginsenoside PPD This is a western blot analysis showing the result of analyzing the level change. As shown in FIG. 3B, it was confirmed that the level of cyclin D1 involved in cell cycle regulation expressed in glioblastoma cells was decreased by treatment with ginsenoside C-K or PPD.
Example 4 Cytotoxicity of Ginsenoside C-K or PPD on Glioblastoma Cells
It was confirmed whether the ginsenoside C-K or PPD used in the present invention exhibited cytotoxicity to glioblastoma cells.
First, cultured human glioblastoma cell line U251 was treated with ginsenoside CK, PPD or F2 at various concentrations (0, 10, 20, 30, 40 or 50 占 퐂 / ml), cultured for 24 hours, Lt; / RTI > cells. Ez-cytox solution was added to each of the cells obtained above, reacted for 2 hours, absorbance was measured at 450 nm, and cell viability was calculated using the measured absorbance (FIG. 4A). At this time, cultured glioblastoma cells treated with DMSO were used as a control group.
4A is a graph showing changes in cell survival rate of glioblastoma cells according to treatment concentrations of ginsenoside C-K, PPD or F2. As shown in FIG. 4A, ginsenoside F2 did not significantly affect cell viability at a level similar to that of the control group. However, it was confirmed that ginsenoside C-K or PPD increased cytotoxicity in a concentration-dependent manner and the cell survival rate was decreased. In particular, it was confirmed that the IC50 value of ginsenoside C-K was 30 占 퐂 / ml, and the IC50 value of ginsenoside PPD was 35 占 퐂 / ml.
Next, the cultured human glioblastoma cell line U251 was treated with 40 占 퐂 / ml of ginsenoside CK, PPD or F2, and cultured for 3, 6, 9, 12, 15, 18, 21 or 24 hours, Cultured cells were obtained. Ez-cytox solution was added to each of the cells obtained above, reacted for 2 hours, absorbance was measured at 450 nm, and cell viability was calculated using the measured absorbance (FIG. 4B). At this time, cultured glioblastoma cells treated with DMSO were used as a control group.
4B is a graph showing changes in cell viability of glioblastoma cells according to the treatment time of ginsenoside C-K, PPD or F2. As shown in FIG. 4B, cells treated with ginsenoside F2 did not show cell survival rate of 50% or less even after 24 hours, whereas cells treated with ginsenoside CK showed cell survival after 3 hours And that the cells treated with ginsenoside PPD showed a relatively gradual decrease in cell viability.
Thus, it was found that ginsenoside C-K or PPD exhibited concentration-dependent or time-dependent cytotoxicity on glioblastoma cells.
Claims (7)
Wherein the PPD is a compound having the structure of Formula 1:
[Chemical Formula 1]
Wherein the compound-K is a compound having the structure of Formula 2:
(2)
Wherein said pharmaceutical composition inhibits cell adhesion of a glioblastoma and inhibits metastatic metastasis.
Wherein said pharmaceutical composition is cytotoxic to cells of a glioblastoma, thereby treating the glioblastoma.
Wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150160103A KR20170057474A (en) | 2015-11-16 | 2015-11-16 | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150160103A KR20170057474A (en) | 2015-11-16 | 2015-11-16 | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020170114728A Division KR101787954B1 (en) | 2017-09-07 | 2017-09-07 | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20170057474A true KR20170057474A (en) | 2017-05-25 |
Family
ID=59050710
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150160103A KR20170057474A (en) | 2015-11-16 | 2015-11-16 | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20170057474A (en) |
-
2015
- 2015-11-16 KR KR1020150160103A patent/KR20170057474A/en active Application Filing
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3159353A1 (en) | Cyclic dipeptide-containing composition | |
| KR101683635B1 (en) | Pharmaceutical composition for treating cancer comprising lactate metallic salts | |
| KR20170064486A (en) | Lipid nanoparticle complex containing curcumin comprising ginsenosides | |
| KR102054597B1 (en) | Composition for Improvement of Exercise Performance Using an Extract of Ishige okamurae | |
| KR101722547B1 (en) | Anti-cancer adjuvant comprising panaxadiols compound | |
| JP2019031527A (en) | Pharmaceutical composition for preventing or treating gleevec-resistant leukemia containing ginsenoside f1 or ginsenoside rg3 as an active ingredient | |
| KR101787954B1 (en) | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound | |
| KR20160144608A (en) | Anti obesity composition consisting of lactobionic acid as an efficient component | |
| JP2009114111A (en) | Calcium absorption promoter | |
| JP5144000B2 (en) | Composition for inhibiting transforming growth factor β | |
| WO2020262703A1 (en) | Hepatic fibrosis-inhibiting agent and brown fat cell-activating agent containing taxifolin | |
| KR102102267B1 (en) | Pharmaceutical and fool composition comprising lactic acid bacteria complex and N-acetylglucosamin as an active ingredient for preventing or treating skin moisturizing, osteoporosis | |
| KR20170057474A (en) | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound | |
| JP7231313B2 (en) | Composition for lowering blood pressure | |
| KR101909885B1 (en) | Composition for Improving Meningioma Using a Salidroside and Betulin | |
| KR101392345B1 (en) | Pharmaceutical composition for anticancer comprising extract of Lysimachia foenum-graecum as effective component | |
| KR101513336B1 (en) | Pharmaceutical composition for preventing or treating lung cancer comprising Bifidobacterim spp. probiotics or extract thereof | |
| KR101839186B1 (en) | Use of Aplysia kurodai extract having retinal cell regeneration effect | |
| WO2023249075A1 (en) | Prophylactic or therapeutic agent for non-alcoholic steatohepatitis-derived hepatocarcinoma | |
| KR20160084003A (en) | Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract | |
| KR101556444B1 (en) | Composition for immunosuppressing comprising alcohol extract of chinese pepper or fraction thereof | |
| KR102197296B1 (en) | Pharmaceutical composition for preventing or treating lung cancer comprising extract of Schoenoplectus triqueter | |
| JP2012067041A (en) | Ace activity inhibitor | |
| KR102058323B1 (en) | Composition for preventing, improving or treating of prostate cancer comprising resveratrol derivatives | |
| KR102052189B1 (en) | Composition for Lowering Blood Pressure Using Protamex Hydrolysates of Hippocampus abdominalis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| A107 | Divisional application of patent |