KR20200087500A - Composition for preventing, improving or treating of bladder cancer comprising lauric acid derivatives - Google Patents
Composition for preventing, improving or treating of bladder cancer comprising lauric acid derivatives Download PDFInfo
- Publication number
- KR20200087500A KR20200087500A KR1020190003856A KR20190003856A KR20200087500A KR 20200087500 A KR20200087500 A KR 20200087500A KR 1020190003856 A KR1020190003856 A KR 1020190003856A KR 20190003856 A KR20190003856 A KR 20190003856A KR 20200087500 A KR20200087500 A KR 20200087500A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- bladder cancer
- compound
- compound represented
- scheme
- Prior art date
Links
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 title claims abstract description 54
- 206010005003 Bladder cancer Diseases 0.000 title claims abstract description 53
- 201000005112 urinary bladder cancer Diseases 0.000 title claims abstract description 53
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims description 25
- 235000013376 functional food Nutrition 0.000 claims description 21
- 230000036541 health Effects 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 235000013402 health food Nutrition 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000005639 Lauric acid Substances 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- SGOBDAHMSJUKGA-UHFFFAOYSA-N C(C(C)C)C1=CC=C(C=C1)C(C(=O)OC(CCCCCCCCCCC)=O)C Chemical compound C(C(C)C)C1=CC=C(C=C1)C(C(=O)OC(CCCCCCCCCCC)=O)C SGOBDAHMSJUKGA-UHFFFAOYSA-N 0.000 claims description 6
- FXBVRACVNAPVHP-UHFFFAOYSA-N C(CCCCCCCCCCC)(=O)OC(C1=C(C=CC=C1)OC(C)=O)=O Chemical compound C(CCCCCCCCCCC)(=O)OC(C1=C(C=CC=C1)OC(C)=O)=O FXBVRACVNAPVHP-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- PPKFEYXLUVGNBH-XAHDOWKMSA-N C1=CC(OC(=O)CCCCCCCCCCC)=CC=C1\C=C\C1=CC(OC(=O)CCCCCCCCCCC)=CC(OC(=O)CCCCCCCCCCC)=C1 Chemical compound C1=CC(OC(=O)CCCCCCCCCCC)=CC=C1\C=C\C1=CC(OC(=O)CCCCCCCCCCC)=CC(OC(=O)CCCCCCCCCCC)=C1 PPKFEYXLUVGNBH-XAHDOWKMSA-N 0.000 claims description 5
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 5
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 5
- 235000021283 resveratrol Nutrition 0.000 claims description 5
- 229940016667 resveratrol Drugs 0.000 claims description 5
- JUKHAHUHDUSVMM-UHFFFAOYSA-N 2-(4-acetamidophenyl)dodecanoic acid Chemical compound CCCCCCCCCCC(C1=CC=C(C=C1)NC(=O)C)C(=O)O JUKHAHUHDUSVMM-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- LJDLHYSMJRSCKH-WCWDXBQESA-N [3-dodecanoyloxy-5-[(e)-2-(4-hydroxyphenyl)ethenyl]phenyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC1=CC(OC(=O)CCCCCCCCCCC)=CC(\C=C\C=2C=CC(O)=CC=2)=C1 LJDLHYSMJRSCKH-WCWDXBQESA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 229940125782 compound 2 Drugs 0.000 claims description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 16
- 239000000126 substance Substances 0.000 abstract description 11
- 210000004027 cell Anatomy 0.000 description 44
- -1 lauric acid derivative compound Chemical class 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 17
- 230000030833 cell death Effects 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 235000013305 food Nutrition 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 235000013361 beverage Nutrition 0.000 description 5
- 235000013365 dairy product Nutrition 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 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 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000004121 Annexin A5 Human genes 0.000 description 3
- 108090000672 Annexin A5 Proteins 0.000 description 3
- 241001481710 Cerambycidae Species 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 240000005979 Hordeum vulgare Species 0.000 description 3
- 235000007340 Hordeum vulgare Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 244000299461 Theobroma cacao Species 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000005584 early death Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 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
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 235000004347 Perilla Nutrition 0.000 description 2
- 244000124853 Perilla frutescens Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 235000007215 black sesame Nutrition 0.000 description 2
- 235000021329 brown rice Nutrition 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940041476 lactose 100 mg Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229940083542 sodium Drugs 0.000 description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
- 238000010186 staining Methods 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
- 230000002194 synthesizing effect Effects 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010005052 Bladder irritation Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- YICAMJWHIUMFDI-UHFFFAOYSA-N CC(Nc1ccc(C)cc1)=O Chemical compound CC(Nc1ccc(C)cc1)=O YICAMJWHIUMFDI-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241001107116 Castanospermum australe Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-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
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 238000002965 ELISA Methods 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
- 239000001512 FEMA 4601 Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process 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
- 235000021279 black bean Nutrition 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940037769 calcium carbonate 100 mg Drugs 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 229950010286 diolamine Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 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
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 235000001497 healthy food Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229960003194 meglumine Drugs 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
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229950004864 olamine Drugs 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 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
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Abstract
Description
본 발명은 라우르산 유도체를 포함하는 방광암의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, improving or treating bladder cancer comprising a lauric acid derivative.
암세포는 정상세포와 여러 가지 면에서 다르다. 정상세포는 자신들의 필요에 의해서, 그리고 필요한 장소에서 증식한다. 정상세포는 서로 붙어서 함께하는 모습을 보인다. 또한, 정상세포는 너무 오래되거나 손상되면 자기 스스로 파괴한다. 그러나 암세포는 이들 기능이 모두 결여되어 있어서 궁극적으로 계속 분열을 함으로써 암세포 덩어리인 종양을 형성한다. Cancer cells differ in many ways from normal cells. Normal cells multiply by their needs and where they are needed. Normal cells appear to stick together. In addition, normal cells destroy themselves if too old or damaged. However, because cancer cells lack all of these functions, they ultimately divide, forming tumors that are clusters of cancer cells.
방광암은 방광에 생기는 악성종양이다. 방광에 발생한 암의 대부분은 상피세포로부터 유래된 상피세포종양이며 악성 상피종양에는 요로세포암종, 편평세포암종, 샘암종이 있다. 방광암은 진행단계에 따라 방광 점막이나 점막 하층에만 국한되어 있는 비근침윤성(표재성) 방광암과 방광암이 근육층을 침범한 근침윤성 방광암 그리고 전이성 방광암으로 나뉜다. 최근에 티쎈트릭이 전이성 방광암 치료제로 사용되고 있다.Bladder cancer is a malignant tumor that occurs in the bladder. Most bladder cancers are epithelial cell tumors derived from epithelial cells, and malignant epithelial tumors include urinary cell carcinoma, squamous cell carcinoma, and adenocarcinoma. Bladder cancer is divided into non-muscle-invasive (superficial) bladder cancer, which is limited to the bladder mucosa or submucosal layer, and muscle-infiltrating bladder cancer where the bladder cancer has invaded the muscle layer and metastatic bladder cancer according to the progression stage. Recently, Tibetrick is used as a treatment for metastatic bladder cancer.
방광내 약물 주입법의 부작용은 사용 약물에 따라 다르나 화학 요법제들은 방광 점막에서의 흡수로 인한 전신적인 부작용과 방광자극 증상을 일으킬 수 있다. 전반적으로 기존 항방광암제는 식욕 부진, 오심, 구토, 설사, 전신 쇠약감, 탈모 등을 동반하며, 세포독성이 매우 커 건강한 세포를 멸절시킬 수 있다. 이에 따라, 기존의 항방광암제의 부작용을 최소화하고 미량으로 탁월한 항방광암 활성을 발휘할 수 있는 항방광암제 개발이 필요한 실정이다. The side effects of intra-bladder drug infusion vary depending on the drug used, but chemotherapy agents can cause systemic side effects and bladder irritation symptoms due to absorption from the bladder mucosa. Overall, existing anti-bladder cancer drugs are accompanied by anorexia, nausea, vomiting, diarrhea, general weakness, hair loss, etc., and are highly cytotoxic, which can destroy healthy cells. Accordingly, there is a need to develop an anti-bladder cancer agent that can minimize side effects of the existing anti-bladder cancer agent and exert excellent anti-bladder cancer activity in trace amounts.
본 발명자들은 라우르산 유도체 화합물을 고안하여 총 5종의 라우르산 유도체들을 합성하였으며, 라우르산 유도체 화합물이 우수한 방광암 세포주 사멸효과를 보임을 확인하고 본 발명을 완성하였다.The present inventors devised a lauric acid derivative compound to synthesize a total of 5 lauric acid derivatives, and confirmed that the lauric acid derivative compound showed excellent bladder cancer cell line killing effect and completed the present invention.
본 발명의 목적은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of bladder cancer comprising a compound represented by Formula 1, or a pharmaceutically acceptable salt thereof.
