JP2019019063A - New compound, preventive or therapeutic agent for fatty liver, blood cholesterol lowering agent, and blood cholesterol lowering food composition - Google Patents
New compound, preventive or therapeutic agent for fatty liver, blood cholesterol lowering agent, and blood cholesterol lowering food composition Download PDFInfo
- Publication number
- JP2019019063A JP2019019063A JP2017136784A JP2017136784A JP2019019063A JP 2019019063 A JP2019019063 A JP 2019019063A JP 2017136784 A JP2017136784 A JP 2017136784A JP 2017136784 A JP2017136784 A JP 2017136784A JP 2019019063 A JP2019019063 A JP 2019019063A
- Authority
- JP
- Japan
- Prior art keywords
- blood cholesterol
- cholesterol lowering
- compound
- agent
- fatty liver
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 title claims abstract description 56
- 150000001875 compounds Chemical class 0.000 title claims abstract description 39
- 210000004369 blood Anatomy 0.000 title claims abstract description 27
- 239000008280 blood Substances 0.000 title claims abstract description 27
- 208000004930 Fatty Liver Diseases 0.000 title claims abstract description 12
- 206010019708 Hepatic steatosis Diseases 0.000 title claims abstract description 12
- 208000010706 fatty liver disease Diseases 0.000 title claims abstract description 12
- 231100000240 steatosis hepatitis Toxicity 0.000 title claims abstract description 12
- 235000013305 food Nutrition 0.000 title claims description 14
- 239000000203 mixture Substances 0.000 title claims description 11
- 239000003814 drug Substances 0.000 title claims description 8
- 229940124597 therapeutic agent Drugs 0.000 title claims description 8
- 239000003529 anticholesteremic agent Substances 0.000 title claims description 7
- 229940127226 anticholesterol agent Drugs 0.000 title claims description 7
- 230000003449 preventive effect Effects 0.000 title description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 230000000069 prophylactic effect Effects 0.000 claims 1
- -1 phosphoric acid amide compound Chemical class 0.000 abstract description 14
- 230000007935 neutral effect Effects 0.000 abstract description 5
- 230000002440 hepatic effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 235000012000 cholesterol Nutrition 0.000 description 7
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 241000269959 Xiphias gladius Species 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000021335 sword fish Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 150000001840 cholesterol esters Chemical class 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- PSQLIMBCWDBHHK-OWWNRXNESA-N CCCCCCCCCCCCCCCC/C=C/C(C(COP(N)(O)=O)NC(CCCCCCCCCCCCCC)=O)O Chemical compound CCCCCCCCCCCCCCCC/C=C/C(C(COP(N)(O)=O)NC(CCCCCCCCCCCCCC)=O)O PSQLIMBCWDBHHK-OWWNRXNESA-N 0.000 description 1
- PSQLIMBCWDBHHK-NXCSZAMKSA-N CCCCCCCCCCCCCCCC/C=C/[C@H]([C@H](COP(N)(O)=O)NC(CCCCCCCCCCCCCC)=O)O Chemical compound CCCCCCCCCCCCCCCC/C=C/[C@H]([C@H](COP(N)(O)=O)NC(CCCCCCCCCCCCCC)=O)O PSQLIMBCWDBHHK-NXCSZAMKSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 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
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000005066 dodecenyl group Chemical group C(=CCCCCCCCCCC)* 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005064 octadecenyl group Chemical group C(=CCCCCCCCCCCCCCCCC)* 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 235000021195 test diet Nutrition 0.000 description 1
- 125000005063 tetradecenyl group Chemical group C(=CCCCCCCCCCCCC)* 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000005040 tridecenyl group Chemical group C(=CCCCCCCCCCCC)* 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 125000005065 undecenyl group Chemical group C(=CCCCCCCCCC)* 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Fats And Perfumes (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
Abstract
Description
本発明は、新規化合物、脂肪肝の予防又は治療剤、血中コレステロール低下剤及び血中コレステロール低下用食品組成物に関するものである。 The present invention relates to a novel compound, an agent for preventing or treating fatty liver, a blood cholesterol lowering agent, and a food composition for lowering blood cholesterol.