본 발명의 다른 목적은 상기 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 개선용 건강기능식품 및 건강식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food and a health food composition for the prevention or improvement of bladder cancer comprising the compound represented by Formula 1, or a pharmaceutically acceptable salt thereof.
본 발명의 또 다른 목적은 상기 화학식 1로 표시되는 화합물의 제조방법을 제공하는 것이다.Another object of the present invention is to provide a method for preparing a compound represented by Chemical Formula 1.
상기 목적을 달성하기 위하여,In order to achieve the above object,
본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention or treatment of bladder cancer comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof.
[화학식 1][Formula 1]
상기 화학식 1에 있어서,In Chemical Formula 1,
R1은 , , , 및 로 이루어지는 군으로부터 선택되는 치환기이다.R 1 is , , , And It is a substituent selected from the group consisting of.
또한, 본 발명은 상기 화학식 1로 표시되는 화합물 또는 이의 식품학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving bladder cancer comprising the compound represented by Chemical Formula 1 or a food acceptable salt thereof.
또한, 본 발명은 상기 화학식 1로 표시되는 화합물 또는 이의 식품학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 개선용 건강식품 조성물을 제공한다.In addition, the present invention provides a health food composition for preventing or improving bladder cancer comprising the compound represented by Formula 1 or a food-acceptable salt thereof.
나아가, 본 발명은 하기 반응식 1에 나타낸 바와 같이,Furthermore, the present invention, as shown in
유기용매에 라우르산 및 레스베라트롤을 용해하여 환류하고, 교반하여 화합물 1을 얻는 단계(단계 1);Dissolving lauric acid and resveratrol in an organic solvent, refluxing, and stirring to obtain compound 1 (step 1);
를 포함하는 상기 화학식 1로 표시되는 화합물의 제조방법을 제공한다.It provides a method for producing a compound represented by the formula (1) comprising a.
[반응식 1][Scheme 1]
상기 반응식 1에서,In
상기 R1은 또는 이다.R 1 is or to be.
더 나아가, 본 발명은 하기 반응식 2에 나타낸 바와 같이,Furthermore, the present invention, as shown in
유기용매에 라우르산 및 화합물 2를 용해하여 환류하고, 교반하여 화합물 1을 얻는 단계(단계 1);Dissolving lauric acid and
를 포함하는 상기 화학식 1로 표시되는 화합물의 제조방법을 제공한다.It provides a method for producing a compound represented by the formula (1) comprising a.
[반응식 2][Scheme 2]
상기 반응식 2에서,In
상기 R1은 , 및 로 이루어지는 군으로부터 선택되는 치환기이다.R 1 is , And It is a substituent selected from the group consisting of.
본 발명에 따른 화학식 1로 표시되는 화합물은 항방광암 활성이 우수하므로, 방광암 예방, 개선 및 치료 용도로 유용할 수 있다.Since the compound represented by Formula 1 according to the present invention has excellent anti-bladder cancer activity, it may be useful for preventing, improving and treating bladder cancer.
도 1은 실시예 1의 화합물 처리 농도에 따른 방광암세포주의 세포 형태(morphology) 변화를 현미경으로 관찰한 이미지이다.
도 2는 실시예 1(example 1)의 화합물 처리 농도에 따른 방광암세포주의 MTT assay를 통한 세포의 생존률(%)을 나타낸 그래프(a) 및 IC50 값을 나타낸 그래프(b)이다.
도 3은 실시예 1의 화합물 처리 농도에 따른 방광암세포주의 Annexin V 염색을 통한 세포 사멸을 확인한 결과이다(Live: 세포 생존, Early Apoptosis: 초기 사멸, Late Apop./Dead: 후기 사멸 및 세포 죽음, Dead: 세포 죽음).
도 4는 실시예 1의 화합물 처리 농도에 따른 방광암세포주의 사멸 단계 정도(% Gated)를 나타낸 그래프이다(Live: 세포 생존, Early Apoptosis: 초기 사멸, Late Apop./Dead: 후기 사멸 및 세포 죽음, Dead: 세포 죽음).1 is a microscopic image of changes in cell morphology of bladder cancer cell lines according to the compound treatment concentration of Example 1.
Figure 2 is a graph showing the survival rate (%) of cells through the MTT assay of the bladder cancer cell line according to the compound treatment concentration of Example 1 (example 1) (a) and a graph showing the IC 50 value (b).
3 is a result of confirming cell death through Annexin V staining of bladder cancer cell line according to the compound treatment concentration of Example 1 (Live: cell survival, Early Apoptosis: early death, Late Apop./Dead: late death and cell death, Dead: cell death).
Figure 4 is a graph showing the degree of death (% Gated) of the bladder cancer cell line according to the compound treatment concentration of Example 1 (Live: cell survival, Early Apoptosis: early death, Late Apop./Dead: late death and cell death, Dead: cell death).
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
방광암 예방 또는 치료용 약학적 조성물Pharmaceutical composition for preventing or treating bladder cancer
본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention or treatment of bladder cancer comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof.
상기 화학식 1에 있어서,In Chemical Formula 1,
R1은 , , , 및 로 이루어지는 군으로부터 선택되는 치환기이다.R 1 is , , , And It is a substituent selected from the group consisting of.
본 발명의 상기 약학적 조성물에 있어서, 본 발명에 따른 화학식 1로 표시되는 화합물의 바람직한 예로는 하기의 화합물 군을 들 수 있다.In the pharmaceutical composition of the present invention, preferred examples of the compound represented by Formula 1 according to the present invention include the following compound groups.
1) (E)-5-(4-히드록시스티릴)-1,3-페닐렌 다이도데카노에이트;1) (E)-5-(4-hydroxystyryl)-1,3-phenylene didodecanoate;
2) (E)-5-(4-(도데카노일옥시)스티릴)-1,3-페닐렌 다이도데카노에이트;2) (E)-5-(4-(dodecanoyloxy)styryl)-1,3-phenylene didodecanoate;
3) 4-아세트아미도페닐도데카노에이트;3) 4-acetamidophenyldodecanoate;
4) 2-아세톡시벤조익 도데카노익 안히드라이드; 및4) 2-acetoxybenzoic dodecanoic anhydride; And
5) 도데카노익 2-(4-이소부틸페닐)프로파노익 안히드라이드.5) Dodecanoic 2-(4-isobutylphenyl) propanoic anhydride.
본 발명의 상기 화학식 1로 표시되는 화합물은 약학적으로 허용 가능한 염의 형태로 사용할 수 있으며, 염으로는 약학적으로 허용가능한 유리산(free acid)에 의해 형성된 산부가염이 유용하다. 약학적으로 허용가능한 염이란 표현은 환자에게 비교적 비독성이고 무해한 유효작용을 갖는 농도로서 이 염에 기인한 부작용이 화학식 1의 염기 화합물의 이로운 효능을 떨어뜨리지 않는 화학식 1의 염기 화합물의 어떠한 유기 또는 무기 부가염을 의미한다. 이들 염은 유리산으로는 무기산과 유기산을 사용할 수 있으며, 무기산으로는 염산, 브롬산, 질산, 황산, 과염소산, 인산 등을 사용할 수 있고, 유기산으로는 구연산, 초산, 젖산, 말레산, 푸마린산, 글루콘산, 메탄설폰산, 글리콘산, 숙신산, 타타르산, 갈룩투론산, 엠본산, 글루탐산, 아스파르트산, 옥살산, (D) 또는 (L) 말산, 말레산, 메테인설폰산, 에테인설폰산, 4-톨루엔술폰산, 살리실산, 시트르산, 벤조산 또는 말론산 등을 사용할 수 있다. 또한, 이들 염은 알칼리 금속염(나트륨염, 칼륨염 등) 및 알칼리 토금속염(칼슘염, 마그네슘염 등) 등을 포함한다. 예를 들면, 산부가염으로는 아세테이트, 아스파테이트, 벤즈에이트, 베실레이트, 바이카보네이트/카보네이트, 바이설페이트/설페이트, 보레이트, 캄실레이트, 시트레이트, 에디실레이트, 에실레이트, 포메이트, 퓨마레이트, 글루셉테이트, 글루코네이트, 글루큐로네이트, 헥사플루오로포스페이트, 하이벤제이트, 하이드로클로라이드/클로라이드, 하이드로브로마이드/브로마이드, 하이드로요오디드/요오디드, 이세티오네이트, 락테이트, 말레이트, 말리에이트, 말로네이트, 메실레이트, 메틸설페이트, 나프틸레이트, 2-나프실레이트, 니코티네이트, 나이트레이트, 오로테이트, 옥살레이트, 팔미테이트, 파모에이트, 포스페이트/수소 포스페이트/이수소 포스페이트, 사카레이트, 스테아레이트, 석시네이트, 타르트레이트, 토실레이트, 트리플루오로아세테이트, 알루미늄, 알기닌, 벤자틴, 칼슘, 콜린, 디에틸아민, 디올아민, 글라이신, 라이신, 마그네슘, 메글루민, 올아민, 칼륨, 나트륨, 트로메타민, 아연염 등이 포함될 수 있다.The compound represented by Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. The expression pharmaceutically acceptable salt is a concentration having a relatively non-toxic and harmless effect on a patient, and any organic or organic compound of the basic compound of Formula 1, in which side effects caused by the salt do not decrease the beneficial effect of the basic compound of
본 발명에 따른 산 부가염은 통상의 방법, 예를 들면, 화학식 1로 표시되는 화합물을 유기용매, 예를 들면 메탄올, 에탄올, 아세톤, 메틸렌클로라이드, 아세토니트릴 등에 녹이고 유기산 또는 무기산을 가하여 생성된 침전물을 여과, 건조하여 제조되거나, 용매와 과량의 산을 감압 증류한 후 건조하거나 유기용매 하에서 결정화시켜셔 제조할 수 있다.The acid addition salt according to the present invention is a precipitate produced by dissolving a compound represented by Formula 1 in a conventional method, for example, an organic solvent, for example, methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. It can be prepared by filtration and drying, or by distilling the solvent and excess acid under reduced pressure and drying or crystallization under an organic solvent.
또한, 염기를 사용하여 약학적으로 허용 가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리 토금속 염은 예를 들면 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해하고, 비용해 화합물 염을 여과하고, 여액을 증발, 건조시켜 얻는다. 이때, 금속염으로는 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 제약상 적합하다. 또한, 이에 대응하는 은 염은 알칼리 금속 또는 알칼리 토금속 염을 적당한 은 염(예, 질산은)과 반응시켜 얻는다.In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the inexpensive compound salt, and evaporating and drying the filtrate. At this time, it is suitable to manufacture sodium, potassium or calcium salts as metal salts. Further, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).
나아가, 본 발명은 상기 화학식 1의 화합물 및 이의 약학적으로 허용되는 염뿐만 아니라, 이로부터 제조될 수 있는 가능한 용매화물, 수화물, 이성질체, 광학 이성질체 등을 모두 포함한다.Furthermore, the present invention includes all of the compounds of
본 발명의 화합물은 임상 투여시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있으며, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제조된다.The compound of the present invention can be administered in various dosage forms, oral and parenteral, during clinical administration, and when formulated, diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, surfactants, etc., are usually used. Is manufactured.
경구투여를 위한 고형 제제에는 정제, 환자, 산제, 과립제, 캡슐제, 트로키제 등이 포함되며, 이러한 고형 제제는 하나 이상의 본 발명의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스(sucrose), 락토오스(lactose) 또는 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, etc. These solid preparations include at least one excipient such as starch, calcium carbonate, water in one or more compounds of the present invention. It is prepared by mixing sucrose, lactose, or gelatin. In addition, lubricants such as magnesium stearate talc are used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions or syrups, etc. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, are included. Can.
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁용제, 유제, 동결건조제제, 좌제 등이 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤, 젤라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspension solutions, emulsions, lyophilized preparations, suppositories, and the like. As the non-aqueous solvent and suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, etc. may be used.
또한, 본 발명의 화합물의 인체에 대한 효과적인 투여량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 및 질환 정도에 따라 달라질 수 있으며, 일반적으로 약 0.001~100 mg/kg/일이며, 바람직하게는 0.01~35 mg/kg/일이다. 몸무게가 70 ㎏인 성인 환자를 기준으로 할 때, 일반적으로 0.07~7000 mg/일이며, 바람직하게는 0.7~2500 ㎎/일이며, 의사 또는 약사의 판단에 따라 일정시간 간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다.In addition, the effective dosage of the compound of the present invention to the human body may vary depending on the patient's age, weight, sex, dosage form, health status and disease level, and is generally about 0.001 to 100 mg/kg/day, preferably It is 0.01 to 35 mg/kg/day. When based on an adult patient weighing 70 kg, it is generally 0.07 to 7000 mg/day, preferably 0.7 to 2500 mg/day, once a day at regular time intervals according to the judgment of a doctor or pharmacist It can also be administered in multiple doses.
방광암 예방 또는 개선용 건강기능식품 및 건강식품 조성물Health functional food and health food composition for preventing or improving bladder cancer
본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 식품학적으로 허용가능한 염을 포함하는 방광암의 예방 또는 개선용 건강기능식품 또는 건강식품 조성물을 제공한다.The present invention provides a health functional food or health food composition for preventing or improving bladder cancer comprising a compound represented by the following
[화학식 1][Formula 1]
상기 화학식 1에 있어서,In
R1은 , , , 및 로 이루어지는 군으로부터 선택되는 치환기이다.R 1 is , , , And It is a substituent selected from the group consisting of.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 화학식 1로 표시되는 화합물은 하기 화합물 군으로부터 선택되는 어느 하나인 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the compound represented by
1) (E)-5-(4-히드록시스티릴)-1,3-페닐렌 다이도데카노에이트;1) (E)-5-(4-hydroxystyryl)-1,3-phenylene didodecanoate;
2) (E)-5-(4-(도데카노일옥시)스티릴)-1,3-페닐렌 다이도데카노에이트;2) (E)-5-(4-(dodecanoyloxy)styryl)-1,3-phenylene didodecanoate;
3) 4-아세트아미도페닐도데카노에이트;3) 4-acetamidophenyldodecanoate;
4) 2-아세톡시벤조익 도데카노익 안히드라이드; 및4) 2-acetoxybenzoic dodecanoic anhydride; And
5) 도데카노익 2-(4-이소부틸페닐)프로파노익 안히드라이드.5) Dodecanoic 2-(4-isobutylphenyl) propanoic anhydride.
본 발명에 따른 상기 건강기능식품 조성물 또는 건강식품 조성물은 방광암을 예방 또는 개선시키기 위한 목적으로 상기 화학식 1로 표시되는 화합물, 이의 식품학적으로 허용가능한 염, 또는 이의 광학 이성질체를 식품, 음료 등의 건강기능식품 또는 건강식품에 첨가할 수 있다.The health functional food composition or health food composition according to the present invention is a compound represented by the formula (1) for the purpose of preventing or improving bladder cancer, a food acceptable salt thereof, or an optical isomer thereof, such as food, beverage health It can be added to functional foods or health foods.
상기 식품의 종류에는 특별한 제한은 없다. 본 발명에 따른 화합물을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강식품 및 건강기능성식품을 모두 포함한다.There are no particular restrictions on the type of food. Examples of foods to which the compound according to the present invention can be added are drinks, meat, sausage, bread, biscuits, rice cake, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, There are various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and dairy products, and includes both healthy foods and health functional foods in the ordinary sense.
본 발명에 따른 화합물을 함유하는 건강식품 및 건강기능성식품 조성물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 본 발명에 따른 상기 화합물의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 및 건강기능성식품 중의 상기 화합물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 유지를 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The health food and health functional food composition containing the compound according to the present invention may be added to the food as it is or used with other foods or food ingredients, and may be suitably used according to conventional methods. The mixing amount of the compound according to the present invention can be appropriately determined according to its purpose of use (for prevention or improvement). In general, the amount of the compound in the health food and health functional food can be added in 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term intake for the purpose of maintaining health or for the purpose of controlling health, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
본 발명의 건강식품 및 건강기능성식품 조성물은 지시된 비율로 필수 성분으로서 본 발명에 따른 화합물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트라이톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강기능성 식품 조성물 100 g당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health food and health functional food composition of the present invention are essential ingredients in the indicated proportions, and there are no particular limitations on other ingredients other than those containing the compound according to the present invention, and additional ingredients such as various flavors or natural carbohydrates, such as ordinary drinks It can contain as. Examples of the natural carbohydrates described above include monosaccharides, such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, etc.; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatine, stevia extract (for example, rebaudioside A, glycyrrhizine, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the health functional food composition of the present invention.
상기 외에 본 발명에 따른 화합물을 함유하는 건강식품 및 건강기능성식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품 및 건강기능성식품 조성물은 천연 과일쥬스 및 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition to the above, the health food and health functional food composition containing the compound according to the present invention include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.) ), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonic acid used in carbonated beverages, and the like. In addition, the health food and functional food composition of the present invention may contain natural fruit juice and fruit flesh for the production of fruit juice beverages and vegetable beverages.
이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 유효물질을 함유하는 건강식품 및 건강기능성식품 조성물 100 중량부 당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.These ingredients can be used independently or in combination. The ratio of these additives is not so important, but is generally selected from the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and functional food composition containing the active substance of the present invention.
제조방법 1 및 2
본 발명은 하기 반응식 1에 나타낸 바와 같이,The present invention, as shown in
유기용매에 라우르산 및 레스베라트롤을 용해하여 환류하고, 교반하여 화합물 1을 얻는 단계(단계 1);Dissolving lauric acid and resveratrol in an organic solvent, refluxing, and stirring to obtain compound 1 (step 1);
를 포함하는 상기 화학식 1로 표시되는 화합물의 제조방법을 제공한다.It provides a method for producing a compound represented by the formula (1) comprising a.