シジミは古くから味噌汁や佃煮として食されてきた一般的な和食材であると同時に、「肝臓に良い」、「黄疸によい」などの理由から民間療法として利用されてきた。更に、近年の健康志向の高まりからシジミ抽出物食品が栄養補助食品、健康補助食品やサプリメントとして流通している。 Shijimi is a traditional Japanese food that has been eaten as miso soup and boiled for a long time, and at the same time it has been used as a folk remedy for reasons such as “good for the liver” and “good for jaundice”. Furthermore, due to the recent increase in health consciousness, shijimi extract foods are distributed as nutritional supplements, health supplements and supplements.
特許文献1は、シジミ抽出物を含む血中コレステロール低下剤を開示している。
非特許文献1は、シジミ抽出物中のコレステロール低下作用を有する分画を記載し、スフィンゴ脂質を含む分画にコレステロール低下作用があることが記載されている。
Non-Patent
シジミ抽出物が血中コレステロール低下作用を有することは公知であるが、シジミ抽出物中には数多くの成分が存在し、血中コレステロール低下作用を有する物質は特定されていなかった。 Although it is known that a shijimi extract has a blood cholesterol lowering action, there are many components in the shijimi extract, and no substance having a blood cholesterol lowering action has been identified.
本発明は、血中コレステロール低下作用を有する新規化合物、該化合物を含む脂肪肝の予防又は治療剤、血中コレステロール低下剤及び血中コレステロール低下用食品を提供することを目的とする。 An object of the present invention is to provide a novel compound having a blood cholesterol lowering action, a preventive or therapeutic agent for fatty liver containing the compound, a blood cholesterol lowering agent, and a food for lowering blood cholesterol.
本発明者は、血中コレステロール低下作用に基づいてシジミ抽出物を分画し、血中コレステロール低下作用を有する新規化合物を見出した。該化合物は、血中コレステロール低下作用及び肝臓中性脂肪の低下作用を有し、脂肪肝の予防又は治療剤として有用である。 The inventor of the present invention fractionated shijimi extract based on blood cholesterol lowering action and found a novel compound having blood cholesterol lowering action. The compound has a blood cholesterol lowering action and a liver neutral fat lowering action, and is useful as an agent for preventing or treating fatty liver.
本発明は、以下の新規化合物、脂肪肝の予防又は治療剤、血中コレステロール低下剤及び血中コレステロール低下用食品組成物を提供するものである。
項1. 下記式
The present invention provides the following novel compounds, preventive or therapeutic agents for fatty liver, blood cholesterol lowering agents, and food compositions for lowering blood cholesterol.
(式中、R1は炭素数1〜24のアルキル基又はアルケニル基を示す。R2は炭素数1〜24のアルキル基又はアルケニル基を示す。)で表わされる化合物。
項2. 下記式
(Wherein R 1 represents an alkyl group or alkenyl group having 1 to 24 carbon atoms; R 2 represents an alkyl group or alkenyl group having 1 to 24 carbon atoms).
で表わされる、項1に記載の化合物。
項3. 項1又は2に記載の化合物を含む、脂肪肝の予防又は治療剤。
項4. 項1又は2に記載の化合物を含む、血中コレステロール低下剤。
項5. 項1又は2に記載の化合物を含む、血中コレステロール低下用食品組成物。
The compound of claim |
本発明の化合物は、血液、血清、血漿中の総コレステロール、遊離コレステロール、コレステロールエステル、LDL-コレステロール、さらに肝臓中性脂肪を低下させることができる。 The compounds of the present invention can lower total cholesterol, free cholesterol, cholesterol esters, LDL-cholesterol, and liver neutral fat in blood, serum and plasma.
本発明によれば、血中コレステロール低下作用及び肝臓中性脂肪低下作用を有する化合物が提供される。この化合物は血中コレステロール低下用食品組成物あるいは脂肪肝の予防又は治療剤として摂取することで、血中コレステロールを低下させ、脂肪肝を予防又は治療することができる。 According to the present invention, a compound having a blood cholesterol lowering action and a liver neutral fat lowering action is provided. This compound can be taken as a food composition for reducing blood cholesterol or as a preventive or therapeutic agent for fatty liver, thereby reducing blood cholesterol and preventing or treating fatty liver.