[반응식 1][Scheme 1]
상기 반응식 1에서,In
상기 R1은 또는 이다.R 1 is or to be.
바람직하게, 상기 반응식 1로부터 제조되는 화학식 1로 표시되는 화합물의 바람직한 예로는 하기의 화합물 군을 들 수 있다.Preferably, a preferable example of the compound represented by
1) (E)-5-(4-히드록시스티릴)-1,3-페닐렌 다이도데카노에이트; 및1) (E)-5-(4-hydroxystyryl)-1,3-phenylene didodecanoate; And
2) (E)-5-(4-(도데카노일옥시)스티릴)-1,3-페닐렌 다이도데카노에이트.2) (E)-5-(4-(dodecanoyloxy)styryl)-1,3-phenylene didodecanoate.
또한, 본 발명은 하기 반응식 2에 나타낸 바와 같이,In addition, the present invention, as shown in
유기용매에 라우르산 및 화합물 2를 용해하여 환류하고, 교반하여 화합물 1을 얻는 단계(단계 1);Dissolving lauric acid and
를 포함하는 상기 화학식 1로 표시되는 화합물의 제조방법을 제공한다.It provides a method for producing a compound represented by the formula (1) comprising a.
[반응식 2][Scheme 2]
상기 반응식 2에서,In
상기 R1은 , 및 로 이루어지는 군으로부터 선택되는 치환기이다.R 1 is , And It is a substituent selected from the group consisting of.
바람직하게, 상기 반응식 2로부터 제조되는 화학식 1로 표시되는 화합물의 바람직한 예로는 하기의 화합물 군을 들 수 있다.Preferably, a preferable example of the compound represented by
3) 4-아세트아미도페닐도데카노에이트;3) 4-acetamidophenyldodecanoate;
4) 2-아세톡시벤조익 도데카노익 안히드라이드; 및4) 2-acetoxybenzoic dodecanoic anhydride; And
5) 도데카노익 2-(4-이소부틸페닐)프로파노익 안히드라이드.5) Dodecanoic 2-(4-isobutylphenyl) propanoic anhydride.
본 발명에 따른 제조방법에 있어서, 상기 유기용매는 에탄올, 테트라히드로퓨란(THF), 벤젠, KOH/MeOH, MeOH, 톨루엔, CH2Cl2, 헥산, 디메틸포름아미드(DMF), 디이소프로필에테르, 디에틸에테르, 디옥산, 디메틸아세트아미드(DMA), 디메틸설폭사이드(DMSO), 아세톤, 클로로벤젠 등을 단독으로 또는 혼합하여 사용할 수 있다. 바람직하게, 상기 반응식 1 및 반응식 2의 단계 1의 유기용매로는 테트라히드로퓨란(THF)을 사용할 수 있다.In the production method according to the present invention, the organic solvent is ethanol, tetrahydrofuran (THF), benzene, KOH/MeOH, MeOH, toluene, CH 2 Cl 2 , hexane, dimethylformamide (DMF), diisopropyl ether , Diethyl ether, dioxane, dimethylacetamide (DMA), dimethylsulfoxide (DMSO), acetone, chlorobenzene and the like can be used alone or in combination. Preferably, tetrahydrofuran (THF) may be used as the organic solvent of
이하, 본 발명을 하기의 실시예에 의하여 더욱 상세하게 설명한다. 단, 하기의 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기의 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples.
라우르산Lauric acid 유도체의 제조 Preparation of derivatives
<<
실시예Example
1-2> 라우르산 유도체의 제조 1 1-2> Preparation of
실시예 1 및 2의 라우르산 유도체를 합성한 방법은 하기 반응식 1에 나타낸 바와 같다.The method of synthesizing the lauric acid derivatives of Examples 1 and 2 is as shown in
구체적으로, Deanstark 기구를 이용하여 실온에서 충분히 건조시킨 250mL one necked round-bottomed flask에 라우르산(lauric acid; 6.06 g, 0.03 mol) 및 레스베라트롤(resveratrol; 2.28g, 0.01mol)을 테트라히드로퓨란(tetrahydrofuran; THF) 20 mL를 용매로 하여 환류(reflux)하였다. 24시간 교반 후, deanstark으로 제거된 물을 확인하고 TLC로 반응의 정도와 완결을 확인하였다. 얻어진 고체상의 반응물을 flash column chromatography하여 화학식 1로 표시되는 실시예 1 및 2의 화합물을 제조하였다.Specifically, lauric acid (6.06 g, 0.03 mol) and resveratrol (2.28 g, 0.01 mol) were added to tetrahydrofuran in a 250 mL one necked round-bottomed flask sufficiently dried at room temperature using a Deanstark instrument. Tetrahydrofuran (THF) was refluxed with 20 mL of solvent as a solvent. After stirring for 24 hours, the water removed by deanstark was checked, and the degree and completion of the reaction were confirmed by TLC. The obtained solid phase reactants were subjected to flash column chromatography to prepare compounds of Examples 1 and 2 represented by
[반응식 1][Scheme 1]
실시예Example 1 : (E)-5-(4- 1: (E)-5-(4- 히드록시스티릴Hydroxystyryl )-1,3-)-1,3- 페닐렌Phenylene 다이도데카노에이트Daido Decanoate ((E)-5-(4-Hydroxystyryl)-1,3-phenylene didodecanoate) ((E)-5-(4-Hydroxystyryl)-1,3-phenylene didodecanoate)
상기 방법을 통하여 수득된 갈색 고체 성상의 실시예 1의 화합물(1.60g, 수득률 27.0%)의 특성은 다음과 같다.The properties of the compound of Example 1 (1.60 g, yield 27.0%) of the brown solid property obtained through the above method are as follows.
Yield: 27.0%; Yield: 27.0%;
mp: 513~514 ℃; mp: 513-514°C;
Rf: 0.4(TLC eluent; E.A:n-Hexane = 3:7 v/v); R f : 0.4 (TLC eluent; EA:n-Hexane = 3:7 v/v);
MASS(70eV), m/z(rel. intensity %); 592.4(100), 593.4(41.2), 591.4(8.2); MASS (70 eV), m/z (rel. intensity %); 592.4(100), 593.4(41.2), 591.4(8.2);
1H NMR(CDCl3, 400MHz): δ 0.87(s, 6H), 1.25(m, 32H), 1.61(d, 4H), 2.55(d, 4H), 6.17(t, 4H), 6.87(s, 1H) 6.91(t, 4H); 1 H NMR (CDCl 3 , 400 MHz): δ 0.87 (s, 6H), 1.25 (m, 32H), 1.61 (d, 4H), 2.55 (d, 4H), 6.17 (t, 4H), 6.87 (s, 1H) 6.91 (t, 4H);
13C NMR(CDCl3, 100MHz): δ 178.997(1C), 173.920(1C), 156.390(1C), 148.537(2C), 138.889(2C), 133.671(2C), 129.835(2C), 121.185(1C), 115.238(4C), 33.963(1C) 31.914(1C), 29.607(12C), 24.725(1C), 22.695(1C), 14.133(2C); 13 C NMR (CDCl 3 , 100 MHz): δ 178.997 (1C), 173.920 (1C), 156.390 (1C), 148.537 (2C), 138.889 (2C), 133.671 (2C), 129.835 (2C), 121.185 (1C) , 115.238 (4C), 33.963 (1C) 31.914 (1C), 29.607 (12C), 24.725 (1C), 22.695 (1C), 14.133 (2C);
Anal. calc. for C38H56O5: C 76.99, H 9.52, O 13.49; Found: C 77.02, H 9.52, O 13.48.Anal. calc. for C 38 H 56 O 5 : C 76.99, H 9.52, O 13.49; Found: C 77.02, H 9.52, O 13.48.
실시예Example 2 : (E)-5-(4-( 2: (E)-5-(4-( 도데카노일옥시Dodecanoyloxy )) 스티릴Styryl )-1,3-)-1,3- 페닐렌Phenylene 다이도데카노에이Daido de Cano A 트 ((E)-5-(4-(Dodecanoyloxy)styryl)-1,3-phenylene ((E)-5-(4-(Dodecanoyloxy)styryl)-1,3-phenylene didodecanoatedidodecanoate ))
상기 방법을 통하여 수득된 연갈색 액체 성상의 실시예 2의 화합물(3.02g, 수득률 50.7%)의 특성은 다음과 같다.The properties of the compound of Example 2 (3.02 g, yield 50.7%) in the form of a light brown liquid obtained through the above method are as follows.
Yield: 50.7%; Yield: 50.7%;
mp: sticky oil, mp: sticky oil,
Rf: 0.3(TLC eluent; E.A:n-Hexane = 3:7 v/v); R f : 0.3 (TLC eluent; EA:n-Hexane = 3:7 v/v);
MASS(70eV), m/z(rel. intensity %); 774.6(100) 775.6(54.1) 776.6(14.3);MASS (70 eV), m/z (rel. intensity %); 774.6 (100) 775.6 (54.1) 776.6 (14.3);
1H NMR(CDCl3, 400MHz): δ 0.79(t, 9H), 1.17(s, 48H), 1.61(m, 6H), 2.40(m, 6H), 6.17(s, 3H), 6.67(s, 2H), 6.91(s, 4H); 1 H NMR (CDCl 3 , 400 MHz): δ 0.79 (t, 9H), 1.17 (s, 48H), 1.61 (m, 6H), 2.40 (m, 6H), 6.17 (s, 3H), 6.67 (s, 2H), 6.91 (s, 4H);
13C NMR(CDCl3, 100MHz): δ 180.363(3C), 156.451(1C), 156.400(1C), 153.653(1C), 133.457(2C), 129.432(2C), 115.295(7C), 34.150(1C), 31.942(1C), 29.637(24C) 24.725(1C), 22.718(1C), 14.132(3C); 13 C NMR (CDCl 3 , 100 MHz): δ 180.363 (3C), 156.451 (1C), 156.400 (1C), 153.653 (1C), 133.457 (2C), 129.432 (2C), 115.295 (7C), 34.150 (1C) , 31.942 (1C), 29.637 (24C) 24.725 (1C), 22.718 (1C), 14.132 (3C);
Anal. calc. for C50H78O6: C 77.47, H 10.14, O 12.38, Found: C 77.44, H 10.12, O 12.37.Anal. calc. for C 50 H 78 O 6 : C 77.47, H 10.14, O 12.38, Found: C 77.44, H 10.12, O 12.37.
<<
실시예Example
3-5> 라우르산 유도체의 제조 2 3-5> Preparation of
실시예 3 내지 5의 라우르산 유도체를 합성한 방법은 하기 반응식 2에 나타낸 바와 같다.The method of synthesizing the lauric acid derivatives of Examples 3 to 5 is as shown in
구체적으로, 상기 실시예 1-2와 실질적으로 동일한 방법을 행하여 제조하되, 상기 라우르산을 다른 농도(2.00g, 0.01mol)로 첨가하고, 레스베라트롤 대신 화합물 2(실시예 3: R1=4-아세트아미도페닐-, 1.51g, 0.01mol; 실시예 4: R1=2-아세톡시벤조일-, 1.80g, 0.01mol; 실시예 5: R1=2-(4-이소부틸페닐)프로파노일-, 2.06g, 0.01mol)를 이용하여 화학식 1로 표시되는 실시예 3, 실시예 4 및 실시예 5의 화합물을 제조하였다.Specifically, it was prepared by performing substantially the same method as in Example 1-2, but the lauric acid was added at a different concentration (2.00 g, 0.01 mol), and instead of resveratrol, Compound 2 (Example 3: R 1 =4 -Acetamidophenyl-, 1.51 g, 0.01 mol; Example 4: R 1 =2-acetoxybenzoyl-, 1.80 g, 0.01 mol; Example 5: R 1 =2-(4-isobutylphenyl)pro Compounds of Example 3, Example 4, and Example 5 represented by
[반응식 2][Scheme 2]
실시예Example 3 : 43: 4 -- 아세트아미도페닐도데카노에이트Acetamidophenyldodecanoate (4-Acetamidophenyldodecanoate) (4-Acetamidophenyldodecanoate)
상기 방법을 통하여 수득된 흰색 고체 성상의 실시예 3의 화합물(0.35g, 수득률 10.5%)의 특성은 다음과 같다.The properties of the compound of Example 3 (0.35 g, yield 10.5%) of the white solid phase obtained through the above method are as follows.
Yield: 10.5%; Yield: 10.5%;
mp: 289~290℃; mp: 289-290°C;
Rf: 0.3(TLC eluent; E.A:n-Hexane = 3:7 v/v); R f : 0.3 (TLC eluent; EA:n-Hexane = 3:7 v/v);
MASS(70eV), m/z(rel. intensity %); 332.2(100), 334.2(21.6), 335.2(2.2); MASS (70 eV), m/z (rel. intensity %); 332.2(100), 334.2(21.6), 335.2(2.2);
1H NMR(CDCl3, 400MHz): δ 0.81(s, 3H), 1.12(m, 24H), 1.69(d, 2H), 2.05(s, 3H), 2.47(d, 2H), 6.92(s, 2H), 7.38(s, 2H), 7.59(s, 1H); 1 H NMR (CDCl 3 , 400 MHz): δ 0.81 (s, 3H), 1.12 (m, 24H), 1.69 (d, 2H), 2.05 (s, 3H), 2.47 (d, 2H), 6.92 (s, 2H), 7.38 (s, 2H), 7.59 (s, 1H);
13C NMR(CDCl3, 100MHz): δ 172.770(1C), 168.559(1C), 146.797(1C), 135.441(1C), 121.899(2C), 120.824(2C), 34.350(1C), 31.895(1C), 29.590(6C), 24.913(1C) 24.311(1C), 22.677(1C), 14.119(1C); 13 C NMR (CDCl 3 , 100 MHz): δ 172.770 (1C), 168.559 (1C), 146.797 (1C), 135.441 (1C), 121.899 (2C), 120.824 (2C), 34.350 (1C), 31.895 (1C) , 29.590 (6C), 24.913 (1C) 24.311 (1C), 22.677 (1C), 14.119 (1C);
Anal. calc. for C20H31NO3: C 72.04, H 9.37, N 4.20, O 14.39; Found: C 72.02, H 9.35, N 4.21, O 14.38.Anal. calc. for C 20 H 31 NO 3 : C 72.04, H 9.37, N 4.20, O 14.39; Found: C 72.02, H 9.35, N 4.21, O 14.38.
실시예Example 4 : 24: 2 -- 아세톡시벤조익Acetoxybenzoic 도데카노익Dodecanoic 안히드라이드Anhydride (2- (2- AcetoxybenzoicAcetoxybenzoic dodecanoic anhydride) dodecanoic anhydride)
상기 방법을 통하여 수득된 흰색 고체 성상의 실시예 4의 화합물(2.31g, 수득률 47.0%)의 특성은 다음과 같다.The properties of the compound of Example 4 (2.31 g, yield 47.0%) of the white solid phase obtained through the above method are as follows.
Yield: 47.0%; Yield: 47.0%;
mp: 218~219℃; mp: 218-219°C;
Rf: 0.5(TLC eluent; E.A:n-Hexane = 5:5 v/v); R f : 0.5 (TLC eluent; EA:n-Hexane = 5:5 v/v);
MASS(70eV), m/z(rel. intensity %); 362.2(100), 363.2(22.7), 364.2(2.5);MASS (70 eV), m/z (rel. intensity %); 362.2 (100), 363.2 (22.7), 364.2 (2.5);
1H NMR(CDCl3, 400MHz): δ 0.92(t, 3H), 1.26(m, 16H), 1.57(t, 2H), 2.15(s, 3H), 2.57(t, 2H), 7.31(d, 2H), 7.84(d, 2H); 1 H NMR (CDCl 3 , 400 MHz): δ 0.92 (t, 3H), 1.26 (m, 16H), 1.57 (t, 2H), 2.15 (s, 3H), 2.57 (t, 2H), 7.31 (d, 2H), 7.84 (d, 2H);
13C NMR(CDCl3, 100MHz): δ 175.521(2C), 151.101(1C), 150.897(1C), 134.732(1C), 132.553(1C), 126.004(1C), 124.136(1C), 123.809(1C), 31.920(1C), 34.141(1C), 29.655(14C), 24.491(1C), 22.698(1C), 14.139(1C); 13 C NMR (CDCl 3 , 100 MHz): δ 175.521 (2C), 151.101 (1C), 150.897 (1C), 134.732 (1C), 132.553 (1C), 126.004 (1C), 124.136 (1C), 123.809 (1C) , 31.920 (1C), 34.141 (1C), 29.655 (14C), 24.491 (1C), 22.698 (1C), 14.139 (1C);
Anal. calc. for C20H38O3: C 73.57, H 11.73, O 14.70; Found: C 73.58, H 11.72, O 14.72.Anal. calc. for C 20 H 38 O 3 : C 73.57, H 11.73, O 14.70; Found: C 73.58, H 11.72, O 14.72.
실시예Example 5 : 5: 도데카노익Dodecanoic 2-(4- 2-(4- 이소부틸페닐Isobutylphenyl )) 프로파노익Propanoic 안히드라이드Anhydride (Dodecanoic 2-(4- (Dodecanoic 2-(4- isobutylphenylisobutylphenyl )) propanoicpropanoic anhydride) anhydride)
상기 방법을 통하여 수득된 갈색 고체 성상의 실시예 3의 화합물(1.16g, 수득률 29.9%)의 특성은 다음과 같다.The properties of the compound of Example 3 (1.16 g, yield 29.9%) of the brown solid property obtained through the above method are as follows.