本発明は、血中コレステロール低下作用を有する以下の式(I)の化合物を提供するものである。好ましい立体配置を式(IA)に示す。 The present invention provides a compound of the following formula (I) having a blood cholesterol lowering action. A preferred configuration is shown in Formula (IA).
(式中、R1は炭素数1〜24のアルキル基又はアルケニル基を示す。R2は炭素数1〜24のアルキル基又はアルケニル基を示す。)
炭素数1〜24のアルキル基としては、例えば、メチル、エチル、n−プロピル、イソプロピル、n−ブチル、イソブチル、tert−ブチル、ペンチル、ヘキシル、オクチル、2−エチルヘキシル、ノニル、デシル、ウンデシル、ドデシル、トリデシル、テトラデシル、ペンタデシル、ヘキサデシル、ヘプタデシル、ヘプタデシル、ステアリル、イソステアリル、ノナデシル、イコシル、ヘンイコシル、ドコサニル、トリコサニル、テトラコサニルなどの直鎖又は分岐を有する炭素数1〜24、好ましくは炭素数4〜22、より好ましくは炭素数8〜20のアルキル基が挙げられる。
(In the formula, R 1 represents an alkyl group or alkenyl group having 1 to 24 carbon atoms. R 2 represents an alkyl group or alkenyl group having 1 to 24 carbon atoms.)
Examples of the alkyl group having 1 to 24 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, octyl, 2-ethylhexyl, nonyl, decyl, undecyl and dodecyl. , Tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, heptadecyl, stearyl, isostearyl, nonadecyl, icosyl, heicosyl, docosanyl, tricosanyl, tetracosanyl, etc., having 1 to 24 carbon atoms, preferably 4 to 22 carbon atoms More preferably, an alkyl group having 8 to 20 carbon atoms is used.
炭素数1〜24のアルケニル基としては、例えば、ビニル、アリル、ブテニル、イソブテニル、ペンテニル、ヘキセニル、ヘプテニル、オクテニル、ノネニル、デセニル、ウンデセニル、ドデセニル、トリデセニル、テトラデセニル、ペンタデセニル、ヘキサデセニル、ヘプタデセニル、オクタデセニル、イソオクタデセニル、ノナデセニル、イコセニル、ヘンイコセニル、ドコセニル、トリコセニル、テトラコセニルなどの直鎖又は分岐を有する炭素数2〜24、好ましくは炭素数4〜22、より好ましくは炭素数8〜20のアルケニル基が挙げられる。 Examples of the alkenyl group having 1 to 24 carbon atoms include vinyl, allyl, butenyl, isobutenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, isodecenyl, A straight chain or branched alkenyl group having 2 to 24 carbon atoms, preferably 4 to 22 carbon atoms, more preferably 8 to 20 carbon atoms, such as octadecenyl, nonadecenyl, icocenyl, heicosenyl, dococenyl, tricocenyl, tetracocenyl, etc. Can be mentioned.
好ましいR1としては、以下のものが挙げられる: Preferred R 1 includes the following:
好ましいR2としては、以下のものが挙げられる: Preferred R 2 includes the following:
本発明のさらに好ましい化合物を以下に示す。 Further preferred compounds of the present invention are shown below.
本発明の化合物が1以上の不斉炭素を有する場合、各不斉炭素の立体配置はR体、S体、R体とS体の任意の割合の混合物(ラセミ体を含む)を包含する。したがって、本発明の化合物は、各種エナンチオマー及びジアステレオマーを含む。 When the compound of the present invention has one or more asymmetric carbons, the configuration of each asymmetric carbon includes R isomers, S isomers, and mixtures of R isomers and S isomers in any proportion (including racemic isomers). Accordingly, the compounds of the present invention include various enantiomers and diastereomers.