Yield: 29.9%; Yield: 29.9%;
mp: 218~219℃;mp: 218-219°C;
Rf: 0.8(TLC eluent; E.A:n-Hexane = 3:7 v/v); R f : 0.8 (TLC eluent; EA:n-Hexane = 3:7 v/v);
MASS(70eV), m/z(rel. intensity %); 388.3(100), 389.3(27.0), 390.3(2.7);MASS (70 eV), m/z (rel. intensity %); 388.3 (100), 389.3 (27.0), 390.3 (2.7);
1H NMR(MeOD, 400MHz): δ 0.87(t, 9H), 1.28(s, 16H), 1.59(dd, 6H), 2.26(m, 2H), 2.42(t, 2H), 4.08(d, 1H), 7.08(d, 2H), 7.16(d, 2H); 1 H NMR (MeOD, 400 MHz): δ 0.87 (t, 9H), 1.28 (s, 16H), 1.59 (dd, 6H), 2.26 (m, 2H), 2.42 (t, 2H), 4.08 (d, 1H) ), 7.08 (d, 2H), 7.16 (d, 2H);
13C NMR(MeOD, 100MHz): δ 175.145(1C), 173.952(1C), 137.977(1C), 128.980(1C), 126.815(4C), 44.663(1C), 33.695(1C), 31.716(1C), 29.393(1C), 25.845(1C), 24.728(1C), 21.415(3C), 17.423(1C), 13.164(1C); 13 C NMR (MeOD, 100 MHz): δ 175.145 (1C), 173.952 (1C), 137.977 (1C), 128.980 (1C), 126.815 (4C), 44.663 (1C), 33.695 (1C), 31.716 (1C), 29.393 (1C), 25.845 (1C), 24.728 (1C), 21.415 (3C), 17.423 (1C), 13.164 (1C);
Anal. calc. for C25H40O3: C 77.27, H 10.38, O 12.35; Found: C 77.28, H 10.37, O 12.35.Anal. calc. for C 25 H 40 O 3 : C 77.27, H 10.38, O 12.35; Found: C 77.28, H 10.37, O 12.35.
<< 실험예Experimental Example 1> 방광암 세포주에 대한 세포 사멸 효과 평가 1> Evaluation of cell death effect on bladder cancer cell line
실시예 1에 따른 라우르산 유도체 화합물의 항방광암 효과를 평가하기 위하여 다음과 같이 방광암 세포주(5637)을 대상으로 세포 형태 변화 분석 및 세포 사멸 효과 분석을 실시하였다. 방광암 세포주(5637)는 10% 소 혈청(FBS, Capricorn Scientific GmbH, Ebsdorfergrund, Germany) 및 페니실린/스트렙토마이신(각각 100U/ml, 100㎍/㎖, Capricorn Scientific GmbH)이 첨가된 RPMI1640 배지(Capricorn Scientific GmbH)를 이용하여 95%의 습도가 유지되는 37℃ 및 5% CO2 조건의 가습 배양기(incubator)에서 배양하여 하기 실험예에 사용하였다.In order to evaluate the anti-bladder cancer effect of the lauric acid derivative compound according to Example 1, an analysis of cell morphology and cell death effect was performed on the bladder cancer cell line (5637) as follows. The bladder cancer cell line (5637) was RPMI1640 medium (Capricorn Scientific GmbH) with 10% bovine serum (FBS, Capricorn Scientific GmbH, Ebsdorfergrund, Germany) and penicillin/streptomycin (100 U/ml, 100 μg/ml, Capricorn Scientific GmbH, respectively) added. ) Was used in the following experimental example by culturing in a humidified incubator at 37° C. and 5% CO 2 conditions where 95% humidity was maintained.
1-1. 세포의 형태 변화 분석1-1. Analysis of cell morphology
상기 방광암 세포주(5637)를 24칸 배양 접시에 4×104 밀도로 24시간 배양한 다음, 실시예 1에 따른 라우르산 유도체 화합물을 각각 0, 1, 1.5, 2, 2.5 및 3mM의 농도로 처리하고, 24시간 추가 배양한 후에 현미경으로 세포의 형태(morphology)를 관찰하여 그 결과를 도 1에 나타내었다.The bladder cancer cell line (5637) was cultured in a 24 cell culture dish at a density of 4×10 4 for 24 hours, and then the lauric acid derivative compound according to Example 1 was added at a concentration of 0, 1, 1.5, 2, 2.5 and 3 mM, respectively. After treatment, and further cultured for 24 hours, the morphology of the cells was observed under a microscope, and the results are shown in FIG. 1.
그 결과, 화합물 처리 농도가 높아짐에 따라 무처리군(0mM)과 비교했을 때 세포의 형태가 변하는 것을 확인하였고, 세포의 수가 줄어드는 것을 확인하였다.As a result, it was confirmed that the morphology of the cells changed as compared to the untreated group (0 mM) as the compound treatment concentration increased, and it was confirmed that the number of cells decreased.
1-2. 1-2. MTTMTT assay를 통한 세포 활성 분석 Cell activity analysis through assay
상기 방광암 세포주(5637)를 96칸 배양 접시에 1Х104 밀도로 24시간 배양한 다음, 실시예 1에 따른 라우르산 유도체 화합물을 각각 0, 1, 2, 3, 4 및 5mM의 농도로 처리하고, 24시간 추가 배양하였다. 그 다음 PBS 완충액에 녹인 MTT(최종 0.5 mg/mL)용액을 각 세포에 분주하여 4시간 추가 배양하여 formazan 형성을 유도시켰다. 반응 후 well 바닥에 형성된 formazan(보라색 침전물)이 흩어지지 않게 상등액(배지)을 제거하고 디메틸설폭사이드(dimethylsulfoxide)를 분주하여 10분 동안 흔들어 준 후 ELISA reader를 이용하여 550 nm 파장으로 흡광도를 측정하였다. 세포생존율(Cell Viability, %)은 하기 수학식 1에 따라 계산하였다.The bladder cancer cell line (5637) was cultured for 24 hours at a density of 1Х10 4 in a 96-cell culture dish, and the lauric acid derivative compounds according to Example 1 were treated at concentrations of 0, 1, 2, 3, 4, and 5 mM, respectively. Incubated for 24 hours. Then, the MTT (final 0.5 mg/mL) solution dissolved in PBS buffer was dispensed into each cell and further cultured for 4 hours to induce formazan formation. After the reaction, the supernatant (medium) was removed so that the formazan (purple precipitate) formed on the well bottom did not scatter, dimethylsulfoxide was shaken for 10 minutes, and absorbance was measured at a wavelength of 550 nm using an ELISA reader. . Cell viability (%) was calculated according to
[수학식 1][Equation 1]
세포생존율(%) = {1-(화합물 처리군 흡광도/화합물 무처리군 흡광도)}×100Cell viability (%) = {1-(absorbance of compound-treated group/absorbance of compound-untreated group)}×100
그 결과, 도 2에 나타난 바와 같이, 상기 실시예 1의 화합물의 처리에 의해 방광암 세포가 사멸되었으며, 농도의존적으로 방광암세포의 생존율(세포 활성)이 감소되어 3 내지 5 mM 처리군에서는 5637 세포의 생존세포 수가 매우 극적으로 감소하는 것을 확인하였다. 또한, IC50(halfmaximalinhibitoryconcentration)은 2.267 mM로 계산되었다. As a result, as shown in FIG. 2, the bladder cancer cells were killed by the treatment of the compound of Example 1, and the survival rate (cell activity) of the bladder cancer cells was decreased depending on the concentration, so that 5637 cells were treated in the 3 to 5 mM treatment group. It was confirmed that the number of viable cells decreased dramatically. In addition, IC 50 (halfmaximalinhibitoryconcentration) was calculated to be 2.267 mM.
따라서, 본 발명의 상기 실시예 1에 따른 라우르산 유도체 화합물은 방광암세포에 특이적으로 작용하여 세포를 사멸시키는 항방광암 효과를 가짐을 알 수 있었다. Therefore, it was found that the lauric acid derivative compound according to Example 1 of the present invention has an anti-bladder cancer effect that acts specifically on bladder cancer cells and kills the cells.