本発明の化合物は、例えば以下のスキーム1〜3のようにして合成することができる。スキーム4は、原料である化合物(4)の製造法を示す。
The compound of the present invention can be synthesized, for example, as shown in the following
(式中、R1、R2は前記に定義されるとおりである。)
化合物(1)1モルに対し、酸クロライド(2)を1モルから過剰量使用し、必要に応じて塩基の存在下に溶媒中で反応させることにより、式(I)の化合物を得ることができる。反応温度は0〜100℃程度であり、反応時間は30分から12時間程度である。塩基としては、炭酸カリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸水素ナトリウムなどのアルカリ金属炭酸塩又は炭酸水素塩、トリエチルアミン、ジイソプロピルエチルアミン、DBUなどが挙げられる。溶媒としては、テトラヒドロフラン、ジエチルエーテル、酢酸エチル、クロロホルム、塩化メチレンなどが挙げられる。
(Wherein R 1 and R 2 are as defined above.)
The compound of the formula (I) can be obtained by using an acid chloride (2) in an excess amount from 1 mol to 1 mol of the compound (1) and reacting in a solvent in the presence of a base as necessary. it can. The reaction temperature is about 0 to 100 ° C., and the reaction time is about 30 minutes to 12 hours. Examples of the base include alkali metal carbonates or bicarbonates such as potassium carbonate, sodium carbonate, potassium bicarbonate and sodium bicarbonate, triethylamine, diisopropylethylamine, DBU and the like. Examples of the solvent include tetrahydrofuran, diethyl ether, ethyl acetate, chloroform, methylene chloride and the like.
(式中、R1、R2は前記に定義されるとおりである。)
化合物(3)1モルに対し、アンモニアを1モルから過剰量使用し、必要に応じて塩基の存在下に溶媒中で反応させることにより、式(I)の化合物を得ることができる。反応温度は室温から100℃程度であり、反応時間は30分から12時間程度である。塩基としては、炭酸カリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸水素ナトリウムなどのアルカリ金属炭酸塩又は炭酸水素塩、アンモニア、トリエチルアミン、ジイソプロピルエチルアミン、DBUなどが挙げられる。溶媒としては、テトラヒドロフラン、ジエチルエーテル、酢酸エチル、クロロホルム、塩化メチレン、ジメチルホルムアミド、ジメチルスルホキシドなどが挙げられる。
(Wherein R 1 and R 2 are as defined above.)
A compound of formula (I) can be obtained by using an excess amount of ammonia from 1 mol to 1 mol of compound (3) and reacting in a solvent in the presence of a base as necessary. The reaction temperature is from room temperature to about 100 ° C., and the reaction time is from about 30 minutes to about 12 hours. Examples of the base include alkali metal carbonates or bicarbonates such as potassium carbonate, sodium carbonate, potassium bicarbonate and sodium bicarbonate, ammonia, triethylamine, diisopropylethylamine, DBU and the like. Examples of the solvent include tetrahydrofuran, diethyl ether, ethyl acetate, chloroform, methylene chloride, dimethylformamide, dimethyl sulfoxide and the like.
(式中、R1、R2は前記に定義されるとおりである。)
化合物(4)1モルに対し、アンモニアを1モルから過剰量使用し、DICのようなカルボジイミド縮合剤を等モルから過剰量使用し、溶媒中で反応させることにより、式(I)の化合物を得ることができる。反応温度は0℃から100℃程度であり、反応時間は30分から12時間程度である。溶媒としては、テトラヒドロフラン、ジエチルエーテル、酢酸エチル、クロロホルム、塩化メチレン、ジメチルホルムアミド、ジメチルアセトアミド、ジメチルスルホキシド、ピリジンなどが挙げられる。
(Wherein R 1 and R 2 are as defined above.)
The compound of formula (I) is reacted by using an excess amount of ammonia from 1 mol to 1 mol of compound (4), using a carbodiimide condensing agent such as DIC in an excess amount from an equimolar amount and reacting in a solvent. Can be obtained. The reaction temperature is about 0 ° C. to 100 ° C., and the reaction time is about 30 minutes to 12 hours. Examples of the solvent include tetrahydrofuran, diethyl ether, ethyl acetate, chloroform, methylene chloride, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, pyridine and the like.