1-3. 1-3. AnnexinAnnexin V를 통한 세포 사멸 분석 Analysis of cell death through V
상기 방광암 세포주(5637)를 6칸 배양 접시에 2Х105 밀도로 24시간 배양한 다음, 실시예 1에 따른 라우르산 유도체 화합물을 각각 0, 1, 2, 3, 4 및 5 mM의 농도로 처리하고, 24시간 추가 배양하였다. 그 다음 실시예 1의 화합물 처리에 따른 방광암 세포주 사멸 정도를 확인하기 위해 MuseTM Annexin V & Dead cell kit (Millipore, Billerica, MA, USA)를 이용하여 세포막 바깥쪽으로 이동된 포스파디딜세린(phosphatidylserine)을 Annexin-V 염색으로 측정하였고, 그 결과를 도 3 및 도 4에 나타내었다(Live: 세포 생존, Early Apoptosis: 초기 사멸, Late Apop./Dead: 후기 사멸 및 세포 죽음, Dead: 세포 죽음).The bladder cancer cell line (5637) was cultured for 24 hours at a density of 2Х10 5 in a 6-cell culture dish, and then treated with the lauric acid derivative compounds according to Example 1 at concentrations of 0, 1, 2, 3, 4 and 5 mM, respectively. And further cultured for 24 hours. Then, to confirm the degree of bladder cancer cell line death according to the compound treatment of Example 1, Muse TM Annexin V & Dead cell kit (Millipore, Billerica, MA, USA) was used to move phosphatidylserine (phosphatidylserine) out of the cell membrane. Was measured by Annexin-V staining, and the results are shown in FIGS. 3 and 4 (Live: cell survival, Early Apoptosis: early death, Late Apop./Dead: late death and cell death, Dead: cell death).
그 결과, 상기 실시예 1의 라우르산 유도체 화합물의 처리에 의해 농도의존적으로 방광암 세포주의 사멸이 증가하는 것을 확인하였다. As a result, it was confirmed that the death of the bladder cancer cell line increased in a concentration-dependent manner by treatment with the lauric acid derivative compound of Example 1 above.
따라서, 본 발명의 상기 실시예 1에 따른 라우르산 유도체 화합물은 방광암 세포에 작용하여 세포를 사멸시키는 항방광암 효과를 가짐을 알 수 있었다. Accordingly, it was found that the lauric acid derivative compound according to Example 1 of the present invention has an anti-bladder cancer effect by acting on bladder cancer cells and killing the cells.
상기와 같은 결과는 본 발명의 실시예에 따른 화합물이 항방광암 활성을 가짐을 시사하는 것이다.The above results suggest that the compound according to the embodiment of the present invention has anti-bladder cancer activity.
<제제예 1> 약학적 제제의 제조<Formulation Example 1> Preparation of pharmaceutical formulation
<1-1> 산제의 제조<1-1> Preparation of powder
화학식 1의 화합물
2 gCompound of
유당 1 gLactose 1 g
상기의 성분을 혼합한 후, 기밀포에 충진하여 산제를 제조하였다.After mixing the above components, the air-tight fabric was filled to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of tablets
화학식 1의 화합물
100 ㎎Compound of
옥수수전분
100 ㎎
유 당
100 ㎎
스테아린산 마그네슘
2 ㎎
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional tablet manufacturing method.
<1-3> 캡슐제의 제조<1-3> Preparation of capsules
화학식 1의 화합물
100 ㎎Compound of
옥수수전분
100 ㎎
유 당
100 ㎎
스테아린산 마그네슘
2 ㎎
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsules were prepared by filling the gelatin capsules according to a conventional capsule preparation method.
<1-4> 주사액제의 제조<1-4> Preparation of Injection Solution
화학식 1의 화합물
10 ㎍/㎖Compound of
묽은 염산 BP pH 3.5로 될 때까지Dilute hydrochloric acid BP until pH 3.5
주사용 염화나트륨 BP 최대 1 ㎖Sodium chloride BP for injection Up to 1 ml
적당한 용적의 주사용 염화나트륨 BP 중에 본 발명에 따른 화학식 1의 화합물을 용해시키고, 생성된 용액의 pH를 묽은 염산 BP를 사용하여 pH 3.5로 조절하고, 주사용 염화나트륨 BP를 사용하여 용적을 조절하고 충분히 혼합하였다. 용액을 투명 유리로 된 5 ㎖ 타입 I 앰플 중에 충전시키고, 유리를 용해시킴으로써 공기의 상부 격자하에 봉입시키고, 120 ℃에서 15 분 이상 오토클래이브시켜 살균하여 주사액제를 제조하였다.Dissolve the compound of
<< 제제예Formulation example 2> 건강기능식품 및 건강식품의 제조 2> Production of health functional food and health food
<2-1> 건강기능식품의 제조<2-1> Preparation of health functional food
화학식 1의 화합물
100 mgCompound of
비타민 혼합물 적량Vitamin mixture Proper
비타민 A 아세테이트 70 μgVitamin A acetate 70 μg
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 μgVitamin B12 0.2 μg
비타민 C 10 mgVitamin C 10 mg
비오틴 10 μgBiotin 10 μg
니코틴산아미드 1.7 mgNicotinamide 1.7 mg
엽산
50 μg
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture Proper
황산제1철 1.75 mgFerrous sulfate 1.75 mg
산화아연 0.82 mgZinc oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium Phosphate 15 mg
제2인산칼슘 55 mgDicalcium phosphate 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘
100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능성 식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능성 식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능성 식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy functional food in a preferred embodiment, the mixing ratio may be arbitrarily modified, and the above components are mixed according to a conventional method for producing a healthy functional food. Then, the granules can be prepared and used in the preparation of a health functional food composition according to conventional methods.
<2-2> 건강 기능 음료의 제조<2-2> Preparation of health functional beverage
화학식 1의 화합물
100 mgCompound of
구연산
100 mg
올리고당 100 mgoligosaccharide 100 mg
매실농축액 2 mgPlum concentrate 2 mg
타우린
100 mg
정제수를 가하여 전체 500 mLPurified water added 500 mL
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 1 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. 상기 조성비는 비교적 기호 음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용 용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.After mixing the above components according to a conventional health drink manufacturing method, after stirring and heating at 85° C. for about 1 hour, the resulting solution is filtered, obtained in a sterilized 1 container, sealed and sterilized, then stored in a refrigerator and then stored in the present invention. It is used for the preparation of healthy beverage compositions. Although the above composition ratio is a mixture of components suitable for a preference drink in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, country of demand, and usage.
<2-3> 유제품(dairy products)의 제조<2-3> Manufacture of dairy products
본 발명의 화학식 1의 라우르산 유도체 화합물 0.01-1 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.0.01-1 parts by weight of the lauric acid derivative compound of
<2-4> <2-4> 선식의Linear 제조 Produce
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 상기에서 제조한 곡물류 및 종실류의 건조분말과 본 발명의 화학식 1의 라우르산 유도체 화합물을 다음의 비율로 배합하여 제조하였다.The brown rice, barley, glutinous rice, and yulmu were alpha-polished by a known method to distribute the dried one, and then prepared into a powder having a particle size of 60 mesh with a grinder. Black soybeans, black sesame seeds, and perilla seeds were also steamed and dried by a known method, and then distributed in a pulverizer to prepare a powder having a particle size of 60 mesh. The dry powder of the grains and seeds prepared above and the lauric acid derivative compound of
곡물류(현미 34 중량부, 율무 19 중량부, 보리 20 중량부),Cereals (34 parts by weight of brown rice, 19 parts by weight of barley, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds),
화학식 1의 화합물 (2 중량부),Compound of formula 1 (2 parts by weight),
영지(1.5 중량부), 및Territory (1.5 parts by weight), and
지황(1.5 중량부).Turmeric (1.5 parts by weight).
Claims (7)
[화학식 1]
(상기 화학식 1에 있어서,
R1은 , , , 및 로 이루어지는 군으로부터 선택되는 치환기이다).
A pharmaceutical composition for preventing or treating bladder cancer comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof:
[Formula 1]
(In the above formula 1,
R 1 is , , , And It is a substituent selected from the group consisting of).
상기 화학식 1로 표시되는 화합물은 하기 화합물 군으로부터 선택되는 어느 하나인 것을 특징으로 하는 방광암의 예방 또는 치료용 약학적 조성물:
1) (E)-5-(4-히드록시스티릴)-1,3-페닐렌 다이도데카노에이트;
2) (E)-5-(4-(도데카노일옥시)스티릴)-1,3-페닐렌 다이도데카노에이트;
3) 4-아세트아미도페닐도데카노에이트;
4) 2-아세톡시벤조익 도데카노익 안히드라이드; 및
5) 도데카노익 2-(4-이소부틸페닐)프로파노익 안히드라이드.
According to claim 1,
The compound represented by Formula 1 is a pharmaceutical composition for the prevention or treatment of bladder cancer, characterized in that any one selected from the following group of compounds:
1) (E)-5-(4-hydroxystyryl)-1,3-phenylene didodecanoate;
2) (E)-5-(4-(dodecanoyloxy)styryl)-1,3-phenylene didodecanoate;
3) 4-acetamidophenyldodecanoate;
4) 2-acetoxybenzoic dodecanoic anhydride; And
5) Dodecanoic 2-(4-isobutylphenyl) propanoic anhydride.