(式中、R1、R2は前記に定義されるとおりである。)
化合物(5)1モルに対し、化合物(6)を1モルから過剰量使用し、塩基の存在下に溶媒中で反応させ、さらにt−BuOOHと反応させることにより、式(I)の化合物を得ることができる。反応温度は−78℃から室温程度であり、反応時間は30分から12時間程度である。塩基としては、トリエチルアミン、ジイソプロピルエチルアミン、DBU、DIPEAなどが挙げられる。溶媒としては、テトラヒドロフラン、ジエチルエーテル、酢酸エチル、クロロホルム、塩化メチレン、ジメチルホルムアミド、ジメチルスルホキシドなどが挙げられる。
(Wherein R 1 and R 2 are as defined above.)
Compound (6) is used in an excess amount from 1 mol to 1 mol of compound (5), reacted in a solvent in the presence of a base, and further reacted with t-BuOOH to give a compound of formula (I). Can be obtained. The reaction temperature is about −78 ° C. to room temperature, and the reaction time is about 30 minutes to 12 hours. Examples of the base include triethylamine, diisopropylethylamine, DBU, DIPEA and the like. Examples of the solvent include tetrahydrofuran, diethyl ether, ethyl acetate, chloroform, methylene chloride, dimethylformamide, dimethyl sulfoxide and the like.
本発明の脂肪肝の予防又は治療剤及び血中コレステロール低下用食品組成物は、製剤の形態が好ましい。製剤としては、具体的には錠剤、カプセル剤(ハードカプセル、ソフトカプセル)、丸剤、チュアブル錠、口腔内崩壊錠、顆粒剤、散剤、液剤、ドリンク剤、懸濁剤、乳濁剤などが挙げられる。 The preventive or therapeutic agent for fatty liver and the food composition for lowering blood cholesterol of the present invention are preferably in the form of a preparation. Specific examples of the preparation include tablets, capsules (hard capsules, soft capsules), pills, chewable tablets, orally disintegrating tablets, granules, powders, solutions, drinks, suspensions, emulsions, and the like. .
本発明の脂肪肝の予防又は治療剤及びコレステロール低下用食品組成物は、本発明の化合物とともに製剤用の担体を含むことができる。このような担体としては、固形製剤の場合、賦形剤、結合剤、崩壊剤、滑沢剤、着色剤、矯味・矯臭剤などが挙げられ、液状製剤の場合、溶剤、溶解補助剤、懸濁化剤、等張化剤、緩衝剤などが挙げられる。また、必要に応じて防腐剤、抗酸化剤、着色剤、甘味剤、安定化剤等の製剤添加物を用いることもできる。カプセル剤の担体としては、ハードカプセルの場合には、カプセル皮膜としてゼラチンを挙げることができ、ソフトカプセルの場合には、カプセル用皮膜として、ゼラチン、多価アルコール(グリセリン、ソルビトール、マンニトール、マルチトール等)等を挙げることができる。ソフトカプセルはさらに水を含んでいてもよい。賦形剤としては、乳糖、白糖、D-マンニトール、ブドウ糖、デンプン、炭酸カルシウム、カオリン、微結晶セルロース、無水ケイ酸等が挙げられる。 The preventive or therapeutic agent for fatty liver and the food composition for lowering cholesterol of the present invention can contain a pharmaceutical carrier together with the compound of the present invention. Examples of such carriers include excipients, binders, disintegrants, lubricants, coloring agents, flavoring and flavoring agents in the case of solid preparations, and solvents, dissolution aids, suspensions in the case of liquid preparations. Examples include turbidity agents, tonicity agents, buffering agents, and the like. Moreover, formulation additives such as preservatives, antioxidants, colorants, sweeteners, stabilizers and the like can be used as necessary. Examples of the capsule carrier include gelatin as a capsule film in the case of a hard capsule, and gelatin and polyhydric alcohol (glycerin, sorbitol, mannitol, maltitol, etc.) as a capsule film in the case of a soft capsule. Etc. The soft capsule may further contain water. Examples of the excipient include lactose, sucrose, D-mannitol, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, and anhydrous silicic acid.
結合剤としては、水、エタノール、1-プロパノール、2-プロパノール、単シロップ、ブドウ糖液、α-デンプン液、ゼラチン液、D-マンニトール、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルスターチ、メチルセルロース、エチルセルロース、シェラック、リン酸カルシウム、ポリビニルピロリドン等が挙げられる。 As binders, water, ethanol, 1-propanol, 2-propanol, simple syrup, glucose solution, α-starch solution, gelatin solution, D-mannitol, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, Shellac, calcium phosphate, polyvinylpyrrolidone and the like can be mentioned.
崩壊剤としては、乾燥デンプン、アルギン酸ナトリウム、カンテン末、炭酸水素ナトリウム、炭酸カルシウム、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド、乳糖等が挙げられる。 Examples of the disintegrant include dry starch, sodium alginate, agar powder, sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, and lactose.
滑沢剤としては、精製タルク、ステアリン酸塩ナトリウム、ステアリン酸マグネシウム、ホウ砂、ポリエチレングリコール等が挙げられる。 Examples of the lubricant include purified talc, sodium stearate, magnesium stearate, borax, and polyethylene glycol.
着色剤としては、酸化チタン、酸化鉄等が挙げられる。 Examples of the colorant include titanium oxide and iron oxide.
矯味・矯臭剤としては白糖、橙皮、クエン酸、酒石酸等が挙げられる。 Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.
緩衝剤としては、クエン酸ナトリウム等が挙げられる。 Examples of the buffer include sodium citrate.
安定剤としては、トラガント、アラビアゴム、ゼラチン等が挙げられる。 Examples of the stabilizer include tragacanth, gum arabic, and gelatin.
本発明の食品組成物は、サプリメントの形態であってもよい。 The food composition of the present invention may be in the form of a supplement.
本発明において、食品としては、グミ、飲料、ドリンクゼリー、キャンデー、クッキー、ビスケットなどが挙げられる。 In the present invention, foods include gummi, beverages, drink jelly, candy, cookies, biscuits and the like.
本発明の化合物は、健常な成人1日当たり5ng〜1mg程度、好ましくは20ng〜0.5mg程度、より好ましくは100ng〜0.1mg程度摂取されることが望ましい。 It is desirable that the compound of the present invention is ingested by about 5 ng to 1 mg, preferably about 20 ng to 0.5 mg, more preferably about 100 ng to 0.1 mg per day for a healthy adult.
以下に参考例、実施例及び試験例を挙げて本発明を更に具体的に説明するが、これらは本発明を限定するものではない。 Hereinafter, the present invention will be described in more detail with reference to Reference Examples, Examples and Test Examples, but these do not limit the present invention.
実施例1
特許文献1の実施例1の記載に従い2.5kgのシジミエキス粉末を得た。得られたシジミエキス粉末2.5kgを、図1のプロトコールに従い分画した。
Example 1
According to the description in Example 1 of
得られた分画のうち、フラクション1-2-7において、以下の構造式の化合物を単離した。 Among the obtained fractions, a compound having the following structural formula was isolated in fraction 1-2-7.
上記化合物のマススペクトルの物性値を以下に示す。
C36H73N2O5P
Exact Mass: 644.5
Mol. Wt.: 644.9
(+)HR-FABMS C36H74N2O5P [M+H]+ 645.5339 Δ+0.4mmu
C36H73N2O5PNa [M+Na]+ 667.5165 Δ+1.1mmu
The physical property values of the mass spectrum of the above compound are shown below.