[화학식 1]
(상기 화학식 1에 있어서,
R1은 , , , 및 로 이루어지는 군으로부터 선택되는 치환기이다).
Health functional food composition for preventing or improving bladder cancer comprising a compound represented by the following formula (1) or a food-acceptable salt thereof:
[Formula 1]
(In the above formula 1,
R 1 is , , , And It is a substituent selected from the group consisting of).
[화학식 1]
(상기 화학식 1에 있어서,
R1은 , , , 및 로 이루어지는 군으로부터 선택되는 치환기이다).
Health food composition for preventing or improving bladder cancer comprising a compound represented by the following formula (1) or a food-acceptable salt thereof:
[Formula 1]
(In the above formula 1,
R 1 is , , , And It is a substituent selected from the group consisting of).
유기용매에 라우르산 및 레스베라트롤을 용해하여 환류하고, 교반하여 화합물 1을 얻는 단계(단계 1);
를 포함하는 제1항의 화학식 1로 표시되는 화합물의 제조방법:
[반응식 1]
(상기 반응식 1에서,
상기 R1은 또는 이다).
As shown in Scheme 1 below,
Dissolving lauric acid and resveratrol in an organic solvent, refluxing, and stirring to obtain compound 1 (step 1);
Method for preparing a compound represented by Formula 1 of claim 1 comprising:
[Scheme 1]
(In Scheme 1 above,
R 1 is or to be).
유기용매에 라우르산 및 화합물 2를 용해하여 환류하고, 교반하여 화합물 1을 얻는 단계(단계 1);
를 포함하는 제1항의 화학식 1로 표시되는 화합물의 제조방법:
[반응식 2]
(상기 반응식 2에서,
상기 R1은 , 및 로 이루어지는 군으로부터 선택되는 치환기이다).
As shown in Scheme 2 below,
Dissolving lauric acid and compound 2 in an organic solvent to reflux and stirring to obtain compound 1 (step 1);
Method for preparing a compound represented by Formula 1 of claim 1 comprising:
[Scheme 2]
(In Scheme 2 above,
R 1 is , And It is a substituent selected from the group consisting of).
상기 단계 1의 유기용매는 에탄올, 테트라히드로퓨란(THF), 벤젠, KOH/MeOH, MeOH, 톨루엔, CH2Cl2, 헥산, 디메틸포름아미드(DMF), 디이소프로필에테르, 디에틸에테르, 디옥산, 디메틸아세트아미드(DMA), 디메틸설폭사이드(DMSO), 아세톤 및 클로로벤젠으로 이루어지는 군으로부터 선택되는 1종 이상인 것을 특징으로 하는 제조방법.The method of claim 5 or 6,
The organic solvent of step 1 is ethanol, tetrahydrofuran (THF), benzene, KOH/MeOH, MeOH, toluene, CH 2 Cl 2 , hexane, dimethylformamide (DMF), diisopropyl ether, diethyl ether, di A production method characterized by at least one member selected from the group consisting of oxane, dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), acetone and chlorobenzene.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190003856A KR102144628B1 (en) | 2019-01-11 | 2019-01-11 | Composition for preventing, improving or treating of bladder cancer comprising lauric acid derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190003856A KR102144628B1 (en) | 2019-01-11 | 2019-01-11 | Composition for preventing, improving or treating of bladder cancer comprising lauric acid derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20200087500A true KR20200087500A (en) | 2020-07-21 |
KR102144628B1 KR102144628B1 (en) | 2020-08-13 |
Family
ID=71832901
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020190003856A KR102144628B1 (en) | 2019-01-11 | 2019-01-11 | Composition for preventing, improving or treating of bladder cancer comprising lauric acid derivatives |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR102144628B1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080255382A1 (en) * | 2004-01-20 | 2008-10-16 | Brigham Young University | Novel Sirtuin Activating Compounds and Methods for Making the Same |
KR101797813B1 (en) | 2015-07-10 | 2017-11-16 | 제주대학교 산학협력단 | Compositions for preventing or treating bladder cancer comprising citrus fermentd broth with Kombucha as an active ingredient |
KR101845203B1 (en) * | 2017-09-22 | 2018-04-05 | 동아대학교 산학협력단 | Lauric acid derivatives, preparation method thereof and anticancer agent comprising the same |
-
2019
- 2019-01-11 KR KR1020190003856A patent/KR102144628B1/en active IP Right Grant
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080255382A1 (en) * | 2004-01-20 | 2008-10-16 | Brigham Young University | Novel Sirtuin Activating Compounds and Methods for Making the Same |
KR101797813B1 (en) | 2015-07-10 | 2017-11-16 | 제주대학교 산학협력단 | Compositions for preventing or treating bladder cancer comprising citrus fermentd broth with Kombucha as an active ingredient |
KR101845203B1 (en) * | 2017-09-22 | 2018-04-05 | 동아대학교 산학협력단 | Lauric acid derivatives, preparation method thereof and anticancer agent comprising the same |
Also Published As
Publication number | Publication date |
---|---|
KR102144628B1 (en) | 2020-08-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2550038C2 (en) | Novel derivative of purinylpyridinylamino-2,4-difluorophenylsulphonamide, its pharmaceutically acceptable salt, method of its obtaining and pharmaceutical composition, which has inhibition activity with respect to raf-kinase, containing claimed compound as active ingredient | |
KR102410619B1 (en) | A composition comprising the isolated compound 1 from an extract of alder tree for treating and preventing skeleton muscle-related disorder | |
KR101845203B1 (en) | Lauric acid derivatives, preparation method thereof and anticancer agent comprising the same | |
KR102132525B1 (en) | A composition comprising a tussilagone isolated from the extract of Tussilago farfara. for treating and preventing cancer disease | |
KR102022279B1 (en) | A composition comprising an extract of Angelica keiskei for treating and preventing muscle-related disorder | |
KR102144628B1 (en) | Composition for preventing, improving or treating of bladder cancer comprising lauric acid derivatives | |
AU2016273886B2 (en) | A novel compound (KS 513) isolated from pseudolysimachion rotundum var. subintegrum, the composition comprising the same as an active ingredient for preventing or treating allergy disease, inflammatory disease, asthma or chronic obstructive pulmonary disease and the use thereof | |
KR102058323B1 (en) | Composition for preventing, improving or treating of prostate cancer comprising resveratrol derivatives | |
KR101603279B1 (en) | Pharmaceutical composition for prevention or treatment of diseases induced by activation of NFAT5 containing protoberberine derivative or pharmaceutically acceptable salts as an active ingredient | |
KR102157466B1 (en) | Composition for preventing, improving or treating of bladder cancer comprising hexahydrotriazine derivatives | |
KR101864085B1 (en) | Valproic acid derivatives, preparation method thereof and anticonvulsant comprising the same | |
KR102040119B1 (en) | A composition comprising the isolated compounds from an extract of Angelica keiskei for treating and preventing muscle-related disorder | |
KR102058291B1 (en) | Composition comprising ester and acid anhydride compounds or salts thereof for preventing or treating obesity and liver diseases | |
KR102144153B1 (en) | Ester and acid anhydride having antipyretic, analgesic and anti-inflammatory activity and preparation method thereof | |
KR20090016804A (en) | Novel benzyl ester compounds and the composition comprising the same for preventing and treating of obesity, diabetes and hyperlipidemia | |
KR101747044B1 (en) | Phamaceutical composition for preventing or treating of cancers containing cristazine | |
KR101697062B1 (en) | Novel geranyl flavonoid derivative having improved solubility in water, a method for preparing the same and a pharmaceutical composition comprising the same for prevention and treatment of cancer | |
KR101678646B1 (en) | Compositions for anti-Tumor comprising extract or fractions of Artocarpus altilis leaves or stem | |
KR102496887B1 (en) | Composition for preventing, improving or treating of breast cancer comprising butein derivatives or pharmaceutically acceptable salts | |
KR101721490B1 (en) | Phenyl derivatives, preparation method thereof and pharmaceutical composition for prevention or treatment of the cellproliferative diseases containing the same as an active ingredient | |
KR102202867B1 (en) | Composition for preventing, improving or treating of breast cancer comprising hexahydrotriazine derivatives | |
KR102134389B1 (en) | New benzonitrile glycoside compounds and compositions for preventing or treating cancer comprising them | |
KR100686362B1 (en) | A composition comprising an extract of zizyphus jujuba mill. var. inermis rehder for treating and preventing obesity | |
KR100909572B1 (en) | The composition for the treatment of diabetes and metabolic syndrome containing obovatol and its synthesized derivatives | |
KR100833464B1 (en) | (e)-1-(3,4-dihydroxyphenyl)-3-oxopropyl 3-(3,4-dihydroxyphenyl)acrylate derivatives, preparation method thereof and pharmaceutical composition for skin whitening containing the same as an active ingredient |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
E701 | Decision to grant or registration of patent right |