C 36 H 73 N 2 O 5 P
Exact Mass: 644.5
Mol. Wt .: 644.9
(+) HR-FABMS C 36 H 74 N 2 O 5 P [M + H] + 645.5339 Δ + 0.4mmu
C 36 H 73 N 2 O 5 PNa [M + Na] + 667.5165 Δ + 1.1mmu
上記化合物を含むフラクション1-2-7及びコントロールについて、非特許文献1の記載に従い、高コレステロール食を与えたラットについて、血清総コレステロールを測定した。コントロールはコレステロール0.5%、コール酸ナトリウム0.25%を含む高コレステロール食を自由摂食させたラットである。フラクション1-2-7は同様の高コレステロール食に0.23%添加した試験食を自由摂食させたラットである。結果を表1に示す。血清総コレステロール、LDL-コレステロール、遊離コレステロール、コレステロールエステル及び肝臓中性脂肪の測定は、常法に従い行った。
Regarding fractions 1-2-7 containing the above compounds and controls, serum total cholesterol was measured for rats fed with a high cholesterol diet according to the description in
本発明の化合物が、強力な血中コレステロール低下作用及び肝臓中性脂肪の低下作用を有することが明らかになった。 It was revealed that the compound of the present invention has a strong blood cholesterol lowering action and liver triglyceride lowering action.
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017136784A JP6242532B1 (en) | 2017-07-13 | 2017-07-13 | Novel compound, agent for preventing or treating fatty liver, blood cholesterol lowering agent, and food composition for lowering blood cholesterol |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017136784A JP6242532B1 (en) | 2017-07-13 | 2017-07-13 | Novel compound, agent for preventing or treating fatty liver, blood cholesterol lowering agent, and food composition for lowering blood cholesterol |
Publications (2)
Publication Number | Publication Date |
---|---|
JP6242532B1 JP6242532B1 (en) | 2017-12-06 |
JP2019019063A true JP2019019063A (en) | 2019-02-07 |
Family
ID=60570382
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017136784A Active JP6242532B1 (en) | 2017-07-13 | 2017-07-13 | Novel compound, agent for preventing or treating fatty liver, blood cholesterol lowering agent, and food composition for lowering blood cholesterol |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6242532B1 (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07265089A (en) * | 1994-03-30 | 1995-10-17 | Yakurigaku Chuo Kenkyusho:Kk | Method for producing ceramide from fish or shellfish |
JP2004256456A (en) * | 2003-02-26 | 2004-09-16 | Nitto Kasei Co Ltd | 2-bromoethyldialkyl phosphite, method for producing the same, and method for producing phosphoric ester derivative using the same |
JP2005002324A (en) * | 2003-03-19 | 2005-01-06 | Fisheries Research Agency | Method for producing sphingolipid using hydrosphere organism as raw material |
JP2009024050A (en) * | 2007-07-18 | 2009-02-05 | Fisheries Research Agency | Recovery method of polar lipid fraction from molluscous part of hydrosphere organism |
WO2012119781A2 (en) * | 2011-03-10 | 2012-09-13 | University Of Geneva | Novel lipids, phospholipids, phospholipid and lipid compositions and their use |
WO2016092878A1 (en) * | 2014-12-08 | 2016-06-16 | 武彦 藤野 | Ether phospholipid and method for producing same |
-
2017
- 2017-07-13 JP JP2017136784A patent/JP6242532B1/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07265089A (en) * | 1994-03-30 | 1995-10-17 | Yakurigaku Chuo Kenkyusho:Kk | Method for producing ceramide from fish or shellfish |
JP2004256456A (en) * | 2003-02-26 | 2004-09-16 | Nitto Kasei Co Ltd | 2-bromoethyldialkyl phosphite, method for producing the same, and method for producing phosphoric ester derivative using the same |
JP2005002324A (en) * | 2003-03-19 | 2005-01-06 | Fisheries Research Agency | Method for producing sphingolipid using hydrosphere organism as raw material |
JP2009024050A (en) * | 2007-07-18 | 2009-02-05 | Fisheries Research Agency | Recovery method of polar lipid fraction from molluscous part of hydrosphere organism |
WO2012119781A2 (en) * | 2011-03-10 | 2012-09-13 | University Of Geneva | Novel lipids, phospholipids, phospholipid and lipid compositions and their use |
WO2016092878A1 (en) * | 2014-12-08 | 2016-06-16 | 武彦 藤野 | Ether phospholipid and method for producing same |
Non-Patent Citations (5)
Title |
---|
BJORKBOM, ANDERS ET AL.: "Importance of the phosphocholine linkage on sphingomyelin molecular properties and interactions with", BIOCHIMICA ET BIOPHYSICA ACTA, vol. vol.1778 vol.6, JPN6017031810, 2008, pages 1501 - 1507, ISSN: 0003661964 * |
CHIJIMATSU, TAKESHI ET AL.: "Lipid components prepared from a freshwater Clam(Corbicula fluminea) extract ameliorate hypercholest", FOOD CHEMISTRY, vol. 136, JPN6017031809, 2013, pages 328 - 334, ISSN: 0003661963 * |
KRATZER, BERND ET AL.: "Efficient synthesis of sphingosine-1-phosphate, ceramide-1-phosphate, lysosphingomyelin, and sphingo", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 1995, no. 6, JPN6017031811, 1995, pages 957 - 963, XP002323212, ISSN: 0003661965 * |
千々松武司ほか: "二枚貝,特にシジミの機能性因子に関する研究", NEW FOOD INDUSTRY, vol. 55, no. 8, JPN6017031812, 2013, pages 23 - 31, ISSN: 0003661962 * |
望月聡 ほか: "脂質代謝を中心とした二枚貝の生理作用に関する研究", 科学研究費助成事業 研究成果報告書 [オンライン], JPN6017031808, 11 June 2014 (2014-06-11), ISSN: 0003631161 * |
Also Published As
Publication number | Publication date |
---|---|
JP6242532B1 (en) | 2017-12-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HUE033401T2 (en) | Novel 5-fluorouracil derivative | |
CA2726020A1 (en) | 2-alkoxy-substituted dicyanopyridines and use thereof | |
JP5228912B2 (en) | Antihypertensive agent | |
JP5979376B2 (en) | Highly soluble pyrroloquinoline quinone salt and method for producing the same | |
JP2000273044A (en) | Reducing agent for adverse effect | |
US10563270B2 (en) | Solid forms of menaquinols | |
JPWO2008035686A1 (en) | Insulin resistance improving agent | |
CN1032785A (en) | L-Dopa derivatives or its acid salt, its production method and uses thereof | |
AU2017387070B2 (en) | Nrf2 activator | |
JP6242532B1 (en) | Novel compound, agent for preventing or treating fatty liver, blood cholesterol lowering agent, and food composition for lowering blood cholesterol | |
WO1999011640A1 (en) | Epoxysuccinamide derivatives | |
JP2011231022A (en) | Imidazolone derivative | |
JP7428327B2 (en) | Cancer cell growth inhibiting composition and processed food | |
EP4316487A1 (en) | Composition for preventing or treating neurodegenerative disease comprising compound inducing expression of anti-aging gene klotho | |
CN108863831A (en) | A kind of hydrochloride for injection Propacetamol and preparation method thereof | |
MX2009012644A (en) | Di(hetero)arylcyclohexane derivatives, their preparation, their use and pharmaceutical compositions comprising them. | |
CA2806154A1 (en) | Panthenyl docosahexaeneoate and its use for treating and preventing cardiovascular diseases | |
WO2017060418A1 (en) | Protected carboxylic acid-based metabolites for the treatment of mitochondria-related diseases | |
JP2010126462A (en) | Cerebral function ameliorating composition and functional food containing the composition | |
EP2578588A1 (en) | Novel 1,4-diazepam pde-5 inhibitor derivatives | |
KR20210029993A (en) | Novel dibenzooxaphosphinine oxide derivative compounds and pharmaceutical composition for preventing or treating degenerative disease comprising the same as an active ingredient | |
JP2013513642A (en) | Novel phenylhydrazone derivatives and their use as pharmaceuticals | |
HK1113353A1 (en) | Piperidinesulfonylureas and-thioureas, their preparation, their use and pharmaceutical compositions comprising them | |
JPH07138248A (en) | Ester compound from retinoid and ascorbic acid and derivative therefrom and their production | |
JPS62174060A (en) | 5-fluorouracil derivative and drug preparation containing same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171006 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20171017 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20171107 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6242532 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |